WO 2006/116171 PCT/US2006/015217
TREATMENT OF PAIN
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to United States Provisional Patent Application
serial number 60/674,087, filed April 22, 2005, the entirety of which is hereby incorporated
herein by reference.
BACKGROUND OF THE INVENTION
[0002] Pain has been characterized and described in various different ways in the
literature. For example, pain can be intense, localized, sharp or stinging, and/or dull, aching,
diffuse or burning in nature. Pain can also be centralized (i.e., taking place in the dorsal horn
of the spinal cord, the brain stem and brain), or peripheral (i.e., taking place at the injury site
and surrounding tissue). Pain that occurs for extended periods of time (i.e., is persistent) is
generally referred to as chronic pain. Examples of chronic pain include neuropathic pain,
inflammatory pain, and cancer pain. These pains can be related to hyperalgesia and/or
allodynia, where hyperalgesia refers to an increase in sensitivity to a typically noxious
stimulus and allodynia refers to an increase in sensitivity to a typically non-noxious stimulus.
[0003] A type of chronic pain that currently lacks adequate pharmacological treatment is
neuropathic pain. Neuropathic pain is generally thought of as a chronic pain caused by
damage to or pathological changes in the peripheral or central nervous systems. Examples of
pathological changes related to neuropathic pain include prolonged peripheral or central
neuronal sensitization, central sensitization related damage to nervous system inhibitory
and/or excitatory functions and abnormal interactions between the parasympathetic and
sympathetic nervous systems. A wide range of clinical conditions may be associated with or
form the basis for neuropathic pain including for example diabetSs, post traumatic pain of
amputation, lower back pain, cancer, chemical injury or toxins, other major surgeries,
peripheral nerve damage due to traumatic injury compression, nutritional deficiencies, or
infections such as shingles or HIV.
[0004] There are various types of agents currently being used to treat pain such as for
example, non-narcotic analgesics such as aspirin, acetaminophen or ibuprofen; non-steroidal
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anti-inflammatory drugs (NSAIDs); narcotic analgesics such as morphine, hydromorphone,
fentanyl, codeine or meperidine; steroids such as prednisone of Hexamethasone; tricyclic
antidepressants such as amitriptyline, desipramine, or imipramine; antiepileptics such as
gabapentin, carbamazepine, topiramate, sodium valproate or phenytoin; or combinations of
these different agents. However, these agents are typically unsatisfactory for treating pain of
a chronic nature, and can have adverse effects such as drowsiness, dizziness, dry mouth,
weight gain, memory impairment, and/or orthostatic hypotension.
[0005] There has also been recent interest in treating pain with inhibitors of the N-
methyl-D-aspartate ("NMDA") receptors to treat pain (hereinafter called "NMDA receptor
antagonists"). While some such compounds show promise, their clinical usefulness has been
limited due to adverse effects such as headache, increased heart rate, increased blood
pressure; disturbances of motor function such as ataxia, or sedation; and/or psychotomimetic
effects such as dizziness, hallucinations, dysphoria, or disturbances of cognitive function that
are observed when they are administered at analgesic doses.
Thus, there remains a need for improved therapies for the treatment of pain.
SUMMARY OF THE INVENTION
[0006] The present invention provides a method of treating pain in a mammal that
includes administering to a mammal in need of such treatment a pain treating effective
amount of at least one compound having the formula I:

or a pharmaceutically acceptable salt thereof, wherein:
n is one or two;
each of R2 and R3 is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl
or cyclopropyl;
each R1 is independently hydrogen, halogen, OH, lower alkyl* lower alkoxy, lower haloalkyl,
lower haloalkoxy, or CN;
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Ar is thienyl, furyl, pyridyl, or phenyl, wherein Ar is optionally substituted with one or more
Rx substituents;
each Rx is independently selected from halogen, OH, lower alkyl, lower alkoxy, lower
haloalkyl, lower haloalkoxy, or CN; and
y is 0-3.
[0007] The present invention also provides pharmaceutical compositions that contain a
pain treating effective amount of the compound of formula I, or a pharmaceutically
acceptable salt thereof,; and at least one pharmaceutical carrier or other ingredient.
[0008] In some embodiments of the invention, the compound of formula I is administered
in combination with another pain relieving agent and/or with one or more agents for reducing
side effects of the pain relieving agent(s).
[0009] The present invention also provides pharmaceutical compositions comprising one
or more compounds of formula I formulated for administration to treat pain in a mammal. In
some embodiments, the pharmaceutical composition is provided in unit dosage form. The
present invention further provides therapeutic packages containing one or more compounds
of formula I in unit dosage form for treating pain in a mammal.
[0010] It is well known that the neurotransmitter 5-HT plays a major role in inhibition of
nociceptive transmission. The present invention encompasses the Various studies have
demonstrated that at least 4 families of 5-HT receptors are present in pain processing
pathways and include 5-HT1, 5-HT2, 5-HT3, and 5-HT4 (1-2). Furthermore, although exact
mechanisms are poorly understood, it appears that 5-HT2C receptors have an inhibitory role
in neuropathic pain (3-5). In summary, 5-HT2C agonists may be effective in the treatment
of diabetic neuropathy, post herpetic neuralgia, low back pain, phantom limb pain, visceral
pain (chronic and acute), irritable bowel syndrome pain, irritable bowel disease pain,
fibromyalgia and complex regional pain syndrome.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Figure 1 shows the effectiveness of Compound 1 in the tactile allodynia model.
[0012] Figure 2 shows the effectiveness of Compound 2 in the mechanical hyperalgesia
model.
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DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION
1. Compounds
[0013] Compounds useful for treating pain according to the present invention include
compounds of formula I
or a pharmaceutically acceptable salt thereof, wherein:
n is one or two;
each of R2 and R3 is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl
or cyclopropyl;
each R1 is independently hydrogen, halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl,
lower haloalkoxy, or CN;
Ar is thienyl, furyl, pyridyl, or phenyl, wherein Ar is optionally substituted with one or more
Rx substituents;
each Rx is independently selected from halogen, OH, lower alkyl, lower alkoxy, lower
haloalkyl, lower haloalkoxy, or CN; and
y is 0-3.
[0014] The term "lower alkyl," as used herein, refers to a hydrocarbon chain having up to
4 carbon atoms, preferably 1 to 3 carbon atoms, and more preferably 1 to 2 carbon atoms.
The term "alkyl" includes, but is not limited to, straight and branched chains such as methyl,
ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or t-butyl.
[0015] The term "alkoxy," as used herein, refers to the group -OR, wherein R is a lower
alkyl group.
[0016] The terms "halogen" or "halo," as used herein, refer to chlorine, bromine, fluorine
or iodine.
[0017] The term "haloalkyl," as used herein, or as part of a moiety such as "haloalkoxy"
refers to an alkyl group, as defined herein, that has one or more halogen substituents. In
certain embodiment, every hydrogen atom on said alkyl group is replaced by a halogen atom.
Such haloalkyl groups include -CF3. Such haloalkoxy groups include -OCF3.
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[0018] It will be appreciated by those of ordinary skill in the art that reference to a
compound herein is intended to include reference to any and all related forms such as
stereoisomers, polymorphs, hydrates, etc. Also, compounds may be provided as pro-drugs or
other forms converted into the active agent during manufacture, processing, formulation,
delivery, or in the body.
[0019] The term "pharmaceutically acceptable salts" or "pharmaceutically acceptable
salt" refers to salts derived from treating a compound of formula I with an organic or
inorganic acid such as, for example, acetic, lactic, citric, cinnamic, tartaric, succinic, fumaric,
maleic, malonic, mandelic, malic, oxalic, propionic, hydrochloric, hydrobromic, phosphoric,
nitric, sulfuric, glycolic, pyruvic, methanesulfonic, ethanesulfonic, toluenesulfonic, salicylic,
benzoic, or similarly known acceptable acids. In certain embodiments, the present invention
provides the hydrochloride salt of a compound of formula I.
[0020] As defined generally above, each of the R2 and R3 groups of formula I is
independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl or cyclopropyl. In
certain embodiments, one of the R2 and R3 groups of formula I is hydrogen and the other R2
or R3 group of formula I is hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl or
cyclopropyl. In other embodiments, neither of the R2 and R3 groups of formula I is
hydrogen. In still other embodiments, both of the R2 and R3 groups of formula I are
hydrogen.
[0021] As defined generally above, each R1 group of formula I is independently
hydrogen, halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or CN.
In certain embodiments, each R1 group of formula I is hydrogen. In other embodiments, at
least one of R1 group of formula I is halogen.
