Field of the Invention
The present invention provides acylide derivatives, which can be used as antibacterial
agents. Compounds disclosed herein can be used for the treatment or prevention of a condition
caused by or contributed to by Gram-positive, Gram-negative or anaerobic bacteria, more
particularly against bacterium such as Staphylococci, Streptococci, Enterococci, Haemophilus,
Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter,
Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae. Processes for the
preparation of disclosed compounds, pharmaceutical compositions thereof, and method of treating
bacterial infections are also provided.
Background of the Invention
The first generation macrolides erythromycin A and the early derivatives are characterized
by bacteriostatic or bactericidal activity for most Gram-positive bacteria, atypical pathogens, and
many community acquired respiratory infections and in patients with penicillin allergy. However,
erythromycin A causes numerous drug-drug interactions, has relatively poor absorption, poor
local tolerance, loses its antibacterial activity under acidic conditions by degradation and the
degraded products are known to be responsible for undesired side effects (Itoh, Z et al., Am. J.
Physiol., 247: 688, (1984); Omura, S et al., J. Med. Chem., 30: 1943, (1987). Various
erythromycin A derivatives have been prepared to overcome the acid instability and other
problems associated with it.
Roxithromycin, clarithromycin and azithromycin have been developed to address
limitations of erythromycin A. Both clarithromycin and azithromycin have proved to be
important drugs in the treatment and prophylaxis of atypical Mycobacterial infectious in patients
with HIV.
Macrolides have proved to be effective drugs in the treatment of many respiratory tract
infections. However, increasing resistance among S. pneumoniae has prompted the search for
new compounds that retain favorable safety profile, a wide spectrum of activity which is confined
to respiratory pathogens. Consequently, investigators have prepared chemical derivatives of
erythromycin A in an attempt to obtain analogs having modified or improved profiles of antibiotic
activity.
WO 01/10878, 01/10879 and 01/10880 disclose erythromycin derivatives allegedly having
potent antibacterial effects on erythromycin-resistant bacteria and Haemophilus influenzas. WO
99/21870 discloses erythromycin A, 11,12-carbamate derivatives described as having antibacterial
activity against not only erythromycin-sensitive bacteria but also erythromycin-resistant bacteria.
U.S. Patent No. 5,444,051 discloses erythromycin compounds, antibiotic compositions and a
method of combating bacteria infection in warm-blooded animals. U.S. Patent No. 6,191,118
discloses erythromycin A derivatives having strong antibacterial activity against erythromycinresistant
bacteria. U.S. Patent No. 5,631,354 discloses 5-O-desosaminylerythronolide derivatives
possessing antibacterial activity. U.S.Patent No. 6,020,521 discloses a class of macrolide
compounds, which are antagonists of luteinizing hormone-realising hormone (LHRH).
Summary of the Invention
Herein are provided acylide derivatives, which can be used in the treatment or prevention
of bacterial infection, and processes for the synthesis of these compounds. Pharmaceutically
acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, and polymorphs
of these compounds having same type of activity are also provided. Pharmaceutical compositions
containing the disclosed compounds together with pharmaceutically acceptable carriers,
excipients or diluents, which can be used for the treatment of bacterial infection, are also
provided.
Other aspects will be set forth in accompanying description which follows and in part will
be apparent from the description or may be learnt by the practice of the invention.
In accordance with one aspect, there are provided compounds having the structure of Formula I,
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs
or polymorphs thereof, wherein:
R1 can be hydrogen or a hydroxyl protecting group;
R2 and R3 can be independently alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle,
aralkyl or (heterocycle)alkyl (with the proviso that R2 and R3 simultaneously can not be methyl);
R4 can be alkyl, alkenyl or alkynyl;
R can be alkyl, aryl or heterocycle;
R can be no atom, hydrogen, aryl or heterocycle;
R' can be alkyl, -(CH2)q-U-V (wherein q can be an integer of from 1 to 4, U can be alkenyl
or alkynyl, V can be hydrogen, aryl or heterocycle);
W can be alkenyl, -G(CH2)mJ, -CR9R10, -NR9- or -SO2 - {[wherein m can be an integer of
from 2 to 6, G can be no atom, -CO, -CS, -SO2 or -NR9, J can be no atom, or -N((R9)(CH2)n(
wherein n can be an integer of from 1 to 4, R9 and R10 can be independently hydrogen or alkyl)]};
Y can be -Q(CH2)k-, {wherein k can be an integer of from 1 to 6, Q can be no atom, -NR9- or
oxygen [wherein R9 can be hydrogen or alkyl]}, further alkylene chain of -Q(CH2)k- can be
optionally substituted with alkyl, hydroxy or alkoxy; and
Z can be oxygen, sulphur or NOR8 (wherein R8 can be hydrogen, alkyl or aralkyl).
According to one embodiment, compounds of Formula I have the following attributes:
R1 can be hydrogen; R can be no atom or heterocycle; R2 and R3 can be alkyl, alkenyl or
alkynyl (however R2 and R3 simultaneously cannot be methyl); R4 can be ethyl; R5 can be alkyl,
aryl or heterocycle; R' and R4 can be alkyl; W can be alkenyl or -G(CH2)mJ-; Z can be oxygen or
sulphur; Y can be -Q(CH2)k, wherein G, J, Q, m and k are the same as defined earlier.
In accordance with a second aspect, there is provided a method for treating or preventing a
mammal suffering from a condition caused by or contributed to by Gram-positive, Gram-negative
or anaerobic bacteria, comprising administering to said mammal a therapeutically effective
amount of a compound or a pharmaceutical composition disclosed herein.
The bacterial infection may be caused by bacterium such as Staphylococci, Streptococci,
Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp.,
Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or
Enter obactericeae.
The conditions may be, for example, community-acquired pneumonia, upper- and lowerrespiratory
tract infections, skin and soft tissue infections, hospital-acquired lung infections or
bone and joint infections, and other bacterial infections such as mastitis, catether infection,
foreign body, prosthesis infections or peptic ulcer disease.
In accordance with a third aspect, there are provided processes for the preparation of
disclosed compounds.
The following definitions apply to terms as used herein:
The term "alkyl," unless otherwise specified, refers to a monoradical branched or
unbranched saturated hydrocarbon chain having from 1 to 20 carbon atoms. This term can be
exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tbutyl,
n-pentyl, isopentyl, neopentyl, n-hexyl, n-decyl, tetradecyl, and the like. Alkyl groups may
be substituted further with one or more substituents selected from alkenyl, alkynyl, alkoxy,
cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen,
hydroxy, oxo, thiocarbonyl, carboxy, carboxyalkyl, aryl, heterocyclyl, heteroaryl, arylthio, thiol,
alkylthio, aryloxy, nitro, aminosulfonyl, aminocarbonylamino, -NHC(=O)Rf, -NRfRq, -
C(=0)NRfRq, -NHC(=0)NRfRq,, -C(=O)heteroaryl, C(=O)heterocyclyl, -O-C(=O)NRfRq
(wherein Rf and Rq are independently selected from alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl,
aralkyl, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl}, nitro, or -SO2R6 (wherein Re
is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl, heterocyclyl, heteroaryl, heteroarylalkyl or
heterocyclylalkyl). Unless otherwise constrained by the definition, alkyl substituents may be
further substituted by 1-3 substituents selected from alkyl, carboxy, -NRfRq, -C(=O)NRfRq, -
OC(=O) NRfRq, -NHC(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), hydroxy,
alkoxy, halogen, CF3, cyano, and -SO2R6, (wherein R6 are the same as defined earlier); or an
alkyl group also may be interrupted by 1-5 atoms of groups independently selected from oxygen,
sulfur or -NRa- {wherein Ra is selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl,
alkynyl, aryl, acyl, aralkyl,-C(=O)ORf (wherein Rf is the same as defined earlier), SO2R6 (where
Re is as defined earlier), or -C(=O)NRfRq (wherein Rf and Rq are as defined earlier)}. Unless
otherwise constrained by the definition, all substituents may be substituted further by
substituents selected from alkyl, carboxy, -NRfRq, -C (=O)NRfRq, -O-C(=O)NRfRq (wherein Rf
and Rq are the same as defined earlier), hydroxy, alkoxy, halogen, CFa, cyano, and -SO2Re (where
Re is same as defined earlier); or an alkyl group as defined above that has both substituents as
defined above and is also interrupted by 1-5 atoms or groups as defined above.
The term "alkylene," as used herein, refers to -(CH)n- wherein n can be an integer of from
0 to 4 and one or more hydrogen can optionally be substituted with alkyl, hydroxy, halogen or
oximes. Alkylene can also be optionally interrupted by -CONH-, -C=O or -C=NOH.
The term "alkenyl," unless otherwise specified, refers to a monoradical of a branched or
unbranched unsaturated hydrocarbon group having from 2 to 20 carbon atoms with cis, trans, or
geminal geometry. In the event that alkenyl is attached to a heteroatom, the double bond cannot
be alpha to the heteroatom. Alkenyl groups may be substituted further with one or more
substituents selected from alkyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino,
acyloxy, -NHC(=O)Rf, -NRfRq, -C(=O)NRfRq, -NHC(=O)NRfRq, -O-C(=O)NRfRq (wherein Rf
and Rq are the same as defined earlier), alkoxycarbonylamino, azido, cyano, halogen, hydroxy,
oxo, thiocarbonyl, carboxy, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, heterocyclyl,
heteroaryl, heterocyclyl alkyl, heteroaryl alkyl, aminosulfonyl, aminocarbonylamino,
alkoxyamino, nitro, or SO2R6 (wherein R6 are is same as defined earlier). Unless otherwise
constrained by the definition, alkenyl substituents optionally may be substituted further by 1-3
substituents selected from alkyl, carboxy, hydroxy, alkoxy, halogen, -CF3, cyano, -NRfRq, -
C(=O)NRfRq, -O-C(=O)NRfRq (wherein Rf and Rq are the same as defined earlier) and -SO2R6(
where Re is same as defined earlier).
The term "alkynyl," unless otherwise specified, refers to a monoradical of an unsaturated
hydrocarbon, having from 2 to 20 carbon atoms. In the event that alkynyl is attached to a
heteroatom, the triple bond cannot be alpha to the heteroatom. Alkynyl groups may be substituted
further with one or more substituents selected from alkyl, alkenyl, alkoxy, cycloalkyl,
cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy,
oxo, thiocarbonyl, carboxy, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl,
aminocarbonylamino, nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, -
NHC(=O)Rf, -NRfRq, -NHC(=O)NRiRq , -C(=O)NRfRq, -O-C(=O)NRfRq (wherein Rf and Rq are
the same as defined earlier), or -SOaRe (wherein R6 is as defined earlier). Unless otherwise
constrained by the definition, alkynyl substituents optionally may be substituted further by 1-3
substituents selected from alkyl, carboxy, carboxyalkyl, hydroxy, alkoxy, halogen, CF3, -NRfRq, -
C(=0)NRfRq, -NHC(=O)NRfRq , -C(=0)NRfRq (wherein Rf and Rq are the same as defined
earlier), cyano, or -SC^Re (where Re is same as defined earlier).
The term "cycloalkyl," unless otherwise specified, refers to cyclic alkyl groups of from 3
to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may optionally
contain one or more olefinic bonds, unless otherwise constrained by the definition. Such
cycloalkyl groups can include, for example, single ring structures, including cyclopropyl,
cyclobutyl, cyclooctyl, cyclopentenyl, and the like, or multiple ring structures, including
adamantanyl, and bicyclo [2.2.1] heptane, or cyclic alkyl groups to which is fused an aryl group,
for example, indane, and the like. Spiro and fused ring structures can also be included.
Cycloalkyl groups may be substituted further with one or more substituents selected from alkyl,
alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy,
alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, carboxy, carboxyalkyl,
arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl, aminocarbonylamino, -NRfRq, -
NHC(=O)NRfRq, -NHC(=O)Rf, -C(=O)NRfRq, -O-C (=O)NRfRq (wherein Rf and Rq are the same
as defined earlier), nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, or -SC^Re
(wherein Re is same as defined earlier). Unless otherwise constrained by the definition,
cycloalkyl substituents optionally may be substituted further by 1-3 substituents selected from
alkyl, carboxy, hydroxy, alkoxy, halogen, CF3, -NRfRq, -C(=O)NRfRq, -NHC(=O)NRfRq , -
OC(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), cyano or -SO2R6 (where Re is
same as defined earlier). "Cycloalkylalkyl" refers to alkyl-cycloalkyl group linked through alkyl
portion, wherein the alkyl and cycloalkyl are the same as defined earlier.
As used herein the term "halogen or halo" refers to fluorine, chlorine, bromine or iodine.
As used herein the term "hydroxyl-protecting group" includes, but are not limited to, acyl,
aroyl, alkyl, aryl, butyldiphenylsilyl, methoxymethyl and methylthiomethyl, and the like.
As used herein the term "thio" refers to the group -SH.
As used herein the term "alkoxy" stands for a group O-R wherein R refers to alkyl or
cycloalkyl. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, cyclopentoxy
and the like.
As used herein the term "thioalkyl" refers to -SR wherein R refers to alkyl or cycloalkyl.
As used herein the term "haloalkyl" refers to alkyl of which one or more hydrogen (s)
is/are replaced by halogen.
The term "aryl," unless otherwise specified, refers to carbocyclic aromatic groups, for
example, phenyl, biphenyl or napthyl ring and the like, optionally substituted with 1 to
substituents selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl,
alkoxy, acyl, aryloxy, CF3, cyano, nitro, COORe (wherein Re is hydrogen, alkyl, alkenyl,
cycloalkyl, aralkyl, heterocyclylalkyl, heteroarylalkyl), NHC(=O)Rf, -NRfRq, -C(=O)NRfRq, -
NHC(=O)NRfRq, -O-C(=O)NRfRq (wherein Rf and Rq are the same as defined earlier), -SO2R6
(wherein R6 is same as defined earlier), carboxy, heterocyclyl, heteroaryl, heterocyclylalkyl,
heteroarylalkyl or amino carbonyl amino. The aryl group optionally may be fused with a
cycloalkyl group, wherein the cycloalkyl group may optionally contain heteroatoms selected from
O, N or S.
