CONTROL OF PARASITES IN ANIMALS BY THE USE OF NOVEL TR1FLUOROMETHANESULFONANILIDE QXIME ETHER DERIVATIVES
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to new trifiuoromethanesuifonanilide oxime ether derivatives useful as parasiticides, compositions containing the compounds, and methods of treatment using the compounds, especially to control animal parasites, e.g., ecto- and endoparasites such as fleas, acaridae, helminths, and nematodes. The invention also relates to the use of a combination of a parasiticide of this invention and one or more additional parasiticides or other agents useful in killing parasites.
Background
The control of animal parasites is essential, especially in the areas of production and companion animals. Existing methods of treatment are being compromised due to growing resistance to current commercial parasiticides, such as the benzimidazoies and ivermectins. The discovery of more effective ways to control animal parasites is therefore imperative.
Trifluoromethanesuifonaniiide oxime ether derivatives have been reported in the patent literature.
in JP 08291146 trifluoromethanesuifonaniiide oxime ether derivatives of Formula A have been disclosed:


wherein:
R" is either hydrogen, C2-C10 alkanoyl or benzoyl optionally substituted by 1 or 2 substituents selected from halo or C1-C4 alkyi;
R2 is either methoxycarbonyl, acetyl, -C(=NOCH3)CH3 or C(=NOCH2CH3)CH3; and
Q is either 2-pyrimidinyl, 5-ha!o-2-pyrimidinyl or 6-halo-3-pyridazinyl.
These compounds have been said to show potent herbicidal activity without damaging rice seedlings.
in JP 10007657 trifluoromethanesulfonaniiide oxime ether derivatives of Formula 8 have been disclosed:
wherein:
R1 is either hydrogen, C2-C6 alkanoyl or benzoyl;
R2 and R3 are independently selected from hydrogen, halo, nitro, cyano, (substituted)iower alkyl, (substituted)lower alkoxy, lower alkoxycarbonyl, acetyl, -C(=NOCH3)CH3 or R2 and R3 is Ph to form a naphthalene ring; and Q is either (substituted)pyrazinyl, (substituted)4-pyrimidinyl, (substituted)oxazolyl, (substituted)thiazoiyl, (substituted)quinoxalyl, (substituted )quinazoiyl, (substituted)thiadiazolyi, (substituted)tetrazoiyl, (substituted)benzoxazoiyi, (substituted)benzothiazoiyi, (substituted)triazofyl, (substituted)triazinyl, (substituted)pyrazotyl or (substituted)isoxazolyl.

These compounds have been said to show herbicidal activity without damaging rice plants.
In JP 10017419 and JP 10025213 tri'fluoromethanesulfonanilide oxime ether derivatives of Formula C have been disclosed:
wherein:
R1 is either hydrogen or C2-C5 alkanoyl; and
R2 is either hydrogen; chlorine, methoxycarbonyl or C(=NOCH3)CH3;
These compounds have been said to show herbicidal activity without damaging rice seedlings.
in JP 11060562 trifluoromethanesulfonanilide oxime ether derivatives of Formula D have been disclosed:
wherein:
R1 is (optionally)substituted alkyl or (optionally)substituted aikenyi;
R2 is either hydrogen, halo, (optionally)substituted alkoxy or (optionally)substituted alkyl;
R3 is either, hydrogen, (optionally)substituted alkyl, benzyl, acyl, alkoxycarbonyl, (optionally)substituted carbamoyl, (optionally)substituted thiocarbamoyl or -S02R1;
Q is either -CH(NR4R5) or C(=NR6) [R4, R5 and R6 is either hydrogen, (optionally)substituted alkyl, alkenyl. alkynyi, cycloalkyl, (optionally)substtfuted phenyl, acy!, alkoxycarbonyl, (optionally)substituted carbamoyl, (optionally)substituted


atom, may form a nitrogen-containing heterocyclic group which possesses one or more heteroatoms]; and m is 1 to 4;
These compounds have been said to show herbicidal activity, in PCT Int. Appl. WO 2004 11, 429 trifluoromethanesulfonanilide oxime ether' derivatives of Formula E nave been disclosed:

wherein:
R1 is haloC1-C6alkyi;
R2 is either hydrogen C1-C6 alkyi or the tike,
A is C1-C6 alkylene or the like;
G is O, S, NR3, NOR4 or NNR5R6;
m is 0 or 1;
X is substituted phenyl, phenoxy, or the like; and
Q is an optionally substituted heterocycle having at least one ring-constituent nitrogen atom at which the heterocycle is bonded to A.
These compounds have been said to show herbicidal activity. In the general area of insecticidal and acaricidai control. Japanese Laid-open Patent 57-156407A discloses trifluoromethanesulfonanilide compounds of Formula F:
wherein:
R is selected from atkyl. alkoxyalkyl haloalkyl, haloalkoxy. alkylcarbonyl, alkoxycarbonyi or halo; and

A pesticidai composition which comprises the ester 2-methoxycarbonyl-4-chlorotrifluoromethanesulfonanilide (Formula G) as an active ingredient is disclosed in US 6,177,465 and US 6:333:022. Examples of the pests controlled by the composition include insects and acarina such as indoor mites, fleas, cockroaches and so on. The composition is said to be very effective for controlling house dust mites.

In spite of the forgoing, work in this area has continued to provide improved methods of controlling insects and acarina as well as compounds useful for the same and related purposes.
The citation of any reference herein should not be construed as an admission that such reference is available as "prior art" to the instant application.

Accordingly, the present invention provides oxime ether derivatives that are effective anti-parasite agents.
In one embodiment the invention provides a trifluoromethanesuifonaniiide oxime ether compound of Formula (I)

or a pharmaceutically acceptable salt thereof or a solvate thereof.
R-i, R2, R3 and R4 are independently selected from the following: hydrogen, formyl, carboxyl, cyano, hydroxy, amino, nitro, thiol, halo and the following optionally substituted moieties: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl,

or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein:
Ri is hydrogen:
R2 is hydrogen or haloalkyl, e.g.. C1-C5haloalkyl;
R3 is hydrogen, halo or haloalkyl, e.g., (C1-s) haloalkyl;C5R4 is hydrogen;
R5 is aJkyl. e.g.. C1-C5alkyl cycloalkyl, e.g. C3-C10cycloalkyl, or (optionally substituted) aryf;
R8 and R12 are independently hydrogen or aikyl, e.g., C1-C6alkyl;
R9 and Rm are independently hydrogen., halo or haloalkyl, e.g., (C1 C6)haloalkyi; and
R10 is hydrogen, alkyi, e.g., C1-C6alkyl, cyano, halo, haloalkyl, e.g., (C1 C6)haloatkyl or haloalkcxy e.g., C1-C6haloalkoxy.
Preferably, R-, is hydrogen; R2 is hydrogen or trifluoromethyl; R3 is hydrogen, chlorine or trifluoromethyi; R4 is hydrogen;
R5 is methyl, ethyl, n-propyl, /-propyl, t-butyl. cyclohexy! or phenyl; R8 is hydrogen or methyl;
Ro is hydrogen, fluorine, chlorine or trifluoromethyl;
R-so is hydrogen, methyl, cyano, fluorine, chlorine, bromine, trifluoromethyl or trifluoromethoxy;
R-in is hydrogen: and R12 is hydrogen.

An.effective amount and concentration ofat least one compound according to the invention is admixed, dispersed, emulsified, or dissolved in the liquid carrier. Such liquid compositions optionally further include emulsifiers, detergents, anti-foaming agents, stabilizers, preservatives., coloring agents, perfumes, additional art-known active agents selected to provide synergistic anti-parasite killing activity, and/or agents selected to complement the parasite killing spectrum of the inventive compound or compounds. Such optional diluents or carriers are selected for compatibility with the selected inventive compound, as well as for environmental compatibility and safety, while allowing for administering the inventive compound or compounds into an area.or location of interest at concentrations effective for the intended purpose.
More preferably, the invention provides for a pharmaceutical composition for treatment of animals infected with parasites that comprises a therapeutically effective dosage amount of the trifluoromethanesulfonanilide oxime ether compound of Formula (i), Formula (!!), Formula (II!), Formula (IV), Formula (V) and/or combinations thereof, and a pharmaceutical acceptable excipient. The pharmaceutical composition is contemplated to be administered to animals by any art known route, including, e.g., oral, parenteral, topical, and/or rectal, routes of administration.
In a solid form, the pharmaceutical composition includes pharmaceutically acceptable excipients, and carriers, and is prepared as a powder that is optionally dispensed in soluble capsules for oral ingestion, in any art-known tabieted form. A solid composition according to the invention is also optionally formulated into a patch for transdermal administration.
In a liquid form, the pharmaceutical composition is provided, together with any optional pharmaceutically acceptable excipients. and carriers, in solution and/or in suspension in a pharmaceutically acceptable liquid composition for administration orally, by infusion or injection and/or by spray or inhalation, and the like.
In a sixth embodiment, the invention provides for methods for killing parasites, both ex vivo, e.g., in the environment, as well as methods of treating a parasite infestation in animals, comprising administering to an animal in need of such treatment an effective amount of a trifluoromethanesulfonanilide oxime ether compound as described above for Formulas (1), (II), (III), (IV), (V) and/or combinations thereof.

and/or helminth parasites. In a further preferred optional embodiment of the invention there are provided methods of preventing or treating parasite infestation in crop plants, stored grain or other stored plant or agricultural products, and people or animals, comprising administering a parasite-suppressive or parasite killing amount of at least one inventive compound or combinations thereof, into an environmental area where parasites of interest are present, or may become present. By "administering" in this context is meant contacting environmental materials or surfaces with amounts of the inventive compound or with a selected mixture or combination of more than one of the inventive compounds that is effective to kill, suppress and/or repel one or more parasites of interest.
Compositions that include solutions, emuisifications, suspensions and dry forms of the inventive compound(s) are discussed supra. The process of administering such compositions can be achieved by methods well known in the art. These include oral, parenteral, spraying, brushing, dipping, rinsing, washing, dusting, using art-known equipment, in a selected area. The selected area to be treated optionally includes plants, a.g., crops, and/or animals, in a particular embodiment, a composition comprising a compound of the invention is placed on a minor portion of the outer surface of an animal, generally as a line or spot on the animal's back (e.g., ' as a pour-on application) and the compound migrates over the whole external surface of the animal to protect the animal [see, US6,492!419 B1, the contents of which are hereby incorporated by reference in their entireties].
Environmental areas contemplated to be treated in this way include, e.g., fields. orchids; gardens and the like, buildings and their environs, including landscaping; storage facilities., transport or fixed storage that contains or analogous structures and structural components, such as walls, floors, roofs, fences, windows and window screens, and the like. Animal living spaces are also included, e.g., animal pens, chicken coops, corals, barns and the like. Human homes and other human residential, business or commercial and educational facilities are also contemplated to be treated or contacted with the inventive compounds or compositions thereof as described above.
These and other aspects of the present invention will be better appreciated by reference to the following drawings and Detailed Description.

BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A illustrates reaction scheme 1 for preparing a compound of Formula (I) from a starting compound 1, FIG. 1B illustrates reaction scheme 2. FIG. 2A illustrates reaction scheme 3. FIG. 2B illustrates reaction scheme 4. FIG. 2C illustrates reaction scheme 5. FIG. 3A illustrates reaction scheme 6. FIG. 3B illustrates reaction scheme 7. FIG. 3C illustrates reaction scheme 8.
FIG. 4 illustrates the preparative reactions of Examples 1A through 1H. FIG. 5 illustrates the preparative reactions of Examples 2A through 2H, FIG. 6 illustrates the preparative,reactions of Examples 3A and 3B. FIG. 7 illustrates the preparative reactions of Examples 4A through 4F. FIG. 8 illustrates the preparative reactions of Examples 5A through 5F. FIG. 9 illustrates the preparative reactions of Examples 6A through SC. FIG. 10 illustrates the preparative reactions of Examples 7A through 7C. FIG. 11 illustrates the preparative reactions of Examples 8A and 8B. FIG. 12 illustrates the preparative reaction of Examples 9A and 9B,
DESCRIPTION OF THE INVENTION
Accordingly, the invention provides a series of new trifluoromethanesuifonaniiide cxime ether compounds that are highly active against parasites, and having particular activity and utility as endoparasitides, ectoparasiticides, anthelmintics, insecticides and acaricides.
In order to more fully appreciate the description of the invention, the following definitions are provided. As used herein, the following terms are employed as defined beiow, unless otherwise indicated.
The use of singular terms for convenience in description is in no way intended to be so limiting. Thus: for example, reference to a parasite" includes reference to one or more of such parasites. As used herein the term "approximately" is used

interchangeably-with-the. term "about" and generally, signifias that a value is within twenty percent of the indicated value.
An oxime ether is one of a class of compounds with the formula of

wherein R is a substituted carbon atom.
In this specification "optionally substituted" means that a functional group is either substituted or unsubstituted, at any available position. Substitution can be with one or more functional groups selected from, e.g., aikyl, alkenyl, alkynyl, cycloalky!, cycloalkenyl, aryi, heterocyclyl, heteroaryl, formyl, alkanoyl, cycloaikanoyl, aroyl, heteroaroyi, carboxyl, alkoxycarbonyl, cycioalkyloxycarbonyl, aryloxycarbonyl, heterocyciyloxycarbonyl, heteroaryioxycarbonyl, alkylaminocarbonyt, cycloalkylaminocarbonyl, arylarninocarbonyl, heterocyclylaminocarbonyl, heteroarylaminocarbonyl, cyano, hydroxy, alkoxy: cycloalkoxy, aryloxy, hsterocyclylcxy. heteroaryloxy. alkanoate. cydoalkanoate, aryioate, heterocyclyioate, heteroaryloate, amino, alkylamino, cycloalkylamino, arylamino, heterocyclylamino, heteroarylamino, alkylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, . heterocyclylcarbonylamino, heteroarylcarbonyiamino, nitro, thiol, alkylthio, cycloalkylthio, arylthio, heterocyciyfthio, heteroarylthio, alkylsulfinyL cycloalkylsuifinyl, arylsutfinyt, heterocyclysulfinyl, heteroarylsulfinyl, alkyisuifinyl, cycloalkylsuifinyl, arylsuifinyl, heterocyclysulfinyl, heteroarylsulfinyl, halo, haloalkyl, haloaryl, haloheterocyclyl, haloheteroaryl, haloalkoxy, and haloalkyisuifonyl, to name but a few such functional groups.
"Alky!" whether used alone, or in compound words such as alkoxy, alky!thio: aikyiamino, dialkylamino or haloalkyl, represents straight or branched chain hydrocarbons ranging in size from one to about 20 carbon atoms, or more. Thus alkyl moieties include, without limitation, moieties ranging in size, for example, from one to about 6 carbon atoms or greater, such as, methyl, ethyl, n-propyl,iso-propyl and/or butyl, pentyl, hexyl, and higher isomers, including, e.g., those straight or branched chain hydrocarbons ranging in size from about 6 to about 20 carbon atoms, or greater.

"Alkenyr whether used alone, or in compound words such as alkenyloxy or haloalkenyi, represents straight or branched chain hydrocarbons containing at least one carbon-carbon double bond, including, without limitation, moieties ranging in size from two to about 6 carbon atoms or greater such as, methylene, ethylene, 1-propenyl, 2-propenyl, and/or butenyl, pentenyl. hexenyl. and higher isomers: including. e.g., those straight or branched chain hydrocarbons ranging in size, for example, from about 6 to about 20 carbon atoms, or greater.
"AikynyP whether used alone, or in compound words such as alkynyloxy, represents straight or branched chain hydrocarbons containing at least one carbon-carbon triple bond, including, without limitation, moieties ranging in size from, e.g., two to about S carbon atoms or greater, such as, ethynyl, 1-propynyl, 2-propynyl, and/or butynyl, pentynyl, hexynyl, and higher isomers, including, e.g., those straight or branched chain hydrocarbons ranging in size from,, e.g., about 6 to about 20 carbon atoms, or areater.
"Cycloa!kyl" represents a mono- or poiycarbocyclic ring system of varying sizes, e.g., from about 3 to about 20 carbon atoms, e.g., cyclopropyl, cyclobutyl, cyciopentyi, cyclohexyl or cycloheptyl. The term cycloaikyloxy represents the same groups linked through an oxygen atom such as cyclopentyioxy and cyciohexyioxy. The term cycioalkylthio represents the same groups linked through a sulfur atom such as cyclopentylthio and cyciohexylthio.
'Cycioaikenyl1' represents a non-aromatic mono- or poiycarbocyclic ring system, e.g., of about 3 to about 20 carbon atoms containing at least one carbon-carbon double bond, e.g., cyclopentenyl, cyclohexenyl or cycloheptenyl. The term "cycloalkenyloxy" represents the same groups linked through an oxygen atom such as cyclopentenyloxy and cyclohexenyloxy. The term "cycloalkenylthio" represents the same groups linked through a sulfur atom such as cyciopentenyfthio and cyclohexenylthio.
The terms, "carbocyciic" and "carbocyclyl" represent a ring system, e.g., of about 3 to about 20 carbon atoms, which may be substituted and/or carry fused rings. Examples of such groups include cyciopentyi, cydohexyl, or fully or partially hydrogenated phenyl, naphthyl and fluorenyi.
"Aryl" whether used alone, or in compound words such as arylalkyl, aryloxy or arylthto, represents: (i) an optionally substituted mono- or polycyclic aromatic

naphthyl orfluorenyi; or, (ii) an optionally substituted partially saturated polycyclic carbocyciic aromatic ring system in which an aryi and a cycloalkyi or cycloalkenyl group are fused together to form a cyclic structure such as a tetrahydronaphthyl, indenyt or indanyl ring.
"Heterocycyl or "heterocyclic whether used alone, ox in compound words such as heterocyciyioxy represents: (i) an optionally substituted cycloalkyi or cycloalkenyl group, e.g., of about 3 to about 20 ring members, which may contain one or more heteroatoms such as nitrogen, oxygen, or sulfur (examples include pyrroiidinyl, morpholino, thiomorpholino, or fully or partially hydrogenated thienyl, fury!, pyrrolyl, thiazolyl, oxazoiyl, oxazinyl, thiazinyl, pyridyl and azepinyi); (ii) an optionally substituted partially saturated polycyclic ring system in which an aryi (or heteroaryl) ring and a heterocyclic group are fused together to form a cyclic structure (examples include chromanyi. dlhydrobenzofuryl and indoiinyl); or (iii) an optionally substituted fully or partially saturated polycyclic fused ring system that has one or more bridges (examples include quinuclidinyi and dihydro-1.4-epoxynaphthy!).
"Heteroaryl" whether used alone, or in compound words such as heteroaryloxy represents: (i) an optionally substituted mono- or polycyclic aromatic organic moiety, e.g., of about 5 to about 20 ring members in which one or more of the ring members ' is/are element(s) other than carbon, for example nitrogen, oxygen or sulfur; the heteroatom(s) interrupting a carbocyciic ring structure and having a sufficient number of deiocalized pi electrons to provide aromatic character, provided that the rings do not contain adjacent oxygen and/or sulfur atoms. Typical 6-membered heteroaryl groups are pyrazinyi, pyridazinyl, pyrazolyl, pyridyl and pyrimidinyl. Ail regioisomers are contemplated, e.g., 2-pyridyl, 3-pyridyl and 4-pyridyI. Typical 5-membered heteroaryl rings are fury!, imidazoiyL oxazoiyl. isoxazolyi. isothiazolyl, oxadiazolyl, pyrrolyl, 1,3,4-thiadiazoiyl, thiazolyl, thienyl and triazolyl. All regioisomers are contemplated, e.g., 2-thienyl and 3-thienyl. Bicyclic groups typically are benzo-fused ring systems derived from the heteroaryl groups named above, e.g., benzofuryl, benzimidazolyl, benzthiazolyl. indolyl, indolizinyl, isoquinolyl, quinazolinyt, quinolyl and benzothienyl; on (ii) an optionally substituted partially saturated polycyclic heteroaryl ring system in which a heteroaryl and a cycloalkyi or cycloalkenyl group are fused together to form a cyciic structure such as a tetrahydroquinolyl or pyrindinyl ring.

"Aikanoyl" represents a -C(=0)-alkyl group in which the alky I group is as defined supra. In a particular embodiment, an aikanoyl ranges in size from about C2-C20. One example is acyl.
"Aroyl" represents a -C(=0)-aryl group in which the aryi group is as defined supra. In a particular embodiment, an aroyl ranges in size from about C7-C2O. Examples include benzoyl and 1-naphthoyl and 2-naphthoyI.
"HeterocycloyP represents a -C(=0)-heterocyclyi group in which the heterocylic group is as defined supra, in a particular embodiment, an heterocycioyi ranges in size from about C4-C20.
"Heteroaroyl" represents a -C(=0)-heteroaryl group in which the heteroaryl group is as defined supra. In a particular embodiment, a heteroaroyl ranges in size from about C6-C2o. An example is pyridylcarbonyl.
"Carboxyi" represents a -C02H moiety.
"Oxycarbonyln represents a carboxylic acid ester group -C02R which is linked to the rest of the molecule through a carbon atom.
"Alkoxycarbonyl" represents an -C02-alkyi group in which the alkyl group is as defined supra. In a particular embodiment, an alkoxycarbonyi ranges in size from about C2-C6. Examples include methoxycarbonyl and ethoxycarbonyl.
"ArySoxycarbonyl" represents an -C02-aryl group in which the aryl group is as defined supra. Examples include phenoxycarbonyl and naphthoxycarbonyf.
"Heterocycfyloxycarbonyi" represents a -C02-heterocyclyl group in which the heterocyclic group is as denned supra.
"Heteroaryloxycarbonyl" represents a -C02-heteroaryl group in which the heteroaryl group is as defined supra.
"Aminocarbonyl11 represents a carboxylic acid amide group -C(=0)NHR or -C(=0)NR2 which is linked to the rest of the molecule through a carbon atom.
"Alkylaminocarbonyl" represents a -C(=0)NHR or -C(=0)NR2 group in which R is an alkyl group as defined supra.
"Arylaminocarbonyl" represents a -C(=0)NHR or -C(=0)NR2 group in which R is an aryl group as defined supra.

''Heter-oayclylaminocarbonyi-represents.a-C(-=0)NHR or -C(==0)NR2 group in which R is a heterocyclic group as defined supra. In certain embodiments, NR2 is a heterocyclic ring, which is optionally substituted.
"Heteroarylaminocarbonyl" represents a -C(=0)NHR or -C(=0)NRs group in which R is a heteroaryl group as defined supra. In certain embodiments, NR2 is a heteroaryi ring, which is optionally substituted.
"Cyano" represents a ~CN moiety, and "hydroxy" represents the -OH moiety,
"Alkoxy" represents an -O-alkyl group in which the alky! group is as defined supra. Examples include methoxy, ethoxy, /7-propoxy, is-opropoxy, and the different butoxy. pentcxy, hexyloxy and higher isomers.
"Aryloxy" represents an -O-aryl group in which the aryl group is as defined supra. Examples include, without [imitation, phenoxy and naphthoxy.
"Alkenyloxy" represents an -Oalkenyi group in which the aikenyl group is as defined supra. An example is allyloxy.
"Heterocyclyloxy" represents an -O-heterocycfyl group in which, the heterocyclic group is as defined supra.
"Heteroaryioxy11 represents an -O-heteroary) group in which the heteroaryl group is as defined supra. An example is pyridyloxy.
"Alkanoate" represents an -OC(=0)-R group in which R is an alkyl group as defined supra.
"Aryloate" represents a -OC(=0)-R group in which R is an aryl group as defined supra.
"Heterocyclyloate" represents an -OC(=0)-R group in which R is a heterocyclic group as defined supra.
"Heferoaryloate" represents an -OC(=0)-R group in which R is a heteroaryl group as defined supra.
"Sulfonate" represents an -OS02R group that is linked to the rest of the molecule through an oxygen atom.
"Alkylsulfonate" represents an -OSCValkyl group in which the alkyl group is as defined supra.
"Arylsulfonate'1 represents an -OS02-aryl group in which the aryl group is as defined supra.

Heterocyciyisulfonate" represents an -OS02-heterocyclyl group in which the heterocyclic group is as defined supra.
"Heteroarylsulfonate" represents an -OS02-heteroaryl group in which the heteroaryl group is as defined supra.
''Amino" represents an -NH2 moiety.
"AikyIaminoc represents an -NHR or -NR2 group in which R is an alkyi group as defined supra. Examples include, without [imitation, methylamino, ethylamino, n-propylamino, /so-propyiamino, and the different butyiaminb, pentyiamino, hexyiamino and higher isomers.
"Aryiamino" represents an -NHR or -NR2 group in which R is an ary! group as defined supra. An example is phenylamino.
"Heterocyclylamino" represents an -NHR or -NR2 group in which R is a heterocyclic group as defined supra. In certain embodiments, NR2 is a heterocyclic ring, which is optionally substituted.
"Heteroarylamino" represents a -NHR or -NR2 group in which R is a heteroaryl group as defined supra. In certain embodiments, NR2 is a heteroaryl ring, which is optionally substituted.
"Carbonylamino" represents a carboxylic acid amide group -NHC(=0)R that is linked to the rest of the molecule through a nitrogen atom.
"Alkylcarbonylamino' represents a-NHC(=0)R group in which R is an alkyi group as defined supra.
"Aryicarbonylarnino" represents an -NHC(=0)R group in which R is an aryl group as defined supra.
"Heterocyclylcarbonylamino" represents an -NHC(=0)R group in which R is a heterocyclic group as defined supra.
"Heteroarylcarbonylarnino" represents an -NHC(=0)R group in which R is a heteroaryl group as defined supra.
"Nitro" represents a -N02 moiety.
"Alkylthio" represents an -S-alkyl group in which the alkyi group is as defined supra. Examples include, without limitation, methylthio, ethylthio, n-propylthio, iso propylthio, and the different butylthio, pentylthio, hexylthio and higher isomers.
"Arylthio" represents an -S-aryl group in which the aryl group is as defined supra. Examples include phenylthio and naphthyithio.

"HeterocyclyIthio-xepresents an S--heter.ocyclyI-gr-oup in which the heterocyclic group is as defined supra.
"Heteroaryithio" represents an -S-heteroaryl group in which the heteroaryl group is as defined supra.
"Sulfinyf represents an -S(=0)R group that is linked to the rest of the molecule through a sulfur atom.
"Alkylsulfinyi" represents an -S(=0)-alkyI group in which the alkyl group is as defined supra. An example is thioacyl.
"Arylsulfinyl" represents an -S(=0)-aryl group in which the aryl group is as defined supra. An example is thiobenzoyL
"Heterocyclylsulfinyl" represents an -S(=0)-heterocyclyl group in which the heterocylic group is as defined supra.
"Heteroarylsulfinyl" represents an -S(=0)-heteroaryi group in which the heteroaryl group is as defined supra.
"SuSfonyi" represents an -S02R group that is linked to the rest of the molecule through a sulfur atom.
"A!kyisuIfonyfI! represents an -SCValkyl group in which the alkyl group is as defined supra.
"Arylsulfonyl" represents an -S02-aryl group in which the aryl group is as defined supra.
"Heterocyclylsutfonyl" represents an -SG2-heterocyclyI group in which the heterocyclic group is as defined supra.
"Heteroarylsuffonyl" represents an -S02-heteroaryl group in which the heteroar/1 group is as defined supra.
The term "halo," whether employed alone or in compound words such as haloalkyl, haloalkoxy or haloalkylsulfonyl, represents fluorine, chlorine, bromine or iodine. Further, when used in compound words such as haloalkyl, haloalkoxy or haloalkylsulfonyl, the alkyi may be partially halogenated or fully substituted with halogen atoms which may be independently the same or different. Examples of haloalkyl include, without limitation, -CH2CH2F, -CF2CF3 and -CH2CHFCI. Examples of haloalkoxy include, without limitation, -OCHF2, -OCF3, -OCH2CCI3, -OCH2CF3 and -OCH2CH2CF3. Examples of haloalkylsulfonyl include, without limitation, -S02CF3, -S02CC!3, -S02CH2CF3 and -S02CF2CF3.