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[0022] According to another embodiment, y is 1 and Rl is at the 5-position of the
dihydrobenzofuran ring of formula I, thus forming a compound of formula la:


WO 2006/116171 PCT/US2006/015217
or a pharmaceutically acceptable salt thereof, wherein each of R , R , R , Ar, and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0023] According to yet another embodiment, y is 1 and R1 is at the 6-position of the
dihydrobenzofuran ring of formula I, thus forming a compound of formula la':

or a pharmaceutically acceptable salt thereof, wherein each of R1, R2, R3, Ar, and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0024] As defined generally above, the Ar group of formula I is thienyl, furyl, pyridyl, or
phenyl, wherein Ar is optionally substituted with one or more substiruents independently
selected from halogen, OH, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, or CN. In
certain embodiments, the Ar group of formula I is unsubstituted phenyl. In other
embodiments, the Ar group of formula I is phenyl with at least one substituent in the ortho
position. In other embodiments, the Ar group of formula I is phenyl with at least one
substituent in the ortho position selected from halogen, lower alkyl, lower alkoxy, or
trifluoromethyl. According to another aspect the present invention provides a compound of
formula I wherein Ar is phenyl di-substituted in the ortho and meta positions with
independently selected halogen lower alkyl, or lower alkoxy. Yet another aspect of the
present invention provides a compound of formula I wherein Ar is phenyl di-subsituted in the
ortho and para positions with independently selected halogen lower alkyl, or lower alkoxy.
In other embodiment, the present invention provides a compound of formula I wherein Ar is
phenyl di-subsituted in the ortho positions with independently selected halogen lower alkyl,
or lower alkoxy. Exemplary substiruents on the phenyl moiety of the Ar group of formula I
include OMe, fluoro, chloro, methyl, and trifluoromethyl.
[0025] In certain embodiments, the present invention provides a compound of formula
la' wherein Ar is phenyl with one substituent in the ortho position selected from halogen,
lower alkyl, lower alkoxy, or trifluoromethyl.
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[0026] According to one embodiment, Ar is phenyl substituted with one Rx substituent in
the ortho-position, thus forming a compound of formula lb, or with an Rx substituent in both
ortho-positions, thus forming a compound of formula Ic:

or a pharmaceutically acceptable salt thereof, wherein each R1, R2, R3, Rx, y and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0027] In certain embodiments, the Ar group of formula I is selected from the following:

[0028] According to yet another embodiment, the present invention provides a compound
of formula Id or Ie:
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or a pharmaceutically acceptable salt thereof, wherein each R1, R2, R3, Rx, y and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0029] According to another embodiment, the present invention provides a compound of
formula If or Ig:

or a pharmaceutically acceptable salt thereof, wherein each R1, R2, R3, Rx, and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0001] In certain embodiments, the present invention provides a compound of formula Ih
orli:

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or a pharmaceutically acceptable salt thereof, wherein each R , R2, R3, Rx, and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0030] Compounds of the present invention contain asymmetric carbon atoms and thus
give rise to stereoisomers, including enantiomers and diastereomers. Accordingly, it is
contemplated that the present invention relates to all of these stereoisomers, as well as to
mixtures of the stereoisomers. Throughout this application, the name of the product of this
invention, where the absolute configuration of an asymmetric center is not indicated, is
intended to embrace the individual stereoisomers as well as mixtures of stereoisomers. In
certain embodiments of the invention, compounds having an absolute (R) configuration are
preferred.
[0031] In certain embodiments, the present invention provides a compound of formula
VlaorVIb:

or a pharmaceutically acceptable salt thereof, wherein each R1, R2, R3, Rx, y and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
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[0032] According to another embodiment, the present invention provides a compound of
formula VIc or VId:


WO 2006/116171 PCT/US2006/015217
or a pharmaceutically acceptable salt thereof, wherein each R1, R2, R3, Rx, y and n are as
defined above for compounds of formula I and in classes and subclasses as described above
and herein.
[0033] Where an enantiomer is preferred, it may, in some embodiments be provided
substantially free of the corresponding enantiomer. Thus, an enantiomer substantially free of
the corresponding enantiomer refers to a compound which is isolated or separated via
separation techniques or prepared free of the corresponding enantiomer. "Substantially free,"
as used herein, means that the compound is made up of a significantly greater proportion of
one enantiomer. In certain embodiments the compound is made up of at least about 90% by
weight of a preferred enantiomer. In other embodiments of the invention, the compound is
made up of at least about 99% by weight of a preferred enantiomer. Preferred enantiomers
may be isolated from racemic mixtures by any method known to those skilled in the art,
including chiral high pressure liquid chromatography (HPLC) and the formation and
crystallization of chiral salts or prepared by methods described herein. See, for example,
Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York,
1981); Wilen, S.H., et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon
Compounds (McGraw-Hill, NY, 1962); Wilen, S.H. Tables of Resolving Agents and Optical
Resolutions p. 268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972).
[0034] It is further recognized that atropisomers of the present compounds may exit. The
present invention thus encompasses atropisomeric forms of compounds of formula I as
defined above, and in classes and sublcasses described above and herein.
[0035] Exemplary compounds useful for the methods of the present invention are set
forth in Table 1, below.
Table 1. Exemplary Compounds of Formula I
(±)-1 - { 7- [3,5-bis(trifluoromethyl)phenyl] -2,3 -dihydro-1 -benzofuran-2-yl }methanamine,
(±)-l-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(3,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(+)-(l -(7-phenyl-2,3 -dihydro-1 -benzofuran-2-yl)methanamine,
(-)-1 -(7-phenyl-2,3 -dihydro-1 -benzofuran-2-yl)methanamine,
(±)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(-)4-[7-(3-methylphenyl)-23-dihydro-l-beDaofuran-2-yl]methanamine,
(±)-1 -(7-thien-3 -yl-2,3 -dihydro-1 -benzofuran-2-yl)methanamine,
(+)-1 -(7-thien-3-yl-2,3 -dihydro-1 -benzofuran-2-yl)methanamine,
(-)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(±)-1 -[7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(+)-l -[7-(2-methylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(-)-l-[7-(2-methylphenyl)-233-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2-fluorophenyl)-23-dihydro-l-benzofuran-2-yl]rnethanamine5
(-)-1 -[7-(2-fiuorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-{7-[2-(trifluoromethyl)phenyl]-253-dihydro-l-benzofliran-2-yl}methanamine,
(-)-l-{7-[2-(trifluoromethyl)phenyl]-23-dihydro-l-benzofuran-2-yl}methanamine,
(+)-l-{7-[2-(Mfluoromethyl)phenyl]-23-dihydro-l-benzof\ttan-2-yl}methanamine,
(±)-l-[7-(2,6-dime1hylphenyl)-23-dihydro-l-berizofuran-2-yl]methanamine,
(-)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanarnine,
(+)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2-methoxyphenyl)-253-dihydro-l-benzofuran-2-yl]rnethariaraine,
(±)-l-[7-(2-crilorophenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(3-chlorophenyl)-253-dihydro-l:benzofuran-2-yl]methanamine,
(+)-1 - [7-(3 -chlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)4-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(±)-1 -[7-(4-methylphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(+)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(4-methylphenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(4-fluorophenyl)-233-dihydro-l-benzofuran-2-yl]methanamine3
(+)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]rnethanamine5
(-)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(±)-1 -[7-(4-chlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(+)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(-)-l -[7-(4-chlorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]me1hanarnine,
(±)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l -[7-(4-methoxyphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-{7-[4-(1iifluoromethyl)phenyl]-23-dihydro-l-benzofuran-2-yl}rne1ianamine,
(±)-l-[7-(2,4-dicUorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-(5-chloro-7-phenyl-2,3-dib.ydro-l-benzoftiran-2-yl)methanamineJ
(+)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(-)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(±)-l-[5-chloro-7-(2-cUorophenyl)-2,3-dihydro-l-benzofuran-2-yl]rnethanamine5
(±)-l-[5-cMoro-7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylamine,
(-)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylamine,
(+)-(5-chloro-7-thien-3 -yl-2,3 -dihydro-1 -benzofuran-2-yl)methylamine,
(+)-JV-[(5-cMoro-7-tWen-3-yl-2,3-diJiydro-l-benzofuran-2-yl)methyl]-A^-metliylamine3