The term "aralkyl," unless otherwise specified, refers to alkyl-aryl linked through an alkyl
portion (wherein alkyl is as defined above) and the alkyl portion contains 1-6 carbon atoms and
aryl is as defined below. Examples of aralkyl groups include benzyl, ethylphenyl and the like.
The term 'heterocyclyl," unless otherwise specified, refers to a non-aromatic monocyclic
or bicyclic cycloalkyl group having 5 to 10 atoms wherein 1 to 4 carbon atoms in a ring are
replaced by heteroatoms selected from O, S or N, and optionally are benzofused or fused
heteroaryl having 5-6 ring members and/or optionally are substituted, wherein the substituents are
selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, aryl,
alkoxy, aralkyl, cyano, nitro, oxo, carboxy, heterocyclyl, heteroaryl, -O-C(=O)Rf, -O-C(=O)ORf,
-C(=0)NRfRq, S02R6, -O-C(=0)NRfRq, -NHC(=O)NRfRq, -NRfRq (wherein Ra, Rf and Rq are
as defined earlier) or guanidine. Heterocyclyl can optionally include rings having one or more
double bonds. Unless otherwise constrained by the definition, the substituents are attached to the
ring atom, i.e., carbon or heteroatom in the ring. Also, unless otherwise constrained by the
definition, the heterocyclyl ring optionally may contain one or more olefmic bond(s). Examples
of heterocyclyl groups include oxazolidinyl, tetrahydrofuranyl, dihydrofuranyl, dihydropyridinyl,
dihydroisoxazolyl, dihydrobenzofuryl, azabicyclohexyl, dihydroindolyl, pyridinyl, isoindole 1,3-
dione, piperidinyl or piperazinyl.
As used herein the term "(heterocycle) alkyl" stands for heterocycle, which is bonded to
an alkylene chain. Examples of heterocycle alkyl include, but are not limited to, isothiazolidinyl
ethyl, isothiazolyl propyl, pyrazinyl methyl, pyrazolinyl propyl and pyridyl butyl, and the like.
Aryl and heterocycle groups may optionally be substituted with one or more substituent(s) such as
hydroxy, nitro, mercapto, cyano, alkyl, halogen, haloalkyl, alkoxy, thioalkyl, optionally
substituted aryl, optionally substituted heterocyclyl, -NR6R7, -CONR6R7, -COOR7, -CONHR7, -
OCOR7, -COR7, -NHSO2R7, and -SO2NHR7, wherein R6 and R7 can be hydrogen or alkyl.
As used herein the term "polymorphs" includes all crystalline forms and amorphous forms
for compounds described herein.
The term "pharmaceutically acceptable solvates" refers to solvates with waters (i.e
hydrates) or pharmaceutically acceptable organic solvents. Such solvates are also
encompassed within the scope of this invention.
The phrase "pharmaceutically acceptable salts" denotes salts of the free base, which
possess the desired pharmacological activity of the free base and which are neither biologically
nor otherwise undesirable. Suitable pharmaceutically acceptable salts may be prepared from an
inorganic or organic acid. Example of such inorganic acids include, but not limited to,
hydrochloric, sulfuric, phosphoric acid, and the like. Appropriate organic acids include, but not
limited to, aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of
organic acids, for example, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,
tartaric, citric, ascorbic, glucuronic, maleic, fumeric, pyruvic, aspartic, glutamic, benzole,
anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),
methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-
hydroxyethanesulfonic, sulfanilic, stearic, algenic, beta-hydroxybutyric, cyclohexylaminosulfonic,
galactaric and galacturonic acid, and the like.
"The term pharmaceutically acceptable carriers" is intended to include non-toxic, inert
solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any
type.
The compounds of present invention include stereoisomers. The term "stereoisomer"
refers to compounds, which have identical chemical composition, but differ with regard to
arrangement of the atoms and the groups in space. These include enantiomers, diastereomers,
geometrical isomers, atropisomer and comformational isomers. Geometric isomers may occur
when a compound contains a double bond or some other feature that gives the molecule a certain
amount of structural rigidity. An enantiomer is a stereoisomer of a reference molecule that is the
nonsuperimposable mirror image of the reference molecule. A diastereomer is a stereoisomer of a
reference molecule that has a shape that is not the mirror image of the reference molecule. An
atropisomer is a conformational of a reference compound that converts to the reference compound
only slowly on the NMR or laboratory time scale. Conformational isomers (or conformers or
rotational isomers or rotamers) are stereoisomers produced by rotation about CT bonds, and are
often rapidly interconverting at room temperature. Racemic mixtures are also encompassed
within the scope of this invention.
The present invention also includes within its scope prodrugs of these agents. In general,
such "prodrugs" will be functional derivatives of these compounds, which are readily convertible
in vivo into the required compound. Conventional procedures for the selection and preparation of
suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H
Bundgaard, Elsevier, 1985.
Detailed Description of the Invention
The compounds provided herein may be prepared by techniques well known in the art and
familiar to the average synthetic organic chemist. In addition, the compounds of the present
invention may be prepared by following reaction sequences such as those depicted in Schemes I,
II and III.
Formula XII( Fomiila 1. wherein R'=R2=CH,:R4=C2HS;Z=O:R,=H)
The compound of Formula XII can be prepared according to Scheme I. Thus, clarithromycin of
Formula II is hydrolyzed to give a compound of Formula III, which on protection with a reagent
of Formula R'2O or R.'X (wherein X is halogen) gives a compound of Formula IV (wherein R1 is -
COPh), which on desmethylation at 3'-N-dimethyl group gives a compound of Formula V, which
on alkylation with a reagent of Formula R3CHO, R3
2CO or R3X gives a compound of Formula VI
(wherein R3 is the same as defined earlier), which on reaction with a suitable reagent gives a
compound of Formula VII, which on reaction with a suitable organic base gives a compound of
Formula VIII, which on acylation with a reagent of Formula R5YCOOH, (R5YCO)2O, R5YCOX
or R5YCOOR10 (wherein R10 is leaving group such as pivaloyl, p-toleuensulfonyl,
isobutoxycarbonyl, ethoxycarbonyl or isopropoxycarbonyl) gives a compound of Formula IX
(wherein Y and R5 are the same as defined earlier), which on reaction with N, N'-carbonyl
diimidazole gives a compound of Formula X, which on reaction with a compound of Formula RW-
NHa gives a compound of Formula XI (wherein R and W are the same as defined earlier),
which is finally deprotected to give a compound of Formula XII.
The hydrolysis of clarithromycin of Formula II to give a compound of Formula III can be
carried out in the presence of an inorganic or organic acid, for example, hydrochloric acid,
sulphuric acid or dichloroacetic acid.
The hydroxyl protection of a compound of Formula III to give a compound of Formula IV
can be carried out in a solvent, for example, dichloromethane, dichloroethane, chloroform or ethyl
acetate, in the presence of an organic base, for example, triethylamine, pyridine, tributylamine or
4-N-dimethylaminopyridine.
The desmethylation of a compound of Formula IV to give a compound of Formula V can
be carried out in the presence of a demethylating agent, for example, N-iodosuccinamide or
diisopropyl azodicarboxylate in a solvent, for example, acetonitrile, tetrahydrofuran,
dichloromethane, dichloroethane, ethyl acetate or mixture thereof. The quenching of
desmethylation reaction can be carried out in the presence of a quenching agent, for example,
sodium bisulphite, sodium carbonate or mixture thereof.
The alkylation of a compound of Formula V to give a compound of Formula VI can be
carried out in a solvent, for example, dimethylformamide, acetonitrile or tetrahydrofuran. in
presence of an inorganic or organic base, for example, sodium hydrogen carbonate, potassium
carbonate, sodium hydride, pyridine, triethylamine or diisopropyl ethylamine. The alkylation of a
compound of Formula V can also be carried out with a reagent of Formula R3CHO with a
reducing agent, for example, sodium cyanoborohydride, sodium borohydride
or sodium triacetoxyborohydride in the presence of an organic acid, for example, acetic acid or
dichloroacetic acid in a solvent, for example, methanol, ethanol, propanol or isopropanol.
The reaction of a compound of Formula VI to give a compound of Formula VII can be
carried out in the presence of a reagent, for example, triphosgene or ethylene carbonate, in a
solvent, for example, chloroform, dichloromethane, carbon tetrachloride or dichloroethane. , in
the presence of an organic base, for example, triethylamine, pyridine, tributylamine or 4-Ndimethylaminopyridine.
10
The reaction of a compound of Formula VII to give a compound of Formula VIII can be
carried out in a solvent, for example, dimethylformamide, tetrahydrofuran or dimethylsulphoxide
in the presence of an organic base, for example, tetramethyl guanidine, pyridine or
trimethylamine.
The reaction of a compound of Formula VIII to give a compound IX can be carried out in
a solvent, for example, dichloromethane, dichloroethane, acetone, ethyl acetate or
tetrahydrofuran, in the presence of an inorganic or organic base, for example, sodium bicarbonate,
potassium carbonate, triethylamine, pyridine, tributylamine or 4-N-dimethylaminopyridine with
an activating agent, for example, dicyclohexylcarbodiimide or l-ethyl-3- (3-
dimethylaminopropyl) carbodiimide hydrochloride.
The reaction of a compound of Formula IX with N, N'-carbonyl diimidazole to give a
compound of Formula X can be carried out in a solvent, for example, dimethylformamide,
tetrahydrofuran or mixture thereof, in the presence of an inorganic base, for example, sodium
hydrogen carbonate, potassium carbonate or sodium hydride.
The reaction of a compound of Formula X with a compound of Formula R-W-NF^ to give
a compound of Formula XI can be carried out in a solvent, for example, acetonitrile, water,
dimethylformamide or mixture thereof.
The deprotection of a compound of Formula XI to give a compound of Formula XII can
be carried out in an alcohol, for example, methanol, ethanol, propanol or isopropanol.
The compound of Formula XII can further be converted into its salt by following a
conventional method, for example, those known in the prior art.
The compounds of Formula XV and XVII can be prepared according to Scheme II. Thus,
a compound of Formula X (from scheme I) is reacted with hydrazine hydrate to give a compound
of Formula XIII, which on deprotection gives a compound of Formula XIV,
(a) which is finally reacted with a compound of Formula R (CH2)mCHO to give a compound of
Formula XV (wherein R and m are the same as defined earlier), or
(b) which on reaction with a compound of Formula RgONF^ . hydrochloride gives a compound of
Formula XVI (wherein RS is the same as defined earlier), which is finally reacted with a
compound of Formula R (CH2)mCHO to give a compound of Formula XVII ( wherein R and m
are the same as defined earlier).
The reaction of a compound of Formula X with hydrazine hydrate to give a compound of
Formula XIII can be carried out in a solvent, for example, dimethylformamide, tetrahydrofuran or
dimethylsulphoxide.
The deprotection of a compound of Formula XIII to give a compound of Formula XIV can
be carried out in a solvent, for example, methanol, ethanol, propanol or isopropanol.
The reaction of a compound of Formula XIV with a compound of Formula R(CH2)mCHO
to give a compound of Formula XV can be carried out in a solvent, for example, methanol,
ethanol, propanol or isopropanol, in the presence of an organic acid, for example, acetic acid or
dichloroacetic acid in the presence of a reducing agent, for example, sodium borohydride, sodium
cyanoborohydride or sodium triacetoxyborohydride.
The reaction of a compound of Formula XIV with a compound of Formula
R80NH2.hydrochloride to give a compound of Formula XVI can be carried out in a solvent,
for example, methanol, ethanol, propanol or isopropanol.
The reaction of a compound of Formula XVI with a compound of Formula R(CH2)mCHO
to give a compound of Formula XVII can be carried out in a solvent, for example, methanol,
ethanol, propanol or isopropanol,in the presence of a reducing agent, for example, sodium
borohydride, sodium cyanoborohydride or sodium triacetoxyborohydride.
The compounds of Formula XV and XVII can further be converted into their salt by following a
conventional method, for example those known in the prior art.
Fomwla XII( FoniulH [. \vtierein R'-Kr(JH,:R*=C:Hs:/.O.K, --H)
A compound of Formula XII can also be prepared according to Scheme III. Thus, reaction of a
compound of Formula IV (wherein R1 is -COPh) with a reagent gives a compound of Formula
XVIII, which on reaction with an organic base gives a compound of Formula XIX, which on
desmethylation at 3'-N-dimethyl group gives a compound of Formula XX, which on alkylation
with a reagent of Formula R3CHO, R32CO or R3X gives a compound of Formula VIII (wherein R3
is the same as defined earlier), which on acylation with a reagent of Formula R5YCOOH,
(R5YCO)2O, R5YCOX or R5YCOOR10 (wherein R10 is leaving group such as pivaloyl, ptoleuensulfonyl,
isobutoxycarbonyl, ethoxycarbonyl or isopropoxycarbonyl) gives a compound of
Formula IX (wherein Y and R5 are the same as defined earlier), which on reaction with N, N'-
carbonyl diimidazole gives a compound of Formula X, which on reaction with a compound of
Formula R-W-NFb gives a compound of Formula XI (wherein R and W are the same as defined
earlier), which is finally deprotected to give a compound of Formula XII.