The term "prodrug" as used herein refers to a compound which is convertible in use, e.g., on an environmental surface and/or in vivo, by metabolic means or other processes (e.g., by hydrolysis) to one of the compounds of the invention, e.g., a compound of Formulas (I). (II). (Ill), (IV) and/or (V). For example, derivatization of the NH-acidic group of a compound of Formula (1) is contemplated to provide a compound convertible by hydrolysis in vivo io the parent molecule. In certain optional embodiments, delivery of the active compound in prodrug form achieves improved delivery of the inventive compound by improving its physicochemical/pharmacokinetic properties, e.g., by enhancing systemic absorption, delaying clearance or breakdown, in vivo.
Suitable groups for derivatization of the NH-acidic group of compounds of Formula (I) are, for example, alky I, aikoxyalkyl, alkyicarbonyloxyaikyl, alkanoyl and alkoxycarbonyi.
A parasite 'infestation" refers to the presence of parasites in numbers that pose a risk to humans or animals. The presence can be in the environment e.g., on plants, in animal bedding, on the skin or fur of an animal etc. When the infestation that is referred to is within an animal, e.a. in the blood or other interna! tissues, the term infestation is also intended to be synonymous with the term, "infection," as that term is generally understood in the art, unless otherwise stated.
An 'effective amount," is the amount or quantity of a compound according to the invention that is required to alleviate or reduce parasite numbers in a sample of such parasites, and/or to reduce the numbers of such parasites in and/or on an animal, and/or to inhibit the development of parasite infestation in or on an animal, in whole or in part. This amount is readily determined by observation or detection of the parasite numbers both before and after contacting the sample of parasites with the compound, directly and/or indirectly, e.g., by contacting articles, surfaces, foliage, or animals with the compound. For an in vivo administration of the compound according to the invention, an effective amount is synonymous with a "pharmaceutically effective amount," which is the dose or amount that treats or ameliorates symptoms and/or signs of parasite infection or infestation by the treated animal. This later amount is also readily determined by one of ordinary skill in the art, e.g., by observing or detecting changes in clinical condition or behavior of treated animals, as well as by observing or detecting relative changes in parasite numbers after such treatment.

Whetherthe-compound-is-applied in vivo or-ex vivothe-treatment is- effective when the parasite count is reduced, after a first application or administration, by an amount ranging from 5% to about 100%. Alternatively, the reduction in parasite count ranges from about 10% to about 95%, relative to the parasite count in an equivalent untreated sample.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiorners. diastereomers and geometric isomers. Those skilled in the art will appreciate that one stereoisomer may be more active than the other(s). in addition, the skilled artisan would know how to separate such stereoisomers. Accordingly, the present invention comprises mixtures, individual stereoisomers, and optically active mixtures of the compounds described herein.
For example, although Formulas (I), (III), (IV), and (V) have been drawn as the anti(E)-isomers, it should be understood that the compounds of the present invention may also exist as syn(Z)-somers, or mixtures thereof, and therefore, such isomers or mixtures thereof are clearly included within the present invention.
Certain compounds of the present invention wiil be acidic in nature and can form pharmaceutically acceptable metal, ammonium and organic amine salts. The metal salts include alkali metal {e.g., lithium, sodium and potassium), alkaline earth metal (e.g.. barium, calcium and magnesium) and heavy metal (e.g., zinc and iron) salts as well as other metal salts such as aluminium. The organic amine salts include the salts of pharmaceutical acceptable aliphatic (e.g., aikyl), aromatic and heterocyclic amines, as well as those having a mixture of these types of structures.
Amines useful in preparing the salts of the invention can be primary, secondary or tertiary and preferably contain not more than 20 carbon atoms. The salts of the invention are prepared by contacting the acid form with a sufficient amount of the appropriate base to produce a salt in the conventional manner. The acid forms may be regenerated by treating the salt with a suitable dilute aqueous acid solution. The acid forms differ from their respective salt forms somewhat in certain physical properties, such as solubility in polar solvents, but the salts are otherwise equivalent to their respective acid forms for the purposes of the invention.
All such salts are intended to be pharmaceutically acceptable within the scope of the invention and all salts are considered equivalent to the acid form for the purposes of the invention.

The Compounds-of the-present inventioncan also-form-stabie complexes with solvent molecules that remain intact after the non-complexed solvent molecules are removed from the compounds. These complexes are referred to herein as "solvates". Solvates of the compounds of the present invention are also included in the present invention. In a particular embodiment the solvent molecule is water (i.e., forming a hydrate).
For all of the methods and new compounds described herein, it is also contemplated that the identified compounds are readily employed in combination with one or more art-known agents for killing or controlling various types of parasites, e.g., including all of the ecto- and endoparasites described herein. Thus, although the inventive compounds and methods are preferred over previously known agents and methods of using previously known agents, in certain optional embodiments they are contemplated to be employed in combination, simultaneously, or sequentially {e.g. in the same composition or in separate compositions), with other art-known agents or combinations of such art-known agents employed for killing or controlling various types of pests.
These additional agents include, for example, art-known anthelmintics, such as, for example, avermectins {e.g. ivermectin, moxidectin, milbemycin), benzimidazoles (e.g. albendazole, triclabendazole), salicylanilides (e.g. closantel, oxyclozanide), substituted phenols (e.g. nitroxynil), pyrimidines (e.g. pyrantel), imidazothiazoles (e.g. ievamisole) and praziquantel.
Additional art-known agents for killing or controlling pests include the organophosphate pesticides. This class of pesticides has very broad activity, e.g. as insecticides and. in certain instances, anthelmintic activity. Organophosphate pesticides include, e.g., dicrotophos, terbufos, dimethoate. diazinon, disulfoton, trichiorfon, azinphos-methyl, chlorpyrifos, malathion, oxydemeton-methyl, methamidophos, acephate, ethyl parathion, methyl parathion, mevinphos, phorate, carbofenthion, phosalone, to name but a few such compounds. It is also contemplated to include combinations of the inventive methods and compounds with carbamate type pesticides, including, e.g., carbaryl, carbofuran, aldicarb, molinate, methomyl, carbofuran, etc., as well as combinations with the organochlorine type pesticides. It is further contemplated to include combinations with biological pesticides, including e.g. repellents, the pyrethrins (as well as synthetic variations

employed as an acaricide. Other contemplated combinations are with miscellaneous pesticides including: bacillus thuringensis, chiorobenzilate, formamidines, {e.g. amtitaz), copper compounds, e.g., copper hydroxide, cupric oxychloride sulfate, cyfluthrin, cypermethrin, dicofol, endosuifan, esenfenvalerate, fenvaferate, lambda-cyhaiothrin, methoxychior and sulfur.
In addition, for all of the methods and new compounds described herein, it is further contemplated that the identified compounds can be.readily employed in combination with syngergists such as piperonyl butoxide (PBO) and triphenyi phosphate (TPP); and/or with Insect Growth Regulators (IGRs) and Juvenile Hormone Analogues (JHAs) such as diflubenzuron, cyromazine, methoprene, etc., thereby providing both initial and sustained control of parasites (at all stages of insect development, including eggs) on the animal subject, as well as within the environment of the animal subject.
Combinations with cyclodienes, ryanta, KT-199 and/or older art-known anti-heiminth agents, such as avermectins (e.g., ivermectin, moxidectin, milbemycin), benzimidazoies {e.g., albendazole, thiabendazole), salicylanilides {e.g., closantei, oxyciozanide), substituted phenols (e.g., nitroxynii), pyrimidines (e.g., pyrantel), imidazothiazoles (e.g., levamisole), praziquantel and some organophosphates such as naphthaiophos and pyraclofos, are also contemplated to be employed in such combinations.
In particular, additional antiparasitic compounds useful within the scope of the present invention are preferably comprised of the class of avermectin compounds. As stated above, the avermectin family of compounds is a series of very potent antiparasitic agents known to be useful against a broad spectrum of endoparasites and ectoparasites in mammals.
A preferred compound for use within the scope of the present invention is vermectin. ivermectin is a semi-synthetic derivative of avermectin and is generally produced as a mixture of at least 80% 22,23-dihydroavermectin B1a and less than 20% 22,23-dihydroavermectin B1b. Ivermectin is disclosed in U.S. Pat. No. 4,199,569, hereby incorporated by reference. Ivermectin has been used as an antiparasitic agent o treat various animal parasites and parasitic diseases since the mid-1980's.

Abamee-tin is an avermectin that is disclosed as avermectin B-1a/B1 b in U.S. Pat. No. 4,310,519, which is hereby incorporated by reference in its entirety. Abamectin contains at least 80% of avermectin B1a and not more than 20% of avermectin B1b.
Another preferred avermectin is Doramectin also known as 25-cyciohexyi-avermectin B-i. The structure and preparation of Doramectin, is disclosed in U.S. Pat. No. 5,089,480, which is hereby incorporated by reference in its entirety.
Another preferred avermectin is Moxidectin. Moxidectin, also known as LL-F28249 alpha is known from U.S. Pat. No. 4,916,154, which is hereby incorporated by reference in its entirety.
Another preferred avermectin is Selamectin. Seiarnectin is 25-cyclohexyl-25-de(1-methylpropyl}-5-deoxy-22r23-dihydro-5-(hydroxyimino)-avermectin B-i monosaccharide.
Milbemycin, or B41. is a substance which is isolated from the. fermentation broth of a Milbemycin producing strain of Streptomyces. The microorganism, the fermentation conditions and the isolation procedures are more fully described in U.S. Pat. No. 3,950,360 and U.S. Pat. No. 3,984,564.
Emamectin (4"-deoxy-4"-epimethylaminoavermectin B1), which can be prepared as described in U.S. Pat. No. 5,288,710 or 5,399,717, is a mixture of two homologues, 4"-deoxy-4"epi-methylaminoavermectin B1a and 4"-deoxy-4"-epi-methylaminoavermectin B1b. Preferably, a salt of Emamectin is used. Non-limiting examples of salts of Emamectin which may be used in the present invention include the salts described in U.S. Pat. No. 5.288,710, e.g., salts derived from benzoic acid, substituted benzoic acid, benzenesuifonic acid, citric acid, phosphoric acid, tartaric acid, maleic acid, and the like. Most preferably, the Emamectin salt used in the present invention is Emamectin benzoate.
Eprinomectin is chemically known as 4"-epi-Acetylamino-4"-deoxy-avermectin B1. Eprinomectin was specifically developed to be used in all cattle classes and age groups. It was the first avermectin to show broad-spectrum activity against both endo-and ecto-parasites while also leaving minimal residues in meat and milk. It has the additional advantage of being highly potent when delivered topically.
The composition of the present invention optionally comprises combinations of one or more of the following antiparasite compounds.

Application Ser. No. 11/019,597, filed on December 22, 2004, incorporated by reference herein.
The antiparasite 1-(4-mono and di-halomethylsuIphonylphenyl)-2-acylamino-3-fluoropropanol compounds, as described by U.S. Application Ser. No. 11/018,156, filed on December 21, 2004, incorporated by reference herein.
The antiparasite phenyl-3-(1/+pyrrol-2-yl)acryIonitriIe compounds, as described by U.S. Provisional Application Ser. No. 60/629,699, filed'on November 19, 2004, incorporated by reference herein.
The antiparasiten-[(phenyioxy)pheny[]-1,1.1-trifluoromethanesuifonamide and n-[(phenylsulfany phenyl]-1,1,1-trifluoromethanesulfonamide derivatives, as described by U.S. Provisional Application Ser. No. 60/688,898, filed on June 9, 2005, incorporated by reference herein.
The composition of the present invention optionally comprises combinations of one or more of the following antiparasite compounds.
The antiparasite imidazo[1,2-b]pyridazine compounds as described by U.S. Application Ser. No. 11/019.597, filed on December 31 j 2003, incorporated by reference herein.
The antiparasite 1 -(4-fluoromethylsulphonylphenyI)-2-acylamino-3-fluoropropanol compounds, as described by U.S. Application Ser. No. 11/018,156, filed on December 31. 2003, incorporated by reference herein.
The antiparasite phenyl-3-(1H-pyrrol-2-yl)acrylonitrile compounds, as described by U.S. Provisional Application Ser. No. 60/612,539, filed on September 23, 2004, incorporated by reference herein.
The antiparasite trifluoromethanesulfonanilide oxime ether compounds, as described by U.S. Provisional Application Ser. No. 60/629,699, filed on November 9, 2004, incorporated by reference herein.
The compositions of the present invention may also further comprise a flukicide. Suitable flukicides include, for example, Triclabendazole, Fenbendazoie, Albendazole, Clorsulon and Oxibendazole. It will be appreciated that the above combinations may further include combinations of antibiotic, antiparasitic and anti-fluke active compounds.

combinations of the inventive methods and compounds, as described herein, with other animal health remedies such as trace elements, anti-inflammatories, anti-infectives, hormones, dermatological preparations, including antiseptics and disinfectants, and immunobioiogicais such as vaccines and antisera for the prevention of disease.
For example, such antinfectives include one or more antibiotics that are optionally co-administered during treatment using the inventive compounds or methods, e.g., in a combined composition and/or in separate dosage forms. Art-known antibiotics suitable for this purpose include, for example, those listed hereinbelow.
One useful antibiotic is Rorfenicol, also known as D-(threo)-1-(4-methylsuifonylphenyI)"2-dichloroacetamido-3-ftuoro-1 -propanoL Another preferred antibiotic compound is D-(threo)-1-(4-methyisulfonyphenyl)-2-difluoroacetamido-3-fluoro-1-propanoL Another useful antibiotic is Thiamphenicol. Processes for the manufacture of these antibiotic compounds, and intermediates useful in such processes, are described in U.S. Pat. Nos. 4,311..857; 4,582,918; 4,973,750; 4,876,352; 5,227,494; 4,743,700; 5,567,844; 5,105,009; 5,382,673; 5,352,832; and 5,663,361, hereby incorporated by reference. Other florfenicol analogs and/or prodrugs have been disclosed and such analogs also can be used in the compositions and methods of the present invention [see e.g., U.S. Patent Application Publication No; 2004/0082553, and U.S. Patent Application Sen No. 11/016,794, both of which are hereby incorporated by reference in their entireties]. When the antibiotic compound is Florfenicol, the concentration of Florfenicol typically is from about 10% to about 50% w/v, with the preferred level between about 20% and about 40% w/v, even more preferred being at least about 30% w/v.
Another useful antibiotic compound is Tilmicosin. Tilmicosin is a macrolide antibiotic that is chemically defined as 20-dihydro-20-deoxy-20-(c/s-3,5-dimethylpiperidin-1-yI)-desmycosin and which is reportedly disclosed in U.S. Pat No. 4,820,695, hereby incorporated by reference. Also disclosed in U.S. Pat. No. 4,820,695 is an injectable, aqueous formulation comprising 50% (by volume) propylene glycol, 4% (by volume) benzyl alcohol, and 50 to 500 mg/m! of active ingredient. Tilmicosin may be present as the base or as a phosphate. Tilmicosin has

haemolytica infections in cattle when administered by injection over a 4 day treatment period. Accordingly, Tilmicosin may be used in treatment of, for example, neonatal calf pneumonia and bovine respiratory disease. When Tilmicosin is present, it is present in an amount of about 1% to about 50%, preferably 10% to about 50%, and in a particular embodiment, 30%.
Another useful antibiotic for use in the present invention is Tulathromycin. Tulathromycin has the following chemical structure.

Tulathromycin maybe identified as 1-oxa-6-azacycIopentadecan-15-one, 13-[(23-dideoxy-3-C-methyl-3-0-methyl-4-C-[(propylamino)methyl]-a/p/?a-L-r/5o-hexopyranosyQoxy]-2-ethyl-3,4J0-trihydroxy-3,5I81012,14-hexamethyl-11 -[[3,4,6-trideoxy-3"(dimethyIamino)-beta-D-xy/o-hexopyranosyi]oxy]-f {2R, 3S, 4R, SR, BRS 10R, 11 Rt 12S, 13S, 14R). Tulathromycin may be prepared in accordance with the procedures set forth in U.S. Patent Publication No. 2003/0064939 A1, which is hereby incorporated by reference in its entirety. Tulathromycin may be present in injectable dosage forms at concentration levels ranging from about 5.0% to about 70% by weight. Tulathromycin is most desirably administered in dosages ranging from about 0.2 mg per kg body weight per day (mg/kg/day) to about 200 mg/kg/day in single or divided doses (i.e., from 1 to 4 doses per day), and more preferably 1.25, 2.5 or 5 mg/kg once or twice weekly, although variations will necessarily occur depending upon the species, weight and condition of the subject being treated. Tulathromycin may be present in injectable dosage forms at concentration levels ranging from about 5.0% to about 70% by weight.

Further-antibiotics-for use in-the-presen invention include the cephalosporins
such as, for example, Ceftiofur, Cefquinome, etc. The concentration of the cephalosporin in the formulation of the present invention optionally varies between about 1 mg/ml to 500 mg/ml.
Another useful antibiotic includes the fluoroquinolones, such as, for example, Enrofloxacin, Danofloxacin, Difloxacin, Orbrfloxacin and Marbofloxacin. in the case of Enrofloxacin, it may be administered in a concentration of about 100 mg/ml. Danofloxacin may be present in a concentration of about 180 mg/ml.
Other useful macrolide antibiotics include compounds from the class of ketolides, or, more specifically, the azaiides. Such compounds are described in, for example, U.S. Pat Nos. 6,514,945, 6,472,371, 6,270, 768, 6,437,151 and 6,271,255, and U.S. Pat. Nos. 6,239,112, 5,958,888, and U.S. Pat. Nos. 6,339,063 and 6,054,434, all of which are hereby incorporated by reference in their entireties.
Other useful antibiotics include the tetracyclines, particularly Chiortetracycline and Oxytetracycline. Other antibiotics may include p-lactams such as penicillins, e.g., Penicillin, Ampicifiin, Amoxicillin, or a combination of Amoxicillin with Clavulanic acid or other beta lactamase inhibitors
Additionally, the present invention optionally includes a composition for the treatment of a microbial and parasitic infection in an animal that comprises one or more of the above-listed antibiotics admixed and/or in combination with one or more of the inventive compounds, and an optional carrier and/or excipient.
Further, it is also contemplated that the inventive methods and compounds be advantageously employed in combination, simultaneously or sequentially, with art-known animal health remedies e.g., trace elements, vitamins, anti-inflammatories, anti-infectives and the like, in the same or different compositions.
PREPARATION OF INVENTIVE COMPOUNDS The compounds of the invention can be prepared by a number of methods. Simply by way of example, and without limitation, the compounds can be prepared using one or more of the reaction schemes and methods described below. Some of the compounds useful in this invention are also exemplified by the following preparative examples, which should not be construed to limit the scope of the disclosure.

abbreviations indicated: acetic acid (AcOH), aluminium trichloride (AlCb), ammonium chloride (NH4CI), boron trichloride (BCI3), n-butylamine (n-BuNH2), cuprous chloride (CuCl), 1,2-dichloroethane (DCE), dichloromethane (CH2CI2), diethyl azodicarboxylate (DEAD), diethyl ether (Et20), N,Nimethylethylenediamine [H2N(CH2)2N(CH3)2], NtN-dirnethylformamide (DMF), dimethyl sulfoxide (DMSO), ethanol (EtOH), ethyl acetate (EtOAc), hydrazine monohydrate (N2H4.H20)5 hydrochloric acid (HCI), hydrogen (H2), iron powder (Fe), magnesium sulfate (MgSO"). methanol'(MeOH), nitric acid (HN03), petroleum ether; b.p. 40-60°C (PE), platinum oxide (Pt02), potassium carbonate (K2CO3), potassium permanganate (KMnO").. sodium acetate (NaOAc), sodium carbonate (Na2C03), sodium hydride (NaH), sodium hydrosulfite (Na2S204)5 sulfuric acid (hfeSCXO, triethylamine (Et3N), trifluoromethanesulforiic anhydride I(CF3S02)20], triphenylphosphine (PPh3), water (H20). RT is room temperature.
Preferred methods of synthesis of the compounds of Formula (I), wherein R-u R2, R3 and FU are independently selected from hydrogen, (C1-C6)alkyl, C1-C6a!koxy or halo, R5 is C1-C6aLkyl, and R6 is the same as that set forth above, commence from R5-substituted aryl ketone derivatives of Formula 1 as shown in Scheme 1 of FIG. 1A.
Thus, by way of a nonlimiting example, and with reference to FIG. 1A, the reaction of R5-substituted aryl ketone derivatives of the Formula 1 with a mixture of fuming nitric and concentrated sulfuric acids affords R5-substituted ORHTO-nitroaryl ketone compounds of Formula 2 using the procedure by Simpson, J. C. E.; Atkinson, C. M.; Schofield, K.; Stephenson, 0. J. Chem, Soc, 1945, 646-657. Reduction of the nitro group is preferentially achieved with iron powder in the presence of an acid such as NH4C! (using the method by Tsuji, K.; Nakamura, K.; Konishi, N.; Okumura, H.; Matsuo, M. Chem. Pharm. Bulk, 1992; 40, 2399-2409), or alternatively with Pt02/H2 (using the general method by Leonard, N. J.; Boyd, S. N. J. Org. Chem,, 1946, 11, 405-418), to afford R5-substituted ort/70-aminoaryl ketone compounds of Formula 3. Compounds of Formula 3 are dissolved in a solvent such as dichloromethane and treated with trifluoromethanesulfonic anhydride to yield trifluoromethanesulfonanilide compounds of Formula 4 (using a modification of the procedure by Harrington, J. K.; Robertson, J. E.; Kvam, D. C; Hamilton, R. R.; McGurran: K. T.; Trancik, R. J.; Swingle, K. R; Moore, G. G. I.; Gerster, J. F. J. Med. Chem., 1970, 13, 137). Compounds of Formula 4 are dissolved in a solvent such as EtOH and treated with

base such as NaOAc (using the general procedure by Pfeiffer, P. Chem. Ben, 1930, 63, 1811-1814), to afford trifluoromethanesulfonanilide O-substituted oxime ether derivatives of Formula (!). Compounds of Formula (I) are obtained as either single isomers or as a mixture of E- and Z-Osubstituted oxime ether derivatives.
A preferred method for preparing compounds of Formula (I), wherein R-,, R2, R3, and R4 are independently selected from hydrogen or halo, R5 is hydrogen and Rs is the same as that set forth above, involves commencing from an ortho nitrobenzaldehyde derivative of Formula 2 (wherein R5 is hydrogen) as shown in Scheme 1 of FIG. 1 A. Reduction of the nitro group with Na2S204j in the presence of a base such as Na2C03, affords ortho-aminobenzaldehyde compounds of Formula 3 (using the method of Horner, J. K.; Henry, D. W. J. Med. Chem. 1988, 11, 946-949) which are converted in two steps to trifiuoromethanesuifonaniiide O-substituted oxime ether derivatives of Formula (I) using the methods, illustrated in Scheme 1.
A preferred method for preparing compounds Formula (I), wherein R1, R2, R3, and R4 are independently selected from hydrogen or halo, R5 is (optionally substituted)aryl and R6 is the same as that set forth above, involves commencing from an aminobenzophenone derivative of Formula 3 [wherein R6 is (optionally substituted)aryl] as shown in Scheme 1. Compounds of Formula 3 are then converted in two steps to trifiuoromethanesuifonaniiide O-substituted oxime ether derivatives of Formula (I) using the methods illustrated in Scheme 1 of FIG. 1 A.
A preferred method for preparing compounds of Formula (I), wherein R1, R2, Rs, and R> are independently, selected from hydrogen or halo, R5 is C1-C6aIkyI, (C2-Cs)a!kenyL (C3-C10)cycloaikyL (optionally substituted)aryl, (optionally substituted)aryi(C-i-C6)aIkyi, (optionally substituted)heteroaryl, C1-C5haloalkyl or (C2-Ce)haloa!kenyl and R6 is the same as that set forth above, involves commencing from arytnitrile derivatives of Formula 6 as shown in Scheme 2 of FIG 1B.
Thus, by way of a nonlimiting example, reaction of an arylnitrile derivative of Formula 6 with an appropriate organomagnesium halide of Formula 7, in the presence of a catalytic amount of a copper salt such as CuCI, affords R5-substituted aryl ketone derivatives of Formula 1 (using the procedure by Weiberth, F. J.; Hail, S. S. J. Org. Chem., 1987, 52, 3901-3904). Compounds of Formula 1 are then converted in four