(-)-7^-[(5-chloro-7-thien-3-yl-23-dihydro-l-benzofuran-2-yl)metiiyl]-Ar-methylamine,
(±)-l-[5-cUoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 -(4-fluoro-7-phenyl-2,3-dihydro-1 -benzofuran-2-yl)methanamine,
(±)-l-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2-chlorophenyl)-5-fluoro-2J3-dihydro-l-benzofwan-2-yl]methanamine,
(-)-l-[7-(2-chlorophenyl)-5-fluoro-233-dihydro-l-benzofliran-2-yl]methanamineJ
(±)-l-(5-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(±)-1 -[5-fluoro-7-(2~methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine5
(+)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 -[5-fluoro-7-(2-fluorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl] methanamine,
(±)-l-{5-fluoro-7-[2-(trifluorome1hyl)phenyl]-2,3-dihydro-l-benzof\u:an-2-yl}methanamine)
(±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methylamine5
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(±).l-[455.difluoro-7-(2-methylphenyl)-23-dihydro-l-beiizofkran-2-yl]methanamine,
(±)-l-(5-chloro-2-methyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine5
(±)-(5-cMoro-2-methyl-7-thien-3-yl-23-dihydro-l-benzofuran-2-yl)methylamine5
(±)-(5-cMoro-2-metiiyl-7-tWen-2-yl-23-dihydro-l-benzofuran-2-yl)methylamine,
(+)-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzoflu:an-2-yl]metb.anamine3
(-)-1 -[7-(2-chlorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(+)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-{7-[3-(trifluorometb.yl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(+)-l-{7-[3-(trifluoromethyl)phenyl]-23-dihydro-l-benzofuran-2-yl}methanamine,
(+)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(-)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(±)-l-[7-(2,6-difluorophenyl)-253-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanaraine,
(-)-l-[7-(2,6-dichlorophenyl)-2J3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(2,4-dimethoxyphenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofbran-2-yl]methanamine,
(-)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]metbanamme,
(-)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-1 -[7-(2,4-dichlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(-)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(+)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]"2,3-dihydro-l-benzofiu:an-2-yI}methanamine,
(±)-l-[7-(23-dimetb.ylphenyl)-2s3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-{[7-(2,3-dimethoxyphenyl)-253-dihydro-l-benzofuran-2-yl]methyl}amine3
(-)-{[(7-(2,3-dimethoxyphenyl)-253-dihydro-l-benzofuran-2-yl]methyl}amine,
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(+)- {[(7-(2,3 -dimethoxyphenyl)-2^-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(-)- {[7-(4-chloro-2-methylphenyl)-2,3-dihydro-1 -benzofaran-2-yl]methyl} amine,
(±)- {[7-(2,3-difluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dimethylphenyl)-23-dibydro-l-berizofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dichlorophenyl)-233-dib.ydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,5-dichlorophenyl)-2,3-dib.ydro-l-benzofliran~yl]methyl} amine,
(±)-{[7-(254,6-trichlorophenyl)-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(±)-{[7-(4-cWoro-2-methylphenyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(5-chloro-2-methylphenyl)-233-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-[(7-pyridin-3-yl-253-dihydro-l-benzofuran-2-yI)methyl]amine,
(+)-{[7-pyridm-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}amme,
(-)-{[7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(3-jEluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(3-methylphenyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fl-uoTo-7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-fluoro-7-(4-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-{[5-fluoro-7-(3-furyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-pyridin-2-yl-2,3-dihydro-l-benzoftiran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(-)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(+)-{[5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-pyridin-4-yl-253-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyrimidin-5-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
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(±)-{[7-(2,3-dichlorophenyl)-5-fluoro-23-dihydro-l-benzofuraii-2-yl]methyl}amine,
(±)- {[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)- {[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)- {[7-(2,4-dichlorophenyl)-5 -fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[5-fiuoro-7-(2,4-dichlorophenyl)-2J3-dihydro-l-benzofliran-2-yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-fluoro-2,3-dib.ydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl}amine,
(±)- {[7-(2,6-difiuorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[7-(2,6-dimethylphenyl)-5 -fluoro-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)- {[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-N- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-
yljmethyl} cyclopropanamine,
(±)-l-cycIopropyl-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-
yljmethyl} methanamine,
(±)-N-{[7-(2J6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}ethanamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}dimethylamine,
(±)-{[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(3-fiiryl)-2,3-dib.ydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(+)-{[5-chloro-7-(23-difluorophenyl)-23-dihydro-l-benzoiuran-2-yl]me1hyl}amine5
(±)-{[5-chloro-7-(2,3-dichIorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(23-dimethylphenyl)-23-dihydro-l-benzofiKan-2-yl]methyl}amine,
(±)-{ [5-cMoro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)-{[5-cUoro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,4-dichIorophenyl)-2,3-dihydro-l-benzofuraa-2-yl]methyl}amine,
(-)-{[5-chloro-7-(2>4-dichlorophenyl)-23-dihydro-l-benzofean-2-yl]methyl}amiiie,
(+)- {[5-chloro-7-(2,4-dichlorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(255-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(3,4-difluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[5-chloro-7-(256-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)- {[5-chloro-7-(2,6-dimethylphenyl)-2,3 -dihydro-1 -benzofiiran-2-yl] methyl} amine,
(±)- {[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methy] Jamine,
(+)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine3
(-)- {[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[(5-chloro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-N- {[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1 -benzofuran-2-
yl] methyl} cyclopropanamine,
(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-
yl] methyl} (cyclopropylmethyl)amine,
(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}ethanamine,
(±)- {[(5-methyl-7-phenyl-2,3-dihydro-1 -benzofuran-2-yl)methyl] amine,
(±)- {[7-(2-methylphenyl)-5-methyl-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)- {[7-(2-fluorophenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-yl3methyl} amine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-({ 5-methyl-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1 -benzofuran-2-yl }methyl)amine,
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(±)- {[7-(3 -chlorophenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(4-methylphenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(4-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine3
(±)-{[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,3-dimethoxyphenyl)-5-methyl-253-dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine}
(±)- {[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)- {[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)- {[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[7-(2,6-dimethylphenyl)-5 -methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[7-(2,6-dichlorophenyI)-5 -methyl-2,3-dihydro- l-benzofuran-2-yl]methyl} amine,
(-)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)- {[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yI]methyl} amine,
(±)- {[5-ethyl-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-ethyl-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{ [5-(trifluoromethyl)-7-(2-fluorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl} amine,
(±)-{[5-(trifluoromethyI)-7-(2-(triiluoromethyl)phenyl)-2,3-dihydro-l-benzofuran-2-
yl] methyl} amine,
(±)- {[5-(trifluoromethyl)-7-(3-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl] methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(3-fluorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(3 -methoxyphenyl)-2,3 -dihydro-1 -benzofiiran-2-
yl]methyl} amine,
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(±)-{[5-(1xifluoromethyl)-7-(3-(ta^
yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(4-methylphenyl)-23-dihydro-l-ben2ofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(4-fiuorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(4-chlorophenyl)-2,3-dmydro-l-benzofuran-2-yl]methyl}amme,
(±)- {[5-(trifluoromethyl)-7-(4-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl} amine,
(±)- {[5-(trifiuoromethyl)-7-(4-(trifluoromethyl)phenyl)-2,3 -dihydro-1 -benzofuran-2-
yl]methyl} amine,
(±)-{ [7-(2,3-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofliran-2-
yl]methyl}amine,
(±)-{[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,3-dimemoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,4-difluorophenyl)-5-(1xifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2,4-dimethoxyphenyI)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)- {[7-(3,4-difluorophenyl)-5 -(trifluoromethyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl} amine,