The reaction of a compound of Formula IV to give a compound of Formula XVIII can be
carried out in the presence of a reagent, for example, triphosgene or ethylene carbonate, in a
solvent, for example, chloroform, dichloromethane, carbon tetrachloride or dichloroethane, in the
presence of an organic base, for example, triethylamine, pyridine, tributylamine, 4-Ndimethylaminopyridine
or diisopropyl ethyl amine.
The reaction of a compound of Formula XVIII to give a compound of Formula XIX can(Figure Removed)
be carried out in a solvent, for example, dimethylformamide, tetrahydrofuran or
dimethylsulphoxide, in the presence of an organic base, for example, tetramethyl guanidine,
pyridine, trimethylamine or diisopropyl ethyl amine.
The desmethylation of a compound of Formula XIX to give a compound of Formula
can be carried out in the presence of a demethylating agent, for example, N-iodosuccinamide,
iodine in acetic acid or diisopropyl azodicarboxylate, in a solvent, for example, acetonitrile,
tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate
or mixture thereof. The quenching of desmethylation reaction can be carried out in the presence
of a quenching agent, for example, sodium bisulphite, potassium carbonate, sodium acetate,
sodium carbonate or mixture thereof.
The alkylation of a compound of Formula XX with a reagent of Formula R3X to give a
compound of Formula VIII can be carried out in a solvent, for example, dimethylformamide,
acetonitrile or tetrahydrofuran, in an inorganic or organic base, for example, sodium hydrogen
carbonate, potassium carbonate, sodium acetate, sodium thiosulfate, sodium hydride, pyridine,
triethylamine or diisopropyl ethyl amine. The alkylation of a compound of Formula XX can also
be carried out with a reagent of Formula R3CHO or R32 O with a reducing agent, for example,
sodium cyanoborohydride, sodium borohydride or sodium triacetoxyborohydride in the presence
of an organic acid, for example, acetic acid or dichloroacetic acid in a solvent, for example,
methanol, ethanol, propanol or isopropanol.
The reaction of a compound of Formula VIII to give a compound IX can be carried out in
a solvent, for example, dichloromethane, dichloroethane, acetone, ethyl acetate or
tetrahydrofuran, in the presence of an inorganic or organic base, for example, sodium bicarbonate,
potassium carbonate, triethylamine, pyridine, tributylamine or 4-N-dimethylaminopyridine with
an activating agent, for example, dicyclohexylcarbodiimide or l-ethyl-3- (3-
dimethylaminopropyl) carbodiimide hydrochloride.
The reaction of a compound of Formula IX with N, N'-carbonyl diimidazole to give a
compound of Formula X can be carried out in a solvent, for example, dimethylformamide,
tetrahydrofuran or mixture thereof. The reaction of a compound of Formula IX can be carried out
in the presence of an inorganic base, for example, sodium hydrogen carbonate, potassium
carbonate or sodium hydride.
The reaction of a compound of Formula X with a compound of Formula R-W-NH2 to give
a compound of Formula XI can be carried out in a solvent, for example, acetonitrile, water,
dimethylformamide or mixture thereof.
The deprotection of a compound of Formula XI to give a compound of Formula XII can
be carried out in an alcohol, for example, methanol, ethanol, propanol or isopropanol.
The compound of Formula XII can further be converted into its salt by following a
conventional method, for example those known in the prior art.
In the above schemes, where the specific bases, activating agents, solvents, etc., are
mentioned, it is to be understood that bases, activating agents, solvents, etc., known to those
skilled in the art may be used. Similarly, the reaction temperature and duration may be adjusted
according to the desired needs. The compounds provided, or their intermediates can be converted
to epimers during the course of reaction and such epimers are also encompassed within the scope
of this invention.
The compounds (No.l- 237) disclosed herein possess antibacterial activity against Gram-positive,
Gram-negative and anaerobic bacteria. They are useful as antibacterial agents for the treatment of
bacterial infections in human and animal.
In another aspect, there are provided pharmaceutical compositions, which may be
administered to an animal for treatment orally, topically, rectally, internasally, or by a parenteral
route. The pharmaceutical compositions of the compounds provided comprise a pharmaceutically
effective amount of such compound, formulated together with one or more pharmaceutically
acceptable carriers.
Solid form preparation for oral administration includes capsules, tablet, pills, powder,
granules, cachets and suppositories. For solid form preparation, the active compound is mixed
with at least one inert, pharmaceutically acceptable excipients or carrier, for example, sodium
citrate, dicalcium phosphate and/or a filler or extenders, for example, starches, lactose, sucrose,
glucose, mannitol and silicic acid; binders, for example, carboxymethylcellulose, alginates,
gelatins, polyvinylpyrrolidinone, sucrose, and acacia; disintegrating agents, for example, agaragar,
calcium carbonate, potato starch, alginic acid, certain silicates and sodium carbonate;
absorption accelerators, for example, quaternary ammonium compounds; wetting agents, for
example, cetyl alcohol, and glycerol mono stearate; adsorbants, for example, Kaolin; lubricants,
for example, talc, calcium stearate, magnesium stearate, solid polyethyleneglycol, sodium lauryl
sulphate and mixtures thereof. In the case of capsules, tablets, pills, the dosage form may also
comprise bufferring agents.
The solid preparation of tablets, capsules, pills and granules can be prepared with coating
and shells, for example, enteric coating and other coatings well known in the pharmaceutical
formulating art.
Liquid form preparations for oral administration includes pharmaceutically acceptable
emulsions, solutions, suspensions, syrups and elixirs. For liquid form preparations, the active
compound is mixed with water or other solvent, solubilizing agents and emulsifiers, for example,
ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate,
propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, for example, (cottonseed,
groundnut, corn, germ, olive, castor and sesame oil), glycerol, and fatty acid esters of sorbitan and
mixture thereof. Besides inert diluents, the oral composition can also include adjuants, for
example, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavouring
agents and perfuming agents.
Injectable preparations, for example, sterile injections, aqueous suspensions may be
formulated according to the art using suitable dispersing or wetting and suspending agents.
Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution
and isotonic sodium chloride.
Dosage forms for tropical or transdermal administration of a compound of the present
invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or
patches. The active compound is admixed under sterile condition with a pharmaceutically
acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic
formulations, eardrops, eye ointments, powder and solution are also contemplated as being within
the scope of this invention.
The pharmaceutical preparation can be presented in unit dosage form. In such forms, the
preparation is subdivided into unit doses containing appropriate quantities of the active
component. The unit dosage form can be a packaged preparation, the package containing discrete
capsules, powders, in vials or ampoules, and ointments capsule, sachet, tablet, gel, cream itself or
it can be the appropriate number of any of these packaged forms. The quantity of active
compound in unit dose of preparation may be varied or adjusted from less than 1 mg to several
grams according to the particular application and potency of the active ingredient.
In therapeutic use as agents for treating bacterial infections, the compounds utilizing in the
pharmaceutical method of this invention can be administered at an initial dosage of about 3 mg to
about 40 mg per kilogram daily. The dosages, however, may be varied depending upon the
requirements of the patients and the compound being employed. Determination of the proper
dosage for a particular situation may be within the smaller dosages, which are less than the
optimum dose. Small increments until the optimum effect under the daily dosage may be divided
and administered in portion during the day if desired.
Examples set forth below demonstrate the general synthetic procedure for the preparation
of representative compounds. The examples are provided to illustrate particular aspects of the
disclosure and do not constrain the scope of the present invention as defined by the claims.
EXAMPLES
Scheme I
Example 1: Preparation of compound of Formula III
To a solution of hydrochloric acid was added clarithromycin of Formula II (25g, 33.4
mmol). The reaction mixture was neutralized with solid sodium bicarbonate and the aqueous
layer was extracted with ethyl acetate. The organic layer was washed with water, brine, and dried
over anhydrous sodium sulphate. The solvent was removed under reduced pressure to give the
desired product. The crude product was crystallized by using ethyl acetate- hexane mixture.
Example 2: Preparation of compound of Formula IV
To a solution of compound of Formula III (lequiv) in dry dichloromethane was added
benzoic anhydride (2.5 equiv), triethylamine (6 equiv) and stirred at ambient temperature. The
reaction was quenched by aqueous sodium bicarbonate solution. The aqueous layer was extracted
with dichloromethane, washed successively with water and brine, and dried over anhydrous
sodium sulphate, and then the solvent was removed under reduced pressure to give a crude
product. The crude product was crystallized by using ethyl acetate - hexane mixture.
Example 3: Preparation of compound of Formula V
To a solution of compound of Formula IV (1 equiv) in dry acetonitrile: dichloromethane
(2:1) was added N-iodosuccinimide (2 equiv). The reaction mixture was stirred with
sodiumbisulphite solution followed by stirring with sodium carbonate solution. Dichloromethane
was evaporated under reduced pressure. The aqueous matter was extracted with ethyl acetate,
washed successively with water and brine, and dried over anhydrous sodium sulphate, and then
the solvent was removed under reduced pressure to yield a crude product. The crude product was
purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using
10-20% acetone in hexane.
Example 4: Preparation of compound of Formula VI
To a solution of compound of Formula V (1 equiv) in acetonitrile was added solid sodium
bicarbonate (5 equiv) and a reagent of Formula R3X (6 equiv) under argon at ambient
temperature. The reaction mixture was diluted with ethyl acetate and washed with water followed
by brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield
a crude product. The crude product was purified by silica gel column chromatography
(thoroughly neutralized with triethylamine) using 10-20% acetone in hexane.
Example 5: Preparation of compound of Formula VII
To a solution of compound of Formula VI (1 equiv) in dichloromethane was added
triphosgene (1.5 equiv) with stirring. Then to it was added pyridine (15 equiv) slowly. After
complete addition, reaction mixture was stirred under inert atmosphere. The reaction was
quenched by addition of water. The reaction mixture was diluted with dichloromethane and
washed with water and brine, dried over anhydrous sodium sulphate, and concentrated under
reduced pressure to afford the desired product.
Example 6: Preparation of compound of Formula VIII
To a solution of a compound of Formula VII (1 equiv) in dimethylformamide was added
tetramethyl guanidine (2.2 equiv) and reaction mixture was heated. The reaction mixture was
cooled to an ambient temperature and water was added and extracted with ethyl acetate. Organic
layer was washed with water followed by brine, dried over anhydrous sodium sulphate and
concentrated under reduced pressure to obtain the desired product.
Example 7: Preparation of compound of Formula IX
To a solution of compound of Formula VIII (1 equiv) in dichloromethane was added a
reagent of Formula R5YCOOH (2.5 equiv), 4-N-dimethylaminopyridine (2.5 equiv) and N, N'-
dicyclohexylcarbodiimide (2.5 equiv) was added. Pyridine (4 equiv) was added to it. The whole
reaction mixture was stirred and then filtered through a celite bed. The filtrate was washed with
water and brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure
to afford the desired product. The crude product was purified by silica gel column
chromatography (thoroughly neutralized with triethylamine) using 10-20% acetone in hexane.
Example 8: Preparation of compound of Formula X
To a solution of compound of Formula IX (1 equiv) in
dimethylformamide:tetrahydrofuran (3:2) was added N,N'-carbonyldiimidazole (3 equiv),
followed by sodium hydride in portions. The reaction was quenched by addition of ice cold water
and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried
over anhydrous sodium sulphate and concentrated under reduced pressure to afford the desired
product.
Example 9: Preparation of compound of Formula XI
A compound of Formula X (1 equiv) and a compound of Formula R-W-NH2 (3 equiv)
were taken in 10% water in acetonitrile and heated. The reaction mixture was cooled to an
ambient temperature; acetonitrile was evaporated under reduced pressure. The resulting residue
was taken in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulphate,
and concentrated under reduced pressure. The resulting residue was purified by column
chromatography using 25-30% acetone in hexane to afford the desired product.
Example 10: Preparation of compound of Formula XII
A solution of compound of Formula XI (560mg, 0.6mmol) in methanol was refluxed. The
reaction mixture was cooled to an ambient temperature and methanol was evaporated under
reduced pressure. Purification of the solid mass was done over silica gel (thoroughly neutralized
triethylamine) using 30-35% acetone in hexane or 2-8% methanol in dichloromethane.
Scheme II
Example 11: Preparation of compound of Formula XIII
A solution of compound of Formula X (1 mmol) in dry dimethylformamide and hydrazine
hydrate (2.0 mmol) was added to it. The reaction mixture was stirred at room temperature for
about 1.5 hour. It was quenched with water and extracted in ethyl acetate. The solvent was
removed under reduced pressure and the residue was redissolved in tetrahyrofuran. Potassium-fbutoxide
(2.354 mmol) was added to it at 0°C and the reaction mixture was stirred for about 2 hr.
It was extracted with ethyl acetate, washed with water and brine, and dried over sodium sulphate
to give the desired isomer.
Example 12: Preparation of compound of Formula XIV
A solution of compound of Formula XIII in methanol was heated at 70°C for about 20
hours. The solvent was removed and the residue was purified over silica gel column to afford the
product.
Example 13: Preparation of compound of Formula XV
A compound of Formula XIV (1.0 mmol) and heterocyclyl alkyl aldehyde (5.0 mmol,
(prepared by following the procedure given in WO 00/17218), a compound of Formula
R(CH2)mCHO (5.0 mmol) were dissolved in methanol. Glacial acetic acid (5.0 mmol) was
added. The resulting mixture was stirred at room temperature for about 1-2 hour. Sodium
cyanoborohydride (5.0 mmol) and glacial acetic and (5.0 mmol) were added to it. The mixture
was stirred at room temperature for about 12 hours, solvent was removed, the reaction mixture
was extacted with dichloromethane, washed with water, brine and dried over sodium sulphate.
The solvent was removed under reduced pressure and the residue was purified over silica gel
column to afford the product.