Formula (I) using the methods illustrated in Scheme 1 of FIG. 1 A.
A further preferred method for preparing compounds of Formula (I), wherein R1, R2j Rs, and R4 are independently selected from hydrogen or halo, R5 is C1-C6alkyl: (C2-C5)alkenylJ (Cs-C-jo)cyclcaIkyis (optionally substituted)aryl, (optionally substituted)arylC1-C6alkyi: (optionally substituted)heteroaryt) (optionally substituted)heterocyclyI, C1-C5haIoalkyl or (C2-C6)haloalkenylJ involves commencing from aniline derivatives of Formula 8 as shown in Scheme 3 of FIG 2A.
Thus, by way of a noniimiting example, anilines of Formula 8 can be ortho-acyiated with an R5-substituted nitrite of Formula 9 in the presence of a stoichiometric amount of BCb and AICl3 (using the method of Sugasawa, T.; Toyoda, T.; Adachi, M.; Sasakura, K. J. Am. Chem. Soc., 1978, 100: 4842-4852). This method gives compounds of Formula 3 which are then converted in two steps to trifluoromethanesulfonanilide O-substituted oxime ether derivatives of Formula (() using the processes illustrated in Scheme 1 of FIG. 1A.
A preferred method for preparing compounds of Formula (I), wherein R1( R2, Rs, and R4 are independently selected from hydrogen or C1-C6haloalkyl: R5 is (C1 C5)alkyl and R6 is the same as that set forth above, involves commencing from ortho-nitroaryl chloride derivatives of Formula 10 as shown in Scheme 4 of FIG. 2B.
Thus, by way of a noniimiting example, reaction of an orf/70-nitroaryI chloride of Formula 10 with the salt of an appropriate R5-substituted nitroalkane of Formula 11 affords cx-aryl R5-substituted nitroalkane derivatives of Formula 12 (using a modification of a procedure by Reid, J. G,; Reny Runge, J. M. Tetrahedron Lett., 1990, 31,1093-1096), Subjecting compounds of Formula 12 to an oxidative Nef reaction (using the procedure of Kornblum, N.; Erickson, A. S.; Kelly, W. J.; Henggeler, B. J, Org. Chem., 1982, 47, 4534-4538) affords compounds of Formula 2, which are then converted in three steps to trifluoromethanesulfonanilide O-substituted oxime ether derivatives of Formula (I) using the methods illustrated in Scheme 1 of FIG. 1A.
A particularly preferred method of synthesis of compounds of Formula (I), wherein Rt, R2, R3, R4, R5 and R6 are the same as that set forth above, is by a one-pot procedure involving the reaction of R6-substituted hydroxylamine derivatives of

compounGis-of Formula 4 as shown in . Scheme 5 of FIG. 2C.
Thus, byway of a nonlimiting example, Re-substituted hydroxylamine compounds of Formula 5a are generated in situ by reaction of FVsubstituted O-phthaiimide derivatives of Formula 13 with a base such as NtN-dirnethylethylenediamine, and subsequently condensed in a one-pot procedure with compounds of Formula 4 to afford trifluoromethanesulfonaniiide O-substituted oxime ether derivatives of Formula (I).
A preferred method of synthesis of O-substituted hydroxylamine hydrochloride salts of Formula 5, wherein R5 is (C-!-C6)alkyl (C2-C6Jalkenyl, (C2-C6)alkynyl, (C3-C1o)cycloa!kyi, (C3-C10)cycloalkenyl, (C3-C1c)cycloalkyl(CrCs)alkyl, (C3-Cio)cycloalkenyl(C1-C5)alky[) (optionally substituted)arylC1-C6aIkyl, (optionally substituted)aryl(C1-C6)alkenyl, (optionally substituted) heterocyclyi, (optionally substituted)heterocycly!(CrCs)alkyL (optionally substituted)heteroarylC1-C6aikyl, (optionally substituted)heteroaryl(C2-C5)a[kenyl, cyanoC1-C6a!kyls C1-C6alkoxy(C1 C5)alkyl, (C3-CiD)cycloalkoxy((C1-C6)aIkylJ (optionally substituted)a^ioxy(C1-C6)alkyl, C1-C6alkylthioC1-C6alkyIJ C3-C10cyc)oa!kyIthioC1-C6alkyIJ (optionally substituted)anylthioC1-C6alkyi! C1-C6aIkyisulfinylC1-C6alkyi, (C3-Cio)cycloalkylsulfinyiC1-C6alkyl, (optionally substituted)aryIsulfinyIC1-C6alkyl, (C1-Ce)aIkylsulfonyi(CrC5)alkyi, (C3-C10)cycloalkylsuifonyKC1-C6)alky|, (optionally substituted)ary!sulfonylC1-C6alkyI! C1-C6haloalkyl or (C2-Cs)ha!oaIkenyi, generally commences from R6-substituted halide derivatives of Formula 14 as shown in Scheme 6 of FIG. 3A.
Thus, by way of a nonlimiting example, R5-substituted halide derivative 14 is dissolved in a solvent such as DMF and reacted with N-hydroxyphthalimide, in the presence of a base such as triethylamine or potassium carbonate, to give Rs-substrtuted O-phthaiimjde derivatives of Formula 13 (using the general method of McKay, A. F.; Garmaise, D. L; Paris, G. Y.; Gelbium, S. Can. J. Chem., 1960, 38, 343-358). Compounds of Formula 13 are dissolved in a solvent such as EtOH and treated with an organic base such as />BuNH2 to liberate the free amine, which is treated with HCI to afford Rs-substituted hydroxylamine hydrochloride salt derivatives of Formulas.

derivatives of Formula 13, wherein R6 is the same as that set forth above, is shown in Scheme 7 of FIG. 3B.
Thus, by way of a non-limiting example, compounds of Formula 13 can be prepared from the reaction of W-hydroxyphthalimide with an FVsubstituted alcohol of Formula 15 in the presence of a betaine formed between DEAD and PPh3 (using the method of Grochowski, E.; Jurczak, J. Synthesis, 1976, 682-684). Compounds of Formula 13 can then be converted to Re-substituted hydroxylamine hydrochloride salt derivatives of Formula 5 as illustrated in Scheme 6 of FIG. 3A.
A preferred method for preparing O-substituted hydroxylamine hydrochloride salt derivatives of Formula 5, wherein R6 is (optionally substituted)aryi or (optionally substituted)heteroaryl, is shown in Scheme 8 of FIG. 3C.
Thus, by way of a non-limiting example, an R5-substituted boronic acid 16 and N-hydroxyphtha!imide are dissolved in a solvent such as 1,2-DCE and coupled together in the presence of a stoichiometric amount of a copper salt such as CuCl, a base such as pyridine, and a drying agent such as 4A molecular sieves, to afford compounds of Formula 13 (using the method of Petrassi, M. H.; Sharpless, K. B.; Kelly, J. W. Org. Lett., 2001, 3, 139-142). Compounds of Formula 5 are generated by dissolving FVsubstituted Ophthalimide derivative 13 in a solvent such as ethanol and treating with hydrazine monohydrate to give the free amine, which is treated with HCI to afford Re-substituted hydroxylamine hydrochloride salt 5.
ANIMALS TO BE TREATED The present invention provides compounds and/or compositions for use in the prevention and/or treatment of infestation, diseases and/or related disorders caused by, or as a result of, parasites or other pests that are killed or inhibited (e.g., growth-suppressed) by such compounds and/or compositions. The animal is preferably a vertebrate, and more preferably a mammal, avian or fish. The compound or composition may be administered directly to the animal subject and/or indirectly by applying it to the local environment in which the animal dwells (such as bedding, enclosures, or the like). Appropriate animal subjects include those in the wild, livestock (e.g., raised for meat, milk, butter, eggs, fur, leather, feathers and/or wool),

beasts of bupden-research animals, companion-animals,as-welI as those raised for/in zoos, wild habitats and/or circuses.
In a particular embodiment, the animal subject is a mammal (including great apes such as humans). Other mammalian subjects include primates (e.g., monkeys), bovine (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), ovine (e.g., goats or sheep), equine (e.g., horses), canine (e.g., dogs), feline (e.g., house cats), camels, deer, antelopes, rabbits, and rodents (e.g., guinea pigs, squirrels, rats, mice, gerbils, and hamsters). Avians include Anatidae (swans, ducks and geese), Columbidae (e.g.. doves and pigeons), Phaslanidae (e.g., partridges, grouse and turkeys), Thesienidae (e.g., domestic chickens), Psittacines (e.g., parakeets, macaws, and parrots), game birds, and ratites, (e.g., ostriches).
Birds treated or protected by the inventive compounds can be associated with either commercial or noncommercial aviculture. These include e.g., Anatidae, such as swans, geese, and ducks, Columbidae, e.g., doves and pigeons, such as domestic pigeons, Phaslanidae, e.g., partridge, grouse and turkeys, Thesienidae, e.g., domestic chickens, Psittacines, e.g., parakeets, macaws, and parrots, e.g., raised for the pet or collector market, among others.
For purposes of the present invention, the term "fish" shall be understood to include without limitation, the Teieosti grouping of fish, i.e., teleosts. Both the Salrnoniformes order (which includes the Salmonidae family) and the Perciformes order (which includes the Centrarchidae family) are contained within the Teieosti grouping. Examples of potential fish recipients include the Salmonidae family, the Serranidae family, the Sparidae family, the Cichlidae family, the Centrarchidae family, the three-Line Grunt (Parapristipoma trilineatum), and the Blue-Eyed. Plecostomus {Piecostomus spp), among others.
Other animals are also contemplated to benefit from the inventive compounds, including marsupials (such as kangaroos), reptiles (such as farmed turtles) and other economically important domestic animals for which the inventive compounds are safe and effective in treating or preventing parasite infection or infestation.

CROPSTOBE TREATED
The inventive compounds are also contemplated to be active against agricultural pests that attack plants. In particular, plants include crops of economic or other importance, i.e., in agriculture and related endeavers. Agricultural pests contemplated to be controlled by the inventive compounds include, for example, insect pests. Insect pests include these that can attack stGred grains, e.g., Thbolium sp., Tenebrio sp. Other agricultural pests include spider mites (Tetranychus sp.}, aphids (Acyrthiosiphon sp.), migratory orthopterans such as locusts, and the immature stages of insects that live on plant tissue such as the Southern army worm and Mexican bean beetle larvae.
Further pests of agricultural importance include, e.g., Acrobasis vaccina, Agrotis spp, Atsophila pometaria, Archips spp. Argyrotaenia citrana, A velutinana, Autographa caiifomica, Bacillus thuringiensis, Caliopistria floridensis, Choristoneura fumiferana, C occidentalis, C pinus, C rosaceana, Cryptophlebia ombrodelta, Cydia (Laspeyresia) pomonelia, C caryana, Dasychira pinicola. Datana rninistra, Desmia funeralis. Diairea saccharaiis, Dichoorocis punctiferaiis, Dioryctria Zimmerman, Ectropis excursaria, Ematurga amitaria, Ennomos subsignaria, Eoreuma ioftini, Epiphyas postvittana, Euprociis chrysorrhoea, Grapholita packardi, Hellula rogatalis, Homoeosorna vagella, Hyphantria cunea, Lambdina fiscellaria, Liphophane antennata, Lobesia botrana, Lophocampa maculata, Lymantria dispar, Malacosoma spp, Manduca spp, Megalopyge operculahs, Mnesampela privata, Orgyia pseudotsugaia, O vetusta, Ostrinia nubilalis, Platynota flavedana, P stultana, Pseudaletia unipuncta, Rhopobota naevana, Rhyacionia spp, Spodoptera eridania, S exigua, S frugiperda, S omithogalli, Thaumatopoea pityocampa, Thridopieroc ephemeraeformis. Thyrinzeina arnobia, and others too numerous to mention.
Crops that can be treated in order to kill, remove or present infestation with crop-related pests include, e.g., alfalfa, apples, avocados, blueberries, brassicas, breadfruit, brocolli. bush berries, cabbage, cane berries, cherry, citrus, citrus oil, clover, cole crops, cotton, cucumber, cranberries, currants, apples, eucalyptus, forestry, beet roots and tops, grapes, grapefruit, gooseberries, hay, huckleberries, kiwi fruit, leafy and fruiting vegetables, legumes, lemon, lime, macadamia nuts, mint, orange, ornamentals, peaches, pears, pecans, peppers, plums, pome fruit, potatoes, raspberry, shrubs, soy, starfruit, sugarcane, sunflower, squash, table beets, tangerine,

.
SUSCEPTABLE PARASITES The inventive compounds are broadly described as endectoparasiticides, in that the inventive compounds include those that are active against ectoparasites (arthropods, acarines, etc.) and endoparasites (helminths, e.g., nematodes, trematodes, cestodes, canthocephalans, etc.). including pests that prey on agricultural crops and stored grains (spider mites, aphids, caterpillars, migratory orthopterans such as locusts). Protozoa parasites (Flagellata, Saroodina Ciliophora, and Sporozoa, etc.) are also contemplated to be treated by the inventive compounds. The inventive compounds are also active against household pests, and particularly against arthropod pests, such as spiders, mites, and insects, including flies, mosquitoes, ants, termites, sitverfish. cockroach, clothes moth, and a myriad of beetles and beetle larvae that impact households.
1. Helminths
The disease or group of diseases described generally as helminthiasis is due to infection of an animal host with parasitic worms known as helminths. Helminthiasis is a prevalent and serious economic problem with domesticated animals such as swine, sheep, horses, cattle, goats, dogs, cats and poultry. Among the Helminths, the group of worms described as nematodes causes widespread and at times serious infection in various species of animals. Nematodes that are contemplated to be treated by the inventive compounds include, without limitation, the following genera:
Acanihocheilonema, Aelurostrongylus, Ancylostoma, Angiostrongyius, Ascaridia, Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Crenopoma, Dictyocaulus, Dioctophyme, Dipetalonema, Diphyliobothrium, Diplydium, Dirofilaria, Dracunculus, Enterobius, Filaroides.Haemonchus, Heterakis, Lagochilascaris, Loa, Mansonella, Muellerius, Nanophyetus, Necator, Nernatodirus, Oesophagostomum, Opisthorchis, Ostertagia, Oxyuris, Parafilaria, Paragonimus, Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca, Spirometra, Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichonema, Trichostrongylus, Trichuris, Uncinaria, and Wuchereria.

Of the above, the most common genera-otnematodes infecting the animals referred to above are Haemonchus, Trichostrongylus, Osiertagia, Nemaodirus, Cooperia, Ascaris, Bunostomum, Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyccaulus, Capfflaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Unicinaria, Toxascaris and Parascaris. Certain of these, such as Nematodirus, Cooperia and Oesophagostomum attack primarily the intestinal tract while others, such as Haemonchus and Ostertagia, are more prevalent in the stomach while others such as Dictyocaulus are found in the lungs.' Still other parasites may be located in other tissues such as the heart and blood vessels, subcutaneous and lymphatic tissue and the like. Table 1 A, below, lists a number of these, by Family and Genus, that are of economic (medical and veterinary) importance.

The most common genera of parasites of the gastrointestinal tract of man are Ancylostoma, Necator, Ascaris, Strongyloides} Trichinella, Capillaria, Trichuris, and Enterobius. Other medically important genera of parasites which are found in the blood or other tissues and organs outside the gastrointestinal tract are the filarial worms such as Wuchereria, Brugia, Onchocerca and Loas Dracunculus and extra intestinal stages of the intestinal worms Strongyloides and Trichinella.

genera-and-species are known to the art, and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in TEXTBOOK OF VETERINARY CLINICAL PARASITOLOGY, VOLUME 1. HELMINTHS, by E.J.L Soulsby, Publ. F.A. Davis Co., Philadelphia, Pennsylvania; HELMINTHS, ARTHROPODS AND PROTOZOA (Sixth Ed. of MONNIG'S VETERINARY HELMINTHOLOGY AND ENTOMOLOGY) by E.J.L Soulsby, Pubi. The Williams and Wilkins Co., Baltimore, Maryland, the contents of both of which are incorporated by reference herein in their entireties.
The parasitic infections known as helminthiasis lead to anemia, malnutrition, weakness, weight loss, severe damage to the walls of the intestinal tract and other tissues and organs and, if left untreated, may result in death of the infected host. The compounds described herein have unexpectedly high activity against these parasites, and in addition are also active against Dirofilaria in dogs, and Narnatospiroides, Syphacia, Aspiculuris in rodents. The inventive compounds are also useful as a nematocide for the control of soil nematodes and plant parasites such as Meloidogyne spp,
2. Arthropods
It is also contemplated that the inventive compounds are effective against a number of ectoparastides of animals, e.g., arthropod ectoparasites of mammals and birds. Athropods include those summarized in Table 1B, as foiiows.



Thus, insect pests include, e.g., biting insects, such as flies and mosquitoes, mites, ticks, lice, fleas, true bugs, parasitic maggots, and the like.
Biting insects include, e.g., migrating diperous larvae as Hypoderrna sp. in cattle, Gastrophiius in horses, and Cuterebra sp. in rodents, as well as biting flies and mosquitoes of all types. For example, bloodsucking adult flies include, e.g., the horn fly or Haemaiobia irritans, the horse fly or Tahanus spp., the stable fly or Stomoxys calcitrans, the black fly or Simulium spp., the deer fly or Chrysops spp.; the louse fly or Melophagus ovinus, the tsetse fly or iossina spp. Parasitic fly maggots include, e.g., the bot fly (Oestrus ovis and Cuterebra spp.], the blow fly or Phaenicia spp., the screwworm or Cochliornyia hominivorax, the cattle grub or Hypoderrna spp., and the fleeceworm. Mosquitoes, include, for example, Culex-spp., Anopheles spp., and Aedes spp.
Mites include Mesostigmata spp., e.g., mesostigmatids such as the chicken mite, Dermanyssus gallinae; itch or scab mites such as Sarcoptidae spp., for example, Sarcopies scabier, mange mites such as Psoroptidae spp., including Chorioptes bovis and Psoropies o\ns\ chiggers, e.g., Trombicuiidae spp., for example the North American chigger, Trombicula alfreddugesi.
Ticks include, e.g., soft-bodied ticks including Argasidae spp., for example Argas spp. and Omithodoros spp.; hard-bodied ticks including Ixodidae spp., for example Rhipicephalus sanguineus, and Boophilus spp.
Lice include, e.g., sucking lice, e.g., Menopon spp. and Bovicola spp.; biting lice, e.g., Haematopinus spp., Linognathus spp. and Solenopotes spp.

cam's) and cat i\ea(Cienocephaltdes fells); Xenopsylla spp.: such as oriental rat flea (Xenopsylla cheopis)] and Pulex spp., such as human flea (Pulex icritans).
True bugs include, e.g., Cimicidae or e.g., the common bed bug (Cimex leciularius)\ Triaiominae spp., including triatomid bugs also known as kissing bugs: for example Rhodnius prolixus and Triaioma spp.
Generally, flies, fleas, lice, mosquitoes, gnats, mites, ticks and helminths cause tremendous losses to the livestock and companion animal sectors. Arthropod parasites also are a nuisance to humans and can vector disease-causing organisms in humans and animais.
Numerous other arthropod pests and ectoparasites are known to the artT and are also contemplated to be treated by the compounds of the invention. These are enumerated in great detail in MEDICAL AND VETERINARY ENTOMOLOGY, by D.S. Kettle, Publ. John Wiley & Sons, New York and Toronto; CONTROL OF ARTHROPOD PESTS OF LIVESTOCK: A REVIEW OF TECHNOLOGY, by P.O. Drummand, J.E. George, and S.E. Kunz., Publ. CRC Press, Boca Raton, Florida, the contents of both of which are incorporated by reference herein in their entireties.
3. Protozoa
tt is also contemplated that the inventive compounds are effective against a number of protozoa endoparasites of animals, including those summarized by Table 1C, as follows.

pharmaceutically acceptable oral or parenteral composition, or in the feed or water or other liquid composition, as discussed in greater detail, below.
Generally, good results are obtained with the inventive compound by the systemic administration of from about 0.001 to 100 mg per kg of animal body weight, or more particularly, from about 0.01 to 10 mg per kg of animal body weight, such total dose being given at one time or in divided doses over a relatively short period of time such as 1-5 days. With the disclosed inventive compound, excellent control of such parasites is obtained in animals, e.g., by administering from about 0.025 to 50 mg per kg of body weight in a single dose, or more particularly, from about 0.025 to about 5 mg per kg of body weight in a single dose. Repeat treatments are given as required to combat re-infections and are dependent upon the species of parasite and the husbandry techniques being employed. The techniques for administering these materials to animals are known to the artisan, the exact amount of the inventive compound given will of course depend on several factors including the specific compound selected, the animal being treated, the parasite(s) infecting the animal, severity of infection, etc. and all such factors being considered by the artisan in calculating the required effective dose without undue experimentation.
In one preferred embodiment, the inventive compound is administered to animals in an oral unit dosage form, such as a capsule, bolus or tablet, or as a liquid drench where used as an anthelmintic in mammals. The drench is normally a solution, suspension or dispersion of the active ingredient usually in water together with a suspending agent such as bentonite and a wetting agent or like excipient Generally, the drenches also contain an antifoaming agent. By way of example, drench formulations generally 0.0001 to about 50% by weight of the inventive compound. Preferred drench formulations contain from about 0.001 to about 10% by weight of the inventive compound. More preferred drench formulations contain from about 0.1 to about 5% by weight of the inventive compound. The drench capsules and boluses comprise the active ingredient admixed with a carrier vehicle such as starch, talc, magnesium stearate, or di-calcium phosphate. In certain optional embodiments, e.g., for large animals, such drench formulations are applied topically, and provide a surface concentration on the animal that is effective to kill or suppress parasites, e.g., by providing a concentration of the inventive compound ranging from about 0.001

or more preferably, from about 0.01 g/cm2 to about In certain other optional embodiments, the inventive compounds may be administered in a controlled release form, e.g., in a subcutaneous slow release formulation; or in the form of a controlled release device affixed to an animal such as a so-called fieacollar. Collars for the controlled release cf an insecticide agent for long term protection against flea infestation in a companion animal are art-known, and are described, for example, by
U.S. Patent Nos. 3,852,416, 4,224,901, 5,555,848, and 5,184,573, incorporated herein by reference.
Where it is desired to administer the inventive compounds in a dry, solid unit dosage form, capsules, boluses or tablets containing the desired amount of active compound usually are employed. These dosage forms are prepared by intimately and uniformly mixing the active ingredient with suitable finely divided diluents, fillers, disintegrating agents and/or binders such as starch, lactose, talc, magnesium stearate, vegetable gums and the like. Such unit dosage formulations may be varied widely with respect to their total weight and content of the antiparasitic agent depending upon factors such as the type of host animal to be treated, the severity and type of infection and the weight of the host.
When the inventive compound is to be administered via an animal feedstuff, it is intimately dispersed in the feed or used as a top dressing or in the form of pellets which may then be added to the finished feed or optionally fed separately.
Alternatively, the inventive compound may be administered to animals parenteraliy, for example, by intraruminal, intramuscular, intratracheal, or subcutaneous injection in which event the active ingredient is dissolved or dispersed in a liquid carrier vehicle. For parenteral administration, the active material is suitably admixed with an acceptable vehicle, preferably of the vegetable oil variety such as peanut oil, cotton seed oil and the like. Other
parenteral vehicles such as organic preparation using solketal, glycerol formal, and aqueous parenteral formulations are also used. The selected inventive compound is dissolved or suspended in the parenteral formulation for administration; such formulations generally contain from 0.005 to 5% by weight of the active compound.

The inventive compounds-may-also be used to prevent and-treat diseases caused by other parasites, for example, arthropod parasites such as ticks, lice, fleas, mites and other biting insects in domesticated animals, including poultry. It is also effective in treatment of parasitic diseases that occur in other animals inducing humans. The optimum amount to be employed for best results will, of course, depend upon the particular compound employed, the species of animal to be treated and the type and severity of parasitic infection or infestation.
When the compound described herein is administered as a component of the feed of the animals, or dissolved or suspended in the drinking water, compositions are provided in which the active compound or compounds are intimately dispersed in an inert carrier or diluent. An inert carrier is one that will not react with the antiparasitic agent and one that may be administered safely to animals. Preferably, a carrier for feed administration is one that is, or may be, ah ingredient of the anima! ration.
Suitable compositions include feed pre-mixes or supplements in which the active ingredient is present in relatively large amounts and which are suitable for direct feeding to the animal or for addition to the feed either directly or after an intermediate dilution or blending step. Typical carriers or diluents suitable for such compositions include, for example, distillers' dried grains, corn meal, citrus meal, fermentation residues, ground oyster shells, wheat shorts, molasses solubles, corn cob meal, edible bean mill feed, soya grits, crushed limestone and the like. The active inventive compounds are intimately dispersed throughout the carrier by methods such as grinding, stirring, milling or tumbling. Compositions containing from about 0.05 to about 5.0%, or from about 0.005 to about 2.0% by weight of the active compound are particularly suitable as feed pre-mixes. Feed supplements, which are fed directly to the animal contain from about 0.0002 to 0.3% by weight of the active compounds.
Such supplements are added to the animal feed in an amount to give the finished feed the concentration of active compound desired for the treatment and control of parasitic diseases. Although the desired concentration of active compound will vary depending upon the factors mentioned supra as well as upon the particular inventive derivative employed, the compound described in this invention is usually fed at concentrations of between about 0.0001 to 0.02% or from about 0.00001 to about 0.002% in the feed in order to achieve the desired antiparasitic result. The compounds of this invention are also useful in combating agricultural pests that inflict

damage upen-erops while they are-growing or while in storage. The compound is applied using known techniques as sprays, dusts, emulsions and the like, to the growing or stored crops to effect protection from such agricultural pests.
Routes of Administration for Animals
As used herein, the terms, "administer" or "administration" refer to the delivery of a compound, salt, solvate, or prodrug of the present invention or of a pharmaceutical composition containing a compound, salt/solvate, or prodrug of this invention to an organism for the purpose of treating or preventing a parasite infestation in animals.
Suitable routes of administration may include, without limitation, oral, rectal, topical, transmucosai, intramuscular, subcutaneous, intramedullary, intrathecal, direct intraventricular, intravenous, intravitreai, intraperitoneal, intranasal, aura! or intraocular. The preferred routes of administration are oral and parenteral.
Alternatively, one may administer the compound in a local rather than systemic manner, for example: by preparation as a salve or topically applied formulation that is appiied directly to the infected area or by injection of the compound directly into infected tissue. In either case, a sustained release formulation may be used.
Thus, administration of the compounds of the invention, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities. The routes of administration can be any known to those of ordinary skill. The inventive compounds are given to those in need thereof in any art recognized form, Le solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, in unit or multi-dosage forms suitable for simple administration of precise dosages. The compositions will include a conventional pharmaceutical carrier or excipient and a compound of the invention as the active agent, and, in addition, may include other medicinal agents, pharmaceutical agents, carriers, etc.
For aquatic animal species, e.g., vertebrate fish species, methods of administering the inventive compound(s) include the foregoing, e.g., by Injection or by admixing the effective compounds in the feed of farmed fish, and so forth. Method of

adrninisering-to aquatic-animal species-also-include dipping-the-fish-into water • comprising an effective concentration of the inventive compound(s)s spraying the fish with an effective concentration of the inventive compound(s), while the fish is briefly separated from the water, and so forth.
Composition/Formulation for Animals
Pharmaceutical compositions of the present invention may be manufactured by processes well known in the art, e.g., using a variety of well-known mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. The compositions may be formulated in conjunction with one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutical^. Proper formulation is dependent upon the route of administration chosen.
For injection, including, without limitation, intravenous, intrarnuscluiar and subcutaneous injection, the compounds of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers known to those of ordinary skill, as well as other excipients or other materials known to those of ordinary skill. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.
For oral administration, the compounds can be formulated by combining the active compounds with pharmaceutical acceptable carriers well-known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, lozenges, dragees, capsules, liquids, gels, syrups, pastes, slurries, solutions, suspensions, concentrated solutions and suspensions for diluting in the drinking water of a patient, premixes for dilution in the feed of a patient, and the like, for oral ingestion by a patient. Pharmaceutical preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding other suitable auxiliaries if desired, to obtain tablets or dragee cores. Useful excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol, cellulose preparations such as, for example, maize starch, wheat starch, rice starch and potato starch and other materials such as gelatin,

methylcellulose, and/or polyvinylpyrrolidone (PVP). if desired, disintegrating agents may be added, such as cross-linked PVP, agar, or alginic acid. A salt such as sodium alginate may also be used.
Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used which may optionally contain gum arabic, talc, PVP, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.
Pharmaceutical compositions that can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with a filler such as .lactose, a binder such as starch, and/or a lubricant such as taic or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. Stabilizers also may be added in these formulations.
For administration by inhalation, the compounds of the present invention can conveniently be delivered in the form of an aerosol spray using a pressurized pack or a nebulizer and a suitable propellant, e.g., without limitation, dichlorodifluoromethane, trichiorofluoromethane, dichlorotetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit may be controlled by providing a valve to deliver a metered amount. Capsules and cartridges of, for example, gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
The compounds may also be formulated for parenteral administration, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers. Useful compositions include, without limitation, suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain adjuncts such as suspending, stabilizing and/or dispersing agents. Pharmaceutical compositions for parenteral administration include aqueous solutions of a water soluble form, such as, without limitation, a salt, of the active