(±)- {[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3 -dihydro-1 -benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-4-[2-(aminomethyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-7-yl]benzonitrile
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(±)-{[7-(3-furyl)-5-(trifluorome%l)-2,3-dihydro4-benzofuran-2-yl]methyl}amine,
(±)-{[7-tMen-3-yl-5-(trifluoromethyl)-23^ihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydro^-benzofuran-2-yl]methyl}amine}
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro4-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-cUoropbenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}ainine5
(±)-{[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-methoxy-7-(3-thienyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyI}amine5
(±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofiaran-2-yl]methyl}amine5
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzoftiran-2-yl]methyl}aniine,
(±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofliran-2-yl]methyl}amine,
(±)-{[7-(2,4-dicblorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]me1iiyl}amine)
(±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)- {[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yI]methyl} amine,
(-)- {[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dmydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-dimethoxylphenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-[(N-methyl-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)- [(N-methyl-1 -[7-(3 -methylphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(3-chlorophenyl)-2J3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(4-methylphenyl)-233-dihydro-l-benzofuran-2-yl]methanamme,
(±)-[(N-methyl-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamme,
(±)-[(N-methyl-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(±)-[(N-methyl-l-[7-(23-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methan
(±)-[(N-methyl-l -[7-(2,3 -dimethoxyphenyl)-2,3-dihydro-1 -benzofiiran-2-yl]methanamine}
(±)-[(N-methyl-l-[7-(2,4-difluorophenyl)-23-dihydro-l-benzofliran-2-yl]methaiiamine,
(±)-[(N-methyl-l-[7-(234-dichlorophenyl)-23-dihydro-l-benzofliran-2-yl]methanamineJ
(±)-[(N-methyl-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzotoan-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-dime%lphenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-difluorophenyl)-253-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-dicUorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine)
(±)-[(N-me1hyl-l-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methanamine,
(±)-[(N-methyl4-[7-(5-cMoro-2-methylphenyl)-23-dihydro4-benzofuran-2-
yl]methanamine,
(±)- [(N-methyl-1 -[7-(2,6-dimethylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-[(N-me1iiyl-l-[7-(2,6-dicMorophenyl)-23-dihydro-l-benzofi]ran-2-yl]methanamine,
(-)- {[7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(+)- {[7-(2,6-dichlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl}methylamine,
(±)-N-methyl-1 -(7-pyridin-3-yl-2,3-dihydro-1 -benzofuran-2-yl)methanamine,
(±)-[(N-methyl-l-[7-(23-difluorophenyl)-233-dihydro-l-benzofuran-2-yl]methanamine,
(±)- {[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-cbiorophenyl)-233-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2-methylphenyl)-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(-)- [7-(2,4-dichlorophenyl)-5 -fluoro-2,3 -dihydro-1 -benzofliran-2-yl] methyl} methylamine,
(+)-[7-(2,4-dichlorophenyl)-5-fluoro-233-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,5-dichIorophenyl)-5-fluoro-2,3-dihydro-1 -benzofbran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2,5-dicWorophenyl)-2,3-dihydro-l-be]Xzofuran-2-yl]methyl}methylamineJ
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(-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro4-benzofuran-2-yl]me%l}methylamine,
(±)- {[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro4-benzof\Han-2-yl]methyl}methylamine,
(±)-{[7<256-dicUorophenyl)-5-fluoro-2,3-dihydro4-benzofltran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(5-methoxy-2-meth.ylphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)- {[7-(5-chloro-2-methoxyphenyl)-5-fluoro-253-dihydro-1 -benzofuran-2-
yl]methyl}methylamine,
(±)-[(5-jEluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]methylamineJ
(±)-[(5-chloro-7-(2-methoxyphenyl)-23-dihydro-l-beiizofijran-2-yl]methyl}methylamine,
(±)-{[5-cUoro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]metb.yl}methylamine,
(±)-{[5-cUoro-7-(23-dicMorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-cbJoro-7-(2,4-diflxiorophenyl)-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl}methylamine,
(±)- {[5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(±)-{[5-cbJoro-7-(2,5-dichlorophenyl)-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l -benzofuran-2-
yl] methyl} methylamine,
(±)-{[5-cWoro-7-(34-difluorophenyl)-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl} methylamine,
(±)-{[7-(2-fluorophenyl)-5-methyl-253-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl3methyl}methylamine,
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(±)- {[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(3-methylphenyl)-5-methyl-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(3 -chlorophenyl)-5-methyl-2,3 -dihydro-1 -berizofuran-2-yl]methyl} methylamine,
(±)- {[7-(4-methylphenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} methylamine,
(±)-{[7-(4-cUorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-l-benzofiiTan-2-yl]methyl}methylamine,
(±)- {[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} methylamine,
(±)- {[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-
yl]methyl }methylamine,
(±)- {[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-1 -benzofiiran-2-yl]methyl}methylamine3
(±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofliran-2-yl]methyl}methylamine,
(+)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzoftiran-2-yl]methyl}methylamine,
(-)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-l -benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2-chlorophenyl)-5-methoxy-2,3 -dihydro-1 -benzofuran-2-yl]methyl} methylamine,
(±)-{[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofiaran-2-
yl]methyl}methylamine,
(±)- {[7-(2,3-dichlorophenyl)-5-methoxy-2,3rdihydro-1 -benzoforan-2-
yl]methyl}methylamine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl} methylamine,
(±)- {[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-l -benzofuran-2-
yl] methyl} methylamine,
(±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl] methyl} methylamine,
(±)- {[7~(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-
yl] methyl} methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yljmethyl} methylamine,
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(±)-{[7-(255-dimethoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofiiran-2-
yl]methyl}methylamine,
(±)-{[7-(5-chIoro-2-methoxyphenyl)-5-methoxy-253-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(236-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-N-methyl4-[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methanamine,
(±)-N-methyl-l-[7-(3,4-difluorophenyl)-5-(trifluoromethyl)-2j3-dihydro-l-benzofuran-2-
yljmethanamine,
(±)-N-methyl-l-[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzof\iran-2-
yljmethanamine,
(±)-N-methyl-l-[7-(23-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-'
yljmethanamine,
(±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl }methylamine,
(±)-N-methyl-l-[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-253-dihydro-l-benzofuran-2-
yljmethanamine,
(+) {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(-){[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(R)-[7-(2-chloro-phenyl)-(5-Fluoro-2,3-dihydro-benzofliran-2-ylmethyl)methyl-amme,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]ethylamine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-253-dihydro-benzofuran-2-ylmethyl]dimethylamine,
{[(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
{[(2R)-7-(4-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)- {[7-(2,6-dichlorophenyl)-5-fluoxo-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,6 dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]ethyl}amine,
(±)- {N-methyl-1 - [(7-(2,4,6-trichlorophenyl)-2,3 -dihydro-1 -benzofuran-2~yl]methanamine,
(+)-{N-methyl-l-[(7-(2,4,6-tiichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(-)-{N-methyM-[(7<2,4,6-1richlorophen^
(+)-{[7-(236-dimethylphenyl)-5-fluoro-23-dihydro-l-benzofuran-2-yl]methyl}methy^
(-)-{[7-(236-dimethylphenyl)-5-fluoro-2,3-dihydro4-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzoftiran-2-
yl]methyl} methylamine,
(+)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofittan-2-yl]me1hyl}methyIamine,
(-)-{[5-cUoro-7-(2,5-dicUorophenyl)-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-cMoro-7-(2,6-dimethylphenyl)-253-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,6-diinethylphenyl)-2,3-dihydro-l-benzofiu:an-2-yl]methyl}methylamine3
(+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2J3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(-)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-
yljmethyl} methylamine,
(-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
or
(+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-
yl]methyl}methylamine;
or a pharmaceutically acceptable salt thereof.
[0036] In certain embodiments, exemplary compounds of formula I are as set forth in
Table 1-a, below.