Example 14: Preparation of compound of Formula XVI
A compound of Formula XIV (0.298 mmol) and a compound of Formula
R8ONH2. hydrochloride (4.471 mmol) in ethanol were stirred at 80°C for about 48 hours. The
solvent was evaporated. The reaction mixture was redissolved into ethyl acetate, washed with
water and brine, dried over sodium sulphate and solvent was evaporated get the product.
Example 15: Preparation of compound of Formula XVII
A compound of Formula XVI (1.0 mmol) and heterocyclyl alkyl aldehyde, a compound of
Formula R(CH2)mCHO (5.0 mmol) (prepared by following the procedure given in WO 00/17218),
were dissolved in methanol. Glacial acetic acid (5.0 mmol) was added. The resulting mixture
was stirred at room temperature for about 1-2 hour. Sodium cyanoborohydride (5.0 mmol) and
glacial acetic and (5.0 mmol) were added to it. The mixture was stirred at room temperature for
about 12 hours, solvent was removed, the reaction mixture was extracted with dichloromethane,
washed with water, brine and dried over sodium sulphate. The solvent was removed under
reduced pressure and the residue was purified over silica gel column to afford the product.
Scheme III
Example 16: Preparation of compound of Formula XVIII
To a solution of compound of Formula IV (1 equiv) in dichloromethane at 0°C was added
triphosgene (1.5 equiv) with stirring. Then to it was added pyridine (15 equiv) slowly. After
complete addition, reaction mixture was stirred for about 3h at 0-5°C. the reaction was quenched
by drop wise addition of water, was diluted with dichloromethane and washed with water and
brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford
the desired product.
Example 17: Preparation of compound of Formula XIX
To a solution of a compound of formula XVIII (1 equiv) in dimethylformamide was added
tetramethyl guanidine (2.2 equiv) and reaction mixture was heated at 90°C for about 8 hours. The
reaction mixture was cooled to an ambient temperature and water was added and extracted with
ethyl acetate, the organic layer was washed with water followed by brine, dried over anhydrous
sodium sulphate and concentrated under reduced pressure to obtain the desired product.
Example 18: Preparation of compound of Formula XX
To a solution of compound of Formula VI (1 equiv) in dry acetonitrile: dichloromethane
(2:1) cooled to 0°C, was added N-iodosuccinimide (2 equiv). The reaction mixture was stirred
with sodium bisulphite solution followed by stirring with sodium carbonate solution.
Dichloromethane was evaporated under reduced pressure. The aqueous residue was extracted
with ethyl acetate, washed successively with water, brine, and dried over anhydrous sodium
sulphate and then the solvent was removed under reduced pressure to obtain the crude product,
which was purified by silica gel column chromatography (thoroughly neutralized with triethyl
amine) using 10-20% acetone in hexane to give the product.
Example 19: Preparation of compound of Formula VIII
To a solution of a compound of formula VII (1 equiv) in dimethylformamide was added
tetramethyl guanidine (2.2 equiv) and reaction mixture was heated. The reaction mixture was
cooled to an ambient temperature and water was added and extracted with ethyl acetate. The
organic layer was washed with water followed by brine, dried over anhydrous sodium sulphate
and concentrated under reduced pressure to obtain the desired product.
Example 20: Preparation of compound of Formula IX
To a solution of compound of Formula VIII (1 equiv) in dichloromethane was added a
reagent of Formula R5YCOOH (2.5 equiv), 4-N-dimethylaminopyridine (2.5 equiv) and N, N'-
dicyclohexylcarbodiimide (2.5 equiv) was added. Pyridine (4 equiv) was added to it. The whole
reaction mixture was stirred and then filtered through celite bed. The filtrate was washed with
water, brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to
afford the desired product. The crude product was purified by silica gel column chromatography
(thoroughly neutralized with triethylamine) using 10-20% acetone in hexane.
Example 21: Preparation of compound of Formula X
To a solution of compound of Formula IX (1 equiv) in
dimethylformamide:tetrahydrofuran (3:2) was added N,N'-carbonyldiimidazole (3 equiv),
followed by sodium hydride in portions Reaction was quenched by addition of ice cold water
and extracted with ethyl acetate. The ethyl acetate layer was washed with water, brine dried over
anhydrous sodium sulphate and concentrated under reduced pressure to afford the desired product.
Example 22: Preparation of compound of Formula XI
A compound of Formula X (1 equiv) and a compound of Formula R-W-NH2 (3 equiv)
were taken in 10% water in acetonitrile and heated. The reaction mixture was cooled to an
ambient temperature; acetonitrile was evaporated under reduced pressure. The resulting residue
was taken in ethyl acetate, washed with water, brine, dried over anhydrous sodium sulphate and
concentrated under reduced pressure. The resulting residue was purified by column
chromatography using 25-30% acetone in hexane to afford the desired product.
Example 23: Preparation of compound of Formula XII
A solution of compound of Formula XI (560mg, 0.6mmol) in methanol was refluxed. The
reaction mixture was cooled to an ambient temperature and methanol was evaporated under
reduced pressure. Purification of the solid mass was done over silica gel (thoroughly neutralized
triethylamine) using 30-35% acetone in hexane or 2-8% methanol in dichloromethane.
The following illustrative compounds were prepared by following the above general
procedures.
Compound No. 1: ll,12-Dideoxy-3-0-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11 - [oxycarbonyl-((3 -imidazol-1 -yl)-propyl)-
imino]erythromycin A, MS (+ ion mode): m/z 900.5 [M+l],
Compound No. 2: 1 l,12-Dideoxy-3-0-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 914.6 [M+l],
Compound No. 3: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((3-imidazol-l-yl)-propyl)-
iminojerythromycin A, MS (+ ion mode): m/z 912.6 [M+l],
Compound No. 4: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(3H)-imidazo(4,5-b)-pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 966.6 [M+l],
Compound No. 5: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 965.5 [M+l],
Compound No. 6: ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 976.6 [M+l],
Compound No. 7: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-(prop-2-en-yl)-imino]erythromycin A, MS
(+ ion mode): m/z 844.7 [M+l],
Compound No. 8: ll,12-Dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-N-desmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-imidazol-l-yl)-butyl)-imino]erythromycinA, MS
(+ ion mode): m/z 870.7 [M+l],
Compound No. 9: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-
3'-N-ethyl)-6-0-methyl-12,l l-[oxycarbonyl-((4-imidazol-l-yl)-butyl)-imino]erythromycin A, MS
(+ion mode): m/z 870.6 [M+l],
Compound No. 10: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 920.7 [M+l],
Compound No. 11: ll,12-Dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzimidazol-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 920.5 [M+l],
Compound No. 12: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H)-imidazol-[4,5-b]pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 921.6 [M+l],
Compound No. 13: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 H)-imidazol-[4,5-b]pyridin-1 -yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 921.9 [M+l],
Compound No. 14: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-pyrrolo-[2,3-b]pyridin-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 920.8 [M+l],
Compound No. 15: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-indol-l-yl)-butyl)-imino]erythromycin
A, MS (+ ion mode): m/z 919.6 [M+l],
Compound No. 16: ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-0-methyl-12,11 -[oxycarbonyl-((4(4-phenyl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 946.8 [M+l],
Compound No. 17: ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(lH)-imidazol-[4,5-b]pyridin-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 921.8 [M+l],
Compound No. 18: ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-indol-l-yl)-butyl)-imino]erythromycin
A, MS (+ ion mode): m/z 920.8 [M+l],
Compound No. 19: ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzimidazol-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 919.8 [M+l],
Compound No. 20: 1 l,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11- [oxycarbonyl-((4-pyrrolo- [2,3 -b]pyridin-1 -yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 920.8 [M+l],
22
Compound No. 21: ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H)-imidazol-[4,5-b]pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 921.9 [M+l],
Compound No. 22: ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11- [oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 946.9 [M+l],
Compound No. 23: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((N1-methyl-N1-pyridin-4-ylmethyl)-2-
aminoethyl)-imino]erythromycin A, MS (+ ion mode): m/z 896.49 [M+l],
Compound No. 24: ll,12-dideoxy-3-0-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((N1-methyl-N1-pyridin-2-ylmethyl)-2-
aminoethyl)-imino]erythroniycin A, MS (+ ion mode): m/z 896.42 [M+l],
Compound No. 25: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((N1-methyl-N1-pyridin-3-ylmethyl)-2-
aminoetnyl)-imino]erythromycin A, MS (+ ion mode): m/z 896.42 [M+l],
Compound No. 26: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((N1-methyl-N1-quinolin-4-ylmethyl)-2-
aminoethyl)-imino]erythromycin A, MS (+ ion mode): m/z 946.48 [M+l],
Compound No. 27: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 932.89 [M+l],
Compound No. 28: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(lH)imidazo[4,5-b]pyridin-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 933.94 [M+l],
Compound No. 29: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 933.94 [M+l],
Compound No. 30: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(2-methyl)-benzoimidazo-1 -yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 934.79 [M+l],
Compound No. 31: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(4-phenyl)-imidazol-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 958.98 [M+l],
Compound No. 32: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11-[oxycarbonyl-((4-pyridin-2-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 881.78 [M+l],
Compound No. 33: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-pyridin-4-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 881.85 [M+l],
Compound No. 34: ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-((4-benzoimidazo-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 932.8 [M+l],
Compound No. 35: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-((4-(4-pyridin-3 -yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 959.83 [M+l],
23
Compound No. 36: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-benzotriazol-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 933.94 [M+l],
Compound No. 37: ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 947.96 [M+l],
Compound No. 38: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 947.96 [M+l],
Compound No. 39: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 947.96 [M+l],
Compound No. 40: ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 920.96 [M+l],
Compound No. 41: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3'-N-propargyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 931.94 [M+l],
Compound No. 42: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 933.99 [M+l],
Compound No. 43: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-
3 '-N-allyl)-6-O-methyl-12,11- [oxycarbonyl-((9-(4-amino-butyl)9H-purin-6-yl)-
imino]erythromycin A, MS (+ ion mode): m/z 949.83 [M+l],
Compound No. 44: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzoimidazo-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 933.01 [M+l],
Compound No. 45: ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11- [oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 946.81 [M+l],
Compound No. 46: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 958.82 [M+l],
Compound No. 47: ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbQnyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 921.83 [M+l],
Compound No. 48: ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 921.59 [M+l],
Compound No. 49: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 959.92 [M+l],
Compound No. 50: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 932.66 [M+l],
Compound No. 51: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-propargyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-benzoimidazo-l-yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 930.64 [M+l],
Compound No. 52: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-
iminojerythromycin A, MS (+ ion mode): m/z 921.65 [M+l],
Compound No. 53: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(lH)imidazo[4,5-b]pyridin-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 933.63 [M+l],
Compound No. 54: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 933.7[M+1],
Compound No. 55: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-m ethyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 921.71 [M+l],
Compound No. 56: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-propargyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-l-yl)-
butyl)-imino]erythromycin A, MS (+ ion mode): m/z 930.91 [M+l],
Compound No. 57: 1 l,12-dideoxy-3-0-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 948.42 [M+l],
Compound No. 58: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A, MS (+ ion mode): m/z 964.33 [M+l],
Compound No. 59: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((9-(3-hydrazino-propyl)-9-H-purin-6-yl-
amino)]erythromycin A, MS (+ ion mode): m/z 950.39 [M+l],
Compound No. 60: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 931.44 [M+l],
Compound No. 61: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 943.40 [M+l],
Compound No. 62: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(quinolin-4-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 943.44 [M+l],
Compound No. 63: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 -methyl-1 H-pyrrolo[2,3-b]pyridin-
3-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 946.86 [M+l],
Compound No. 64: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-amino-9H-purin-9-yl butylimino)]
erythromycin A, MS (+ ion mode): m/z 949.62 [M+l],
Compound No. 65: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-amino-9H-purin-9-yl butylimino)]
erythromycin A, MS (+ ion mode): m/z 937.62 [M+l],
Compound No. 66: ll,12-dideoxy-3-0-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 943.62 [M+l],
Compound No. 67: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 931.59 [M+l],
Compound No. 68: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-imidazol-1 -yl)-
butyl)-imino)] erythromycin A, MS (+ ion mode): m/z 964.59 [M+l],
Compound No. 69: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-((4-(4-thiophen-3 -yl-1 H-imidazol-1 -yl)-
butyl)-imino)]erythromycin A hydrochloride salt,
Compound No. 70: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl
butylimino)]erythromycin A, MS (+ ion mode): m/z 977.65 [M+l],
Compound No. 71: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(6-pyrrol-1 -yl-purin-9-yl)-butyl)-
imino)] erythromycin A, MS (+ ion mode): m/z 999.64 [M+l],
Compound No. 72: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-diethylamino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 1005.62 [M+l],
Compound No. 73: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-ethylamino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 978.72 [M+l],
Compound No. 74: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 965.43 [M+l],
Compound No. 75: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl
butylimino)]erythromycin A, MS (+ ion mode): m/z 977.45 [M+l],
Compound No. 76: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-0-methyl-12,11 -[oxycarbonyl-(4-(6-methylamino-9H-purin-9-yl
butylimino)]erythromycin A, MS (+ ion mode): m/z 963.33 [M+l],
Compound No. 77: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-methylamino-9H-purin-9-yl
butylimino)]erythromycin A, MS (+ ion mode): m/z 963.39 [M+l],