prepared in a
lipophilic vehicle. Suitable lipophilic vehicles include fatty oils such as sesame oil, synthetic fatty acid esters such as ethyl oleate and triglycerides, or materials such as liposomes. Aqueous injection suspensions may contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers and/or agents that increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use.
The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other giycerides.
in addition to the formulations described supra, the compounds may also be formulated as depot preparations. Such long acting formulations may be administered by implantation (for example, subcutaneousty or intramuscularly) or by intramuscular or subcutaneous injection. A compound of this invention may be formulated for this route of administration with suitable polymeric or hydrophobic materials (for instance, in an emulsion with a pharmacologically acceptable oti), with ion exchange resins, or" as a sparingly soluble derivative such as, without limitation, a sparingly soluble salt.
Other delivery systems for relatively hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well-known examples of delivery vehicles or carriers for hydrophobic drugs. In addition, organic solvents such as dimethylsulfoxide may be used, if needed.
Additionally, the compounds may be delivered using a sustained-release system, such as semi-permeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various sustained-release materials have been established and are well known by those skilled in the art. Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days. Depending on the chemical nature and the biological stability of the particular compound, additional stabilization strategies may be employed. Pharmaceutical compositions useful herein also may comprise solid or gel phase carriers or excipients. Examples of such carriers or excipients include, but are not

calcium.carbonate,-GaIciurn.phosphate,-various-sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols.
Delivery to Plants/Crops, Facilities, Habitats
The compounds of the invention can be readily formulated by art-known methods for delivery for killing, suppressing or inhibiting endo or ectoparasites in or on plants generally, and particularly in crop plants, e.g., to kill or suppress any of the myriad plant pests enumerated supra, in addition, the compounds of the invention can be applied or distributed into selected environmental areas to kill or suppress endo or ectoparasites where desired. The inventive compounds are readily formulated, by methods known to the art, into compositions suitable for such applications. Such compositions optionally include more than one of the inventive compounds, each selected for an optimal spectrum of activity, tn certain optional embodiments, the compositions include other agents; e.g., other art-known antiparasitic agents, pesticides and the like, as enumerated supra, that may provide a useful complementary or synergistic anti-parasiticidal effect.
It is further contemplated that the compositions optionally include other useful agents, including weed killers, fertilizers, and the like, for efficient agriculture management.
Compositions for such distribution include solutions, suspensions and dry forms of the inventive compound(s) as discussed supra. This process of administering such compositions can be achieved by methods well known to the art. These include spraying, brushing, dipping, rinsing, washing, dusting, using art-known equipment, in a selected area. The selected area optionally includes plants, e.g., crops, and/or animals.
Thus, environmental areas contemplated to be treated in this way include, e.g., fields, orchids, gardens and the like, buildings and their environs, including landscaping; storage facilities, transport or fixed storage containers or analogous structures and structural components, such as walls, floors, roofs, fences, windows and window screens, and the like. Animal living spaces are also included, e.g., animal pens, chicken coops, corals, barns and the like. Human homes and other human residential, business or commercial and educational facilities are also contemplated to

orcornpositions-thereof as described above.
Application can be achieved using art-known spraying devices, e.g., self-pressurized aerosol containers, larger devices employing compressed air or centrifugal distribution, as well as crop dusters, and the like.
EXAMPLES
The following preparative examples of preferred derivatives of the inventive compound serve to provide further appreciation of the invention but are not meant in any way to restrict the effective scope of the invention.
EXAMPLE 1 Preparation of n-(2-acetyi-4-chlorophenyI)tr{fiuoromethanesulfonamide (Formula
19)
The following compounds were prepared according to the reaction scheme illustrated by FIG. 4.
a) To a rapidty stirred solution of fuming HN03 (17 mL) and concentrated H2SO4 (2.5 mL) at -20° C was added portionwise 3-chloroacetophenone (5.0 g, 32.34 mmol) over 15 min. The reaction mixture was allowed to warm to -10° C and stirred for 5 h at this temperature after which ice-water (75 mL) was added and the reaction mixture extracted twice with CH2C!2. The organic layers were combined, washed five times with water, dried over MgSC>4 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PEr 4:1) to afford a paie green oil which was recrystallized from Et20/PE to give 1-(5-chloro-2-nitrophenyI)ethanone 17 (5.45 g, 84%), as pale yellow crystals.
b) A mixture of 1-(5-chioro-2-nitrophenyl)ethanone 17 (4.40 g, 22.05 mmol), Pt02 (40 mg) and charcoal (400 mg) in EtOH (80 mL) was rapidly stirred at RT for 4.5 h under one atmosphere of hydrogen. The reaction mixture was filtered through a pad of celite (the residues washed with CH2CI2) and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 4:1) to afford a pale green oil which was recrystallized from Et20/PE to give 1-(2-amino-5-chlorophenyI)ethanone 18 (3.30 g, 88%), as paie green crystals.

in anhydrous dichloromethane (150 mL) at 0°C was added dropwise (CF3S02)20 (7.0 mL, 41.74 mmol) in anhydrous CH2CI2 (30 mL) over 30 min. and the reaction allowed to warm to RT overnight. The reaction mixture was washed with water, dried over MgSCU and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2Cl2/PE, 3:7) to afford a yellow oil which was recrystallized from Et20/PEto give.A^(2-acetyl-4-chIorophenyl)trifluoromethanesulfonarnide 19 (6.88 g, 82%), as pale yellow crystals. M.p. 35-38°C. 'H n.m.r. (200 MHz, CDCi3) 6 12.01, br s, 1H; 7.91, d, J=2.2Hz, 1H; 7.75, d, J=8.8Hz, 1H; 7.55, dd: J=2.2 and 8.8Hz, 1H; 2.71, s, 3H.
Example 1A: Preparation of W-{2-[1-(2,4-bistrifluoromethylben2yloxyimino)ethyI]-4-chloropheny[}trifluoromethanesu!fonamide (Compound 2).
A solution of N-(2-acetyl-4"ChlorophenyI)trifluoromethanesulfonamide 19 (150 mg, 0.50 mmol), 0-(2,4-bi$trifluoromethylbenzyI)hydroxyiamine hydrochloride (154 mg: 0.52 mmo!) and anhydrous NaOAc (43 mg, 0.52 mmol) in EtOH (20 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (elating with CH2CI2/PE: 7:3). Purification by radial thin layer chromatography (eluting with CH2CL2/PE, 7.5:92.5 to 1:9) afforded a pale yellow solid which was recrystallized from CH2CI2/PE to give W-{2-[1-(2,4-bistrifluoromethyibenzyloxyimino)ethyf]-4-chlorophenyl}trifluoromethanesu!fonamide 2 (240 mg, 89%)? as a coiorless oil. 1H n.m.r. (200 MHz, CDC!3) 5 10.96, br s, 1H; 7.96, s, 1H; 7.85, d, J=8.0Hz, 1H; 7.72, d, J=8.0Hz, 1H; 7.60, d, J=8.8Hz, 1H; 7.49, d, J=2.2Hz, 1H; 7.33, dd: J=2.2 and 8.8Hz, 1H; 5.46, s, 2H; 2.39, s, 3H. HRMS (M+) 542.0102. Preparation of 0-(2,4-bistrifiuoromethy[benzyl)hydroxylamine hydrochloride.
a) To a solution of W-hydroxyphthalimide (1.33 g, 8.14 mmol) in DMF (7 mL) was
added NEt3 (1.25 mL, 8.96 mmol) and 2,4-bis(trifluoromethyi)benzyl bromide (1.53
mL, 8.14 mmol) and the reaction was rapidly stirred for 15 h at RT. MeOH (2 mL) and
H20 (20 mL) were added and the reaction mixture was stirred at RT for 1 h, filtered
and the solids washed with warm (ca. 40°C) water and dried under vacuum \o afford
/V-(2,4-bistrifluoromethylbenzyloxy)phthalimide (3.10 g, 98%), as a white solid.
b) A solution of A/-(2,4-bistrifluoromethylbenzy!oxy)phthalimide (3.10 g, 7.96
mmol) and n-BuNH2 (0.79 mL, 7.96 mmol) was stirred at RTfor 15 h. The reaction

mixture-was-concentrated- under- vacuums-dissolved in-CH2Ci2-(400mL)and warmed with the aid of a heating mantle. 3N HCI (10 ml_) was added dropwise to the warm reaction mixture which was stirred for 5 min. The reaction mixture was then stirred at RT for 5 min, filtered and the soiids dried under vacuum to afford 0-(2,4-bistrifiuoromethylbenzyl)hydroxyiamine hydrochloride {224 g, 95%), as a white solid.
Example 1B: Preparation of W-{2-[1-(2,5-bistrif]uoromethyIben2yloxyimino)ethy[]-4-chlorophenyljtrifluoromethanesulfonamide (Compound 120).
A solution of W-(2-acetyl-4-chioropheny!)trifiuoromethanesulfonamide 19 (300 mg, 0.99 mmol), 0-(2,5-bistrifIuoromethylben2yl)hydroxylamine hydrochloride (296 mg, 1.0 mmol) and anhydrous NaOAc (53 mg, 0.65 mmol) in MeOH (5 mL) and H20 (15 mL) was adjusted to pH 4.5 with AcOH and heated for 15 h at reflux. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eiuting with CH2CI2). Purification by radial thin layer chromatography (eluting with CH2CI2/PE, 1:19 to 1:9) afforded N-{2-[1-(2,5-bisiriffuoromethyIbenzyloxyimino)ethy
120 (100 mg, 19%), as a pale yellow sofid. M.p. 73-75°C. "'H n.rn.r. (200 MHz, CDCi3) S 10.94, br s, 1H; 7.88-7.71, m, 3H; 7.60, d, J=8.8Hz, 1H; 7.50, d, J=2.4Hz, 1H; 7.33, dd, J=2.4 and 8.8Hz, 1H; 5.46, s, 2H; 2.41, s, 3H. Preparation of 0-(2,5-bistrifluoromethylbenzyi)hydroxylamine hydrochloride.
a) To a solution of W-hydroxyphthalimide (5.30 g, 32.49 mmol) in DMF (25 mL) was added NEt3 (4.96 mL, 35.58 mmol) and 2,5-bis(trifluoromethyl)benzyI bromide (10.0 g, 32.57 mmol) and the reaction was rapidly stirred for 15 h at RT. MeOH (2 mL) and H20 (100 mL) were added and the reaction mixture was stirred at RT for 1 h, filtered and the solids washed with warm {oa. 40° C) water and dried under vacuum to afford A/-(2,5-bistrifluoromethy!benzyloxy)phthaiimide (12.0 g, 95%), as a white solid.
b) A solution of A/-(2)5-bistrifluoromethyIbenzyloxy)phtha!imide (12.0 g, 30.83 mmol) and n-BuNH2 (3.10 mL 31.31 mmol) was stirred at RT for 15 h. The reaction mixture was concentrated under vacuum, dissolved in CH2CI2 (200 mL) and warmed with the aid of a heating mantle. 3N HCI (20 mL) was added dropwise to the warm reaction mixture which was stirred for 5 min. The reaction mixture was then stirred at RT for 5 min; filtered and dried under vacuum to afford 0-(2:5-bistrifluoromethylbenzyl)hydroxylamine hydrochloride (7.30 g, 80%), as a white solid.

Example 1C: Preparation of N-{4-chtoro-2-[1-(3-
tnfiuoromethylphenoxyimino)ethyi]phenyl}trffluorornethanesulfonarnide (Compound 134).
A solution of A/-(2-acetyl-4-ch!orophenyl)trif!uoromefhanesulfonamide 19 (310 mg, 1.03 mrnol). 0-(3-trifIuoromethyIphenyI)hydroxy!amfne hydrochloride (220 mg, 1.03 mmol) and anhydrous NaOAc (93 mg, 1.13 mmol) in EtOH (18 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2CI2/PE, 3:2). Purification by radial thin layer chromatography (eluting with CH2CI2/PE, 1:5) afforded N-{4-chloro-2-[1»(3-trifluoromethylphenoxyimino)ethy[]pheny[}trifluoromethanesuifonam!de 134 (430 mg, 91%), as a pale yellow solid. M.p. 63-64°C. 1H n.m.r. (200 MHz, CDCI3) 6 11.00, br s, 1H; 7.71, d, J=9.0Hz, 1H; 7.60: d, J=2.2Hz, 1H; 7.56-7.35, mf 5H; 2.58, s, 3H. 0~(3-Trifluoromethylphenyi)hydroxylamine hydrochloride was prepared in two steps by the procedure of Petrassi, M. H.; Sharpless, K. B.; Kelly, J. W. Org. Lett., 2001, 3,
139-142.
,<
Example 1D: Preparation of /V-{4-chIoro-2~[1-(4-fiuorophenoxyimino)ethyl]phenyl}trifluoromethanesulfonamide (Compound .129).
A solution of N'(2-acetyl-4-chIorophenyI)trifluoromethanesulfonamide 19 (350 mg, 1.16 mmol), (>(4-fluoropheny[)hydroxyIarnine hydrochloride (190 mg, 1.16 mmol) and anhydrous NaOAc (104 mg, 1.27 mmol) in EtOH (16 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2CI2/PE, 3:2) and the solvent removed under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with CH2CI>>/PE, 1:4) to afford N-{4-chloro2-[1-(4-
fluorophenoxyimino)ethyl]phenyl}trifluoromethanesulfonamide 129 (458 mg, 96%), as a pale yellow solid. M.p. 71-73°C. 1H n.m.r. (200 MHz, CDCI3) 5 11.23, br s, 1H; 7.69, d, J=9.0Hz, 1H; 7.59, d, J^2.4Hz5 1H; 7.40, dd, J=2.4 and 9.0Hz, 1H; 7.18-7.03, m, 4H; 2.55, s, 3H.
Preparation of 0(4-fluorophenyl)hydroxylamine hydrochloride.

ToN,hydroxypbthalimide-(J.0 g,-6.-12 mmol),-CuCL(606-mg,-6.12-mmoI),
ground freshly activated 4A molecular sieves (1.53 g) and 4-fluorophenyIboronic acid (1.72 g, 12.29 mmol) was added 1,2-DCE (32 mL) and pyridine (0.544 mL 6.73 mmoi)- The green/brown suspension was protected by a CaC!2 guard tube and stirred for 63 h at RT. Silica ge! (-20 g) was added and the reaction mixture was concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with PE; CH2CI2/PE, 7:3 to 1:4) and the solvent concentrated under vacuum. The residue was purified by preparative chromatography over siiica gel (eluting with CH2Ci2/PE, 1:1 to 3:2) to afford A/-(4-fiuorophenoxy)phthaIimide (460 rng, 29%), as a pale yellow solid.
b) To a solution of /V-(4-fluorophenoxy)phthalimide (690 mg, 2.68 mmol) in MeOH (2.6 mL) and CHCl3 (23.4 mL) was added N2H4.H20 (390 vL, 8.04 mmol) and the reaction was stirred at RT for 15 h. Siiica gel (~6 g) was added and the reaction mixture was concentrated under reduced pressure. The residue was filtered through a pad of siiica (eluting with CH2CI2/PE: 4:1) and the solvent removed under reduced pressure to afford a dark yellow oil. The free amine was dissolved in Et20 (15 mL), cooled to 0C C and acidified with 4N HCI in dioxane (1 mL) to give a white precipitate. The precipitate was washed three times with Et20 and dried under vacuum to yield O-(4-fluorophenyl)hydroxyiamine hydrochloride (400 mg, 91%), as a white solid.
Example 1E: Preparation of iV-[4-ch!oro-2-(1-cyclopentyloxyiminoethyI)pheny!]trifiuoromethanesulfonamide (Compound 163).
M/V-Dlmethylethylenediamine (254 JJL, 2.20 mmoi) was added to a solution of A/-(cyclopentyloxy)phthalimide (345 mg, 1.50 mmol) in EtOH (5 mL), and the reaction allowed to stir at RT for 15 h. Glacial acetic acid (2 mL) was then added to adjustthe mixture to ca. pH 4 followed by a solution of A/-(2-scetyi-4-
chlorophenyl)trifluoromethanesulfonamide 19 (302 mg, 1.0 mmol) in EtOH (2 mL), and the reaction stirred for 2.25 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by radial thin layer chromatography (eluting with CH2CI2/PE, 1:19) to afford A/-[4-chIoro-2-(1-
cyclopentyloxyiminoethyl)pheny!]trifluoromethanesulfonamide 163 (185 mg, 48%), as a pale yellow solid. 1H n.m.r. (400 MHz, CDCI3) 5 12.18, br s, 1H; 7.67, d, J=8.8Hz,

1H; 7.49, d, J=2.4Hz, 1H; 7.31, dd, J=2.4 and 8.8Hz, 1H; 4.80, m, 1H; 2.30, s, 3H; 1.89, m, 4H; 1.74, m, 2H; 1.64, m, 2H. HRMS (M+) 384.0518. /V-(CyclopentyIoxy)phthaIimide was prepared by the procedure of Ishikawa, 7\; Kamiyamar K.; Matsunaga, N.; Tawada, H.; lizawa, Y.: Okonogi, K.; Miyake, A. J. Antibiot, 2000, 53, 1071-1085.
Example 1F: Preparation of N-{4-chloro-2-[1-(2" methoxyethoxyimino)ethy[]pheny[}trifluoromethanesulfonamide (Compound 185).
M/V-Dimethy)ethylenediamine (2.54 mL 22.0 mmol) was added to a solution of A/-(2-methoxyethoxy)phthalimide (3.32 g, 15.0 mmol) in EtOH (50 mL), and the reaction allowed to stir at RT for 15 h. Glacial acetic acid (20 mL) was then added to adjust the mixture to est. pH 4, followed by the addition of a solution of W-(2-acetyl-4-chlorophenyl)trifluoromethanesulfonamide 19 (3.02 g, 10.0 mmoi) in EtOH (2 mL), and the mixture stirred for 65 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eiuting with CH2C!2/PE, 1:1). Purification by radial thin layer chromatography (eiuting with CH2Cl2/PE. 1:9 to 1:1) afforded N-{4-chloro-2-[1 -(2-
methoxyethoxyimino)efhyl]phenyI}trifluoromethanesulfonamide 185 (3.0 g, 80%), as a colorless oil. 1H n.m.r. (400 MHz, CDCl3) 6 11.40, br s, 1H; 7.65, d, J=8.8Hz, 1H; 7.47, d, J=2.4Hz, 1H; 7.33, dd, J=2.4 and 8.8Hz, 1H; 4.37, m, 2H; 3.71, m, 2H; 3.41, s, 3H; 2.32, s, 3H. HRMS.(M") 374.0308.
A/-(2-methoxyethoxy)phthalimide was prepared using an analogous procedure to that described in Example 1A.
Example 1G: Preparation of A/-[4-ch(oro-2-(1-
cyclopropylmethoxyiminoethyl)pheny[3trifiuoromethanesuffonamide (Compound 187). MN-Dimethylethylenediamine (254 pL, 2.20 mmol) was added to a solution of /V-(cyclopropylmethoxy)phthalimide (326 mg, 1.50 mmol) in EtOH (5 mL), and the reaction allowed to stir at RT for 15 h. Glacial acetic acid (2 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of /V-(2-acetyl-4-chlorophenyl)trifluoromethanesutfonamide 19 (302 mg, 1.0 mmol) in EtOH (2 mL), and the mixture stirred for 48 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eiuting with CH2Cl2/PE,

-
cyclopropyimethoxyiminoethy[)phenyl]trif(uoromethanesulfonamide 187 (300 mg, 81%), as a white solid. M.p. 53-54°C. 'H n.m.r. (400 MHz, CDCI3) 6 11.84, br s, 1H; 7.65, d. J=8.8Hz: 1H; 7.49, d, J=2.4Hz, 1H: 7.32, ddf J=2.4 and 8.8Hz, 1H; 4.03, d: J=7.2Hz, 2H; 2.34, s, 3H; 1.22, m, 1H; 0.64: m, 2H; 0.34; m, 2H. Preparation of A/-(cyclopropylmethoxy)phthaIimide.
To a suspension of cyclopropyl methanol (562//I, 6.93 mmoi); triphenylphosphine (2.02 g, 7.63 mmol) and AAhydroxyphthalimide (1.28 g, 7.63 mmo!) in THF (10 mL) at ODC was added dropwise diethyiazodicarboxyiate (1.20 mL, 7.63 mmol) in THF (10 mL). The reaction mixture was allowed to stir for 15 h after which the solvent was removed under vacuum to dryness. Et20 (15 mL) was added to triturate the triphenylphosphine oxide and diethylhydrazinedicarbcxylate, which was filtered off and washed with a little Et20. The ethereal solution was'concentrated under vacuum to give a residue which was filtered through a pad of silica (eluting with EtOAc/PEr 3:7). Removal of the solvent under reduced pressure afforded a pale yellow solid which was recrystallized from CH2CI2/PE to give N-(cyciopropyimethoxy)phthaiimide (1.30 g. 86%). as a white solid.
Example 1H: Preparation of A/-{4-chloro-2-[1-(5-chlorothiophen-2» ylmethoxyimino)ethyl]pheny[}trifluoromethanesulfonamide (Compound 194).
/V,/V-Dimethylethylenediarnine (178 //L 1.54 mmo!) was added to a solution of A/-(5-chlorothiophen-2-ylmethoxy)phthalimide (220 mg, 0.75 mmo!) in EtOH (5 mL), and the reaction allowed to stir at RT for 15 h. Glacial acetic acid (1 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of W-(2-acetyl-4-chloropheny[)trifluoromethanesulfonamide 19 (211 mg, 0.70 mmol) in EtOH (2 mL), and the mixture stirred for 15 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eluting with CH2CI2/PE, 1:1) to afford K44-chloro-2-[1-(5-chIorothiophen-2-
ylmethoxyimino)ethyl]phenyI}trifluoromethanesulfonamide 194 (280 mg, 90%), as white crystals. 1H n.m.r. (400 MHz, CDCI3) 5 11.37.brs, 1H;7.63, d, J=8.8Hz, 1H; 7.48, d; J=2.4Hz, 1H; 7.33, dd, J=2.4 and 8.8Hz, 1H; 6.94; d, J=3.8Hz; 6.81, d, J=3.8Hz; 5.24, s, 2H; 2.33; s, 3H. HRMS (M+) 445.9540.

A/-(5-Chlor-othiophe.n-2-ylmethoxy)phtbaliuii.de was. prepared, using the procedure reported in US 4,071:533.
The following trifluoromethanesulfonanilide oxime ether compounds, as listed by Tables 8 and 8A. infra, were prepared using similar preparative methods: Compounds 1, 3, 4,13-23, 25-29, 32, 33, 35, 36, 38-60, 73, 121-127, 132, 135, 137, 140, 141, 143, 144, 147, 149,151, 158, 160, 161, 172-175, 181, 185,186, 188-190, 202, 203, 223, 242, 244, 246, 249, 253, 255, 258, 260, 261, 263, 264, 266, 267, 269, 270, 272, 273, 275, 276, 278-280, 282, 283, 285, 286, 288 and 289.
Additional data for the compounds of Example 1, supra, is provided by Table 2, beiow.


EXAMPLE 2
Preparation of N-(4-chIoro-2-propionyiphenyl)trifIuoromethanesulfonamide
(Formula 22) The following compounds were prepared according to the reaction scheme illustrated by FIG. 5.
a) To a rapidly stirred solution of fuming HN03 (9 mL) and concentrated H2S04 (1.3 mL) at -20° C was added portionwise 3-chloropropiophenone (2.50 g, 14.82 mmol) over 15 min. The reaction mixture was allowed to warm to -10°C and stirred for 2.25 h at this temperature after which ice-H20 (75 mL) was added and the reaction mixture extracted twice with CH2Cl2. The organic layers were combined, washed five times with water, dried over MgS04 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2Cl2/PE, 7:3) to afford 1-(5-chloro-2-nitropheny!)propan-1-one 20 (2.99 g, 94%), as a pale yellow solid.
b) To a mixture of 1-(5-chIoro-2-nitrophenyI)propan-1-one 20 (2.49 g, 11.66 rnmof) in EtOH (20 mL) and H20 (10 mL) was added iron powder (3.25 g, 58.28 mmol) and NH4CI (312 mg, 5.83 mmol) and the reaction was rapidly stirred at 90°C for 30 min. The hot reaction mixture was filtered (the residues were washed with EtOAc) and further EtOAc and H20 added. The EtOAc layer was separated, dried over MgSCU and concentrated under reduced pressure. The residue was filtered through a pad of' silica (eluting with CH2CI2/PE, 7:3) to afford 1-(2-amino-5-chlorophenyl)propan-1-one 21 (1.95 g, 91%), as a yellow solid.
c) To a solution of 1-(2-amino-5-chIorophenyf)propan-1-one 21 (2.12 g, 11.54 mmol) in anhydrous dichloromethane (80 mL) at 0°C was added dropwise (CF3S02)20 (2.91 mL 17.32 mmol) in anhydrous CH2CI2 (30 mL) over 30 minutes and the reaction allowed to warm to RT overnight. The reaction mixture was washed with water, dried over MgSO< and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2Ci2/PE, 3:2) to afford a yellow oil which was recrystallized from Et20/PE to give W-(4-chloro-2-
propionylphenyl)trifluoromethanesu(fonamide 22 (3.12 g, 86%), as pale yellow crystals. M.p. 54-55°C. 1H n.m.r. (200 MHz, CDCI3) 5 12.06, br s, 1H; 7.93, d, J^2.4Hz, 1H; 7.75 s d, J=9.0Hz, 1H; 7.54, dd, J=2.4 and 9.0Hz, 1H: 3.09, q, J=7.2Hz, 2H; 1.24,t J=7.2Hz,3H.

ch!orophenyl}trifluorornethanesulfonamide (Compound 76).
A solution of A/-(4«chloro-2»propionylphenyI)trifluoromethanesulfonamfde 22
(3.21 rng: 10.17 mmoi), 0(2,4- bistrifluoromethylbenzyl)hydroxyIamine hydrochloride 5 (3.16 mg, 10.68 mmoi) and anhydrous NaOAc (876 mg; 10.68 mmoi) in EtOH (120
mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum
and the residue filtered through a pad of silica (eluting with CH2CI2/PE, 2:3).
Purification by radial thin layer chromatography (eiuting with CH2CI2/PE, 1:9) afforded
a pale yellow solid which was recrystallized from CH2CI2/PE to give /V-{2-[1-(2,4- bistrifluoromethyibenzy!ox>^imino)propy!}-4"Chloropheny[}trifluoromethanesuIfonamide
76 (3.70 g, 65%), as a pale yellow oil. 1H n.m.r. (200 MHz, CDCi3) 5 10.96, br s, 1H;
7.96, s, 1H; 7.85, d, J=8.4Hz, 1H; 7.72, d, J=8.4Hz, 1H; 7.61, d, J=8.3Hz, 1H; 7.49, d,
J=2.4Hz, 1H; 7.33, dd, J=2.4 and 8.8Hz, 1H; 5.45, -s, 2H; 2.88, qf J=7.6Hz, 2H; 1.21, t,
J=7.6 Hzr 3H. HRMS (M+) 556.0254.
0-(2J4-Bistrifiuoromethylbenzyl)hydroxylamine hydrochloride was prepared by
the procedure described in Example 1A.
Example 2B: Preparation of A/-{4-chIoro-2-[1-(4-chlorobenzyloxyimino)propyl]phenyl}trifluoromethanesulfonamide (Compound 11).
A solution of A/-(4-chloro-2-propionylphenyl)trifluoromethanesuifonamide 22 (1.75 g, 5.54 mmoi), 0-(4~chlorobenzyI)hydroxyiamine hydrochloride (1.13 g, 5.82 mmoi) and anhydrous NaOAc (477 mg, 5.82 mmoi) in EtOH (80 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2CI2/PE, 3:2). Purification by radial thin layer chromatography (eluting with CH2CI2/PE, 1:9) afforded a pale yellow solid which was recrystallized from CH2C!2/PE to give A/-{4-chioro-2-[1-(4-
ch!orobenzyloxyimino)propyl]phenyl}trifluoromethanesulfonamide 11 (1.74 mg, 69%), as a while solid. M.p. 54-55°C. 1H n.m.r. (200 MHz, CDC!3) 5 11.55, br s, 1H; 7.63, d, J=8.8Hz, 1H; 7.47, d, J=2.2Hz, 1H; 7.39-7.29, m, 5H; 5.17, s, 2H; 2.84, q, J=7.6Hz, 2H; 1.18, t, J=7.6Hz, 3H.
.3-(4-Chlorobenzyl)hydroxylamine hydrochloride was prepared in two steps using an analogous procedure to that described in Example 1 A.