Table 1-a: Exemplary Compounds of formula I:
(±)-l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(+)-(1 -(7-phenyl-2,3-dihydro-1 -benzofuran-2-yl)methanamine,
(-)-1 -(7-phenyl-253-dihydro-1 -benzofuran-2-yl)methanamine,
(±)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 -[7-(2-fluorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(+)-1 -[7-(2-fluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(±)-l-{7-[2-(trifluoromethyl)p^
(-)-1 - {7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l -benzofuran-2-yl} methanamine,
(+)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(±)-l-[7-(2,6-(Hmethylphenyl)-2,3-dihydro-l-benzofiiran-2-yl]methanamine,
(-)-l-[7-(2,6-dimethylphenyl)-23-dihydro4-benzofuran-2-yl]methanamine,
(+)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]metb.anamine,
(±)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l -[7-(2,4-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-[5-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 -[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1 -benzoftiran-2-yl]methanamine,
(+)-l-[5-chloro-7-(2-methylphenyl)-2>3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-1 -[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(2-cUorophenyl)-5-fluoro-2^-dihydro-l-benzofuran-2-yl]methanamineJ
(+)-l-[7-(2-chlorophenyl)-5-fluoro-253-dihydro-l-benzofliran-2-yl]methanainine,
(-)-l-[7-(2-chIorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]metb.anamine,
(±)-l-[5-fluoro-7-(2-methylphenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-23-dihydro-l-benzoforan-2-yl}methanamine,
(±)-l-[4>5-difluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yI]methanamine,
(±)-l-(5-chloro-2-methyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(+)-1 -[7-(2-methoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(-)-l-[7-(2-chlorophenyl)-233-dihydro-l-benzofuran-2-yl]methanamine3
(+)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(236-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 -[7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine5
(+)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamineJ
(±)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(-)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2,4-dime1ioxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine5
(±)4-[7-(2,4-difluorophenyl)-2,3-dihydro4-benzofuran-2-yl]methanamine,
(+)-l -[7-(2,4-difluorophenyl)-2,3-d^hydro-l -benzofuran-2-yl]methanamine,
(-)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(2,4-dicWorophenyl)-2,3-dibydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(254-dicUorophenyl)-2,3-dihydro4-benzofuran-2-yl]methanamine,
(-)-l-IS-fluoro^-p^trifluoromethy^phenylj^^-dihydro-l-beiizofuran-2-yl}methanamine,
(+)-l-{5-fluoro-7-[2-(trifluorometbyl)phenyl]-23-dihydro-l-benzofuran-2-yl}meihanam
(±)-l-[7-(253-dimethylphenyl)-2,3-dibydro-l-benzofuran-2-yl]methanamine,
(±)- {[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[(7-(2,3-dimethoxyphenyl)-233-dihydro-l-ben2ofuran-2-yl]methyl}amine,
(+)-{[7-(4-cWoro-2-metiiylphenyl)-23-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l-beiizofuran-2-yl]methyl}amine,
(±)-{[7-(233-difluoTophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-dimethylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dimethoxyphenyl)-2!>3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofiiran-2-yl]methyl} amine,
(-)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-yl]methyl}amine,
(±)-{[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(4-chloro-2-methylphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(5-chloro-2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(±)- {[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,3-dichlorophenyl)-5-fluoro-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(+)- {[7-(2,3 -dimethoxyphenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,4-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(-)-{[5-fluoro-7-(2,4-dichlorophenyl)-23-dihycko4-benzofuran-2-yl]methyl}amine,
(+)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-fluoro-23-dihydro4-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-difluorophenyl)-5-fluoro-253-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dicWoropbenyl)-5-fluoro-23-dihydro-l-benzofkran-2-yl]methyl}amine,
(±)-{[7-(2,5-dime1bylphenyl)-5-fluoro-23-dihydro-l-benzofuran-2-yl]metb.yl}amine,
(±)- {[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dih.ydro-l -benzofuran-2-yl]methyl} amine,
(±)-{[5 -fluoro-7-(5 -methoxy-2-methylphenyl)-2,3 -dihydro-1 -benzofuran-2-yl] methyl} amine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,6-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{ [7-(2,6-dichlorophenyl)-5 -fluoro-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)-N- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-
yl]methyl} cyclopropanamine,
(±)-l -cyclopropyl-N-{ [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l -benzoftiran-2-
yl]methyl}methanamine,
(±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}ethanamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}dimethylamine,
(±)-{[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzoniran-2-yl]methyl}amine,
(±)- {[5-chIoro-7-(2,3-difluorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(-)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)- {[5 -chloro-7-(2,3 -difmorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,4-difluorophenyl)-233-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(+)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro4-benzofuran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(2,5-difluorophenyl)-253-dihydro-l-benzofuran-2-yl]metliy]i}amine3
(±)4[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-beiizofuran-2-yl]methyl}amine5
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-253-dmydro-l-benzofuran-2-yl]me1hyl}amin
(±)-{[5-cMoro-7-(2,6-dimethylphenyl)-2,3-dihydro4-benzofuran-2-yl]methyl}amine,
(-)-{[5-chloro-7-(236-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(2,6-dimethylphenyl)-23-dihydro-l-beiizofin'an-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)- {[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)- {[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofljTan-2-
yl]methyl} cyclopropanamine,
(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}(cyclopropylmethyl)amine,
(±)-N- {[5-chloro-7-(2,6-dimethylphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} ethanamine,
(±)-{[7-(2-methyIphenyl)-5-methyl-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)- {[7-(2-fluorophenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-chloropb.enyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-({5-methyl-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl)amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3"dihydro-l-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzoforan-2-yl]methyl}amine,
(±)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(-)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,6-dichlorophenyl)-5-methyl-2)3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2J6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)- {[7-(256-dichlorophenyl)-5-methyl-2,3-dihydro-l -benzoforan-2-yl]methyl}amine,
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(±)-{[5-ethyl-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-ethyl-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(2-fluorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(2-methylphenyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[5-(trifluoromemyl)-7-(2-cWorophenyl)-2,3-dft^^
(±)- {[5-(trifluoromethyl)-7-(2-metihoxyphenyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl} amine,
(±)-{[7<2,3-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzoniran-2-
yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzo&ran-2-
yl]methyl} amine,
(±)-{[7-(2,3-dichloropb.enyl)-5-(trifluorometb.yl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl] methyl} amine,
(±)-{[7-(2,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)- {[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3 -dihydro-1 -benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-memoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(±)-{[7-(2,3-dicWorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-23-dihydro4-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-difluorophenyl)-5-me1iioxy-253-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(2,4-dicHorophenyl)-5-me1hoxy-2J3-dihydro-l-benzofittan-2-yl]metiiyl}amine^
(±)- {[7-(2,5-di£luorophenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-ylJmethyl} amine,
(±)- {[7-(2,5-dichlorophenyl)-5 -methoxy-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)- {[7-(2,5-dichlorophenyl)-5-methoxy-2J3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[7-(2,5-dichlorophenyl)-5-memoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2J5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methy]}amine,
(±)-{[7-(2,5-dimethoxylphenyl)-5-methoxy-253-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-
yl] methyl} amine,
(±)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-[(N-methyl-l -[7-(2-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yI]methanamine,
(±)-[(N-memyl-l-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzoftiran-2-yl]methanamme,
(±)-[(N-memyl-l-[7-(2,3-dimethoxyphenyl)-2,3-dmydro-l-benzofuran'-2-yi]methanamine,
(±)-[(N-methyl-1 -[7-(2,4-difluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yI]methanamine,
(±)-[(N-methyl-1 -[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yi]methanamine,
(±)-[(N-memyl-l-[7-(2,5-difluoropheny])-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]memanamine,
(±)-[(N-methyl-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-memyl-l-[7-(2,6-dicUorophenyl)-2,3-dmydro-l-benzoftiran-2-yl]methanamine,
(-)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(+)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-[(N-methyl-l-[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-{[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuian-2-yI]methyl}methylamine,
(-)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzoftixan-2-yl]methyl}methylamine,
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(±)-{[5-fluoro-7-(2-methoxyphenyl)-23-dihy&^
(±)-{[7-(253-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-[7-(234-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(-)-[7-(2,4-dichlorophenyl)-5-fluoro-23-dihydro-l-beiizofuran-2-yl]methyl}methylamine,
(+)-[7-(2,4-dicMorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuian-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dicWorophenyl)-5-fluoro-2,3-dihydro-l-benzoflu-an-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2,5-dicUorophenyl)-2,3^ihydro-l-benzofcan-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro4-benzofuran-2-yl]methyl}methylamine5
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-23-dihy&^
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dicUorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l-benzofliran-2-
yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} methylamine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofliran-2-
yl]methyl} methylamine,
(±)-[(5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofttran-2-yl]methyl}methylamine,
(±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofiiran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzofUran-2-yI]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2J3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-cUoro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofliran-2-
yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
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(±)-{[5-chloro-7-(2,5-dicMorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofiiran-2-
yl]methyl} methylaniine,
(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro4-benzofuran-2-yl]methyl}methylamine?