Compound No. 78: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-2-fluoroethyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(3H-imidazo[4,5-
b]pyridin-3-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 939.30 [M+l],
Compound No. 79: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-2-fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-b]pyridin-lyl)-
butyl)- imino)]erythromycin A, MS (+ ion mode): m/z 939.37 [M+l],
Compound No. 80: ll,12-dideoxy-3-0-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-2-fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(6-amino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 955.30 [M+l],
Compound No. 81: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-2-fluoroethyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-amino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 955.39 [M+l],
Compound No. 82: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-2-fluoroethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 H-imidazo [4,5 -b]pyridin-1 -
yl)-butyl)-imino)] erythromycin A, MS (+ ion mode): m/z 939.38 [M+l],
Compound No. 83: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-2-fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-
yl)-butyl)-imino)] erythromycin A, MS (+ ion mode): m/z 939.38 [M+l],
Compound No. 84: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 965.39 [M+l],
Compound No. 85: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11- [oxycarbonyl-(4-(6-methylamino-9H-purin-9-yl
butylimino)] erythromycin A, MS (+ ion mode): m/z 965.37 [M+l],
Compound No. 86: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-((4-(purin-9-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 934.35 [M+l],
Compound No. 87: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(purin-9-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 934.34 [M+l],
Compound No. 88: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(lH-imidazo[4,5-c]pyridin-l-yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 933.37 [M+l],
Compound No. 89: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-c]pyridin-3-yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 933.35 [M+l],
Compound No. 90: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-imidazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 964.40 [M+l],
Compound No. 91: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(lH-imidazol[4,5-c]pyridin-l-yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 933.35 [M+l],
Compound No. 92: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H-imidazol[4,5-c]pyridin-3-yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 933.44 [M+l],
Compound No. 93: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 943.39 [M+l],
Compound No. 94: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-oxazol-5-yl-1 H-imidazol-1 yl)-
butyl)-butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 949.62 [M+l],
Compound No. 95: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-imidazol-1 yl)-
butyl)-imino)] erythromycin A, MS (+ ion mode): m/z 948.67 [M+l],
Compound No. 96: ll,12-dideoxy-3-0-decladinosyl-3-O-(3-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-imidazol-1 yl)-
butyl)-imino)] erythromycin A hydrochloride salt,
Compound No. 97: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-imidazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 948.67 [M+l],
Compound No. 98: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-imidazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 948.53 [M+l],
Compound No. 99: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-pyrazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 964.56 [M+l],
Compound No. 100: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-pyrazol-1 yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 948.73 [M+l],
Compound No. 101: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(4-furan-2-yl-lH-pyrazol-lyl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 948.57 [M+l],
Compound No. 102: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-pyrazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 964.70 [M+l],
Compound No. 103: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(6-amino-9H-purin-9-yl
butylimino)]erythromycin A, MS (+ ion mode): m/z 937.50 [M+l],
Compound No, 104: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 931.50 [M+l],
Compound No. 105: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 943.50 [M+l],
Compound No. 106: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-([l,4']bipyrazolyl-l'-yl)-butyl)-
imino)] erythromycin A, MS (+ ion mode): m/z 948.77 [M+l],
Compound No. 107: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-((4(4-thiazol-2-yl-1 H-imidazol-1 -yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 965.68 [M+l],
Compound No. 108: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiazol-2-yl-1 H-imidazol-1 -yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 965.68 [M+l],
Compound No. 109: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-pyrazol-1 yl)-
imino)]erythromycin A, MS (+ ion mode): m/z 948.73 [M+l],
Compound No. 110: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-pyrazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 964.77 [M+l],
28
Compound No. I l l : ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-pyrazol-1 yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 964.81 [M+l],
Compound No. 112: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-pyrazol-1 yl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 948.83 [M+l],
Compound No. 113: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((3-(4-pyridin-3-yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 960.44 [M+l],
Compound No. 114: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-(3 -benzoimidazol-1 -yl)-propyl)-hydrazo)]
erythromycin A, MS (+ ion mode): m/z 933.41 [M+l],
Compound No. 115: (RorS) ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-((3 -(4-pyridin-3 -yl-1 H-im idazol-1 yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 960.63 [M+l],
Compound No. 116: (S or R) ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-((3 -(4-pyridin-3 -yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 960.64 [M+l],
Compound No. 117: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11 - [oxycarbonyl-(3 -(4-pyridin-3 -yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 948.72 [M+l],
Compound No. 118: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-pyridin-3-yl-1 H-imidazol-1 yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 960.24 [M+l],
Compound No. 119: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-pyridin-3-yl-1 H-imidazol-1 yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 948.25 [M+l],
Compound No. 120: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11- [oxycarbonyl-(3 -(3 -(6-amino-9H-purin-9-y 1-
propyl)hydrazo)]erythromycin A, MS (+ ion mode): m/z 938.36 [M+l],
Compound No. 121: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiophen-3-yl)-1 H-imidazol-1 yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 965.39 [M+l],
Compound No. 122: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-isoquinolin-5-yl)-propyl)-
hydrazo)]erythromycin A, MS (+ ion mode): m/z 944.54 [M+l],
Compound No. 123: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-purin-9-yl)-propyl)-
hydrazo)]erythromycin A, MS (+ ion mode): m/z 935.49 [M+l],
Compound No. 124: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((3-purin-9-yl)-propyl)-
hydrazo)]erythromycin A, MS (+ ion mode): m/z 935.49 [M+l],
Compound No. 125: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(furan-2-yl)-1 H-imidazol-1 -
yl)propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 949.54 [M+l],
Compound No. 126: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-(3 -(3 -(6-amino-9H-purin-9-ylpropyl)
hydrazo)] erythromycin A, MS (+ ion mode): m/z 950.70 [M+l],
Compound No. 127: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(furan-3-yl)-1 H-imidazol-1 -
yl)propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 949.62 [M+l],
Compound No. 128: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-(4-(furan-3-yl)-lH-imidazol-lyl)
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 949.66 [M+l],
Compound No. 129: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-(3-(6-amino-9H-purin-9-ylpropyl)
hydrazo)]erythromycin A, MS (+ ion mode): m/z 950.67 [M+l],
Compound No. 130: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-(4-(thiophen-2-yl-lH-imidazol-l-yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 965.57 [M+l],
Compound No. 131: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiophen-2-yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 965.63 [M+l],
Compound No. 132: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiophen-3-yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 965.58 [M+l],
Compound No. 133: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-(imidazo[4,5-b]pyridin-l-yl)-propyl)-
hydrazo)] erythromycin A, MS (+ ion mode): m/z 934.65 [M+l],
Compound No. 134: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-(imidazo[4,5-b]pyridin-3-yl)-propyl)-
hydrazo)] erythromycin A, MS (+ ion mode): m/z 934.79 [M+l],
Compound No. 135: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiazol-2-yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 966.66 [M+l],
Compound No. 136: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiazol-2-yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)]erythromycin A, MS (+ ion mode): m/z 966.66 [M+l],
Compound No. 137: (Ror S) ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-hydrazo]erythromycin A, MS (+ ion
mode): m/z 775.52 [M+l],
Compound No. 138: (S orR) ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-hydrazo]erythromycin A, MS (+ ion
mode): m/z 775.52 [M+l],
Compound No. 139: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-ethyl)-6-O-methyl-12,l l-[oxycarbonyl-hydrazo)]erythromycin A, MS (+ ion
mode): m/z 763.59 [M+l],
Compound No. 140: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-((3 -(4-pyridin-3 -yl-1 H-imidazol-1 -yl)-
propyl)-hydrazo)]erythromycin A, 9-(O-methyl)oxime,MS (+ ion mode): m/z 989.68 [M+l],
Compound No. 141: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-hydrazo]erythromycin A, 9-(Omethyl)
oxime, MS (+ ion mode): m/z 804.58 [M+l],
Compound No. 142: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-(6-fluoro-pyridin-3-yl)-1Himidazol-
l-yl)-butyl)-imino)] erythromycin A, MS (+ ion mode): m/z 977.63 [M+l],
Compound No. 143: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-(6-fluoro-pyridin-3-yl)-1Himidazol-
l-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 977.40 [M+l],
Compound No. 144: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-((4-(4-( 1 H-imidazol-1 -yl)phenyl)-butyl)-
imino)]erythromycin A, MS (+ ion mode): m/z 958.64 [M+l],
Compound No. 145: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(5-(3-aminophenyl)-thiazol-2-yl)-
butyl)-imino)]erythromycin A, MS (+ ion mode): m/z 960.50 [M+l],
Compound No. 146: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(2-amino-pyrimidin)-5-yl)-imidazoll-
yl)-butylimino)] erythromycin A, MS (+ ion mode): m/z 975.5 [M+l],
Compound No. 147: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(2-aminopyridin-4-yl)-imidazol-1
yl)-butylimino)] erythromycin A, MS (+ ion mode): m/z 974.6 [M+l],
Compound No. 148: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(6-aminopyridin-3-yl)-iniidazol-lyl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 974.6 [M+l],
Compound No. 149: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(6-(dimethylamino)-9H-purin-9-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 965.39 [M+l],
Compound No. 150: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-(3 -(5 -pheny 1-tetrazol-1 -yl)propylimino)]
erythromycin A, MS (+ ion mode): m/z 990.4 [M+l],
Compound No. 151: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-pyridin-3-yl-pyrazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 975.64 [M+l],
Compound No. 152: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(2-methyl-2//-tetrazol-5-
yl)phenyl)butylimino)] erythromycin A, MS (+ ion mode): m/z 974.51 [M+l],
Compound No. 153: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-l 2,11 -[oxycarbonyl-(4-(4-(3-thienyl)-imidazol-1 -
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 964.56 [M+l],
Compound No. 154: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(5-methyl-[l,3,4]-oxadiazol-2-
yl)phenyl)butylimino)] erythromycin A, MS (+ ion mode): m/z 974.47 [M+l],
Compound No. 155: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-([2,3']-bithiophenyl-5-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 980.50 [M+l],
Compound No. 156: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-([2,3']-bithiophenyl5-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 980.60 [M+l],
Compound No. 157: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-[3,3']-bithiophenyl-5-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 980.40 [M+l],
Compound No. 158: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-[3,3']-bithiophenyl-5-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 980.40 [M+l],
Compound No. 159: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(5-pyridin-3-yl)-tetrazol-2-
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 961.50 [M+l],
Compound No. 160: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(5-(furan-2-yl)-imidazol-1 -
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 948.60 [M+l],
Compound No. 161: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-methylpropanoyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbony!4-(4-(4-(furan-2-yl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 899.63 [M+l],
Compound No. 162: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(4-methoxy-phenyl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 988.5 [M+l],
Compound No. 163: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(4-methoxy-phenyl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 988.50 [M+l],
Compound No. 164: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(2-methoxy-phenyl)-imidazoll-
yl)-butylimino)] erythromycin A, MS (+ ion mode): m/z 988.50 [M+l],
Compound No. 165: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(2-methoxy-phenyl)-1 //-imidazol-
yl)-butylimino)] erythromycin A, MS (+ ion mode): m/z 988.50 [M+l],
Compound No. 166: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-phenyl-thiophen-2-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 974.60 [M+l],
Compound No. 167: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-phenyl-thiophen-2-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 974.60 [M+l],
Compound No. 168: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-furan-2-yl-thiophen-2-
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 964.40 [M+l],
Compound No. 169: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-furan-2-yl-thiophen-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 964.40 [M+l],
Compound No. 170: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(4-methoxyphenyl)-tetrazol-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 990.50 [M+l],
Compound No. 171: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(4-methoxyphenyl)-tetrazol-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 990.50 [M+l],
Compound No. 172: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-phenyl-tetrazol-2-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 960.50 [M+l],
Compound No. 173: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-4-yl-tetrazol-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 961.50 [M+l],
Compound No. 174: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(5-pyridin-4-yl-tetrazol-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 961.50 [M+l],
Compound No. 175: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-phenyl-tetrazol-2-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 960.50 [M+l],
Compound No. 176: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(6-chloropyridin-3-yl)-imidazol-lyl)
butylimino)] erythromycin A, MS (+ ion mode): m/z 993.50 [M+l],
Compound No. 177: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-3 ((3 -(4-(imidazol-1 -yl)-pyrazol-1 -yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 949.50 [M+l],