Example 2C: Preparation of N-{4-chloro-2-[1-4-
ch!orophenoxyimino)propyl]phenyl}triffuoromethanesulfonamide (Compound 128). A solution of A/-(4-chloro-2-propionylphenyI)trifiuoromethanesuifonamide 22 (450 mg: 1.43 mmol), 0-(4-chloropheny!)hydroxylamine hydrochloride (257 mg, 1.43 mmol) and anhydrous NaOAc (125 mg, 1.52mmol) in EtOH (23 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2CI2/PE, 3:2). The residue was purified by radial thin layer chromatography (eluting with CH2CI2/PE, 1:5) to afford A/-{4-chloro-2-[1-(4-ch(orophenoxyimino)propyl]pheny[}trifluoromethanesulfonamide 128 (455 mg, 72%), as ayellow solid. M.p. 87-88°C. 1H n.m.r. (200 MHz, CDC!S) 5 11.18, brs, 1H; 7.71, d, J=8.8Hz, 1H; 7.58, d, J=2.6Hz, 1H; 7.41, did, J=2.6 and 8.8Hz, 1H; 7.35, d, J=8.8Hz, 2H; 7.11, d, J=8.8Hz, 2H; 3.02, q, J=7.5Hz, 2H; 1.30, t, J=7.6 Hz, 3H. Preparation of 0-(4-chIorophenyI)hydroxyIamine hydrochloride.
a) Ton-hydroxyphthalimide (1.0 g, 6.12 mmol), CuCI (606 mg, 6.12 mmol), ground freshly activated 4A molecular sieves (1.53 g) and 4-chlorophenyIboronic acid (1.92 g, 12.28 mmol) was added 1,2-DCE (32 mL) and pyridine (0,544 mL, 6.73 mmol). The greea'brown suspension was protected by a CaCl2 guard tube and stirred for 29 hours at RT. Silica gel (-10 g) was added and the reaction mixture was adsorbed by concentration of the solvent under reduced pressure. The residue obtained was purified by preparative chromatography over silica gel (eluting with EtOAc/PE, 1:9) to afford /V-(4-chtorophenoxy)phthaIimide (1.02 g, 61%), as a white solid.
b) To a solution of A/-(4-chlorophenoxy)phthalimide (660 mg, 2.41 mmol) in MeOH (2.5 mL) and CHCI3 (22.5 mL) was added N2H4.H20 (0.35 mL, 7.23 mmol) and the reaction was stirred at RT for 15 hours. Silica gel (-6 g) was added and the reaction mixture was adsorbed by concentration of the solvent under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 4:1) and the solvent removed under reduced pressure to afford a dark yellow oil. The free amine was dissolved in Et20 (15 mL), cooled to 0°C, and acidified with 4N HCI in dtoxane (1 mL) to give a white precipitate. The solvent was decanted from the precipitate which was washed twice with Et20 and dried under vacuum to yield 0(4-chlorophenyl)hydroxylamine hydrochloride (340 mg, 79%), as a white solid.

ExampIe-2-D:- Preparation- ef-N-{4-chlero-2-[-1-(4-fluorophenoxyimino)propyi]phenyl}trifluoromethanesulfonamide (Compound 130). A solution of W-(4»ch!oro-2-propionyIphenyl)tnfluoromethanesuifonamide 22 (386 mg, 1.22 mmol), 0-(4-fluorophenyi)hydroxylamine hydrochloride (200 mg: 1.22 mmof) and anhydrous NaOAc (110 mg, 1.34 mmoi) in EtOH (18 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2Cl2/PE; 3:2). The residue was purified by radial thin layer chromatography (eluting with CH2Cf2/PE, 1:4) to afford W-{4-chloro-2-[1-(4-fluorophenoxyimino)propyI]pheny[}trifluoromethanesuifonamide 130 (420 mg, 81%), as a pale yellow solid. M.p. 47-48°C. 'H n.m.r. (200 MHz, CDC!3) 8 11.25, br s, 1H; 7.71, d, J=8.8Hz, 1H; 7.58, d, J=2.4Hz, 1H; 7.40, dd, J=2.4 and 8.8Hz, 1H; 7.18-7.02; m, 4H; 3.02, q, J=7.6Hz, 2H; 1.31, t, J=7.6Hz, 3H.
0-(4-Fluoropheny!)hydroxylamine hydrochloride was prepared by the procedure described in Example-1D.
Example 2E: Preparation of A^-[4-chloro-2-(1-
cyclohexylmethoxyiminopropyOphenyrfirifluoromethanesuifonamide (Compound 104). /V,A/-Dimethylethylenediarnine (1.53 mL, 13.18 mmoi) was added to a solution of N-(cyclohexylmethoxy)phthaiimide (2.33 g, 8.99 mmoi) in EtOH (30 mL), and the reaction allowed to stir at RT for 2 hours. Glacial acetic acid (5 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of N-(4-chloro-2-propionylphenyl)trifluoromethanesulfonamide 22 (1.89 g, 5.99 mmof) in EtOH (10 mL), and the reaction stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in Et20 (50 mL) and washed with water, brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was purified by column chromatography (eluting with CH2CI2/PE, 3:4 to 1:3) to afford A/-[4-ch!oro-2-(1-
cyclohexylmethoxyiminopropyl)pheny!]trifluoromethanesulfonamide 104 (2.34 g, 91%), as colorless crystals. 1H n.m.r. (400 MHz, CDCI3) 5 12.01, br s, 1H; 7.67, d, J=8.8Hz, 1H; 7.48, d, J=2.4Hz, 1H; 7.32, dd, J=2.4 and 8.8Hz, 1H; 4.02, d, J=6Hz, 2H; 2.81, q, J=7.6Hz, 2H; 1.74, m, 6H; 1,27, m, 3H; 1.19, t, J=7.6Hz, 3H; 1.01, m, 2H. HRMS (M+) 426.0971.

Preparation of~/V-(-cydohexylmethoxy)phthaIimide.
To a stirred solution of /V-hydroxyphthalimide (10.0 g, 61.30 mmol) in DMF (40 mL) at RT was added NEt3 (9.40 mL, 67.43 mmoi) and, in a dropwise fashion, (bromomethyl)cyclohexane (9.41 mL: 67.43 mmoi). The reaction was then stirred for 15 hours at 5G°C, after which it was allowed to cool to RT and then concentrated under vacuum. The residue was dissolved in Et20 (100 mL) and washed with water, brine, dried over MgSCU and the solvent removed under reduced pressure. The residue was purified by column chromatography (efuting with CH2CI2/PE, 1:1 to 3:1) to afford /V-(cyclohexyimethoxy)phthalimide (8.40 g, 53%), as a white solid.
Example 2F: Preparation of N-[2-(1-aIlyloxyiminopropyI)-4-chiorophenyljtrifluoromethanesulfonamide (Compound 156).
A solution of A/-(4-chioro-2-propionylphehyl)trifluoromethanesuifonamide 22 (316 mg, 1.0 mmol), O-alJylhydroxylamine hydrochloride (119 mg, 1.05 mmoi) and anhydrous NaOAc (86 mg, 1.05 mmoi) in EtOH (5 mL) was stirred for .15 hours at RT. The reaction mixture was concentrated under vacuum and the residue tittered through a pad of siiica (eiuting with EtOAc/PE, 1:9). The residue was purified by radial thin layer chromatography (eiuting with CH2C!2/PE, 1:99 to 1:19) to afford N-[2-(1 -allyIoxyiminopropyl)-4-chiorophenyi]trifluoromethanesuIfonamide 156 (116 mg, 31%)," as a colorless oil. 1H n.m.r. (400 MHz, CDCf3) 5 11.57, br s, 1H; 7.67, d, J=8.8Hz, 1H; 7.48, d, J=2.4Hz, 1H; 7.33, dd, J^2.4 and 8.8Hz, 1H; 6.00, m, 1H; 5.42, d, 3J=17.2Hz, 1H; 5.36, d, 3J=10.4Hz, 1H; 4.68, d, J=6.0Hz, 2H; 2.83, q, J=7.6Hz, 2H; 1.19, t, J=7.6Hz, 3H. HRMS (M") 370.0350.
Example 2G: Preparation of A/-[4-chioro-2-(1-cyciopropylmethoxyiminopropyl)phenyi]trifluoromethanesulfonamide (Compound 196).
A/,A/-Dimethyiethylenediamine (254//L, 2.20 mmoi) was added to a solution of A/-(cyciopropylmethoxy)pbthaIimide (326 mg, 1.50 mmoi) in EtOH (5 mL), and the reaction allowed to stir at RT for 15 h. Glacial acetic acid (2 mL) was then added to adjust the mixture to ca. pH 4, followed by the addition of a solution of /V-(4-chIoro-2-propionyiphenyi)trifluoromethanesutfonamide 22 (316 mg, 1.0 mmol) in EtOH (2 mL), and the mixture stirred for 65 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eiuting with CH2Cl2/PE,

cyclopropylmethoxyiminopropyl)phenyi]trifluoromethanesulfonamide 196 (205 mg,
53%), as a colorless oil. 1H n.m.r. (400 MHz, CDCI3) §11.88, brs, 1H; 7.66, d,
J=8.8Hz, 1H; 7.49, d, J=2.4Hz, 1H; 7.33, dd, J=2.4 and 8.8Hz, 1H; 4.02, d, J=7.2Hz,
1H; 2.83, q, J=7.6Hz, 2H; 1.22, m, 4H; 0.64, m, 2H; 0.33, m, 2H. HR.MS {W)
384.0515.
N-(cyc!opropylmethoxy)phthalimide was prepared by the procedure described in
Exampie 1G.
Example 2H: Preparation of A/-{4-chloro-2-[1-(thiophen-2-ylmethoxyimino)propyi]phenyl}trifluoromethanesulfonamide (Compound 207).
N,W-Dimethylethylenediamine (254 /A., 2.20 mrnol) was added to a solution of Af^(thiophen-2-ylmethoxy)phthalimide (365 mg, 1.50 mmo!) in EtOH (5 mL), and the reaction allowed to stir at RT foM 5 h. Glacial acetic acid (1 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of Af-(4-chloro-2-propiony!pheny[)trifiuoromethanesuifonamide 22 (316 mg, 1.0 mrnol) in EtOH (2 mL), and the mixture stirred for 15 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eluting with CH2CI2/PE, 1:1) to afford N-{4-chioro-2-[1-(thiophen-2-
y!methoxyimino)propyl]phenyl}trifluoromethanesulfonamide 207 (364 mg, 85%), as a white solid. M.p. 53-54cC. 1H n.m.r. (400 MHz., CDCI3) 5 11.49, br s, 1H; 7.64, d J=8.8Hz, 1H; 7.47, d, J=2.4Hz, 1H; 7.33, m, 2H; 7.16, m, 1H; 7.01, m, 1H; 2.82, q, J=7.6Hz, 2H; 1.17, t, J=7.6Hz, 3H. HRMS (M+) 426.0065. Preparation of ^(thiophen-2-yimethoxy)phthalimtde.
To a suspension of 2-thiophenemethanoI (4.15 mL, 43.64 mmol), triphenylphosphine (12.59 g, 48.01 mmol) and W-hydroxyphthalimide (7.83 g, 48,01 mmol) in THF (120 mL) at 0°C was added dropwise diethylazodicarboxylate (7.56 mL, 48.01 mmol) in THF (20 mL). The reaction mixture was allowed to stir for 15 h after which the solvent was removed under vacuum to dryness. Et20 (50 mL) was added to triturate the triphenylphosphine oxide and dieihylhydrazinedicarboxylate, which was filtered off and washed with a little Et20. The ethereal solution was concentrated under vacuum to give a residue which was filtered through a pad of silica (eluting with

EtOAc/PE, 3:7). Removal of the solvent under reduced pressure afforded A/-(thiophen-2-ylmethoxy)phthalimide (1.50 g, 13%), as a pale yellow solid.
The following trifluoromethanesulfonanilide oxime ether compounds, as listed by Tables 8 and 8A, were prepared using similar preparative methods; Compounds 5-10,12, 34, 37, 72, 74, 75: 77, 79, 84-86, 91, 93, 94, 103, 105-107, 109, 131, 133, 136, 138, 139, 142, 145, 146, 148,150,152-157, 159,170, 171,183,184, 197, 204-206, 207, 208, 224, 243, 245, 247, 248, 250, 254, 256, 257, 259, 262, 265, 268, 271, 274, 277, 281, 284, 287 and 290.


EXAMPLE 3
Preparation of W-(4-chIoro-2-formyIphenyi)trtfiuoromethanesulfonamide
(Formula 24) The following compounds were prepared according to the reaction scheme illustrated by FIG. 6.
a) To a solution of Na2S204 (tech., -85%) (29.72 g, 145.09 mmol) and Na2C03 (12.98 g, 122.46 mmol) in H20 (500 mL) at 45°C was added dropwise 5-ch!oro-2-nitrobenzaldehyde (tech., -80%) (5.31 g, 22.89 mmof) in MeOH (100 mL) over 25 min. The reaction mixture was heated to 65°C, allowed to cool to RT and extracted three times with CH2C!2. The combined organics were washed with H20, dried and the solvent concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 4:1) and the solvent concentrated under reduced pressure to afford 2-amino-5-chlorobenzaldehyde 23 (2.12 g, 60%), as a yeliow oil.
b) To a solution of 2-amino-5-chlorobenzaldehyde 23 (2.12 g, 13.62 mmol) and Et3N (1.99 mL 14.31 mmol) in anhydrous dichioromethane (120 mL) at -78°C was added dropwise (CF3S02)20 (2.41 mL, 14.31 mmo!) in anhydrous CH2Cl2 (30 mL) over 10 min. The reaction mixture was allowed to warm to RT over 15 h, washed with water, dried over MgS04 and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 3:7 to 100% CH2CI2) to afford W-(4-chloro-2-formylphenyl)trifIuoromethanesulfonamide 24 (938 mg, 24%), as a brown oil. 1H n.m.r. (200 MHz, CDCI3) 8 11.11, br s, 1H; 9.89, s, 1H; 7.79-7.74, m, 2H; 7.62, dd, J=2.4 and 8.8Hz, 1H. HRMS (M+) 286.9629.
Example 3A: Preparation of N-{2-[(2,4-bistrifiuoromethylbenzyloxyimino)methyl]-4-chlorophenyljtrifluoromethanesulfonamide (Compound 65).
A solution of W-(4-chloro-2-formyIphenyl)trifluoromethanesuifonamide 24 (180 mg, 0.63 mmof), 0-(2,4- bistrifluoromethylbenzyl)hydroxylamine hydrochloride (342 mg, 1.16 mmol) and anhydrous NaOAc (141 mg, 1.72 mmol) in EtOH (10 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CHCI3). Purification by radial thin layer chromatography (eluting with CH2CI2/PE, 1:9 to 3:7) afforded W-{2-[(2,4-bistrifluoromethyfbenzyloxyimino)methyl]-4-chlorophenyl} -trifluoromethanesulfonamide 65 (192 mg, 58%), as a yellow solid. M.p. 65-67°C. 1H

n.m.r. (200 MHz, CDCI3) 5 10.38, br s,~1-Hr8.20, s, 1H; 7.97, s, 1H; 7.86, d, J=8.0Hz, 1H; 7.75, d, J=8.0Hz, 1H; 7.65, d, J=8.8Hz, 1H; 7.35, dd, J=2.4 and 8.8Hz, 1H; 7.28, d,J=2.4Hz, 1H;5.44, s, 2H.
0-(2,4-Bistrifluoromethylbenzy!)hydroxylaj7iine hydrochloride was prepared by the procedure described in Example 1A.
Example 3B: Preparation of Af-{4-chioro-2-[(3)4-dichloroben2yloxyimino)methy!]phenyi}trifiuorornethanesutfonarnide (Compound 97).
A solution of A/-(4-chloro-2-formyIphenyI)trifluoromethanesuIfonamide 24 (163 mg, 0.57 mmol), 0-(3,4-dichlorobenzyf)hydroxylamine hydrochloride (130 mg, 0.57 mmot) and anhydrous NaOAc (77 mg, 0.94 mmol) in EtOH (10 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CHCfe). Purification by radial thin layer chromatography (eluting with CH2Ci2/PE; 1:9) afforded /V-{4-chloro-2-r(3:4~ dichlorobenzyloxyimino)methy(]phenyl}trifluoromethanesulfonamide 97 (172 mg: 66%), as a colorless oil. 1H n.m.r. (200 MHz, CDCI3) 5 10.65, br s, 1H; 8.14, s, 1H; 7.66, d, J=8.8Hz, 1H; 7.51"7.45, m, 2H; 7.35, dd, J=2.4 and 8.8Hz, 1H; 7,27-7.22, m, 2H; 5.12, s, 2H. HRMS (M") 459.9422.
O(3r4-Dichlorobenzyl)hydroxylamine hydrochloride was prepared in two steps using an analogous procedure to that described in Example 1 A.
The following trifluoromethanesuifonanilide oxime ether compounds, as listed by Tables 8 and 8A, infra, were prepared using similar preparative methods: Compounds 67, 70, 81, 95 and 96.
Additional data for compounds of Example 3 is provided by Table 4, below.


EXAMPLE 4 Preparation of A/-(2-ben2oyl»4-chIorophenyl)trifluoromethanesulfonamide
(Formula 25)
The following compounds were prepared according to the reaction scheme illustrated by FIG. 7.
To a solution of 2-amino-5-chIorobenzophenone (500 mg, 2.16 mmol) in anhydrous CH2Cl2 (30 mL) at 0°C was added dropwise (CF3S02)20 (545 JJL, 3.24 mmol) in anhydrous CH2CI2 (10 mL) over 10 min and the reaction allowed to warm to RT over 15 hours. The reaction mixture was washed with water, dried over MgS04 and concentrated under vacuum. The residue was filtered through a pad of silica (eiuting with CH2CI2/PE, 7:3) to afford A/-(2-benzoyi-4-
chlorophenyI)trifluoromethanesulfonamide 25 (710 mg, 90%), as a pale yellow solid. 1H n.m.r. (200 MHz, CDCl3) 5 7.80-7.69, m, 3H; 7.66-7.51, m, 5H. HRMS (M+) 362.9928.
Example 4A: Preparation of W-{4-chloro-2-[(3I4-
dichiorobenzyloxyimino)phenylmethyl]phenyl}trifluoromethanesu!fonamide (Compound 87).
A solution of A/-(2-benzoyl-4-chloropheny()triffuoromethanesulfonamide 25 (710 mg, 1.95 mmol), 0-(3,4-dichlorobenzyI)hydroxylamine hydrochloride (468 rng, 2.05 mmol) and anhydrous NaOAc (168 mg, 2.05 mmol) in EtOH (50 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eiuting with CH2Cl2/PE, 3:2) and the solvent removed under reduced pressure. An isomeric mixture of E- and Z-oxirne ether derivatives was obtained, which were separated by radial thin layer chromatography (eiuting with ChkCia/PE, 7.5:92.5 to 1:5). The major isomer was obtained as a pale yellow solid which was recrystallized from CH2Ci2/PE to give /V-{4-chloro-2-[(3,4-dichlorobenzyloxyimino)phenylmethyt]phenyl}trifluoromethanesulfonamide 87 (535 mg, 51%), as pale yellow crystals. M.p. 87-88°C. 1H n.m.r. (200 MHz, CDCl3) 5 11.18, br s, 1H; 7.65, d, J=8.8Hz, 1H; 7.55-7.40, m, 5H; 7.34-7.14, m, 4H; 6.88, d, J=2.2Hz; 1H; 5.09, s, 2H. The minor isomer was obtained as a pale yellow solid (315 mg, 30%).

0-(3,4^Dichlorobenzyi)hydrc>xylamine hydrochloride was-prepared in two steps using an analogous procedure to that described in Example 1 A.
Example 4B: Preparation of /V-{2-[(4-bromobenzyloxyimino)phenylmethyi]-4-chlorophenyijtrifluoromethanesuifonamide (Compound 64).
A solution of W-(2-benzoyl-4-cKlorophenyl}trifluorornethanesulfonarnide 25 (370 mg, 1.02 mmol), 0-(4- bromobenzyl)hydroxylamine hydrochloride (270 mg, 1.13 mmo!) and anhydrous NaOAc (90 mg, 1.10 mmol) in EtOH (20 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CH2CI2/PE, 3:2). Purification by radial thin layer chromatography (eluting with CH2Ci2/PE, 1:9) afforded W-{2-[(4-bromobenzyloxyimino)phenylmetby!}-4"Ch)orophenyl}trifluoromethanesulfonamide 64 (210 mg, 38%), as a yellow solid. M.p. 55-56°C. 1H-n.m.r. (200 MHz, CDCi3) 6 11.32, br s, 1H; 7.66: d, J=9.0Hz, 1H; 7^55-7.48, m, 5H; 7.33-7.20, m, 5H; 6.88, d, J=^2.4Hz, 1H;5.11,s:2H.
0-(4-Bromobenzyl)hydroxyiamine hydrochloride was prepared in two steps using an analogous procedure to that described in Example 1A.
Example 4C: Preparation of A/-{4-chloro-2-[(4-
chlorophenoxyimino)phenylmethyI]phenyl}trifiuoromethanesulfonamide (Compound 164).
iVjW-DimethySethylenediamine (82 JJL, 0.75 mmol) was added to a suspension of 0-(4-chIorophenyl)hydroxyiamine hydrochloride (141 mg, 0.51 mmol) in EtOH (15 mL). and the reaction allowed to stir at RTfor 15 hours. Glacial acetic acid (3 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of W-(2-benzoyl-4-chlorophenyl)trifiuoromethanesu!fonamide 25 (170 mg, 0.47 mmol) in EtOH (5 mL), and the reaction stirred for 63 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in CH2CI2 (50 mL), washed with water (twice), brine, dried over MgS04 and the solvent evaporated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2C12/PE, 3:7) and purified by radial thin layer chromatography (eluting with CH2Cf2/PE, 1:19 to 1:4) to afford W-{4-chloro-2-[(4-ch!orophenoxyimino)phenylmethyl]phenyl}trifluoromethanesulfonam(de 164 (140 mg,

/y
61%), as a orange-brown solid. M.p. 86-87°C. 1H n.m.r. (20Q MHz, CDCI3) 8 10.99, br s, 1H; 7.73, d, J=8.8Hz, 1H; 7.54, m, 3H; 7.43-7.27, m, 5H; 7.07, m, 1H; 7.01, m, 2H. 0-(4-Ch!orophenyI)hydroxylamine hydrochloride was prepared by the procedure described in Example 2C.
Example 4D: Preparation of A/-{4-ch!oro-2-[(4-
fluorophenoxyimino)phenylmethyi]phenyi}trifluorornethanesuifonamide (Compound 165).
W,A/-Dimethylethylenediamine (121 //L, 1.10 mmol) was added to a suspension of 0(4-chiorophenyl)hydroxyiamine hydrochloride (194 rng. 0.76 mmof) in EtOH (15 mL), and the reaction allowed to stir at RT for 15 hours. Glacial acetic acid (4 mL) was then added to adjust the mixture to ca. pH 4 followed by a solution of /V-(2-benzoyi-4-chiorophenyl)trifluoromethanesulfonamide 25 (250 mg, 0.69 mmol) in EtOH (5 mL), and the reaction stirred for 48 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in CH2CI2 (50 mL), washed with water (twice), brine, dried over MgSO" and the solvent evaporated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2Cl2/PE, 1 ;1) and purified by radial thin layer chromatography (eluting with CH2C!2/PE, 1:9) to afford /\^-{4-fluoro-2-[(4-chlorophenoxyimino)phenylmethyl]pheny(}trifIuoromethanesulfonamide 165 (110 mg, 34%), as a orange-brown solid. M.p. 90-93°C. 1H n.rn.r. (200 MHz, CDCI3) 5 11.05, br s, 1H; 7.73, d, J=8.8Hz, 1H; 7.55, m, 3H; 7.43-7.34, m, 3H; 7.07, s, 2H; 7.04, d, J=3.0Hz, 2H; 7.00, d, J=2.6Hz: 1H.
0(4-Fluorophenyl)hydroxylamine hydrochloride was prepared by the procedure described in Example 1D.
Example 4E: Preparation of W-[4-chloro-2-(ethoxyiminophenylmethyI)phenyl]trifluoromethanesulfonamide (Compound 177).
/V,W-Dimethylethylenediamine (254 //L, 2.20 mmol) was added to a solution of /V-ethoxyphthalimide (287 mg, 1.50 mmol) in EtOH (5 mL), and the reaction allowed to stir at RT for 15 hours. Glacial acetic acid (2 mL) was then added to adjust the mixture to ca. pH 4, followed by the addition of A/-(2-benzoyl-4-
chlorophenyl)trifluoromethanesulfonamide 25 (364 mg, 1.0 mmol), and the reaction stirred for 22 hours at RT. The reaction mixture was concentrated under vacuum, and

the-residue dissolvedJnJEt2Q450-mL)and washed-with .water,-brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with CH2CI2/PE, 1:99 to 1:9) to afford a single syn(Z) or anti(£)-isomer of ^[4-chIoro-2-
(ethoxyiminophenylmethyi)pheny!]trifluoromethanesuifonamide 177 (48 mg, 12%), as a colorless oil. 'H n.m.r. (400 MHz, CDCI3) 5 11.70, br s, 1H; 7.70, d, J=£.8Hz, 1H; 7.50, m, 3H; 7.32, dd5 J=2.4 and 8.8Hz; 1H; 7.26, m, 2H; 4.25, q, J=7.2Hz, 2H; 1.32, t, J=7.2Hz, 3H. HRMS (M") 406.0358. An isomeric mixture of syn(Z) and anti(£)-A/-[4-chloro-2-
(ethoxyiminophenylmethyl)phenyntrifluoromeihanesuffonamide (compound 178) was also isolated (360 mg, 88%), as a colorless oil.
/V-ethoxyphthatimide was prepared using an analogous procedure to that described in Example 1A.
Example 4F: Preparation of W-{4-chIoro-[(2-
methoxyethoxyimino)phenylmethyQphenyl}trifluoromethanesulfonamicle (Compound 234).
W,N-Dimethylethylenediamine (254//L, 2.20 mmol) was added to a solution of /V-(2-methoxyethoxy)phthalimide (332 mg, 1.50 mmol) in EtOH (5 mL), and the reaction allowed to stir at RT for 7 hours. Glacial acetic acid (2 mL) was then added to adjust the mixture to ca. pH 4, followed by the addition of A/~(2-benzoy!~4-chloropheny[)trifiuoromethanesulfonamide 25 (364 mg, 1.0 mmol), and the reaction stirred for 15 hours at 30° C. The reaction mixture, was concentrated under vacuum, and the residue dissolved in Et20 (50 mL) and washed with water, brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with CH2CI2/PE, 1:19) to afford A/-{4-ch!oro-[(2"methoxyethoxyimino)phenylmethyI]phenyI}trifluoromethanesulfonamide234 (324 mg, 74%), as a colorless oil. 1H n.m.r. (400 MHz, CDCI3) (2:1 mixture of E- and Z-isomers) 5 11.05, br s, 1H; 8.87, brs, 1H; 7.67, d, J=8.8Hz, 1H; 7.54-7.31, m, 13H; 7.10, d, J=2.4Hz, 1H; 6.92, d, J=2.4Hz, 1H; 4.33, m, 4H; 3.67, m, 4H; 3.46, s, 3H; 3.38, s, 3H. HRMS (M+) 436.0465.
A/-(2-methoxyethoxy)phthalimide was prepared using an analogous procedure to that described in Example 1A.