(±)-{[7-(2-chIorophenyl)-5-methyl-23-dihydro-l-beiizofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-23-dihydro-l-benzofuran-2-yl]methyl}methylamine
(±)- {[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,4-dicWorophenyl)-5-methyl-2,3-dihydro-l-benzoftffan-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dicWorophenyl)-5-methyl-23-dihydro-l-benzoftu-an-2-yl]methyl}methylamine,
(+)- {[7-(2,5-dichlorophenyI)-5-methyl-2,3-dib.ydro-1 -benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dimethyIphenyl)-5-methyl-253-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(256-dichJorophenyl)-5-me1hyl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-cWorophenyl)-5-methoxy-23-dihydro-l-benzoflffan-2-yl]methyl}methylaniine5
(±)- {[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yl]methyl} methylamine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(23-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine5
(±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl} methylamine,
(±)- {[7-(2,5 -difluorophenyl)-5 -methoxy-2,3-dihydro-1 -benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
y]]methyl}methylamine,
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(±)-{[7-(2,5-dime1hoxyphenyl)-5-methoxy-2,3-dihydro-l-benzoftiran-2-
yl]methyl}methylamine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
(±)- {[7-(2,6-dimethylphenyl)-5-methoxy-2,3 -dihydro-1 -benzofur an-2-
yl]methyl}methylamine,
(±)-N-methyl-147<2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methanamine,
(±)-N-methyl-l-[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methanamine,
(±)-N-methyl-1 - [7-(2,4-dimethoxyphenyl)-5 -(trifluoromethyl)-2,3 -dihydro-1 -benzofuran-2-
yl]methanamine,
(+){[7-(236-dichJorophenyl)-5-fluoro-2,3-dihydro-l-benzoruran-2-yl]me1b.yl)me1hylamine>
(-){[7-(2,6-dicWorophenyl)-5-fluoro-23-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(R)-[7-(2-cUoro-phenyl)-(5-Fluoro-23-dihydro-benzofuran-2-ylmethyl)methyl-amine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-23-dihydro-benzofiaran-2-ylmethyl]ethylamine,
(R)-[7-(2,6-dicMoro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]dimethylamine,
{[(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
{[(2R)-7-(4-chloro-2-methylphenyl)-5-fluoro-2)3-dihydro-l-benzofuran-2-yl]methyl} amine,
(-)- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,6dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzoruran-2-yl]ethyl}amine,
(±)-{2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]ethyl}amine5
(±)-{N-methyl-l-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(+)- {N-methyl-1 - [(7-(2,4,6-trichlorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(-)-{N-methyl-l-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(+)-{[7-(2,6-dimethylphenyl)-5-fluoro-23-dmydro-l-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzoruran-2-yl]methyl}methylamine,
(-)-{[7-(2}6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
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(+)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzoftiran-2-
yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-cUoro-7-(2,5-dicMorophenyl)-2,3-dihydro-l-benzoflu:an-2-yl]methyl}methylamine,
(-)-{[5-cMoro-7-(2,6-dimetiiylphenyl)-253-dihydro4-beirzofman-2-yl]methyl}methylamine^
(+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzoflu'an-2-yl]methyl}methylamine,
(+)-{[7-(2,3-dimemoxyphenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-
yl]methyl}methylamine,
(-)- {[7-(2,3-dimethoxyphenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-
yl]methyl}methylamine,
(-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-23-dihydro-l-benzofuran-2-yl]methyl}me1hylamine,
or
(+)- {[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-
yl]methyl}methylamine;
or a pharmaceutically acceptable salt thereof.
[0037] Compounds of formula I for use in accordance with the present invention may be
obtained or produced according to any available means including methods described in detail
in United States patent application serial number 10/970,714, filed October 21, 2004, United
States provisional patent application serial numbers 60/621,023, filed October 21, 2004, and
60/621,024, filed October 21, 2004, and PCT publication number WP2005/044812, the
entirety of each of which is hereby incorporated herein by reference.
[0038] Without wishing to be bound by any particular theory, the present inventors note
that compounds of formula I are highly specific agonists of the 5HT2C receptor. Specifically,
the present invention connects the observations that neurotransmitter 5-HT plays a major role
in inhibition of nociceptive transmission and that various studies have demonstrated that at
least 4 families of 5-HT receptors are present in pain processing pathways and include 5-
HT1, 5-HT2, 5-HT3, and 5-HT4 (Doly et al., J Comp Neurol. 476(4):316-329,2004; Ridet et
al, J. Neurosc. Res 38(1):109-21, 1994). Furthermore, although exact mechanisms are
poorly understood, it appears that 5-HT2C receptors have an inhibitory role in neuropathic
pain (Obata et al., Pain 108(l-2):163-9, 2004; Sasaki et al., Anesthesia & Analgesia,
Baltimore, MD, 96(4): 1072-1078, 2003; Obata et al., Brain Research 965(1-2): 114-20,
2003). According to the present invention, therefore, 5-HT2C agonists may be effective in the
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treatment of diabetic neuropathy, post herpetic neuralgia, low back pain, phantom limb pain,
visceral pain (chronic and acute), irritable bowel syndrome pain, irritable bowel disease pain,
fibromyalgia and complex regional pain syndrome. Moreover, the present invention
encompasses the recognition that the unique affinity and selectivity displayed by compounds
of formula I can provide effective treatment of pain. Furthermore, the present invention
recognizes that compounds of formula I may treat pain at lower doses and/or with fewer side
effects than are observed with other available treatments.
2. Pharmaceutical Compositions
[0039] Compounds of formula I may be administered neat in order to treat pain in
accordance with the present invention. More commonly, however, they are administered in
the context of a pharmaceutical composition that, in addition to containing a pain treating
effective amount of one or more compound of formula I, may include one or more
ingredients known to those skilled in the art for formulating pharmaceutical compositions.
Such ingredients include, for example, carriers (e.g., in solid or liquid form), flavoring agents,
lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders, tablet-
disintegrating agents, encapsulating materials, emulsifiers, buffers, preservatives, sweeteners,
thickening agents, coloring agents, viscosity regulators, stabilizers or osmo-regulators, or
combinations thereof.
[0040] Solid pharmaceutical compositions preferably contain one or more solid carriers,
and optionally one or more other additives such as flavoring agents, lubricants, solubilizers,
suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents
or an encapsulating material. Suitable solid carriers include, for example, calcium phosphate,
magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose,
sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes or ion exchange
resins, or combinations thereof. In powder pharmaceutical compositions, the carrier is
preferably a finely divided solid which is in admixture with the finely divided active
ingredient. In tablets, the active ingredient is generally mixed with a carrier having the
necessary compression properties in suitable proportions, and optionally, other additives, and
compacted into the desired shape and size. Solid pharmaceutical compositions, such as
powders and tablets, preferably contain up to 99% of the active ingredient.
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[0041] Liquid pharmaceutical compositions preferably contain one or more compounds
of formula I and one or more liquid carriers to form solutions, suspensions, emulsions,
syrups, elixirs, or pressurized compositions. Pharmaceutically acceptable liquid carriers
include, for example water, organic solvents, pharmaceutically acceptable oils or fat, or
combinations thereof. The liquid carrier can contain other suitable pharmaceutical additives
such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents,
suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-
regulators, or combinations thereof. If the liquid formulation is intended for pediatric use, it
is generally desirable to avoid inclusion of alcohol.
[0042] Examples of liquid carriers suitable for oral or parenteral administration include
water (preferably containing additives such as cellulose derivatives such as sodium
carboxymethyl cellulose), alcohols or their derivatives (including monohydric alcohols or
polyhydric alcohols such as glycols) or oils (e.g., fractionated coconut oil and arachis oil).
For parenteral administration the carrier can also be an oily ester such as ethyl oleate and
isopropyl myristate. The liquid carrier for pressurized compositions can be halogenated
hydrocarbons or other pharmaceutically acceptable propellant.
[0043] Liquid pharmaceutical compositions which are sterile solutions or suspensions can
be administered parenterally, for example by, intramuscular, intraperitoneal, epidural,
intrathecal, intravenous or subcutaneous injection. Pharmaceutical compositions for oral or
transmucosal administration may be either in liquid or solid composition form.
[0044] In certain embodiments of the present invention, the pharmaceutical composition,
in addition to containing a compound of formula I may also contain therapeutically effective
amounts of one or more other pain relieving agents and/or one or more other
pharmaceutically active agents (see below for further discussion). Thus, the present
invention also provides a pharmaceutical composition for treating pain comprising a pain
treating effective amount of at least two different agents that each individually has pain
treating activity, at least one agent being a compound of formula I. Those of ordinary skill in
the art will appreciate that the amount of either agent required to provide a "pain treating
effective amount" in such a combination may be different from the amount that is required to
provide a pain treating effective amount of that agent alone. In certain embodiments, a lower
amount of at least one of the pain treating agents is required in the combination than alone.
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In some embodiments of the invention, pain is treated using a combination of a compound of
formula I and an opioid analgesic.
[0045] In some embodiments of the invention, pharmaceutical compositions are provided
in unit dosage form, such as tablets or capsules. In such form, the composition is sub-divided
in unit dose containing appropriate quantities of the active ingredient(s). The unit dosage
forms can be packaged compositions, for example packeted powders, vials, ampoules, pre-
filled syringes or sachets containing liquids. The unit dosage form can be, for example, a
capsule or tablet itself, or it can be an appropriate number of any such compositions in
package form.
[0046] Thus, the present invention also provides a pharmaceutical composition in unit
dosage form for treating pain in a mammal that contains a pain treating effective unit dosage
of at least one compound of formula I. As one skilled in the art will recognize, the preferred
pain treating effective unit dosage will depend on for example the method of administration.
A typical dosage of compounds of formula I often ranges from about 0.5 mg to about 500
mg, in some embodiments from about 1 mg or about 10 mg to about 500 mg.