Compound No. 178: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(3-(4-pyrazol-1 -yl]-imidazol-1 -yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 950.40 [M+l],
Compound No. 179: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(3-aminophenyl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 973.40 [M+l],
Compound No. 180: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
S'-N-allyO-e-O-methyl-njl-foxycarbonyl-S-^-CCl^-bipyrazol-l'-yO-propyl)-
hydrazo)] erythromycin A, MS (+ ion mode): m/z 949.70 [M+l],
Compound No. 181: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(3-aminophenyl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 937.70 [M+l],
Compound No. 182: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-pyrimidin-5-yl-imidazol-lyl)
butylimino)] erythromycin A, MS (+ ion mode): m/z 960.50 [M+l],
Compound No. 183: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-(3 -(3 -(4-pyrimidin-2-yl-imidazol-1 -y
propyl)-hydrazo] erythromycin A, MS (+ ion mode): m/z 961.50 [M+l],
Compound No. 184: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-(4-(4-pyrimidin-5-yl-imidazol-lyl)
butylimino)] erythromycin A, MS (+ ion mode): m/z 960.50 [M+l],
Compound No. 185: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-2-
yl]butylimino)] erythromycin A, MS (+ ion mode): m/z 950.60 [M+l],
Compound No. 186: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(5 -(thiophen-2-yl)-tetrazol-2-yl]>
butylimino)] erythromycin A, MS (+ ion mode): m/z 966.50 [M+l],
Compound No. 187: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-l-yl]-
butylimino)] erythromycin A, MS (+ ion mode): m/z 972.50 [M+l],
Compound No. 188: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-l-yl]-
butylimino)] erythromycin A, MS (+ ion mode): m/z 972.50 [M+l],
Compound No. 189: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-2-
yl]butylimino)] erythromycin A, MS (+ ion mode): m/z 950.60 [M+l],
Compound No. 190: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-3-yl-tetrazol-2-yl)-
butylimino)] erythromycinA, MS (+ ion mode): m/z 961.50 [M+l],
Compound No. 191: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-2-yl-tetrazol-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 961.40 [M+l],
Compound No. 192: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-2-yl-tetrazol-2-yl)-
butylimino)] erythromycinA, MS (+ ion mode): m/z 961.40 [M+l],
Compound No. 193: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-(4-(5-thiophen-2-yl-tetrazol-l-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 966.50 [M+l],
Compound No. 194: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-(4-(5 -thiophen-2-yl-tetrazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 966.50 [M+l],
Compound No. 195: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(thiophen-2-yl-tetrazol-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 966.50 [M+l],
Compound No. 196: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-( 1 H-benzimidazol-2-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 932.57 [M+l],
Compound No. 197: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(lH-imidazol[4,5-b]pyridin-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 934.00 [M+l],
Compound No. 198: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(lH-imidazol[4,5-b]pyridin-2-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 934.05 [M+l],
Compound No. 199: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-(4-(4-tetrazol-1 -yl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 950.58 [M+l],
Compound No. 200: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N,
desmethyl-3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-tetrazol-1 -yl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 950.52 [M+l],
Compound No. 201: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(lH-benzimidazol-2-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 932.70 [M+l],
Compound No. 202: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-({3-[4-(6-fluoro-pyridin-3-yl-imidazol-
1-yl] propyl}hydrazo] erythromycin A, MS (+ ion mode): m/z 978.6 [M+l],
Compound No. 203: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-({3-[4-(6-fluoro-pyridin-3-yl-imidazol-
1-yl] propyl}hydrazo] erythromycin A, MS (+ ion mode): m/z 978.48 [M+l],
Compound No, 204: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-methyl propanoyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-(4-(benzimidazol-1-yl)-butylimino)]
erythromycin A, MS (+ ion mode): m/z 883.62 [M+l],
Compound No. 205: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-methyl propanoyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(3-pyridyl)-imidazol-1 -yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 932.75 [M+l],
Compound No. 206: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-methyl propanoyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-imidazol[4,5-b]pyridin-l-yl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 884.45 [M+l],
Compound No. 207: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-methyl propanoyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-4-(6-amino-9H-purin-9-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 901.33 [M+l],
Compound No. 208: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-([ 1,4']-bipyrazol-1 '-yl)butylimino]
erythromycin A, MS (+ ion mode): m/z 948.56 [M+l],
Compound No. 209: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-[4-(pyrazol-1 -yl)-imidazol-1 -
yl)butylimino] erythromycin A, MS (+ ion mode): m/z 948.38 [M+l],
Compound No. 210: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-([l,4']-biimidazol-l'-yl) butylimino)]
erythromycin A, MS (+ ion mode): m/z 948.56 [M+l],
Compound No. 211: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-([l,4']-biimidazol-lI-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 949.06 [M+l],
Compound No. 212: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-methylpropanoyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(imidazo[4,5-/7]pyridin-3-
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 983.46 [M+l],
Compound No. 213: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-pyrazol-1 -yl)-imidazol-1 -
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 948.38 [M+l],
Compound No. 214: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(7//-imidazo[4,5-c]pyridin-2-
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 933.60 [M+l],
Compound No. 215: ll,12-dideoxy-3-O-decladmosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(7//-imidazo[4,5-c]pyridin-2-
yl)butylimino)] erythromycin A, MS (+ ion mode): m/z 933.50 [M+l],
Compound No. 216: 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-methylpropanoyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(6-fluoro-pyridin-3-yl)-imidazol-lyl)
butylimino)] erythromycin A, MS (+ion mode): m/z 928.5 [M+l],
Compound No. 217: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-phenyl-thiazol-2-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 975.6 [M+l],
Compound No. 218: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-(4-(4-phenyl-thiazol-2-yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 975.6 [M+l],
Compound No. 219: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-((3-(4-pyrimidin-2-yl)-imidazol-2-
yl)propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 961.6 [M+l],
Compound No. 220: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-3-((3-(4-pyrimidin-5-yl)-imidazol-2-
yl)propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 961.55 [M+l],
Compound No. 221: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-[4-(l//-[l,2,4]-triazol-lyl)
phenyl]butylimino)] erythromycin A, MS (+ ion mode): m/z 956.50 [M+l],
Compound No. 222: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-[4-(l//-[l,2,4]-triazol-lyl)
phenyl]butylimino)] erythromycin A, MS (+ ion mode): m/z 959.5 [M+l],
Compound No. 223: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-(4-(4-pyrimidin-5-yl-phenyl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 970.6 [M+l],
Compound no. 224: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-(3-(4-pyrimidin-5-yl-imidazol-lyl)
propyl)hydrazo)] erythromycin A, MS (+ ion mode): m/z 961.54 [M+l],
Compound No. 225: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11- [oxycarbonyl-(3 -({3- [4-(imidazol-1 -yl)-pyrazol-1 -
yl]propyl}hydrazo)] erythromycin A, MS (+ ion mode): m/z 949.5 [M+l],
Compound No. 226: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(3-{[3-([l,4']-biimidazol-l'-
yl)propyl}hydrazo)] erythromycin A, MS (+ ion mode): m/z 949.7 [M+l],
Compound No. 227: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(3-(4-pyrazol-1 -yl)-imidazol-1 -yl)-
propyl)-hydrazo] erythromycin A, MS (+ ion mode): m/z 949.5 [M+l],
Compound No. 228: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-3-((3-(lH-imidazo[4,5-b]pyridine-l-yl)-
propyl)-hydrazo)] erythromycin A, MS (+ ion mode): m/z 934.5 [M+l],
Compound No. 229: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(oxazol-5-yl)-imidazol-lyl)
butylimino)] erythromycin A, MS (+ ion mode): m/z 949.5 [M+l],
Compound No. 230: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-imidazol-1 -yl)-pyrazol-1 -
yl]butylimino)] erythromycin A, MS (+ ion mode): m/z 948.50 [M+l],
Compound No. 231: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-0-(3'-Ndesmethyl-
3' -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-imidazol-1 -yl)-pyrazol-1 -
yl]butylimino)] erythromycin A, MS (+ ion mode): m/z 948.40 [M+l],
Compound No. 232: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(2//-tetrazol-5-yl)-
phenyl)butylimino)] erythromycin A, MS (+ ion mode): m/z 960.49 [M+l],
Compound No. 233: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-[4-(2//-tetrazol-5-yl)-
phenyljbutylimino)] erythromycin A, MS (+ ion mode): m/z 960.49 [M+l],
Compound No. 234: ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(6-chloropyridin-3-yl)-imidazol-1
yl]butylimino)] erythromycin A, MS (+ ion mode): m/z 993.50 [M+l],
Compound No. 235: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-3-((3-([l,4']-bipyrazol-l-yl)-)-propyl)-
hydrazo)] erythromycin A, MS (+ ion mode): m/z 950.40 [M+l],
Compound No. 236: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-Ndesmethyl-
3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(4-benzimidazol-1 -yl)butylimino)]
erythromycin A, MS (+ ion mode): m/z 976.6 [M+l],
Compound No. 237: ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-Ndesmethyl-
3'-N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(6-fluoro-pyridin-3-yl)-imidazol-lyl)-
butylimino)] erythromycin A, MS (+ ion mode): m/z 977.40 [M+l].
Example 24: Pharmacological activity
Compounds provided herein displayed antibacterial activity in vitro, especially against
strains which are generally resistant to macrolides either due to efflux (mef strains) or ribosomal
modification (erm) strains. These compounds are useful in the treatment of community-acquired
pneumonia, upper- and lower-respiratory tract infections, skin and soft tissue infections, hospitalacquired
lung infections, bone and joint infections, and other bacterial infections, for example,
mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease. Minimum
inhibitory concentration (MIC) has been an indicator of in vitro antibacterial activity widely used
in the art.
Procedure
Medium
a) Cation adjusted Mueller Hinton Agar (MHA-Difco)
b) Trypticase Soya Agar (TSA)
Inoculum preparation
The cultures were streaked on TSA for aerobic cultures and MHA with 5% sheep blood
for fastidious cultures. Aerobic cultures were incubated at 37 °C for about 18-24 hours.
Fastidious cultures were incubated CO2 incubation (5% CO2) at 37 °C for about 18-24 hours.
Three to four well-isolated colonies were taken and saline suspensions were prepared in sterile
densimat tubes. The turbidity of the culture was adjusted to 0.5-0.7 Me Farland standard (1.5 x
37
10s CFU/ml). The cultures were diluted 10 fold in saline to get inoculum size of approximately 1-
2 x 107 organisms/ml.
Preparation of drug concentration
1 mg/ml concentration of stock solution of drugs was prepared in
dimethylsulfoxide/distilled water/solvent given in National Committee for Clinical Laboratory
Standards (NCCLS) manual. Serial two-fold dilutions of the compounds and standard drugs were
prepared as per NCCLS manual. Stock solution was changed according to the need of the
experiment.
Preparation of Agar Plates
Two ml of respective drug concentration was added to 18 ml of Molten Mueller Hinton
agar to get the required range, for example 0.015 ug/ml - 16 u.g/ml. For fastidious cultures, 1 ml
of sheep blood was added in Molten Mueller Hinton agar. For control, MHA and MHA with 5%
sheep blood plates without antibiotic for each set were prepared. One MHA and MHA with 5%
sheep blood plate without antibiotic for determining quality check for media was prepared.
Preparation of Teflon template
1 ul of each culture on each plate was replicated with the help of replicator (Denley's
multipoint replicator). The spots were allowed to dry and the plates were incubated for about 18-
24 hours at 37°C. Fastidious cultures were incubated at 37 °C in CC>2 incubator. The results were
noted comparing with the control plates.
Endpoint definition
The concentration of drug at which there was complete disappearance of growth spot or
formation of less than 10 colonies per spot was considered as Minimum Inhibitory Concentration
(MIC). The MICs of Quality Control (QC) strains were plotted on the QC chart for agar dilution
method. If the MICs were within the range, the results interpreted by comparing MICs of
standards against all organisms with those of test compounds.
Precautions & Quality Control Measures
Quality Control Strains
Staphylococcus aureus ATCC 29213
Enterococcus faecalis ATCC 29212
Eschericia coli ATCC 25922
Pseudomonas aeruginosa ATCC 27853
All 60 cultures were visually checked for purity.
Media Control: NCCLS disc diffusion assay using lOug discs of Gentamicin (Difco)
against Pseudomonas aeruginosa ATCC 27853. A zone diameter of 16-21 mm was considered
for optimum cation (Magnesium and Calcium) content of the media. The diameter was plotted in
the media QC chart.
References:
o National Committee for Clinical Laboratory Standards (NCCLS), Methods for
Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically - Fifth
Edition; Approved Standard. M7-A5, Vol.20. No. 2 (January 2000).
o National Committee for Clinical Laboratory Standards, Performance Standards for
Antimicrobial Susceptibility Testing - Twelfth informational supplement, M 100-S12,
Vol. 22 No. 1 (January 2002).
Results: compounds disclosed herein have shown activity against Staphylococcus aureus,
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis Streptococcus
pyogenes, Enterococcifaecalis, Enterococci faecium and Helicobacter pylori.
The results of the antibacterial activity of the compounds disclosed herein are as follows:
a) The compounds disclosed herein exhibited MIC values against Staphylococcus aureus
(25923) in the range of between about 0.03 ug/mL and about 16 ng/mL, for example,
between about 0.03 ug/mL and about 4 ug/mL, or between about 0.03 ug/mL and
about 0.25 ug/mL or between about 0.03 j^g/mL and about 0.125 ug/mL.
b) The compounds disclosed herein exhibited MIC values against sensitive Streptococcus
pneumoniae (6303, 49619) in the range of between about 0.008 ug/mL to about 16
ug/mL, for example between about 0.008 ug/mL to about 0.125 ug/mL, or between
about 0.008 ug/mL to about 0.06 ug/mL.
c) The compounds disclosed herein exhibited MIC values against erythromycin-resistant
Streptococcus pneumoniae (ABM erm, AB29 erm, 1275 erm, AB34 mef, CS 1687
mef, 3579, 3390, 4745, 994, 5055, or 5051) in the range of between about 0.008
ug/mL to about 16 ug/mL, for example between about 0.008 ug/mL to about lug/mL,
or between about 0.008 ug/mL to about 0.125 ug/mL, or between about 0.008 ug/mL
to about 0.03 ug/mL.
d) The compounds disclosed herein exhibited MIC values against telithromycin-resistant
Streptococcus pneumonia in the range of between about 0.25 |ug/mL to about 16
ug/mL, between about 0.25 ug/mL to about 4 ug/mL, or between about 0.25 ug/mL to
about 1 ug/mL.
e) The compounds disclosed herein exhibited MIC values against Haemophilus
influenzae (49247, 38) in the range of between about 0.03 jag/mL to about 16 ug/mL,
for example between about 0.03 ug/mL to about 2 ug/mL, or from between about 0.03
ug/mL to about 0.125 ug/mL.