The following trifiuoromethanesuifonanilide oxime ether compounds, as listed by Tables 8 and 8A, infra, were prepared using similar preparative methods: Compounds 24, 30, 31, 61-63, 66; 68, 69, 71, 78, 80, 82, 83r 88-90, 162, 176, 178-180,232,233,251 and 252.
Additional data for compounds of Example 4 is provided by Table 5, below.

EXAMPLE 5
The following compounds were prepared according to the reaction scheme illustrated by FIG. 8.
Example 5A: Preparation of /V-{4-chloro-2-[1-(4-
ch!orophenoxyimino)butyl]phenyl}trifluoromethanesulfonamide (Compound 166). A solution of A/-(2-butyryl-4-chiorophenyl)trifluoromethanesulfonamide 29A (333 mg: 1.0 mmol), 0(4-chlorophenyl)hydroxylamine hydrochloride (200 mg, 1.10 mmol) and anhydrous NaOAc (91 mg, 1.10mmol) in EtOH (30 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2CI2/PE; 1:4) and the solvent removed under reduced pressure. The residue was purified by radial thin layer chromatography

(-elyting-W4th-CH2Ci2/PE; 1 ;1-9-to 3:7) to afford~N-{4-chloro-2-[1 -(4- ... ch!orophenoxyimino)butyl]phenyl}trifluoromethanesutfonamide 166 (283 mg, 62%), as
a yellow solid. M.p. 62.5-64.5°C. 1H n.m.r. (200 MHz, CDCI3) 5 11,27, brs, 1H; 7.72, d, J=8.8Hz, 1H; 7.57, d, J=2.4Hz, 1H; 7.41, dd, J=2.4 and 8.8Hz; 1H; 7.35, d, J=8.8Hz, 2H; 7.11, d, J=8.8Hz, 2H; 2.98, m, 2H; 1.71, sextet, 2H; 1.09, t, J=7.4 Hz, 3H.
Preparation of N-(2-butyryi-4-ch!orophenyI)trifiuorornethanesu(fonamide (Formula
29 A),
a) To a stirred solution of 3-chlorobenzonitrile (2.0g, 14.54 mmoi) and n-
propylmagnesium chloride (2M in Et20) (8.0 mL, 15.99 mmoi) in THF (40 mL) was
added CuCI (29 rng, 0.29 mmoi), and the mixture was refluxed for 30 minutes. After
cooling to RT, cold 1N HCl (10 mL) was added cautiously, the THF removed under
reduced pressure, further 1N HCl (30 mL) added and the reaction heated at 90°C for 1
hour. To the cooled reaction mixture was added water (20 mL) and CH2CI2 (50 mL).
the phases separated, and the aqueous phase again extracted with CH2Ci2. The
,i
combined organics were washed with water, dried over MgSO" and the solvent evaporated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2) to afford 1-(3-chlorophenyI)butan-1-one 26A (3.14 g, 97%), as a yellow liquid.
b) To rapidly stirred 1-(3-ch!orophenyl)butan-1-one 26A (2.85 g, 15.66 mmol) at ca. -20°C was added dropwise a mixture of fuming HNO3 (11 mL) and concentrated H2SO4 (1.5 mL) that had been cooled to -20°C. The reaction mixture was allowed to warm to -10DC, stirred for 2 hours at this temperature after which it was poured into ice-water (75 mL) and extracted twice with CH2CI2. The combined organic layers were washed three times with water, once with brine, dried over MgS04 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 3:2) to afford 1-(5-chIoro-2-nitropheny!)butan-1-one 27A (3.40 g, 95%), as a pale green solid.
c) To a mixture of 1-(5-chioro-2-nitrophenyi)butan-1-one 27A (3.40 g, 14.94 mmol) in EtOH (40 mL) and H20 (20 mL) was added iron powder (4.17 g, 74.68 mmol) and NH4CI (400 mg, 7.47 mmoi), and the reaction was rapidly stirred at 90CC for 30 minutes. The hot reaction mixture was filtered, the residues rinsed with EtOAc, and

further H20 added. The phases were separated and the organics were washed with water, brine, dried over MgS04 and concentrated under reduced pressure to afford 1-(2-amino-5-chIorophenyl)butan~1-one 28A (2.81 g, 95%), as a yellow solid, d) To a solution of 1-(2-amino-5-chlordphenyI)butan-T-one 28A (2.81 g, 14.22 mmol) in anhydrous dichloromethane (50 mL) at 0°C was added dropwise (CF3S02)20 (3.59 mL 21.32 mmoi) in anhydrous CH2CI2 (15 mL) over 30 minutes, and the reaction allowed to warm to RT over 15 hours. The reaction mixture was washed with water, brine, dried over MgSO" and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 3:7) to afford A/-(2-butyry!-4-chioropheny[)trifiuoromethanesuffonamfde 29A (3.89 g, 83%), as a yellow solid. 1H n.m.r. (200 MHz, CDCi3) 8 12.05, br s, 1H; 7.93, d, J=2.4Hz, 1H; 7.76, d, J=8.8Hz, 1H; 7.54, dd, J=2.4 and 8.8Hz, 1H; 3.02, .t, J=7.0Hz, 2H; 1.78, sextet, 1H; 1.02, t J=7.4Hz, 3H. HRMS (M+) 329.0098. '
0-(4-Chlorophenyl)hydroxyiamine hydrochloride was prepared by the procedure described in Example 2C.
Example 5B: Preparation of A/-[4-chloro-2-(1-ethoxyiminobutyl)phenyl]trif!uoromethanesulfonamide (Compound 193).
A/,N-Dimethy!ethylenediamine (254 //L, 2.20 mmoi) was added to a solution of' AZ-ethoxyphthalimide (287 mg, 1.50 mmoi) in EtOH (5 mL), and the reaction allowed to stir at RT for 15 hours. Glacial acetic acid (2 mL) was then added to adjust the mixture to ca. pH 4, followed by the addition of A/-(2-butyryl-4-
ch!orophenyl)trif!uoromethanesulfonamide 29A (330 mg, 1.0 mmoi), and the reaction stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in Et20 (50 mL) and washed with water, brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 1:1), the solvent evaporated under reduced pressure and the residue purified by radial thin layer chromatography (eluting with CH2CI2/PE, 1:19) to afford N-[4-ch!oro-2-(1-
ethoxyiminobutyl)phenyl]trifluoromethanesu!fonamide 193 (82 mg, 22%), as a colorless oil. 1H n.m.r. (400 MHz, CDCI3) 5 12.10, br s, 1H; 7.67, d, J=8.8Hz, 1H; 7.47, d, J=2.4Hz, 1H; 7.32, dd} J=2.4 and 8.8Hz, 1H; 4.27, q, J=7.2Hz, 2H; 2.78, m, 2H; 1.59, sextet, 2H; 1.37, t, J=7.2Hz, 3H; 1.02, t, J=7.6Hz, 3H. HRMS (M+) 372.0514.

N-(2-butyryl-4-chlorophenyl)trifiuoromethanesulfonamide 29A was prepared by
the procedure described in Example 5A.
N-ethoxyphthalimide was prepared using an analogous procedure to that described in Example 1A.
Example 5C: Preparation of N-{4-chloro-2-[1-(4-ch!orophenoxyimino)2J2-dimethylpropy!]phenyi}trifiuoromethanesulfonamide (Compound 182).
A solution of A/-[4-chioro-2-(2,2-dimethylpropionyl)phenyl]trifluoromethanesuifonamide 29C (300 mg, 0.87 mmol), O (4-chlorophenyl)hydroxyiamine hydrochloride (173 mg, 0.96 mmol) and anhydrous NaOAc (80 mg, 0.96mmof) in EtOH (20 mL) was stirred for 40 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eiuting with CH2Ct2/PE, 3:7) and the solvent -removed under reduced pressure. The residue was purified by recrystallization from CH2CI2/PE to afford N-{4-chloro-2-[1-(4-chiorophenoxyimino)buty0phenyI}trifluoromethanesulfonamide 182 (40 mg, 10%), as a yellow solid. M.p. 69-70°C. 1H n.m.r. (200 MHz, CDC!3) 5 7.52, d, J=8.8Hz, 1H; 7.43; dd, J=2.2 and 8.8Hz; 1H; 7.25, d, J=9.2Hz, 2H; 7.18, d, J=^2.2Hz: 1H; 7.01, d, J=9.2Hzr 2H; 6.43, br s, 1H; 1,33, s, 9H.
Preparation of A/-[4-chloro-2-(2,2-dimethylpropiony!)phenyf]triftuoromethanesulfonamide (Formula 29C).
a) To a stirred solution of 3-chiorobenzonitrile (2.0g, 14.54 mmol) and tert-butylmagnesium chloride (1M in THF) (15.99 mL, 15.99 mmol) in THF (10 mL) was added CuCI (29 mg: 0.29 mmol), and the mixture was refluxed for 20 hours. After cooling to RT, cold 1N HCI (10 mL) was added cautiously, the THF removed under reduced pressure, further 1N HCI (20 mL) added and the reaction heated at 90°C for 1 hour. To the cooled reaction mixture was added water (20 mL) and CH2Ci2 (50 mL), the phases separated, and the aqueous phase again extracted with CH2Ci2. The combined organics were washed with water, dried over MgS04 and the solvent evaporated under vacuum to afford 1-(3-chlorophenyl)2,2-dimethylpropan-1-one 26C (2.50 g, 87%), as a brown oil.
b) To rapidly stirred 1-(3-chlorophenyl2,2-dimethy!propan-1-one 26C (2.50 g, 12,71 mmol) at ca. -20°C was added dropwise a mixture of fuming HN03 (10 mL) and

. concentrated-H2S04 (1.0 rn(_).that had been cooled to -20°C. The reaction mixture was allowed to warm to -10°C, stirred for 2 hours at this temperature after which it was poured into ice-water (75 mL) and extracted twice with CH2CI2. The combined organic layers were washed three times with water, once with brine, dried over MgS04 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2Ci2/PE, 3:2) to afford 1-(5-chioro-2-nn:ropheny02l2-dimethylpropan--1-one 27C (2.6 g, 85%), as a pale yellow solid.
c) To a mixture of 1-(5-chloro-2-nitrophenyi)2,2-dimethyIpropan-1-one 27C (1.50 g, 6.21 mmo!) in EtOH (10 mL) and H20 (5 mL) was added iron powder (1.73 g, 31.03 mmol) and NhLCI (166 mg, 3.10 mmo!).. and the reaction was rapidly stirred at 90°C for 30 minutes. The hot reaction mixture was filtered, the residues rinsed with EtOAc, and further H20 added. The phases were separated and the organics were washed with water, brine, dried over MgS04 and concentrated under reduced pressure to afford 1-(2"amino-5-chlorophenyl)2:2-dimethyipropan-1-one 28C (920 mg, 70%). as a pale yellow solid.
d) To a solution of 1-(2-amino-5-chioropheny!)2r2-dimethylpropan-1-one 28C (920 mg, 4.35 mmol) in anhydrous dichioromethane (20 mL) at 0°C was added dropwise (CF5S02)20 (1.10 mL; 6.52 mmo!) in anhydrous CH2CI2 (5 mL) over 30 minutes, and the reaction allowed to warm to RT over 15 hours. The reaction mixture was washed' with water, brine, dried over MgS04 and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 3:7) to afford W-^-chioro-2-(2,2-dimethylpropionyt)phenyI]trifluoromethanesulfonamide 29C (1.44 g, 96%), as a yellow solid. 1H n.m.r. (200 MHz, CDC!3) 6 10.05, brs, 1H; 7.87, d, J=2.4Hz, 1H;7.69, d, J=8.8Hz, 1H;7.49, dd, J=2.4 and 8.8Hz, 1H; 1.40, s,9H. 0-(4-ChlorophenyI)hydroxyIamine hydrochloride was prepared by the procedure described in Example 2C.
Example 5D: Preparation of A/-{4-chloro-2-[1-(4-fluorophenoxyimino)2,2-dimethylpropyl]pheny!}trifluoromethanesulfonamide (Compound 198).
A solution of A/-[4-chIoro-2~(2,2-dimethylpropionyl)phenyI]trifiuoromethanesuIfonamide 29C (280 mg, 0.82 mmol), O-(4-fiuorophenyl)hydroxylamine hydrochloride (200 mg, 1.22 mmo!) and anhydrous NaOAc (100 mg, 1.22 mmol) in EtOH (20 mL) was stirred for 48 hours at RT. The

chromatography (eluting with CH2Ci2/PE, 1:4 to 2:3) to affordN-{4-chloro-2-[T-(4-fluorophenoxyimino)2j2-dimethylpropyl]pheny!}trif!uoromethanesulfonamide 198 (40 mg, 11%), as an orange oil. 1H n.rn.r. (200 MHz: CDC!3) 8 7.52; d, J=8.8Hz, 1H; 7.42, dd, J=2.2 and 8.8Hz: 1H; 7.19, df J=2.2Hz, 1H; 7.00, m, 4H; 6.49, br s, 1H; 1.32, s, 9H. HRMS (M") 452.0576.
A/-[4-chloro-2-(2,2-dimethy(propionyl)pheny!]trif!udromethanesulfonamide29C was prepared by the procedure described in Example 5C. •
0-(4-Fiuoropheny!)hydroxyIamine hydrochloride was prepared by the procedure described in Example 1D.
Example 5E: Preparation of N-{4-chioRO2-[(4-
fluorophenoxyimino)cyclohexylmethyl]phenyl}trifluoromethanesulfonamide (Compound 169).
A solution of N-(4-chlorq-2-cyclohexanecarbonylpheny!)trifluoromethanesulfonamide 29E (410 mg, 1.11 mmol), 0-(4-fiuoropheny!)hydroxyiamine hydrochloride (200 mg, 1.22 mmol) and anhydrous NaOAc (100 mg, 1.22 mmol) in EtOH (20 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue purified by column chromatography (eluting with CH2CI2/PE, 3:7 to CH2Ct2) to afford /V-{4-chioro-2-[(4-flurophenoxyimino)cyclohexylmethyl]phenyi}trifluoromethanesulfonamide 169 (200 mg, 38%), as a white solid. 1H n.rn.r. (200 MHz, CDC!3) 5 7.54, d, J=8.8Hz, 1H; 7.43, dd, J=2.2 and 8.8Hz, 1H; 7.24, d, J=2.2Hz, 1H; 7.12-6.95, m, 5H; 2.56, m, 1H; 2.14, m, 1H; 1.93-1,65, m, 5H; 1.29, m, 4H.
Preparation of /V-(4-chloro-2-cyclohexanecarbonyiphenyI)trif!uoromethanesuifonamide (Formula 29E).
a) To a stirred solution of 3-chlorobenzonitrile (2.0g, 14.54 mmol) and cyclohexyimagnesium chloride (2M in Et20) (8.0 mL, 15.99 mmo!) in THF (20 mL) was added CuCi (29 mg, 0.29 mmol), and the mixture was refluxed for 30 minutes. After cooling to RT, cold 1N HCI (10 mL) was added cautiously, the THF removed under reduced pressure, further 1N HCI (30 mL) added and the reaction heated at 90°C for 1 hour. To the cooled reaction mixture was added water (20 mL) and CH2CI2 (50 mL), the phases separated, and the aqueous phase again extracted with CH2C!2. The

" eombined-erganies were washed with water,-dried over MgS04-and-the solvent evaporated under vacuum. The residue was filtered through a pad of silica (elutlng with CH2CI2) to afford (3-chlorophenyI)cyciohexyImethanone 26E (3.14 g, 97%), as a yellow liquid.
b) To rapidly stirred (3-chlorophenyl)cycIohexy!methanone 26E (3,14 g. 14.10 mmol) at ca. -20°C was added dropwise a mixture of fuming HN03 (12 mL) and concentrated H2SO4 (1.6 mL) that had been cooled to -20°C. The reaction mixture was allowed to warm to -10°C, stirred for 2 hours at this temperature after which it was poured into ice-water (75 mL) and extracted twice with CH2C!2. The combined organic layers were washed three times with water, once with brine, dried over MgS04 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 3:2) and recrystallized from CH2CI2/PE to afford (5-chioro-2-nitropheny!)cyclohexyimethanone 27E (2.50 g, 66%), as a pale yellow soiid,
c) To a mixture of (5-chloro-2-nitropheny[)cyciohexylmethanone 27E (580 mg, 2.17 mmol) in EtOH (6 mL) and H20 (3 mL) was added iron powder (605 mg, 10.83 mmol) and NH4CI (58 mg, 1.08 mmol), and the reaction was rapidly stirred at 90°C for 30 minutes. The hot reaction mixture was filtered, the residues rinsed with EtOAc, and further H20 added. The phases were separated and the organics were washed with water, brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was filtered through a pad of silica (eluting with EtOAc/PE; 1:1) to afford (2-amino-5-ch!oropheny!)cyclohexyImethanone 28E (470 mg, 91%), as a yellow soiid.
d) To a solution of (2-amino-5-chiorophenyf)cycIohexyimethanone 28E (470 mg, 1.98 mmof) in anhydrous dichioromethane (10 mL) at 0°C was added dropwise (CF2S02)20 (499//L, 2.97 mmof) in anhydrous CH2CI2 (3 mL) over 30 minutes, and the reaction allowed to warm to RT over 60 hours. The reaction mixture was washed with water, brine, dried over MgSCU and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 2:3) to afford /V-(4-chloro-2-cyclohexanecarbonylphenyl)trifluoromethanesulfonamide 29E (340 mg, 47%), as a white solid. 1H n.m.r. (200 MHz, CDCi3) 6 11.95, brs, 1H; 7.89, d, J=2.4Hz, 1H; 7.75, d, J=8.8Hz, 1H; 7.54: dd, J=2.4 and 8.8Hz, 1H; 3.25, m, 1H; 1,95-1.70, m, 5H; 1.53-1.28, m,5H.
0(4-F!uorophenyJ)hydroxylamine hydrochloride was .prepared by the procedure described in Example 1D.

Example 5F: Preparation of /V-[4-chioro~2-
(cyclohexylisopropoxyiminomethyl)phenyf]trifluoromethanesulfonamide (Compound 210).
N,N-Dimethylethy!enediamine (254 M/L, 2.20 mmot) was added to a solution of AMsopropoxyphthalimide (308mg, 1.50 mmoi) in EfOH (5 mL), and the reaction allowed to stir at RT for 15 hours. Glacial acetic acid (2 mL) was then added to adjust the mixture to ca. pH 4. followed by the addition of N-(4-ch\oro-2-cyclohexanecarbonylphenyI)-trifluoromethanesulfonamide 29E (370 mg, 1.0 mmoi), and the reaction stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue dissolved in Et20 (50 mL) and washed with water, brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was purified by column chromatography (eiuting with CH2CI2/PE, 1:1) to afford A^[4-chioro-2-(cyc!ohexylisopropoxyiminomethy[)phenyIjtrifluoromethanesu}fonamide 210 (390 mg, 91%), as a colorless oil. ^H n.m.r. (400 MHz, CDCI3) (1:1 mixture of E-and Z-isomers) 5 10.59, brs: 1H; 8.11, brs, 1H;7.61, dr J=8.8Hz: 1H:7.49, d, J=8.8Hz, 1H; 7.46, d, J=2.4Hz, 1H; 7.42: dd: J=2.4 and 8.8Hz, 1H; 7.30, dd, J=2.4 and 8.8Hz, 1H; 7.24, d, J=2.4Hz, 1H; 4.49, m, 1H; 4.39, m, 1H; 2.97, m, 1H; 2.45, m, 1H; 1.97-1.71, m, 14H; 1.34-1.24, m, 18H. HRMS (M+) 426.0983. W-(4-chloro-2-cyclohexanecarbonylpheny!)trif!uoromethanesulfonamide 29E was prepared by the procedure described in Example 5E.
W-isopropoxyphthalimide was prepared by the procedure of Ishikawa, T.; Kamiyama. K.; Matsunaga, N.; Tawada, H.; lizawa. Y.: Okonogi, K.; Miyake. A. J. Antibiot, 2000, 53, 1071-1085.
The following trifiuoromethanesulfonanilide oxime ether compounds, as listed by Tables 8 and 8A, infra, were prepared using similar preparative methods: Compounds 168, 191,192,195, 209 and 211-213.
Additional data for compounds of Example 5 is provided by Table 6, below.


EXAMPLE 6
The following compounds were prepared according to the reaction scheme illustrated by FIG. 9.
Example 6A: Preparation of Af-{4-chloro-2-[1-(2J4-dichlorobenzyloxyimino)butyl]}trifluoromethanesulfonamide (Compound 100).
a) To BCI3 (1 M in CH2CI2) (37.62 mL 37.62 mmo!) and 1,2-DCE (30 mL) at 0°C
was added dropwise 4-chIoroaniIine (7.38 g, 57.90 mmo!) in 1,2-DCE (30 mL) and the
ice-cold solution allowed to stir for 30 min. Butyronitrile (2.52 mL, 28.93 mmol) and
AICI3 (5.02 g, 37.62 mmo!) were added in succession and the reaction mixture stirred
at 0°C for 30 min; and heated at 90°C for 24 h. The solution was cooled to 0°C, 2N
HCI (60 mL) added and was then heated at 90°C for 30 minutes. The reaction mixture
was extracted three times with CH2CI2, dried over MgS04 and the solvent
concentrated under vacuum. The residue was filtered through a pad of silica (eluting
with CH2Ci2/PE, 9:1) and the solvent concentrated to afford 1-(2-amino-5-
chlorophenyI)butan-1-one 28A (2.68 g, 47%), as a yellow solid.
b) A/-(2-butyryl-4-chlorophenyi)trifiuoromethanesu!fonamide 29A was prepared by
the procedure described in Example 5A.
-c) A solution of A/-(2~butyryN4-chlorophenyl)trifluoromethanesulfonamide 29A (243 mg, 0.74 mmol), 0-(2,4-dichlorobenzyl)hydroxylamine hydrochloride (176 mg,

0.77 rnmoi) and anhydrous NaOAc (86 mg, 1.05 mmof) in EtOH (10 ml) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eluting with CHCI3). Purification by radial thin layer chromatography (eluting with CH2CI2/PE, 7.5:82.5 to 3:17) afforded /^{4-chloro-2-[1-(2-ch!oro-4-methy!benzyloxyimino)butyl]}trifluoromethanesulfonamide 100 (189 mg, 51%) as a pale yellow solid. M.p. 65-66°C. 1H n.m.r. (200 MHz, CDCI3) 5 11.45, br s, 1H; 7.63, d, J=9.0Hz, 1H; 7.46, d, J=2.6Hz; 1H; 7.44, d, J=1.8Hz, 1H; 7.41-7.34, m, 2H; 7.30-7.25, m, 1H; 5.27, sf 2H; 2.80, m, 2H; 1.60, m, 2H; 1.02, t, J=7.4Hz, 3).
0(2)4-Dichlorobenzyt)hydroxylamine hydrochloride was prepared in two steps using an analogous procedure to that described in Example 1 A.
Example 6B: Preparation of N42-[1-(2,4-bistrifluoromethylbenzyloxyimino)"2-methylpropyl]-4-chlorophenyI}trifiuoromethanesulfonamide (Compound 116).
a) To BCi3 (1 M in CH2CI2) (37.62 mL, 37.62 mmol) and 1,2-DCE (30 mL) at 0° C was added dropwise 4-chloroaniI'me (7.38 g, 57.90 mmol) in 1,2-DCE (30 mL) and the ice-cold solution allowed to stir for 30 min. Isobutyronitrile (2.63 mL, 28.94 mmof) and AICI3 (5.02 a, 37.52 mmol) were added in succession and the reaction mixture stirred at 0°C for 30 min: and heated at 90°C for 24 hours. The solution was cooled to 0oC, 2N HCI (60 mL) added and was then heated at 90° C for 30 min. The reaction mixture was extracted three times with CH2CI2, dried over MgS04 and the solvent concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 4:1) and the solvent concentrated to afford 1-(2-amino-5-ch)oropheny!)-2-methy)propan-1-one 30B (2.08 g, 36%), as a yellow solid.
b) To a solution of 1-(2-amino-5-chlorophenyl)-2-methyIpropan-1-one 30B (2.08 g, 10.52 mmol) and Et3N (1.54 mL, 11.05 mmol) in anhydrous CH2CI2 (100 mL) at 0°C was added dropwise (CF3S02)20 (1.86 mL, 11.05 mmol) in anhydrous CH2C!2 (50 mL) over 30 min. The reaction mixture was allowed to warm to RT over 15 hours, washed with water, dried over MgS04 and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 4:1) to afford A/-(4-chloro-2-isobutyrylphenyl)trifluoromethanesulfonamide 31B (2.93 g, 84%), as a pale yellow solid. 1H n.m.r. (200 MHz, CDCI3) 5 11.91, brs, 1H: 7.92, d, J=2.6Hz, 1H; 7.76, d, J=9.1 Hz, 1H; 7.55, dd, J=2.6 and 9.1 Hz, 1H, 3.58, quintet J=7.0Hz, 1H; 1.24, d, J=7.0Hz, 6H. HRMS (M+) 329.0093.

c) A solution of N-(4-chIoro-2-isobutyry!phenyl)trifluoromethanesutfonamide 31B (300 mg, 0.91 mrnol), O(2s4-bistrifluoromethylbenzyl)hydroxylamine hydrochloride (270 mg, 0.91 mmol) and anhydrous NaOAc (75 mg, 0.91 mmol) in EtOH (20 mL) was stirred for 15 h at RT. The reaction mixture was concentrated under vacuum and the residue filtered through a pad of silica (eiuting with CHsCyPE, 9:1). Purification by radial thin layer chromatography (eiuting with CH2CyPE? 1:19) afforded A/-{2-[1-(2,4-bistrifiuoromethylbenzyfoxyimino)-2-methyIpropyI]-4-
chlorophenyIJtrifIuoromethanesulfonELmicle.il6 (120 mg; 23%), as a paie yeiiow oil. 1H n.m.r. (200 MHz, CDCt3) 5 9.43, br s, 1H; 7.98, s, 1H; 7.89, d, J=8.0Hz, 1H; 7.74, d, J=8.0Hz, 1H; 7.56, d, J=8.8Hz, 1H; 7.44s d, J=2.4Hzs 1H; 7.33, dd, J=2.4 and 8.8Hz, 1H; 5.45, s, 2H; 3.47, quintet, J=7.0Hz, 1H; 1.37, d, J=7.0Hz, 6H. HRMS (N/T) 570.0417.
0-(2,4-BistrifiuoromethyIbenzy[)hydroxyl'amine hydrochloride was prepared by the procedure described in Example 1 A. -
Example 6C: Preparation of A/-{4-chloro-2-[1-(4-chlorophenoxyimino}-2-methylpropyf]pheny!}trifiuoromethanesuIfonamide (Compound 215). A solution of /V-(4-chloro-2-isobutyry[phenyl)trifIuoromethanesulfonamide 31B (244 mg, 1.11 mmol), 0-(4-ChlorophenyI)hydroxylamine hydrochloride (200 mg, 0.91 mmol) and anhydrous NaOAc (91 mg,' 1.11 mmol) in EtOH (10 mL) was stirred for 48 h at RT. The reaction mixture was concentrated under vacuum, and the residue purified by column chromatography (eiuting with CH2Cl2/PE, 3:7) to afford Af-{4-chloro-2-[1 -(4-chlorophenoxyimino)-2-methylpropyl]phenyl}trifIuoromethanesutfonamide 215 (80 mg, 24%), as an orange oil. 1H n.m.r. (200 MHz, CDCI3) 6 7.56, d, J=8.8Hz: 1H; 7.45, dd, J=2.4 and 8.8Hz, 1H; 7.27, d, J=9.0Hz, 2H; 7.23, d, J=2.4Hz, 1H; 7.07, d, J=9.0Hz, 2H;2.94, m, 1H; 1.37, s;3H; 1.19, s,3H.
An isomeric mixture of syn(Z) and anti {4-chloro-2-[1-(4-chlorophenoxyimino)-2-methylpropy[]phenyi}trifluoromethanesulfonamide was also isolated (210 mg, 62%), as an orange oil,
N-(4-chloro-2"isobutyrylphenyi)trifluoromethanesulfonamide 31B was prepared by the procedure described in Example 6B.
0-(4-ChlorophenyI)hydroxyIamine hydrochloride was prepared by the procedure described in Example 2C.