[0047] The present invention also provides a therapeutic package for dispensing the
compounds of formula I to a mammal being treated for pain. In some embodiments, the
therapeutic package contains one or more unit dosages of the compound of formula I, a
container containing the one or more unit dosages, and labeling directing the use of the
package for treating pain in a mammal. In certain embodiments, the unit dose is in tablet or
capsule form. In some cases, each unit dosage is a pain treating effective amount.
3. Other Agents
[0048] The compounds of formula I may be administered alone in order to treat pain in
accordance with the present invention, or may be combined with one or more other
pharmaceutical agents. In some embodiments of the invention, the additional pharmaceutical
agent(s) also have pain-relief activity. Alternatively or additionally, the additional agents
may relieve one or more side effects associated with the pain-relieving agent(s), or may
relieve one or more other symptoms or conditions associated with the pain or otherwise of
concern to the individual suffering from or susceptible to pain.
[0049] Thus, in accordance with the present invention, the term "pain relieving agents" is
used to refer to any agent that directly or indirectly treats pain or pain symptoms. Examples
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of indirect pain relieving agents include, for example, anti-inflammatory agents, such as anti-
rheumatoid agents.
[0050] Where the present invention involves administration of two or more
pharmaceutical agents, such as for example two or more pain relieving agents, the two or
more agents may be administered simultaneously (such as individually at the same time, or
together in a pharmaceutical composition), and/or successively with one another. In general,
the compound of formula I and the other pharmaceutical agent(s) are administered in a
manner so that both are present in the mammal body for a certain period of time to treat pain.
[0051] Also, the two or more pharmaceutical agents may be delivered via the same route
of administration or by different routes. Desirable routes of administration may well depend
upon the particular agent(s) chosen, many of which have recommended administration
route(s) known to those skilled in the art. For example, opioids are generally administered by
oral, intravenous, or intramuscular administration routes. Similarly, as is known in the art,
doses of pharmaceutical agents in a composition may be affected by administration route. In
general, pharmaceutical agents may be dosed and administered according to practices known
to those skilled in the art such as those disclosed in references such as the Physicians' Desk
Reference, 55 Edition, 2001, published by Medical Economics Co., Inc., Montvale, NJ.
[0052] Examples of pain relieving agents that may be administered with the compounds
of formula I in accordance with present invention include, but are not limited to, analgesics
such as non-narcotic analgesics or narcotic analgesics; anti-inflammatory agents such as non-
steroidal anti-inflammatory agents (NSAIDs), steroids or anti-rheumatic agents; migraine
preparations such as beta adrenergic blocking agents, ergot derivatives, or isometheptene;
tricyclic antidepressants such as amitryptyline, desipramine, or imipramine; anti-epileptics
such as gabapentin, carbamazepine, topiramate, sodium valproate or phenytoin; ct2 agonists;
or selective serotonin reuptake inhibitors/selective norepinepherine uptake inhibitors, or
combinations thereof.
[0053] One skilled in the art will recognize that some agents described herein act to
relieve multiple conditions such as pain and inflammation, while other agents may just relieve
one symptom such as pain. A specific example of an agent having multiple properties is
aspirin, where aspirin is anti-inflammatory when given in high doses, but at lower doses is just
an analgesic. The pain relieving agent may include any combination of the aforementioned
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agents, for example, the pain relieving agent may be a non-narcotic analgesic in combination
with a narcotic analgesic.
[0054] Non-narcotic analgesics useful in the practice of the present invention include, for
example, salicylates such as aspirin, ibuprofen (MOTRIN®, ADVIL®), ketoprofen
(ORUDIS®), naproxen (NAPROSYN®), acetaminophen, indomethacin or combinations
thereof. Examples of narcotic analgesic agents that may be used in combination with
compounds of formula I include opioid analgesics such as fentenyl, sufentanil, morphine,
hydromorphone, codeine, oxycodone, buprenorphine or pharmaceutically acceptable salts
thereof or combinations thereof. Examples of anti-inflammatory agents that may be used in
combination with compounds of formula I include but are not limited to aspirin; ibuprofen;
ketoprofen; naproxen; etodolac (LODINE®); COX-2 inhibitors such as celecoxib
(CELEBREX®), rofecoxib (VIOXX®), valdecoxib (BEXTRA®), parecoxib, etoricoxib
(MK663), deracoxib, 2-(4-ethoxy-phenyl)-3-(4-methanesulfonyl-phenyl)-pyrazolo[l ,5-b]
pyridazine, 4-(2-oxo-3 -phenyl-2,3 -dihydrooxazol-4-yl)benzenesulfonamide, darbufelone,
flosulide, 4-(4-cyclohexyl-2-methyl-5-oxazolyl)-2-fluorobenzenesulfonamide), meloxicam,
nimesulide, l-Methylsulfonyl-4-(l,l-dimethyl-4-(4-fluorophenyl)cyclopenta-2,4-dien-3-
yl)benzene, 4-(l,5-Dihydro-6-fluoro-7-methoxy-3-(trifluoromethyl)-(2)-
benzothiopyrano(4,3-c)pyrazol-l-yl)benzenesulfonamide,4,4-dimethyl-2-phenyl-3-(4-
methylsulfonyl)phenyI)cyclo-butenone, 4-Amino-N-(4-(2-fluoro-5-trifluoromethyl)-thiazol-
2-yl)-benzene sulfonamide, l~(7-tert-butyl-2,3-dihydro-3,3-dimethyl-5-benzo-furanyl)-4-
cyclopropyl butan-1-one, or their physiologically acceptable salts, esters or solvates; sulindac
(CLINORIL®); diclofenac (VOLTAREN®); piroxicam (FELDENE®); diflunisal
(DOLOBID®), nabumetone (RELAFEN®), oxaprozin (DAYPRO®), indomethacin
(INDOCIN®); or steroids such as PEDIAPED® prednisolone sodium phosphate oral solution,
SOLU-MEDROL® methylprednisolone sodium succinate for injection, PRELONE® brand
prednisolone syrup.
[0055] Further examples of anti-inflammatory agents that may be used for treating pain,
for example associated with rheumatoid arthritis, in accordance with the present invention
include naproxen, which is commercially available in the form of EC-NAPROSYN® delayed
release tablets, NAPROSYN®, ANAPROX® and ANAPROX® DS tablets and NAPROSYN®
suspension from Roche Labs, CELEBREX® brand of celecoxib tablets, VIOXX® brand of
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rofecoxib, CELESTONE® brand of betamethasone, CUPRAMINE® brand penicillamine
capsules, DEPEN® brand titratable penicillamine tablets, DEPO-MEDROL brand of
methylprednisolone acetate injectable suspension, ARAVA™ leflunomide tablets,
AZULFIDIINE EN-tabs® brand of sulfasalazine delayed release tablets, FELDENE® brand
piroxicam capsules, CATAFLAM® diclofenac potassium tablets, VOLTAREN® diclofenac
sodium delayed release tablets, VOLTAREN®-XR diclofenac sodium extended release
tablets, or ENBREL® etanerecept products.
[0056] Examples of yet other agents used to treat inflammations, especially rheumatoid
arthritis, include immunosuppressants such as GENGRAF™ brand cyclosporine capsules,
NEORAL® brand cyclosporine capsules or oral solution, or IMURAN® brand azathioprine
tablets or IV injection; INDOCIN® brand indomethacin capsules, oral suspension or
suppositories; PLAQUENIL® brand hydroxychloroquine sulfate; or REMICADE® infliximab
recombinant for IV injection; or gold compounds such as auranofin or MYOCHRISYINE®
gold sodium thiomalate injection.
[0057] The present invention provides pain treatments in which compounds of formula I
are administered with one or more other pharmaceutical agents other than a pain-relieving
agent. For example, in accordance with the present invention, compounds of formula I may
be administered with one or more other pharmaceutical agents active in treating any other
symptom or medical condition present in the mammal that is related or unrelated to the pain
being experienced by the mammal. Examples of such pharmaceutical agents include, for
example, anti-angiogenic agents, anti-neoplastic agents, anti-diabetic agents, anti-infective
agents, or gastrointestinal agents, or combinations thereof.
[0058] A more complete list of pharmaceutically active agents, including pain relieving
agents, can be found in the Physicians' Desk Reference, 55 Edition, 2001, published by
Medical Economics Co., Inc., Montvale, NJ. Each of these agents may be administered in
conjunction with one or more comopunds of formula I according to the present invention.
For most or all of these agents, recommended effective dosages and regimes are known in the
art; many can be found in the above-referenced Physicians' Desk Reference, 55 Edition,
2001, published by Medical Economics Co., Inc., Montvale, NJ.