39
f) The compounds disclosed herein exhibited MIC values against Moraxella catarrhalis
(8176, M6) in the range of between about 0.015 ug/mL to about 16 ug/mL, for
example, between about 0.015 ug/mL to about 1 ug/mL, or from between about 0.015
ug/mL to about 0.06 ug/mL.
g) The compounds disclosed herein exhibited MIC values against sensitive Streptococcus
pyogenes (19615) in the range of between about 0.008 ug/mL to about 2 ug/mL, for
example, between about 0.008 ug/mL to about 0.125 ug/mL, or from about 0.008
ug/mL to about 0.06 ug/mL.
h) The compounds disclosed herein exhibited MIC values against erythromycin-resistant
Streptococcus pyogenes (1721 emb, 2534 erm TR) in the range of between about 0.004
ug/mL to about 16 (ag/mL, for example, between about 0.004 ug/mL to about 0.125
ug/mL, or between about 0.004 ug/mL to about 0.03 ug/mL.
i) The compounds disclosed herein exhibited MIC values against Helicobacter pylori
(43504) in the range of between about 0.03 ug/mL to about 1 ug/mL.
j) The compounds disclosed herein exhibited MIC values against sensitive E. faecalis
(29212) in the range of between about 0.03 ug/mL to about 4 ug/mL, for example
from between about 0.03 ug/mL to about 0.25 ug/mL, or from between about 0.03
ug/mL to about 0.125 ug/mL.
k) The compounds disclosed herein exhibited MIC values against Vancomycin-resistant
Enterococci (346, 6A) in the range of between about 0.125 ug/mL to about 16 ug/mL,
for example, between about 0.125 ug/mL to about 4 ug/mL, or from about between
about 0.125 ug/mL to about 0.5 ug/mL.

WE CLAIM:
1. Compounds having the structure ofpharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers,
prodrugs or polymorphs thereof, wherein:
R1 is hydrogen or a hydroxyl protecting group;
R2 and R3 are independently alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl
or (heterocycle)alkyl (with the proviso that R2 and R3 simultaneously are not methyl);
R4 is alkyl, alkenyl or alkynyl;
R5 is alkyl, aryl or heterocycle;
R is no atom, hydrogen, aryl or heterocycle;
R' is alkyl or -(CH2)q-U-V (wherein q is an integer of from 1 to 4, U is alkenyl or alkynyl,
V is hydrogen, aryl or heterocycle);
W is alkenyl, -G(CH2)mJ, -CR9R10, -NR9- or -SO2 - {[wherein m is an integer of from 2 to
6, G is no atom, -CO, -CS, -862 or -NR9, J is no atom or -N((R9)(CH2)n- (wherein n is an
integer of from 1 to 4, R9and R10are independently hydrogen or alkyl)]}; Y is -Q(CH2)k-,
(wherein k is an integer of from 1 to 6, Q is no atom, -NR9- or oxygen [wherein R9 is
hydrogen or alkyl]}, further alkylene chain of -Q(CH2)k- is optionally substituted with
alkyl, hydroxy or alkoxy; and
Q Q Z is oxygen, sulphur or NOR (wherein R is hydrogen, alkyl or aralkyl
2. The compound according to claim 1, wherein:
R1 is hydrogen; R is no atom or heterocycle; R2 and R3 are independently alkyl, alkenyl or alkynyl
(with the proviso that R2 and R3 simultaneously are not methyl); R4 is ethyl; R5 is alkyl, aryl or
heterocycle; R' and R4 are alkyl; W is alkenyl or -G(CH2)mJ-; Z is oxygen or sulphur; Y is
Q(CH2)k, wherein G, J, Q, m and k are the same as defined in claim 1
3. A compound, which is selected from:
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((3-imidazol-l-yl)-propyl)-imino]erythromycin A,
11,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-imidazol-l-yl)-butyl)-imino]erythromycinA,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11 -[oxycarbonyl-((3-imidazol-1 -yl)-propyl)-imino]erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(3H)-imidazo(4,5-b)-pyridin-3-yl)-butyl)-
iminojerythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-imino]erythromycin
A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11- [oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-imino]erythromycin
A,
11,12-Dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-l 2,11 -[oxycarbonyl-(prop-2-en-yl)-imino]erythromycin A,
11,12-Dideoxy-3-O-decladinosyl-3-O-(4-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-imidazol-l-yl)-butyl)-imino]erythromycin A,
11,12-Dideoxy-3 -O-decladinosyl-3 -O-(2-pyridyl acetyl)-5 -O-(3 '-N-desmethyl-3 '-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-imidazol-l-yl)-butyl)-imino]erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11- [oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-imino] erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-0-(4-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11- [oxycarbonyl-((4-benzimidazol-1 -yl)-butyl)-imino] erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(3H)-imidazol-[4,5-b]pyridin-3-yl)-butyl)-
imino] erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(lH)-imidazol-[4,5-b]pyridin-l-yl)-butyl)-
imino] erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-pyrrolo-[2,3-b]pyridin-1-yl)-butyl)-
imino] erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11- [oxycarbonyl-((4-indol-1 -yl)-butyl)-imino] erythromycin A,
11,12-Dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11- [oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-imino]erythromycin
A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(l H)-imidazol-[4,5-b]pyridin-1 -yl)-butyl)-
imino] erythromycin A,
11,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-0-methyl-12,l l-[oxycarbonyl-((4- indol- l-yl)-butyl)-imino]erythromycin A,
11,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,l l-[oxycarbonyl-((4- benzimidazol- l-yl)-butyl)-imino]erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-pyrrolo-[2,3-b]pyridin-l-yl)-butyl)-
iminojerythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(3H)-imidazol-[4,5-b]pyridin-3-yl)-butyl)-
imino]erythromycin A,
ll,12-Dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-imino]erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 - [oxycarbonyl-((N1 -methyl-N' -pyridin-4-ylmethyl)-2-aminoethyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11-[oxycarbonyl-((N1-methyl-N1-pyridin-2-ylmethyl)-2-aminoethyl)-
imino]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((N1-methyl-N1-pyridin-3-ylmethyl)-2-aminoethyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((Nl-methyl-N1-quinolin-4-ylmethyl)-2-aminoethyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-raethyl-12,ll-[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-l-yl)-butyl)-
iminojerythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 H)imidazo[4,5 -b]pyridin-1 -yl)-butyl)-
imino]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3l-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-butyl)-
imino]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(2-methyl)-benzoimidazo-1 -yl)-butyl)-
iminojerythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-imino]erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-pyridin-2-yl)-butyl)-imino]erythromycin A,
l^n-dideoxy-S-O-decladinosyl-S-O-CS-pyridylacety^-S-O-CS'-N-desmethyl-S'-N-ethyl)-
6-O-methyl-12,11 - [oxycarbonyl-((4-pyridin-4-yl)-butyl)-imino] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-benzoimidazo-l-yl)-butyl)-imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-0-methyl-12,11 - [oxycarbonyl-((4-(4-pyridin-3 -yl)-imidazol-1 -yl)-butyl)-
iminojerythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-l 2,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridylacetyl)-5-0-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-l-yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-l-yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-pyridin-3-yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-l-yl)-butyl)-
imino]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-Npropargyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3t-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((9-(4-amino-butyl)9H-purin-6-yl)-imino]erythromycin
A
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-m ethyl-12,11 -[oxycarbonyl-((4-benzoimidazo-1 -yl)-butyl)-imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-imino]erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-phenyl)-imidazol-1 -yl)-butyl)-imino]erythromycin
A
ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(3H)imidazo[4,5-b]pyridin-3-yl)-butyl)-
iminojerythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(4-pyridylacetyl)-5-O-(3'-N-desmethyl-3l-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxycarbonyl-((4-(4-pyridin-3 -yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A,
l^n-dideoxy-S-O-decladinosyl-S-O-CS-pyridylacetyO-S-O-CS'-N-desmethyl-S'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-Npropargyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-benzoimidazo-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-imino]erythromycin A,
11,12-dideoxy-3 -O-decladinosyl-3 -O-(3 -pyridylacetyl)-5 -O- (3 '-N-desmethyl-3 '-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 H)imidazo[4,5 -b]pyridin-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-benzotriazol-l-yl)-butyl)-imino]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-benzotriazol-1 -yl)-butyl)-imino]erythromycin A,
11,12-dideoxy-3 -O-decladinosyl-3 -O-(2-pyridylacetyl)-5 -O-(3 '-N-desmethyl-3 '-Npropargyl)-
6-O-methyl-l 2,11 -[oxycarbonyl-((4-pyrrolo[2,3-b]pyridin-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-m ethyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl)-imidazol-1 -yl)-butyl)-
imino]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(3[4-(6-amino-9H-purin-9-yl)propyl)hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5 -O-(3' -N-desmethyl-3' -Nethyl)-
6-O-methyl-12,l 1 -[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(quinolin-4-yl)-butyl)-imino)]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 -methyl-1 H-pyrrolo[2,3-b]pyridin-3-yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(6-amino-9H-purin-9-yl butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-m ethyl-12,11 -[oxycarbonyl-(4-(6-amino-9H-purin-9-yl butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-imino)]erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-Q-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-imidazol-1 -yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(4-thiophen-3-yl-lH-imidazol-l-yl)-butyl)-
imino)]erythromycin A hydrochloride salt,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ally
6-O-methyl-12,ll-[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl
butylimino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,11 -[oxycarbonyl-((4-(6-pyrrol-1 -yl-purin-9-yl)-butyl)-imino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-m ethyl-12,11 -[oxycarbonyl-(4-(6-diethylamino-9H-purin-9-yl butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(6-ethylamino-9H-purin-9-yl butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,l 1 -[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(6-methylamino-9H-purin-9-yl
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(6-methylamino-9H-purin-9-yl
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-2-
fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-2-
fluoroethyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(l H-imidazo[4,5-b]pyridin-1 -yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-2-
fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(6-amino-9H-purin-9-yl butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-2-
fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-(4-(6-amino-9H-purin-9-yl butylimino)]
erythromycin A
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-2-
fluoroethyl)-6-O-methyl-12,11- [oxycarbonyl-((4-( 1 H-imidazo[4,5-b]pyridin-1 -yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-2-
fluoroethyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-0-methyl-12,l 1 -[oxycarbonyl-(4-(6-dimethylamino-9H-purin-9-yl butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(6-methylamino-9H-purin-9-yl butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(purin-9-yl)-butyl)-imino)]erythromycm A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,ll-[oxycarbonyl-((4-(purin-9-yl)-butyl)-imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 H-imidazo[4,5 -c]pyridin-1 -yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-c]pyridin-3-yl)-butyl)-
imino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3' -N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-imidazol-1 yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(lH-imidazol[4,5-c]pyridin-l-yl)-butyl)-
imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,11-[oxycarbonyl-((4-(3H-imidazol[4,5-c]pyridin-3-yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-imino)]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-oxazol-5-yl-1 H-imidazol-1 yl)-butyl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-imidazol-1 yl)-butyl)-imino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-imidazol-1 yl)-butyl)-imino)]
erythromycin A hydrochloride salt,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-imidazol-1 yl)-butyl)-
imino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-imidazol-1 yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(thiophen-2-yl)-pyrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxycarbonyl-(4-(4-(furan-2-yl)-pyrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(furan-2-yl)-pyrazol-1 -yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3' -N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 - [oxycarbonyl-(4-(4-(thiophen-2-yl> 1 //-pyrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(6-amino-9H-purin-9-yl
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,l 1 -[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-imino)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,1 l-[oxycarbonyl-4-([l,4']-bipyrazol-r-yl)-butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(2-thiazolyl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(thiazol-2-yl)-imidazol-l-yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(furan-3-yl)-pyrazol-l-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxycarbonyl-(4-(4-(thiophen-3-yl)-pyrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-m ethyl-12,11 -[oxycarbonyl-(4-(4-(thiophen-3-yl)-pyrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(furan-3-yl)-pyrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((3-(4-pyridin-3-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin
A,
(R or 5) ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-
N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((3-(4-pyridin-3-yl-lH-imidazol-lyl)-propyl)-
hydrazo)] erythromycin A,
(Sor R) ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-
N-allyl)-6-O-methyl-12,11 - [oxycarbonyl-((3-(4-pyridin-3-yl-1 H-imidazol-1-yl)-propyl)-
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(4-pyridin-3-yl-lH-imidazol-l-yl)-propyl)-
hydrazo)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(4-pyridin-3 -yl-1 H-imidazol-1 yl)-propyl>
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(4-pyridin-3-yl-1 H-imidazol-1 yl)-propyl)-
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11-[oxycarbonyl-(3-(3-(6-amino-9H-purin-9-ylpropyl)
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(4-(thiophen-3-yl)-lH-imidazol-lyl)-propyl)-
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ally
6-O-methyl-12,ll-[oxycarbonyl-(3-isoquinolin-5-yl)-propyl)-hydrazo)]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-purin-9-yl)-propyl)-hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((3-purin-9-yl)-propyl)-hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(furan-2-yl)-1 H-imidazol-1 -yl)propyl)-
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(3-(6-amino-9H-purin-9-yl-propyl)hydrazo)j
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,11- [oxycarbonyl-(3 -(4-(furan-3 -yl)-1 H-imidazol-1 -yl)propyl)-
hydrazo)]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(furan-3-yl)-1 H-imidazol-1 -yl)propyl)-
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxyc arbonyl-(3-(3 -(6-amino-9H-purin-9-ylpropyl)
hydrazo)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiophen-2-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(4-(thiophen-2-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)] erythromycin A,
49
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3 -(4-(thiophen-3-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3' -N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(imidazo[4,5-b]pyridin-l-yl)-propyl)-hydrazo)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(imidazo[4,5-b]pyridin-3-yl)-propyl)-hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxycarbonyl-(3-(4-(thiazol-2-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3 -(4-(thiazol-2-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)] erythromycin A,