The following trifiuoromethanesulfonanilide oxime ether compounds, as listed by Tables 8 and 8A, infra, were prepared using similar preparative methods; Compounds 92, 98, 99, 101,102, 108, 110-115,117-119,121 and 216.
Additional data for compounds of Example 6 is provided by Table 7, below.

EXAMPLE 7
The following compounds were prepared according to the reaction scheme illustrated by FIG. 10.
Example 7A: Preparation of N-{2-[1"(4-chlorophenoxyimino)ethyI]-5-trifluoromethylphenyljtrifluoromethanesulfonamide (Compound 199).
A solution ofN/-(2-acetyI-5-trifluoromethylpheny[)trifluoromethanesulfonamide 35 (250 mg, 0,75 mmoi), 0-(4-chlorophenyl)hydroxyiamine hydrochloride (148 mg, 0.82 mmo!) and anhydrous NaOAc (67 rng, 0.82 mmo!) in EtOH (15 mL) was stirred for 20 hours at RT. The reaction mixture was concentrated under vacuum, the residue filtered through a pad of silica (eluting with CH2CI2) and the solvent removed under reduced pressure. The residue was purified by recrystallization from CH2CI2/PE to afford /V-{2-[1 -(4-chlorophenoxyimino)ethyl]-5-

trifluoromethylphenyljtrifluorometbanesulfonamide 199-(34 0-mgr-90%), as a pale yellow solid. M.p. 89-90°C. 1H n.m.r. (200 MHz, CDC!3) 5 11.41, br s, 1H; 8.02, s, 1H; 7.76; d, J=8.6Hz, 1H; 7.563 m, 1H; 7.36, d,'J=9.2Hz, 2H; 7.12, d, J=9.2Hz, 2H; 2.60, s,
3H.
Preparation of A^(2-acetyI-5-trifIuoromethyIphenyl)triffuoromethanesulfonamide 35.
a) To a suspension of sodium hydride (1.60 g, 66.50 mmol) in DMSO (60 mL) was added dropwise a mixture of nitroethane (1.91 mL, 26.60 mmol) and 4-ch)oro-3-nitrobenzotrifluoride (3.0 g, 13.30 mmol) dissolved in DMSO (20 mL), and the reaction mixture was stirred for 2 hours at RT. Glacial acetic acid/water (1:1) was added to bring the mixture to ca. pH 4 and EtOAc (50 mL) was added, the phases separated, and the aqueous phase again extracted with EtOAc. The combined organics were twice washed with water, dried over MgSO" and the solvent removed under vacuum. The residue was filtered through a pad of silica'(eluting with CH2CI2/PE; 1:1) to afford 2-nrtro-1-(1-nitroethyI)-4-trifluoromethylbenzene 32 (3.05 g, 87%)T as an orange oil.
b) To sodium hydride (313 mg, 13.02 mmol) in 2-methyl-2-propanoI (20 mL) was added 2-nitro-1-(1-nitroethy!)-4-trifluoromethylbenzene 32 (1.72 g, 6.51 mmof), and the reaction mixture was stirred for 30 minutes at 40°C. Coid EtOAc (50 mL) was added, the reaction cooled to 0°C and ice (-30 g) and a cold solution of potassium permanganate (1.03 g, 6.51 mmol) and boric acid (403 mg, 6.51 mmol) in water (40 mL) was added. After 1 hour of vigorous stirring at 0DC, sodium metabisulfite (1M, 14 mL) and sulfuric acid (1N. 26 mL) was added and the reaction mixture extracted twice with EtOAc. The combined organics were washed with water, brine, dried and the solvent removed under vacuum. The residue was filtered through a pad of silica (eluting with CH2G2/PE; 1:1) to afford 1-(2-nitro-4-trifluoromethylphenyI)ethenone 33 (607 mg: 40%), as a yellow solid.
c) To a mixture of 1-(2-nitro-4-trifluoromethylphenyl)ethenone 33 (1.44 g, 6.18 mmol) in EtOH (30 mL) and H20 (15 mL) was added iron powder (1.72g, 30.88 mmol) and NH4CI (165 mg, 3.09 mmol), and the reaction was rapidly stirred at 90°C for 30 minutes. The hot reaction mixture was filtered, the residues rinsed with EtOAc, and further H20 added. The phases were separated and the organics were washed with water, brine, dried over MgS04 and the solvent removed under reduced pressure. The residue was filtered through a pad of silica (eluting with EtOAc/PE; 1:1) to afford 1-(2-amino-4-trifluoromethylphenyl)ethanone 34 (1.20 g, 96%), as a yellow solid.

d). To a solution of 1-(2-amino-4-trifluoromethyiphenyI)ethanone 34 (1.21 g, 5.96 mmol) in anhydrous dichioromethane (50 mL) at 0°C was added dropwise (CF3S02)20 (2.0 mL, 11.91 mmol) in anhydrous CH2Ci2 (25 mL) over 30 minutes, and the reaction aliowed to warm to RT over 60 hours. The reaction mixture was washed with water., brine, dried over MgS04 and concentrated under vacuum. The residue was filtered through a pad of silica (eiuting with CH2CI2) to afford A/-(2-acety1-5-trifluoromethylphenyl/irifluoromethanesulfonamide 35 (1.23 g, 62%), as a yellow solid. 1H n.m.r. (200 MHz, CDCI3) 5 12.15, br s, 1H; 8.09, m, 2.1; 7.53, m, 1H; 2.77, s, 3H.
0(4-ChlorophenyI)hydroxylamine hydrochloride was prepared by the procedure described in Example 2C.
Example 7B: Preparation of A42-[1-(44!uorophenoxyimino)ethyI]-5-trifluoromethylphenyljtrifluoromethanesulfonamide-(Compound 200).
A solution of A/-(2-acetyl-5-trifluoromethyiphenyl)trifluoromethanesulfonamide 35 (280 mg, 0.84 mmol), 0-(4-fluorophenyl)hydroxyIamine hydrochloride (150 mg, 0.92 mmol) and anhydrous NaOAc (75 mg, 0.92 mmol) in EtOH (15 mL) was stirred for 24 hours at RT, The reaction mixture was concentrated under vacuum, the residue purified by column chromatography (eiuting with CH2CI2/PE; 1:1 to 4:1) and the solvent removed under reduced pressure. Recrystallization from CH2Cl2/PE afforded AA{2-[1-(4-f!uorophenoxyimino)ethyn-5-
trifluoromethylphenyijtrifiuoromethanesulfonamide 200 (300 mg, 81%), as colorless crystals. M.p. 95-96°C. "'H n.m.r. (200 MHz, CDCI3) 5 11.48, brs, 1H; 8.01, s, 1H; 7.76, d, J=8.4Hz, 1H; 7.55, m, 1H; 7.19-7.04, m, 4H; 2.60, s, 3H. <>(4-FIuorophenyl)hydroxylamine hydrochloride was prepared by the procedure described in Example ID.
Example 7C: Preparation of A/-[2-(1-a!lyloxyiminoethyl)-5-trifluoromethylphenyljtrifluoromethanesulfonamide (Compound 241).
A solution of A/-(2-acetyl-5-trifluoromethylphenyl)trifluoromethanesu!fonamide 35-(168 mg, 0.50 mmol), Oallylhydroxylamine hydrochloride (60mg, 0.53 mmol) and anhydrous NaOAc (43 mg, 0.53 mmol) in EtOH (3 mL) was stirred for 15 hours at RT. The reaction mixture was concentrated under vacuum, and the residue purified by radial thin layer chromatography (eiuting with CH2CI2/PE, 1:99) to afford AJ-[2-(1-

80%), as a colorless oil. 1H n.rnx (400 MHz, CDCI3) 5 11.82.. br s, 1H; 7.98, s, 1H; 7.65, d3 J=8.2Hz, 1H; 7.49, dr J=8.2Hz, 1H; 6.02, m, 1H; 5.44, d, 3J=17.2Hz, 1H; 5.37, d, 3J=10.4Hz: 1H; 4.72, d, J=6.0Hz; 2H; 2.38; s, 3H. HRMS (M") 390.0465.
The following trifluoromethanesulfonanilide oxime ether compounds, as listed in Tables 8 and 8A, infra, were prepared using similar preparative methods: Compounds 201, 214, 217-222 and 235-240. .
Additional data for compounds of Example 7 is provided by Table 10, below.

EXAMPLE 8
The following compounds were prepared according to the reaction scheme
illustrated by FIG. 11.
Example 8A: Preparation of W-{4-chloro-2-[5-(2,4-dich!orophenyl)isoxazol-3-
yI]phenyi}trifluoromethanesuffonamide (Compound 229).
a) To a solution of 4-[1-(2,4-dichlorophenyl)vinyi]morpho[ine (1.23 g. 4.77 mmol) and Et3N (731 pL, 5.25 mmol) in anhydrous CHCI3 (30 mL) was added dropwise a solution of 5-chioro-2-nitrobenzohydroximoyl chloride 37 (1.18 g. 5.02 mmol) in anhydrous CHCI3 (15 mL), and the reaction allowed to stir for 24 h at RT. The reaction mixture was then washed with H20 (2 x 30 mL), dried over MgS04 and concentrated under reduced pressure. The residue was then dissolved in THF (22 mL), 2N HCI (42 mL) was added, and the mixture was heated at 75CC for 8 h. Once the reaction mixture had cooled, 5% Na2C03 (110 mL) was added, and it was extracted with CH2Cl2 (2 x 75 mL). The combined organics were washed with H20 (75 mL), dried over MgS04 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 3:2) and the solvent

-eoncentrated-under-redueed-pressure-to-afford 3-(5-chloro-2-nitrophenyl)-5-(2,4-dichlorophenyl)isoxazole 38A (1.23 g, 66%), as a white solid. 1H n.m.r. (200 MHz, CDCI3) 58.04, d, J=8.8Hz, 1H; 7.96, d, J=8.6Hz, 1H; 7.75, d, J=2.2Hz, 1H; 7.63, dd, J=2.2 and 8.6Hz, 1H; 7.56, d, J=2.2Hz, 1H; 7.43, dd, J=2.2 and 8.8Hz, 1H; 7.06, s, 1H.
A suspension of 3-(5-chioro-2-nitropheny!)-5-(2,4-dichlorophenyl)isoxazole 38A (919 mg, 2.49 mmol) in MeOH (90 mL) was stirred for 1 h at RT, and for 30 min at 65°C. To this was added Na2C03 (1.32 g, 12.43 mmol), followed by dropwise addition of a solution of Na2S204 (2.49 g, 12.43 mmol) in H20 (35 mL) over 15 min. The temperature was raised to 70°C and the reaction mixture was stirred for a further 30 min. EtOAc (120 mL) was added and the reaction mixture was allowed to coo! to RT. The solids were removed by filtration and washed with further EtOAc. The organic phase was partitioned and washed with H20, dried over MgS04 and then filtered through a pad of silica (eluting with EtOAc/PE, 1:1). The solvent was concentrated under reduced pressure to afford 4-chloro-2-[5-(2,4-dichlorophenyl)isoxazol-3~yl]phenylamine 39A (554 mg, 68%), as a yellow solid. 1H n.m.r. (200 MHz, CDCI3) 57.93, d, J=8.8Hz, 1H; 7.58, d, J=2.2Hz, 1H; 7.50, d, J=2.2Hz, 1H; 7.42, dd, J=2.2 and 8.8Hz, 1H; 7.27, s, 1H; 7.17, dd, J=2.2 and 8.8Hz, 1H; 6.75, d, J=8.8Hz, 1H.
To a solution of 4-chloro-2-[5-(2!4-dichlorophenyl)isoxazol-3-yf]phenylamine 39A (84 mg: 0.25 mmol) in anhydrous dichloromethane (25 mL) at 0°C was added dropwise (CF3S02)20 (62//L, 0.37 mmol) in anhydrous CH2CI2 (10 mL) over 10 min, and the reaction allowed to warm to RT overnight. The reaction mixture was washed with H20 and then brine, dried over MgS04 and concentrated under vacuum. The residue was filtered through a pad of silica (eluting with CH2CI2/PE, 4:1) and the solvent removed under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with CH2CI2/PE, 1:9 to 1:4) to afford A/-{4-chloro-2-[5-(2,4-dichlorophenyl)isoxazoI-3-y!]phenyl}trifluoromethanesulfonamide 229 (54 mg, 46%), as a white solid. M.p. 142-144°C. 'H n.m.r. (200 MHz, CDCI3) 510.46, brs, 1H; 7.96, d, J=8.4Hz5 1H; 7.79, d, J=9.0Hz, 1H;7.70, d, J=2.4Hz, 1H; 7.61, d, J=1.8Hz, 1H;7.46, m, 2H; 7.34, s, 1H.

a) To a solution of 5-chloro-2-nitrobenzaldehyde (2.85 g, 15.40 mmoi) in EtOH (10 mL) was added sequentially H20 (10 mL)5 ice (~7 mL), hydroxylamine hydrochloride (1.12 gs 16.18 mmol), 50% NaOH (307//L. 3.84 mmol) and EtOH (50 mL). The reaction was allowed to stir for 1 h at RT, after which H20 (10 mL) was added and the mixture extracted with Et20 (2 x 75 mL). The combined organics were dried over MgS04 and concentrated under reduced pressure to ca. 10 mL H20 (50 mL) was then quickly added which formed a precipitate, and this was collected .by filtration to afford 5-chloro-2-nitrobenzaidehyde oxime 36 (2.65 g, 86%), as a yellow solid.
b) To a solution of 5-chloro~2~nitrobenzaldehytie oxime 38 (1.0 g, 4.99 mmol) in 1,2-DCE (25 mL) and 2-PrOH (6.3 mL) at ca. -10°C was added all at once t-butyl hypochlorite (780 ML, 6.48 mmoQ, and the reaction allowed to rapidly stir for 30 min at RT. The solvent was removed under reduced pressure (at 50CC) to afford 5-chloro-2-nitrobenzohydroximcyl chloride 37 (1.11 g, 95%), as a white solid. "H n.m.r. (200 MHz, CDCl3) 58.553 br s, 1H; 7.96, d, J=8.4Hz, 1H; 7.59, m, 2H.
Example 8B: Preparation of A/-{4-chloro-2-[5-(2;4-difluorophenyl)isoxazol-3-
y!]phenyl}trifluoromethanesulfonamide (Compound 231).
a) To a solution of 4"[1-(2,4-dichloropheny!)viny[]morpho!ine (500 mg, 2.22 mmol) and Et3N (340 /JL 2.44 mmol) in anhydrous CHCI3 (20 mL) was added dropwise a solution of 5-chloro-2-nitrobenzohydroximoyl chloride 37 (548 mg, 2.33 mmol) in anhydrous CHC!3 (10 mL), and the reaction allowed to stir for 24 h at RT. The reaction mixture was then washed with H2O (2 x 30 mL), dried over MgS04 and concentrated under reduced pressure. The residue was then dissolved in THF (10 mL), 2N HCI (20 mL) was added, and the mixture was heated at 75° C for 7 h. Once the reaction mixture had cooled, 5% Na2C03 (50 mL) was added, and it was extracted with CH2CI2 (2 x 50 mL). The combined organics were washed with H20 (50 mL), dried over MgS04 and concentrated under reduced pressure. The residue was filtered through a pad of silica (eluting with CH2Cl2/PE; 3:2) and the solvent concentrated under reduced pressure to afford 3-(5-chloro-2-nitropheny!)-5-

—(-2,4-difIu0rophenyJ-)isoxazole-38B-(465-mgr62%)ras a-white solid, 1H n.m.r. (200 MHz, CDC!3) 58.01: m, 2H; 7.73, d, J=2.2Hz, 1H; 7.62, dd, J=2.2 and 8.4Hz; 1H; 7.12-6.93, m, 2H; 6.77, d, J=3.6Hz, 1H.
b) A suspension of 3-(5-chIoro-2-nitrophenyl)-5-(2,4-difluorophenyl)isoxazo!e
38B (250 mg: 0.74 mmol) in MeOH (25 mL) was stirred for 1 h at RT, and
for 30 min ai S5CC. To this was added Na2COs (394 mg, 3.71 mmol),
followed by dropwise addition of a solution of Na2S204 (760 mg, 3.71 mmol)
in H2O (10 mL) over 15 min. The temperature was raised to 70°C and the
reaction mixture was stirred for a further 30 min. EtOAc (30 mL) was added
and the reaction mixture was allowed to cooi to RT. The solids were
removed by filtration and washed with further EtOAc. The organic phase
was partitioned and washed with H20, dried over MgS04 and then filtered
through a pad of silica (etuting with EtOAc/PE, 1:1). The solvent was
concentrated under reduced pressure to afford 4-chloro-2-[5-(2,4-
difiuoropheny[)isoxazol-3-y[]phenylarnine 39B (71 mg, 34%), as a yellow
solid. "'H n.m.r. (200 MHz, CDCl5) 87.89: mr 1H; 7.50: dr J=2.4Hz, 1H; 7.17? dd, J=2.4 and 8.8Hz, 1H; 7.11-6.95, m, 3H; 6.74, d, J=8.8Hz, 1H.
c) To a solution of 4-ch!oro-2-[5-(2,4-dif!uorophenyl)isoxazoi-3-yI]phenylamine
39B (71 mg, 0.23 mmol) in anhydrous dichloromethane (10 mL) at 0°C was
added dropwise (CF3S02)20 (43//L, 0.26 mmol) in anhydrous CH2C!2 (5
mL) over 10 min, and the reaction allowed to warm to RT overnight The
reaction mixture was washed with H20 and then brine, dried over MgS04
and concentrated under vacuum. The residue was filtered through a pad of
silica (eluting with CH2CI2/PE. 4:1) and the solvent removed under reduced
pressure. The residue was purified by radial thin layer chromatography
(eluting with CH2CI2/PE, 1:9 to 3:7) to afford /V-{4-chloro-2-[5-(2)4-
difluorophenyi)isoxazol-3-yi]phenyi}trifluoromethanesulfonamide231 (33
mg, 32%), as a pale yellow solid. M.p. 117-119°C. -H n.m.r. (200 MHz,
CDCI3) 510.46, br s, 1H; 8.02, m, 1H; 7.79, d, J=8.8Hz, 1H; 7.70, d,
J=2.4Hz, 1H; 7.46, dd, J=2.4 and 8.8Hz, 1H; 7.15-6.98, m, 3H.
The following trifluoromethanesulfonanilide oxime ether compounds, as listed in Tables 9 and 9A, infra, were prepared using similar preparative methods:

Additional data for compounds of Example 8 is provided by Table 11, below.

EXAMPLE 9
The following compounds were prepared according to the reaction scheme illustrated by FIG. 12.
Example 9A: Preparation of W-acetyI-A/-{4-chIoro-2"[1-(4-chlorobenzyicxyimino)propy[]phenyI}trifluoromeLhanesu[fonamide (Compound 307).
To a mixture of N-{4-chloro-2~[1-(4-chlorobenzyloxyirnino)propyl]phenyl}trifluoromethanesulfonamide (compound 11) (150 mg, 0.33 mmol) and K2C03 (137 mg, 0.99 mmol) in acetone (5 mL) was added acetyl chloride (70 JJL, 0.99 mmol), and the reaction allowed to stir at RT for 2 hours. The reaction mixture was concentrated under vacuum and the residue dissolved in CHCI3 (20 mL), washed with H20 (15 mL), dried over MgS04 and concentrated under reduced pressure. The residue was purified by radial thin layer chromatography (eluting with EtOAc/PEr 1:19) to afford A/-acetyi-/V-{4-chloro-2-[1-(4- ' chloroben2ylo^imino)propyl]phenyl}trifluoromethanesulfonamide 307 (156 mg, 95%), as a pale yellow solid. M.p. 64-66° C. 1H n.m.r. (400 MHz, CDC!3) 5 7.51, d, J=2.4Hz, 1H; 7.42, dd, J=2.4 and 8.8Hz, 1H; 7.30, m, 4H; 7.23, d, J=2.4Hz, 1H; 5.12, m, 2H; 2.83, mT 1H;2.67, m, 1H; 1.91, s,3H; 1.18, t, J=7.6Hz, 3H.
Example 9B: Preparation of A/-carbonylethoxy-/V-{4-chloro-2-[1-(4-fluorophenoxyimino)ethyi]phenyl}trifluoromethanesulfonamide (Compound 310).

f!uorophenoxyimino)ethy!]phenyl}trifluorornethanesulfonamide (compound 129) (150 mg, 0.37 mmoi) and K2C03(151 mg, 1.10 mmoi) in acetone (5 mL) was added ethyl chioroformate (105 pL 1.10 mmoi), and the reaction allowed to stir at RT for 21 hours. The reaction mixture was concentrated under vacuum and the residue dissolved in Et20 (50 mL), washed with H20 (40 mL) then brine (40 mL), dried over Na2SQ4 and concentrated under reduced pressure. The residue was purified by radia! thin layer chromatography (eluting with EtOAc/PE, 1:19) to afford AAcarbony!ethoxy-W44-chIoro-2-[1-(4-fluorophenoxyimino)ethyI]phenyI}trifiuoromethanesu!fonamide 310 (85 mg. 63% based on recovered starting material), as a pale yellow oil. 1H n.m.r. (400 MHz, CDC!3) S 7.52, df J=2.4Hz? 1H; 7.45, dd, J==2.4 and 8.8Hz5 1H; 7.25, d: J=2.4Hz, 1H; 7.14, m, 2H; 6.98, m, 2H; 4.24, m, 1H; 4.15, m, 1H; 2.41, s, 3H; 1.15, t, J=7.2Hz, 3H. HRMS (M4) 482.0316.
The following trifluoromethanesuifonanflide oxime ether compounds, as listed in
Table 13, infra, were prepared using similar preparative methods:
,<
Compounds 296-305, 308, 309 and 311-323.
Additional data for compounds of Example 9 is provided by Table 12, below.

EXAMPLE 10
Listing of Exemplified Compounds
A total of 323 compounds have been prepared according to the methods of Examples 1 - 9, as described above. These are summarized by Tables 8, 8A, 9, 9A and 13, hereinbelow, as follows.

Abbreviations for Tables 8. 8A, 9, 9A and 13 "C#" is the compound number; "[WI4]" is the mass reading by high resolution mass spectroscopy; and "MP" is the melting point of the compound, in °C, where available.
Soiefy for convenience, ail of the compounds in these tables have been drawn as single anti(£)-isomers about the C=N bond. However, the compounds of the present invention are not meant to be so limited, but rather, the structures depicted are meant also to represent stereoisomers, and/or mixtures thereof, etc., as discussed supra.
Tabie S provides compounds 1 - 224, based on Formula (I) supra.

EXAMPLE 11
The following assays were used to determine the parasinoidal activity of the compounds of the invention. The compounds tested were prepared according to Examples 1 - 9, above. In certain cases, one or more of the assays were performed by two different laboratories, labeled as Laboratory 1 and Laboratory 2. Due to the nature of the assays, in certain instances the results are better taken qualitatively rather than quantitatively. However, the ultimate effectiveness of the compounds may still be established.
a) Haemonchus Coniortus Larvacidal Assay:
The effect of compounds on larval development was determined in the assay described by Gill et ai (1995, International Journal of Parasitology 25:463 -470). Briefly, in this assay, nematode eggs were applied to the surface of an agar matrix containing the test compound and then aJiowed to develop through to the L3, infective stage (6 days). The wells for each dilution of every compound (from highest to lowest concentration) were inspected to determine the well number corresponding to the lowest concentration at which development was inhibited in 99% of the nematode larvae present (LDcc). Because well numbers correspond to a two-fold serial dilution of each compound, a titre (dilution factor) is generated as 2n"1, where n is the well number. By dividing the highest concentration tested by the titre an LD99 value can be obtained, representing the concentration required to inhibit development in 99% of the nematode larvae present. The compounds supplied as solid and viscous liquids were dissolved in DMSO. Twelve serial one-half dilutions in DMSO solution were prepared from the stock solution, each of which was then diluted 1/5 with water. Afiquots (1 Opt!) of each dilution were transferred to the bioassay plates to give a final concentration range of 0,024 to 50ug/ml.
b) Ctenocephatides felts Adulticide Assay: C.felis single dose screen
The purpose of this example was to confirm that sample compounds or
formulations exhibit significant insecticidal activity against cat fleas contacted with a treated glass surface. Mortality of fleas was the primary endpoinf in the assay. Fleas were considered dead if they didnJt move or were on their sides and unable to walk or right themselves. In the screening assay a singfe concentration of a test compound

was selected to demonstrate insecticidal activity. The concentration chosen (1.26 μg/cm2) was higher than that known to kill 90% of cat fleas (LC90) using the reference compound, permethrin.
The test species was the cat flea (Ctenocephaiides felis). The strain used was obtained from external suppliers as pupae and held in the laboratory under testing conditions until the adults had emerged. Fifteen (15) fleas were used in a minimum of four replicates against a single concentration level (approximately 60 fleas). The insects were selected to be in the adult life stage, aged between 3 and 7 days post emergence.
The compounds to be tested were supplied as solids and were prepared in acetone as described below prior to testing. Samples were stored in a refrigerator (5±1°C) unless otherwise specified.
During the mortality testing, the temperature was maintained at 25±1 °C. Humidity was maintained at 75±5%. The base (area =159 mm2) of a 100 mL glass Erlenmeyer (conical) flask provided the treatment surface. Flasks were pretreated with Coatasil™ glass treatment to maximise bio-availability of test compounds by preventing them from binding to glass the surface. The base of the 100 mL Erlenmeyer flask was treated with 0.5 mL of test sample in acetone and gently swirled. This volume was sufficient to cover the base of the flask. Flasks were left to dry for 24 hours before flea exposure.
Adult cat fleas were placed into a sorting chamber, which allowed fleas to jump into the Erlenmeyer flasks. Fifteen (15) adult cat fleas were collected in each flask. The top of the flasks were then covered in Parafilm'M and small holes were made to allow gas exchange. A 0.5 mL volume of acetone as a solvent control was applied to the base of an Erlenmeyer flask and the testing proceeded in the same manner described above. Cat fleas in the treatment containers were held under testing conditions for 8, 24 and/or 48 hours. Mortality was recorded at 8, 24, 8 and 24, or 24 and 48 hours. Pooled 8, 24, 8 and 24, and 24 and 48 hour mortality data were converted to percentages and are summarized by Tables 14,14A and 14B, below. c) Ctenocephaiides fe//sAdulticide Assay: C. felis dose response
The purpose of this example was to determine the LC5G when cat fleas were contacted with a glass surface treated with sample compounds or formulations prepared as described above. Mortality of fleas was defined as follows: fleas were

considered dead if they didn't move or-were on their sides and unable to walk or right themselves. LC50: Lethal Concentration 50 - concentration of glass surface treatment
at which 50% of the cat fleas were killed. The test species was the cat flea (Cienocephalides felis). The strain used was obtained from externaf suppliers as pupae and held in the laboratory under testing conditions until the adults had
emerged. Fifteen (15) fleas were used in a minimum of four replicates for each dose level (total of 60 fleas per dose level). The insects were selected to be in the adult life stage, aged between 3 and 7 days post emergence.
The compounds to be tested were dissolved in acetone just prior to testing. Samples of compounds were stored in a refrigerator (5±1°C) unless otherwise specified. During the mortality testing, the temperature was maintained at 25±1 °C. Humidity was maintained at 75±5%. The base (area =159 mm2) of a 100 mL glass Erfenmeyer (conical) flask provided the treatment surface. Flasks were pretreated with Coatasil™ glass treatment to maximise bio-availabiiity of test compounds by preventing them from binding to the glass surface.
Six dose levels (concentrations) of test sample, in the form of a serial dilution, were derived from a pilot study and covered a range that produced very low to very high mortality. The base of the 100 mL Erlenmeyer flask was treated with 0.5 mLof test sample in acetone and gently swirled. This volume was sufficient to cover the base of the fiask. Flasks were left to dry for 24 hours before flea exposure. Aduft cat fleas were lightly anaesthetised by cooling and then placed into a sorting chamber, which allowed fleas to revive and jump into the Erlenmeyer flasks. Fifteen (15) adult cat fleas were collected in each flask. The top of the flasks were then covered in ParafilmlM and small holes made to allow gas exchange. A 0.5 mL volume of acetone was applied to the base of an Erlenmeyer flask and the testing proceeded in the same manner described above. Cat fleas in the treatment containers were held under testing conditions for 24 hours. Mortality resulting from the treatments was recorded at 8 and 24 hours. Pooled 24 hour mortality data were subjected to probit analysis to obtain concentration response data (LC50) (Finney, D.J., 1971. Frobit Analysis. 3rd ed. Cambridge Univ. Press, London).
d) Rapid screening protocol for topical application on brown dog ticks (Fthipicaphalus sanguineus)

The-aim-of -the-tesT was -to determine- the -presence- of -significant.acaricidal activity in sample compounds or formulations when applied topically on brown dog ticks. A tick was defined as dead if it gave no apparent response when touched lightly and observed for 1 minute. To assess the experimental compound for acaricidal activity, a single dose level was chosen based on known results from previous, experiments with a commercially available active reference compound. Both permethrin and fipronil were employed as reference compounds. The insect species tested was the Brown Dog Tick {RhipicephaJus sanguineus). Mixed sex adult ticks were used for tests. The strain used was cultured by von Berky Veterinary Services, Woody Point QLD, AU and supplied as unfed adult ticks (mixed sex). Ticks were
maintained in controlled conditions (temp. 18C±2°C, humidity 75±5% RH).
Test compounds (formulations or active ingredients) were stored in a refrigerator (5±leC) unless otherwise specified. Temperature was maintained at 25±1°C and the humidity was ambient. The screening dose chosen was higher than that known to kill 90% of insects (LDSo) using the reference compound. In the case of topical application of active compounds on adult ticks, the reference compound was fipronil and the dose chosen was 10 fjg of active per tick (=10 //g of fipronil / 1//I of acetone). Ticks were each treated on the abdomen with 1 /A of a single dose level of test sample in acetone; ten ticks were treated with solvent only (acetone) in each test Tests were replicated 4 times (total of 40 ticks treated). Ticks were held in recovery containers maintained under appropriate rearing conditions for 24 hours. Mortality resulting from the treatments was recorded at 24 hours. Pooled 24 hour mortality data were converted to percentages.
e) Dose response protocol for topical application on brown dog ticks {Rhiplcephalus sanguineus): The test determines the level of insecticidal activity of sample compounds or formulations when applied topically on brown dog ticks. Sample compounds were stored prior to use in a freezer (-5±1CC), unless otherwise specified.
Definitions:
• Mortality: A tick is defined as dead after it gives no apparent response
when touched lightly or gently breathed upon, while observed for 30 seconds.

LD50 (Lethal Dose 50): The dose of a topically applied treatment at which 50% of the dog ticks are killed.
• Reference compound: To assess an experimental compound for
significant acaricida! activity a single dose level is chosen, which is based upon known
results from previous experiments using a commercially available active i.e.. a
reference compound. The reference compound selected is one in common uses and
one that has a similar mode of action against the Brown Dog Tick (i.e., the test
species).
Recovery container: A recovery container consists of a 500ml round
plastic container measuring 115mm diameter and 70mm height, with a tight fitting lid
that has 10 small (-1 mm) holes inserted for air exchange. A 90mm diameter piece of
filter paper was placed on the bottom of the container and moistened with 1 mL of de
stined water.
Adult, mixed sex; Brown Dog Ticks (Rhipicephalus sanguineus) were reared as follows; (i) cultured, (ii) transferred unfed, to a testing laboratory, and (iii) then maintained under controlled conditions {i.e., temp, 18C±2°C; humidity 75±5% RH). The ticks used were selected for vigor prior to testing, i.e., capable of actively walking and responsive to being touched or gently breathed upon.
During the testing, the temperature was maintained at 25±1°C, and the humidity was ambient Seven dose levels (concentrations) of sample compound, in the form of serial dilutions in acetone, were derived from a pilot study and covered a range that produced very low to very high mortality. Groups of ten ticks were treated topically (on the abdomen) with 1 //L of a single dose level of the sample compound. Each test was replicated four times, i.e., employing a total of 40 ticks per dose level of each sample compound. As a control, ten ticks were treated with solvent only (acetone) for each test Following the treatment, the ticks were held in recovery containers maintained under appropriate rearing conditions for 24 hours. Mortality resulting from the treatments was recorded at 24 hours. Pooled 24 hour mortality data were subjected to probit analysis to obtain concentration response data (LC5o) [see, Finney, D.J., Probit Analysis 3rd ed., Cambridge Univ. Press, London (1971).]
All equipment that was not disposed of was decontaminated by soaking overnight in a 1% (minimum) solution of PYRONEG™ detergent. PYRONEG™ is a

pyrogenically negative cleaner containing 60% alkaline salts. Surfaces were lightly scrubbed after soaking and double rinsed before re-use.
In Tables 14A? 14B and 14C. provided below, are listed the Haemonchus contortus LDo9 values (measured in micrograms/mL), the Cienocephalides felt's rapid screening values (measured in % mortality), the Cienocephalides felis LC50 values (measured in micrograms/cm2), the Rhipicephalus sanguineus rapid screening values (measured in % mortality) and the Rhipicephalus sanguineus LD50 values (measured in micrograms/tick) for selected compounds in accordance with the present invention. The tabulated data confirm that the inventive compounds have significant antiparasite activity for both endo and ectoparasites, as shown.

CONCLUSION
A substantial number of the tested compounds exhibited effective killing of most or all of the test organisms.
While the present invention has been described in conjunction with the specific embodiments set forth above, many alternatives, modifications and variations thereof will be apparent to those of ordinary skill in the art. Ail such alternatives, modifications and variations are intended to fall within the spirit and scope of the present invention.

We claim:
1. A trifiuorornethanesulfonanilide oxime ether compound of Formula (I)

or a pharmaceutical/ acceptable salt thereof or a solvate thereof, wherein:
R1 R2, R3 and R4 are independently selected from the group consisting of hydrogen, formyl, carbcxyl, cyano, hydroxy, amino, nitro, thiol, halo and the following optionally substituted moieties: alkyl, alkenyL alkynyl. cycloalkyi, cycloaikenyl, aryl, heterocyclyl, heteroaryl. alkanoyl, aroyi. heterocycloyl. heteroaroyl, alkoxycarbonyl, aryloxycarbonyi, heterocyclyloxycarbonyl, hetercaryloxycarbonyl. alkylaminocarbonyl. aryiaminocarbonyl, heterocyclyiaminocarbonyl, heteroarylaminocarbonyl, alkoxy, alkenyloxy, cycloaikoxy, cycloalkenyloxy, alkoxy, aryioxy, heterocyciyloxy, alkanoate, aryloate, heterocyclyloate, heteroaryloate, alkylsuifonate, arylsuifonate, heterocyclylsulfonate, heteroarylsuifonate, alkylamino, aikenylamino, arylamino, heterocyclylamino, heteroarylamino, alkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonyiamino, heteroaryicarbonylamino. alkylthio, alkenylthio. cycloalkylthio, cycloalkenylthio. arylthio, heterocyctylthio, heteroarylthio, alkylsulfinyl, alkenylsuifiny], cycloalkylsulfinyl, cycloalkenyisulfinyl. arylsulfinyl, heterocyclylsutfinyl, heieroarylsulfinyl, alkylsulfonyl, aikenylsulfonyl, cycloalkylsulfonyl, cycloalkenylsulfonyl, arylsuifonyi, heterocyclylsulfonyl, heteroarylsuifonyl, haloalkyl, haloalkeny!, haloalkynyl, haloalkoxy, haioalkenyloxy, haloalkylsulfonate, haloalkylcarbonyiaminof haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl;
R5 is selected from hydrogen, halogen, cyano and the following optionally substituted moieties: alkyl, alkenyl, alkynyl, cycloalkyi, cycloaikenyl. cycloalkylalkyl, cycloalkenylalkyl, aryl, arylalkyl, heterocyclyl, haloalkyl, haloalkenyl and haloalkynyl; and

R6 is selected from hydrogen and the-following optionally substituted moieties: alky!, alkenyl, afkynyl, cycloaikyl, cycioalkenyl, cycloalkylalkyl, cycloalkenylaikyl, aryl, arylalkyl, arylalkenyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, alkanoyl, aroyl, heterocycloyi, heteroaroyl. cyanoalkyl. alkoxyalkyl, cycloalkoxyalkyl, aryloxyalkyl, alkylthioalkyl cycloaikyithioalkyl. aryithioalkyl, alkylsulfinylalkyl, cycloalkylsulfinylalkyl, aiylsulfinyialky!, alkylsulfonylaikyi, cycloalkylsulfonylalkyl, arylsulfonylalkyl, haloalkyl, haloalkenyl and haloalkynyi.
2. The trifluoromethanesuifonanilide oxime ether compound of claim 1 wherein R2 and R3 together are part of the same fused carbocyclic, heterocyclic, aryl or heteroaryl ring, that is substituted or unsubstituted.
3. The trifluoromethanesuifonanilide oxime ether compound of claim 1 wherein R4 and R5 together are part of the same fused carbocyclic, heterocyclic, aryl or heteroaryl ring, that is substituted or unsubstituted.
4. The trifluoromethanesuifonanilide compound of claim 1 wherein R5 and R5 together are part of the same fused heterocyclic or heteroaryl ring, that is substituted or unsubstituted.
5. The trifluoromethanesuifonanilide oxime ether compound of claim 1. wherein:
R1 is hydrogen, (C1-C5)alkyl or (C1-C6)aikoxy;
R2 is hydrogen, halo or C1-C6haloalkyl;
R3 is hydrogen, halo or C1-C6haloalkyl;
R2 and R3 together are part of the same fused carbocyclic, heterocyclic, aryl or heteroaryl ring, which is substituted or unsubstituted;
R4 is hydrogen;
R5 is hydrogen, (C1-C6)alkylI C3-C10cycloalkyl or (optionally substituted)aryl; and
R6 is selected from the group consisting of C1-C6alkyl, (C2-C6)alkenyL (C2-C6)alkynyL (C3-C10)cycioalkyl, (C3-C10)cycioalkenyi; (C3-C10)cycloa!kylC1-C6alkyl3 (C3-C1o)cycIoalkenylC1-C6alkyl, and the following optionally substituted moieties: aryl.

ary!C1-C6alkyl, aryl(C2-C6)aikenyl, heterocyc]ylC1-C6alkyl, heteroaryl, heteroaryi(C1-C6)aikyl, cyanoC1-C6alkyl, (C1-C6)alkoxyfCrCeJalkyl, aryloxyC1-C6alkyl, (C1-C6)aIkylthioC1-C6alkyI, C1-C6haloalkyl and (C2-C6)haIoalkenyI.
6. The trifluoromethanesulfonaniiide oxime ether compound of claim 1,
wherein:
R1 is hydrogen, methyl or methoxy;
R2 is hydrogen, fluorine, chlorine or.trifluoromethyl;
R3 is hydrogen, fluorine, chlorine, bromine ortrifluoromethyi;
R2 and R3 together are part of a methylene dioxy ring;
R4 is hydrogen;
R5 is hydrogen, methyl, ethyl, n-propyl, Apropyl, pharmaceutically , cyclohexyl or phenyl; and
Rs is selected from the group consisting of methyl, ethyl, /-propyl, /-butyl, /-butyl, sac-butyl, -CH(CH2CH3)2, ally!, propargyl, cyclopentyi, cyclohexyl. 3-cyclohexenyl, frans-cinnamyl, -CH2C!M, -CH(CK3)CN, -(CH2)2OCH3; -CH2SCH3, -CH2CF5 or one of:

wherein:
n isO, 2 or 3:
m is 2 or 3;
pis 2:
Y is hydrogen or chlorine; and
Z is chlorine or bromine.
7. The trifluoromethanesulfonaniiide compound of Formula (II):


wherein R1, R2, R3 and R4 are defined as for claim 1, R13and R14 are independently selected from the group consisting of hydrogen, formyi, carboxyl, cyano. hydroxy, amino, nitro: thiol, halo and the following optionally substituted moieties: alkyl, alkenyl, alkynyl, cycloalkyl, cycioaikenyi. aryi, heterocyclyl, heteroaryl, alkanoyl, aroyl, heterocycioyl, heteroaroyl, alkoxycarbonyl, aryioxycarbonyl, heterocyctyloxycarbonyl, heteroaryloxycarbonyl, alkylaminocarbonyi, aryiarninocarbonyl, heterocyclylaminocarbonyl, heteroarylaminocarbonyl, alkoxy, alkenyloxy, cycloalkoxy, cycloalkenyloxy. alkoxyalkoxy, aryioxy, heterocyclyloxy, alkanoate, aryloate, heterocyclyloate. heteroaryloate. alkylsulfonate, aryisu!fonate: heterocycty!sulfonate; heteroaryisulfonate, aikylamino. alkenyiamino. arylamino. heterocyclylamino, heteroaryiamino: alkylcarbonylamino. arylcarbonylamino, heierocyclylcarbonylamino, heteroaryicarbonylamino, alkylthio, aikenylthio, cycloalkyithio, cycloaikenylthio, arylthio, heterocyciyithio, heteroarylthio, alkylsulfinyl, aikenylsulfinyl, cycloalkylsulfinyl, cycloalkenylsuifinyL arylsulfinyl, heterocyctylsutfinyi, heteroaryisulfinyl, alkylsulfonyl, alkenylsulfonyl, cyc'caikylsuifonyl, cycloaikenylsuifonyl. arylsulfonyl, heterocyclylsulfonyl heteroarylsulfonyl, haloalkyL haloalkenyl, haloalkynyl, haioalkoxy, haloalkenyloxy, haioalkylsulfonate. haloalkylcarbonyiamino. haloaikylthio, haloalkylsuifiny! and haloaikylsulfonyl.
8. A trifluoromethanesulfonanilide oxime ether compound corresponding to


-Formula (III) -
or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein:
R-, and R7 are independently hydrogen or C1-C6alkyl;
R2 is hydrogen or (Ci-C5)haloa!kyl;
R3 is hydrogen, halo or C1-C6haloalkyI;
R4 is hydrogen;
R5 is hydrogen, C1-C6aikyl or (optionally substituted)aryl;
R8 and R12 are independently hydrogen, cyano, halo or C1-C6haloaikyl;
R9 and Rn are independently hydrogen, (optionally substituted)aryloxy, (optionally su'bstituted)heteroaryloxy; halo or C1-C6haloalkyl; and
R10 is selected from the group consisting of hydrogen, C1-C6alkyl, (C3-C10)cycioalkyls (optionally substituted)aryl, (C1-C6)alkoxycarbonyl! cyano, C1-C6)aIkoxys nitro: halo and C1-C6haloaIky!;
9. The trifiuoromethanesulfonanilide oxime ether compound of claim 8, wherein:
R-i and R7 are independently hydrogen or methyl;
R2 is hydrogen or trifluoromethyl;
R3 is hydrogenr chlorine or trifluoromethyl;
R4 is hydrogen;
R5 is hydrogen, methyl, ethyl, n-propyl, /-propyl or phenyl;
R8 is hydrogen, cyano, fluorine, chlorine or trifluoromethyl;
R9 is hydrogen, fluorine, chlorine, bromine, trifluoromethyl or one of:

R10 is hydrogen, pharmaceutically , cyclohexyl, phenyl, methoxycarbonyl, cyano, methoxy, nitro, fluorine, chlorine, bromine or trifluoromethyl;
R-n is hydrogen, fluorine, bromine or trifluoromethyl; and R12 is hydrogen, fluorine or chlorine.

10. A trifluorornethanesulfonanilide oxime ether compound corresponding to

or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein:
R1 is hydrogen;
R2 is hydrogen or C1-C6haloalkyi;
R3 is hydrogen, halo or C1-C6haloa!kyl;
R2 is hydrogen;
Rs is C1-C6alkyl, (C3-C10)cycioaIkyL or (optionally substituted)aryl;
Rs and Rl2 are independently hydrogen or C1-C6alkyl;
R9 and Rn are independently hydrogen, halo or C1-C6haloalkyl; and
Rio is hydrogen, C1-C6a!kyL cyano, halo, C1-C6haloaIkyl or C1-C5)haloa!koxy;
11. The trifluoromethanesuifonanilide oxime ether compound of claim 9,
wherein:
R2 is hydrogen:
R2 is hydrogen or trifluoromethyl; R3 is hydrogen, chlorine or trifluoromethyl; R4 is hydrogen;
R5 is methyl, ethyl, n-propyl, /-propyl, t-butyl cyclohexyl or phenyl; R8 is hydrogen or methyl;
R9 is hydrogen, fluorine, chlorine or trifluoromethyl:
R-,o is hydrogen, methyl, cyano. fluorine, chlorine, bromine, trifluoromethyl or trifluoromethoxy:

R11 is hydrogen; and R12 is hydrogen.
12. A trifiuoromethanesulfonanilide oxime ether prodrug compound corresponding to

or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein:
R1, R25 R31 FU, R5 and R6 are defined as for claim 1, and A is selected from the following optionally substituted moieties: alkyi, alkenyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, heterocyclyloxyalkyl, heteroaryloxyalkyl, alkylcarbonyloxyalkyl, arylcarbonyloxyalkyl, heterocyciylcarbonyloxyalkyL heteroarylcarbonyloxyalkyl, alkoxycarbonylcxyalkyl. aryloxycarbonyloxyalkyl, heterocyclyloxycarbonyloxyalkyl, heteroaryloxycarbonyioxyaikyl, alkylaminocarbonyloxyalkyl, arylaminocarbonyloxyalkyl heterocyclylaminocarbonyloxyalkyl, heteroarylaminocarbonyloxyalkyk alkylcarbonylaminoalkyl, arylcarbonyiaminoalkyi. heterocyclycarbonylaminoalkyL heteroarylcarbonylaminoaikyl, alkylsulfonylalkyl, arylsulfonylalkyl, heterocyclylsulfonylalkyl, heteroarylsulfonylalkyl, alkanoyt, aroyl, heterocycloyl, heteroaroyl, alkoxycarbonyl, aryioxycarbonyl, heterocyclyloxycarbonyl, heteroaryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, heterocyclylaminocarbonyl, heteroarylaminocarbonyl, alkylaminothiocarbonyi, arylaminothiocarbonyl, heterocyclylaminothiocarbonyl, heteroarylaminothiocarbonyl. alkylsulfonyl, arylsulfonyl. heterocyclylsulfonyl and heteroaryisulfonyl.

13. The trifluoromethanesulfonanilide oxime ether compound of claim 1 that is selected from the compounds 1 through 224 as identified by Table 8.
14. The trifluoromethanesulfonanilide oxime ether compound of claim 7 that is selected from the compounds 225 through 231 as identified by Table 9.
15. A pharmaceutical composition for treatment of animais infected with parasites that comprises a therapeutically effective dosage amount of the trifluoromethanesulfonanilide oxime ether compound of claim 1, and a pharmaceutically acceptable excipient.
16. The pharmaceutical composition of claim 15 wherein the trifluoromethanesulfonanilide oxime ether compound is selected from the compounds 1 through 224 as identified by Table 8, and combinations thereof.
17. A pharmaceutical composition for treatment of animais infected with parasites that comprises a therapeutically effective dosage amount of the trifluoromethanesulfonanilide oxime ether compound of claim 7, and a pharmaceutically acceptable excipient.
18. The pharmaceutical composition of claim 17 wherein the trifluoromethanesulfonanilide oxime ether compound is selected from one of compounds 225 through 231 as identified by Table 9, and combinations thereof.
19. A pharmaceutical composition for treatment of animals infected with parasites that comprises a therapeutically effective dosage amount of the trifluoromethanesulfonanilide oxime ether compound of claim 8 and a pharmaceuticaliy acceptable excipient
20. A pharmaceutical composition for treatment of animals infected with parasites that comprises a therapeutically effective dosage amount of the trifluoromethanesulfonanilide oxime ether compound of claim 10, and a pharmaceuticaliy acceptable excipient.

21. A pharmaceutical composition for treatment of animals infected with parasites that comprises a therapeutically effective dosage amount of the trifiuoromethanesulfonaniiide oxime ether compound of claim 12. and a pharmaceutical acceptable excipient.
22. A method of treating or protecting an animal from a parasite infestation, comprising administering to an animal an effective amount .of a trifiuoromethanesulfonaniiide oxime ether compound of claim 1.
23. A method of treating or protecting an animal from a parasite infestation, comprising administering to an animal an effective amount of a trifiuoromethanesulfonaniiide oxime ether compound of claim 7.
24. A method of treating or protecting an animal from a parasite infestation, comprising administering to an animal an effective amount of a trifiuoromethanesulfonaniiide oxime ether compound of claim 8.
25. A method of treating or protecting an animal from a parasite infestation, comprising administering to an animal an effective amount of a trifiuoromethanesulfonaniiide oxime ether compound of claim 10.
26. A method of treating or protecting an animal from a parasite infestation, comprising administering to an animal an effective amount of a trifiuoromethanesulfonaniiide oxime ether compound of claim 12.
27. The method of claim 22 wherein the parasite is an arthropod or helminth.
28. The method of claim 23 wherein the parasite is an arthropod or helminth.
29. The method of claim 24 wherein the parasite is an arthropod or helminth.
30. The method of claim 25 wherein the parasite is an arthropod or helminth.

31. I he method of claim 26 wherein the parasite is an arthropod or helminth.
32. A method of killing or inhibiting the growth of an arthropod or helminth comprising contacting the arthropod or helminth with an effective amount of the compound of claim 1.
33. A method of killing or inhibiting the growth of an arthropod or helminth comprising contacting the arthropod or helminth with an effective amount of the compound of claim 7.
34. A method of killing or inhibiting the growth of an arthropod or helminth comprising contacting the arthropod or helminth with an effective amount of the compound of claim 8.
35. A method of killing or inhibiting the growth of an arthropod or helminth comprising contacting the arthropod or helminth with an effective amount of the compound of claim 10.
36. A method of killing or inhibiting the growth of an arthropod or helminth comprising contacting the arthropod or helminth with an effective amount of the compound of claim 12.
37. A method of treating or protecting a plant from an arthropod or helminth infestation comprising contacting the arthropod or helminth with an effective amount of the compound of claim 1.
38. A method of treating or protecting a plant from an arthropod or helminth infestation comprising contacting the arthropod or helminth with an effective amount of the compound of claim 7.

39. A method of treating or protecting a plant from an arthropod or helminth
infestation comprising contacting the arthropod or helminth with an effective amount of
the compound of claim 8.
40. A method of treating or protecting a plant from an arthropod or helminth
infestation comprising administering an effective amount of the compound of claim 10.
41. A method of treating or protecting a plant from an arthropod or helminth
infestation comprising administering an effective amount of the compound of claim 12.
42. A method of treating or protecting a plant or animal from a parasite infestation, comprising administering an effective amount of a trifluoromethanesulfonanilide oxime ether compound of claim 13.
43. A method of treating or protecting a plant or animal from a parasite infestation, comprising administering an effective amount of a trifluoromethanesulfonanilide oxime ether compound of claim 14. . .
Dated this 22 day of March 2007