(R or S)ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-
N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-hydrazo]erythromycin A,
(S orR) ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-
N-allyl)-6-O-methyl-12,1 l-[oxycarbonyl-hydrazo]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,l l-[oxycarbonyl-hydrazo)]erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((3-(4-pyridin-3-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)] erythromycin A, 9-(O-methyl)oxime,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-hydrazo]erythromycin A, 9-(O-methyl)oxime,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 - [oxycarbonyl-((4-(4-(6-fluoro-pyridin-3 -yl)-1 H-imidazol-1 -yl)-butyl)-
imino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-(6-fluoro-pyridin-3-yl)-1 H-imidazol-1 -yl)-butyl)-
imino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-((4-(4-( 1 H-imidazol-1 -yl)phenyl)-butyl)-
imino)]erythromycin A,
11,12-dideoxy-3 -O-decladinosyl-3 -O-(2-pyridyl acetyl)-5 -O-(3' -N-desmethyl-3' -N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-((4-(5-(3-aminophenyl)-thiazol-2-yl)-butyl)-
imino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-(4-(4-(2-amino-pyrimidin)-5-yl)-imidazol-l-yl)-
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(2-aminopyridin-4-yl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
50
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-methyl-12,11- [oxycarbonyl-(4-(4-(6-aminopyridin-3 -yl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-Nethyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(6-(dimethylamino)-9H-purin-9-yl)-
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(5-phenyl-tetrazol-1 -yl)propylimino)j
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-aHyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-pyridin-3-yl-pyrazol-1 -yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(2-methyl-2//-tetrazol-5-yl)phenyl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(3-thienyl)-imidazol-1 -yl)butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(5-methyl-[ 1,3,4]-oxadiazol-2-
yl)phenyl)butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-([2,3']-bithiophenyl-5-yl)butylimino)] erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-([2,3']-bithiopheny!5-yl)butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-[3,3']-bithiophenyl-5-yl)butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-[3,3']-bithiophenyl-5-yl)butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-3-yl)-tetrazol-2-yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(5-(furan-2-yl)-imidazol-1 -yl)butylimino)]
erythromycin A,
11,12-dideoxy-3 -O-decladinosyl-3 -O-(2-methylpropanoyl)-5 -O-(3' -N-desmethyl-3' -Nallyl)-
6-O-methyl-12,11- [oxycarbony!4-(4-(4-(furan-2-yl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(4-methoxy-phenyl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(4-methoxy-phenyl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
51
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(2-methoxy-phenyl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxycarbonyl-(4-(4-(2-methoxy-phenyl)-1 //-imidazol-1 -yl)-
butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-phenyl-thiophen-2-yl)-butylimino)] erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-phenyl-thiophen-2-yl)-butylimino)] erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-ruran-2-yl-thiophen-2-yl)butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-furan-2-yl-thiophen-2-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-0-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(4-methoxyphenyl)-tetrazol-2-yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(4-methoxyphenyl)-tetrazol-2-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(5-phenyl-tetrazol-2-yl)-butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-4-yl-tetrazol-2-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-4-yl-tetrazol-2-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(5-phenyl-tetrazol-2-yl)-butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-l 2,11 -[oxycarbonyl-(4-(4-(6-chloropyridin-3-yl)-imidazol-1 -yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-3((3-(4-(imidazol-1 -yl)-pyrazol-1 -yl)- propyl)-hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(3-(4-pyrazol-l-yl]-imidazol-l-yl)- propyl)-hydrazo)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-0-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(3-aminophenyl)-imidazol-l-vl)-butvlimino)l
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-methyl-12,ll-[oxycarbonyl-3-((3-([l,4']-bipyrazol-l'-yl)- propyl)-hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(3-aminophenyl)-imidazol-l-yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-0-methyl-12,ll-[oxycarbonyl-(4-(4-pyrimidin-5-yl-imidazol-l-yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-(3-(4-pyrimidin-2-yl-imidazol-l-yl)-propyl)-hydrazo]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-pyrimidin-5-yl-imidazol-l-yl)butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-2-yl]butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(thiophen-2-yl)-tetrazol-2-yl])-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-l-yl]-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-l-yl]-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-(furan-2-yl)-tetrazol-2-yl]butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-pyridin-3-yl-tetrazol-2-yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(5-pyridin-2-yl-tetrazol-2-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3' -N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(5-pyridin-2-yl-tetrazol-2-yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(5-thiophen-2-yl-tetrazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl>
6-O-methyl-12,ll-[oxycarbonyl-(4-(5-thiophen-2-yl-tetrazol-l-yl)-butylimino)]
erythromycin A,
53
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11-[oxycarbonyl-(4-(5-(thiophen-2-yl-tetrazol-2-yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(lH-benzimidazol-2-yl)-butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(lH-imidazol[4,5-b]pyridin-2-yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(lH-imidazol[4,5-b]pyridin-2-yl )-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-0-methyl-12,11 -[oxycarbonyl-(4-(4-tetrazol-1 -yl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-tetrazol-1 -yl)-imidazol-1 -yl)-butylimino)j
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(lH-benzimidazol-2-yl)-butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-0-methyl-12,11- [oxycarbonyl-(3 -({3 - [4-(6-fluoro-pyridin-3 -yl-imidazol-1 -yl]
propyljhydrazo] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(3-({3-[4-(6-fluoro-pyridin-3-yl-imidazol-l-yl]
propyl}hydrazo] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-methyl propanoyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(benzimidazol-1 -yl)-butylimino)] erythromycin
A,
11,12-dideoxy-3-O-decladinosyl-3-0-(2-methyl propanoyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(3-pyridyl)-imidazol-1 -yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3 -O-decladinosyl-3 -O-(2-methyl propanoyl)-5 -O-(3' -N-desmethyl-3' -Nallyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-imidazol[4,5-b]pyridin-1 -yl)-butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-0-(2-methyl propanoyl)-5-O-(3' -N-desmethyl-3' -Nallyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(6-amino-9H-purin-9-yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-([l,4']-bipyrazol-r-yl)butylimino] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-[4-(pyrazol-1 -yl)-imidazol-1 -yl)butylimino]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-([l,4']-biimidazol-r-yl) butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-([l,4']-biimidazol-r-yl)butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-methylpropanoyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(imidazo[4,5-*]pyridin-3-yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-pyrazol-1 -yl)-imidazol-1 -yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(^-imidaz°[4,5-c]pyridin-2-yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(///-imidazo[4,5-c]pyridin-2-yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-methylpropanoyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11-[oxycarbonyl-(4-(4-(6-fluoro-pyridin-3-yl)-imidazol-lyl)
butylimino)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(4-phenyl-thiazol-2-yl)butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-(4-(4-phenyl-thiazol-2-yl)butylimino)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-((3-(4-pyrimidin-2-yl)-imidazol-2-yl)propyl)-
hydrazo)] erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-3-((3-(4-pyrimidin-5-yl)-imidazol-2-yl)propyl)-hydrazo)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-[4-(l H-[ 1,2,4]-triazol-1 -yl)phenyl]butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11- [oxycarbonyl-(4- [4-( 1H- [ 1,2,4] -triazol-1 -yl)phenyl]butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-pyrimidin-5-yl-phenyl)butylimino)] erythromycin
A,
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-methyl-12,11- [oxycarbonyl-(3 -(3 -(4-pyrimidin-5-yl-imidazol-1 -yl)propyl)hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 - [oxycarbonyl-(3 -({3- [4-(imidazol-1 -yl)-pyrazol-1 -yl]propyl} hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl
6-O-mQ±yl-l2,l\-[oxycarbony\-(3-{[3-([l,4']-bnmidazo\-l'-yl')pTopy\}hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(3-(3-(4-pyrazol-1 -yl)-imidazol-1 -yl)-propyl)-hydrazo]
erythromycin A,
55
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-3-((3-(lH-imidazo[4,5-b]pyridine-l-yl)- propyl)-
hydrazo)] erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(oxazol-5-yl)-imidazol-1 -yl)butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-imidazol-1 -yl)-pyrazol-1 -yl]butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-imidazol-1 -yl)-pyrazol-1 -yl]butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(2//-tetrazol-5-yl)-phenyl)butylimino)]
erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-0-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-[4-(2//-tetrazol-5-yl)-phenyl]butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-(4-(6-chloropyridin-3-yl)-imidazol-1 -yl]butylimino)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,l l-[oxycarbonyl-3-((3-([l,4']-bipyrazol-l-yl)- )- propyl)-hydrazo)]
erythromycin A,
ll,12-dideoxy-3-O-decladinosyl-3-0-(2-nitrophenyl acetyl)-5-O-(3'-N-desmethyl-3'-Nallyl)-
6-O-methyl-12,11 -[oxycarbonyl-(4-benzimidazol-1 -yl)butylimino)] erythromycin
A,
ll,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-
6-O-methyl-12,ll-[oxycarbonyl-(4-(4-(6-fluoro-pyridin-3-yl)-imidazol-l-yl)-butylimino)]
erythromycin A, and
their pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
stereoisomers, prodrugs or polymorph
4. A pharmaceutical composition comprising a therapeutically effective amount of a
compound of claim 1, together with at least one pharmaceutically acceptable carrier,
excipient or diluent.
5. A method for treating or preventing a mammal suffering from a condition caused by or
contributed to by bacterial infection, comprising administering to the mammal a
therapeutically effective amount of a compound of claim 1.
6. A method for treating or preventing a mammal suffering from a condition caused by or
contributed to by bacterial infection, comprising administering to the mammal a
therapeutically effective amount of a pharmaceutical composition of claim 4.
The method according to claim 5 wherein the condition is selected from the group
consisting of community acquired pneumonia, upper and lower respiratory tract
infections, skin and soft tissue infections, hospital acquired lung infections or bone and
joint infections, and other bacterial infections, for example, mastitis, catether infection,
foreign body or prosthesis infections.
The method according to claim 5 wherein the bacterium is Gram-positive, Gramnegative
or anaerobic bacteria.
The method according to claim 8 wherein bacterium is selected from the group
comprising of Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp.,
Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter,
Clostridium, Bacteroides, Corynebacterium, Bacillus and Enterobactericeae.
The method according to claim 9 wherein the bacterium is cocci.
The method according to claim 10 wherein the cocci is drug resistant.
A process for preparing a compound of Formula XII,
Fonmila Xll( Formula 1, \vtierem R-R2=CH,;R4=€2Hi;Z=O;R|=H)
and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
stereoisomers, prodrugs or polymorphs, wherein:
R3, R5, R, W and Y are the same as defined in claim 1, which comprises:
(a) hydrolyzing clarithromycin of Formula II,
to give a compound of Formula III,
(b) the compound of Formula III is protected with a reagent of Formula R^O or R X
(wherein X is halogen) to give a compound of Formula IV (wherein R1 is -COPh),
the compound of Formula IV is desmethylation at 3'-N-dimethyl to give a
compound of Formula V,
(d) the compound of Formula V is alkylated with a reagent of Formula R3CHO,
R32CO or R3X (wherein X is halogen) to give a compound of Formula VI
(wherein R3 is the same as defined earlier),
the compound of Formula VI is reacted with a suitable reagent to give a compound
of Formula VII,
the compound of Formula VII is reacted with a suitable base to give a compound
the compound of Formula VIII is reacted with a compound of
Formula R5YCOOH, (R5YCO)2O, R5YCOX or R5YCOOR10 (wherein R10 is a
leaving group) to give a compound of Formula IX (wherein Y and R5 are the same
as defined earlier),
the compound of Formula IX is reacted with N, N'- carbonyl diimidazole to give a
compound of Formula X,
the compound of Formula X is reacted with a compound of Formula R-W-NF^ to
give a compound of Formula XI (wherein W and R are the same as defined
earlier),
(j) the compound of Formula XI is finally deprotected to give a compound of A process for preparing a compound of Formula XV,
and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
stereoisomers, prodrugs or polymorphs, wherein:
R3, R5, R, m and Y are the same as defined in claim 1,which comprises
(a) reacting a compound of Formula X,
with hydrazine hydrate to give a compound of Formula XIII,
(b) the compound of Formula XIII is deprotected to give a compound of Formula XIV,
(c) the compound of Formula XIV is finai'ly'fe'acted with a compound of Formula
R(CH2)mCHO to give a compound of Formula XV (wherein R and m are the same as
defined earlier).
14) A process for preparing a compound of (Figure Removed)and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
stereoisomers, prodrugs or polymorphs, wherein:
R , R , R, m, Y and R are the same as defined earlier, which comprises
(a) reacting a compound of Formula XIV,
with a compound of Formula R8ONH2. hydrochloride to give a compound of Formula
XVI (wherein R8 is the same as defined earlier),
(b) the compound of Formula XVI is finally reacted with a compound of Formula R
(CH2)mCHO to give a compound of Formula XVII ( wherein R and m are the same
as defined earlier).
15) A process for preparing a compound of Formula XII,
nd its pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
stereoisomers, prodrugs or polymorphs, wherein:
R3, R5, R, W and Y are the same as defined earlier, which comprises:
(a) reacting a compound of Formula IV (wherein R1 is -COPh),
'CIlj
with a reagent to give a compound of Formula XVIII,
(b) the compound of Formula XVIII is reacted with an organic base to give a
compound of Formula XIX,
(c) the compound of Formula XIX is desmethylated at S'-N-dimethyl group to give a
compound of Formula XX,
(d) the compound of Formula XX is alkylated with a reagent of Formula R3CHO,
R3aCO or R3X to give a compound of Formula VIII (wherein R3 is the same as
defined earlier),
(e) the compound of Formula VIII is acylated with a reagent of Formula R5YCOOH,
(R5YCO)2O, R5YCOX or R5YCOOR10 (wherein R10 is a leaving group such as pivaloyl,
p-toleuensulfonyl, isobutoxycarbonyl, ethoxycarbonyl or isopropoxycarbonyl) to give
compound of Formula IX (wherein Y and R5 are the same as defined earlier),
F "' (f) the compound of Formula IXjg^elcted with N, N'-carbonyl diimidazole gives a
compound of Formula X,
the compound of Formula X is reacted with a compound of Formula R-W-NH2 to
give a compound of Formula XI (wherein R and W are the same as defined earlier), (h) the compound of Formula XI is finally deprotected to give a compound of Formula XII.