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4. Uses
[0059] According to the present invention, compounds of formula I are useful for
treating, or delaying the onset of, pain in mammals. By "treating", as that term is used
herein, it is meant partially or completely alleviating, inhibiting, ameliorating and/or relieving
pain. For example, "treating" as used herein includes partially or completely alleviating,
inhibiting or relieving pain for a period of time. "Treating" also includes completely
ameliorating the pain. The term "delay the onset of refers to a delay in the initiation of pain
after a trigger. In some cases, the magnitude of the pain eventually suffered may also be
reduced; in some instances, pain may be completely avoided.
[0060] Thus, in some embodiments of the present invention, compounds of formula I are
administered after the onset of pain; in other embodiments, the compounds are administered
prior to the onset of pain, for example after exposure to a stimulus that is expected or
considered likely to induce pain.
[0061] According to the present invention, compounds of formula I may be used to treat
any of a variety of different types of pains experienced by mammals, such as humans. For
example, the compounds of formula I may be used to treat treating acute pain (short duration)
or chronic pain (regularly reoccurring or persistent), whether centralized or peripheral.
[0062] Examples of pain that can be acute or chronic and that can be treated in
accordance with the methods of the present invention include inflammatory pain,
musculoskeletal pain, bony pain, lumbosacral pain, neck or upper back pain, visceral pain,
somatic pain, neuropathic pain, cancer pain, pain caused by injury or surgery such as burn
pain, or headaches such as migraines or tension headaches, or combinations of these pains.
One skilled in the art will recognize that these pains may overlap one another. For example,
a pain caused by inflammation may also be visceral or musculoskeletal in nature:
[0063] In one embodiment of the present invention, one or more compounds of formula I
is/are administered in mammals to treat chronic pain such as neuropathic pain associated for
example with damage to or pathological changes in the peripheral or central nervous systems;
cancer pain; visceral pain associated with for example the abdominal, pelvic, and/or perineal
regions or pancreatitis; musculoskeletal pain associated with for example the lower or upper
back, spine, fibromylagia, temporomandibular joint, or myofascial pain syndrome; bony pain
associated with for example bone or joint degenerating disorders such as osteoarthritis,
rheumatoid arthritis, or spinal stenosis; headaches such migraine or tension headaches; or
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pain associated with infections such as HIV, sickle cell anemia, autoimmune disorders,
multiple sclerosis, or inflammation such as osteoarthritis or rheumatoid arthritis.
[0064] In some embodiments, the compounds of formula I are used to treat chronic pain
that is neuropathic pain, visceral pain, musculoskeletal pain, bony pain, headache, cancer
pain or inflammatory pain or combinations thereof, in accordance with the methods described
herein. Inflammatory pain can be associated with a variety of medical conditions such as
osteoarthritis, rheumatoid arthritis, surgery, or injury. Neuropathic pain may be associated
with for example diabetic neuropathy, peripheral neuropathy, post-herpetic neuralgia,
trigeminal neuralgia, lumbar or cervical radiculopathies, fibromyalgia, glossopharyngeal
neuralgia, reflex sympathetic dystrophy, casualgia, thalamic syndrome, nerve root avulsion,
or nerve damage cause by injury resulting in peripheral and/or central sensitization such as
phantom limb pain, reflex sympathetic dystrophy or postthoracotomy pain, cancer, chemical
injury, toxins, nutritional deficiencies, or viral or bacterial infections such as shingles or HIV,
or combinations thereof. Inventive treatment methods further include treatments in which the
neuropathic pain is a condition secondary to metastatic infiltration, adiposis dolorosa, burns
or central pain conditions related to thalamic conditions.
[0065] Neuropathic pains described above may also be, in some circumstances, classified
as "painful small fiber neuropathies" such as idiopathic small-fiber painful sensory
neuropathy, or "painful large fiber neuropathies" such as demylinating neuropathy or axonal
neuropathy, or combinations thereof. Such neuropathies are described in more detail, for
example, in the J. Mendell et al, N. Engl J. Med. 2003, 348:1243-1255, which is hereby
incorporated by reference in its entirety.
[0066] In another embodiment, the compounds useful in the present invention may be
administered to totally or partially inhibit a neuropathic pain condition from developing. For
example, compounds of the present invention may be administered to a mammal who is at
risk for developing a neuropathic pain condition such as a mammal who has contracted
shingles or a mammal who is being treated for cancer.
In one embodiment, the compounds useful in the present invention may be administered prior
to or during a surgical procedure to partially or totally inhibit development of pain associated
with the surgical procedure.
[0067] As mentioned previously, the methods of the present invention may be used to
treat pain that is somatic and/or visceral in nature. For example, somatic pain that can be
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treated in accordance with the methods of the present invention includes pain associated with
structural or soft tissue injury experienced during surgery, dental procedures, burns, or
traumatic body injuries. Examples of visceral pain that can be treated in accordance with the
methods of the present invention include those types of pain associated with or resulting from
maladies of the internal organs such as ulcerative colitis, irritable bowel syndrome, irritable
bladder, Crohn's disease, rheumatologic (arthralgias), tumors, gastritis, pancreatitis,
infections of the organs, or biliary tract disorders, or combinations thereof. One skilled in the
art will also recognize that the pain treated according to the methods of the present invention
may also be related to conditions of hyperalgesia, allodynia, or both. Additionally, chronic
pain to be treated in accordance with the present invention may be with or without peripheral
or central sensitization.
[0068] The present invention also provides use of the compounds of formula I to treat
acute and/or chronic pains associated with female conditions, which may also be referred to
as female-specific pain. Such types of pain include those that are encountered solely or
predominately by females, including pain associated with menstruation, ovulation, pregnancy
or childbirth, miscarriage, ectopic pregnancy, retrograde menstruation, rupture of a follicular
or corpus luteum cyst, irritation of the pelvic viscera, uterine fibroids, adenomyosis,
endometriosis, infection and inflammation, pelvic organ ischemia, obstruction, intra-
abdominal adhesions, anatomic distortion of the pelvic viscera, ovarian abscess, loss of pelvic
support, tumors, pelvic congestion or referred pain from non-gynecological causes.
[0069] According to the present invention, compounds of formula I can be administered
in any of a variety of ways including for example by oral, intramuscular, intraperitoneal,
epidural, intrathecal, intravenous, subcutaneous, intramucosal such as sublingual or
intranasal, or transdermal administration. In a certain embodiments of the invention, the
compounds of formula I are administered orally, intramucosally or intravenously.
[0070] The present invention provides treatment methods in which compounds of
formula I are administered in a pain treating effective amount to a mammal needing treatment
for pain. As used herein "a pain treating effective amount" is at least the minimal amount of
the compound of formula I, or a pharmaceutically acceptable salt form thereof, which
reduces, alleviates, delays, and/or eliminates the pain in question.
[0071] To determine the pain treating effective amount of the compound to be
administered in the treatment of pain in a particular circumstance, the physician may, for
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example, evaluate the effects of a given compound of formula I in the patient by
incrementally increasing the dosage, for example from about 0.5 mg to about 1000 mg until
the desired symptomatic relief level is achieved. The continuing dose regimen may then be
modified to achieve the desired result. Similar techniques may be followed by determining
the effective dose range for different administration routes.
EXEMPLIFICATION
Example 1
Assessment of Effectiveness in Treatment of Pain
[0072] Compounds of formula I may be evaluated in accordance with the present
invention to establish the extent of their effectiveness to treat pain, and may optionally be
compared with other pain treatments.
[0073] A variety of methods have been established in the art to evaluate the effectiveness
of compounds for relieving pain. See e.g., Bennett et al, Pain 33: 87-107, 1988; Chaplan et
al, J. Neurosci. Methods 53:55-63, 1994; and Mosconi et al, Pain 64:37-57,1996. Below is a
specific description of one strategy that may be employed.
Procedure
[0074] Individually housed Spraque-Dawley rats are given free access to rat chow and
water. A 12-h light/12-h dark cycle is put in effect (lights on from 6:00 am to 6:00 pm).
Animal maintenance and research are conducted in accordance with the guidelines provided
by the National Institutes of Health Committee on Laboratory Animal Resources. These
subjects are used in the tests as set forth below.
Test Method 1: Prostaglandin E2-induced thermal hypersensitivity.
[0075] The terminal 10 cm of the tail is placed into a thermos bottle containing water
warmed to 38, 42, 46, 50, 54, or 58 °C. The latency in seconds for the animal to remove the
tail from the water is used as a measure of nociception. If the animal does not remove the tail
within 20 sec, the experimenter removes the tail from the water and a maximum latency of 20
sec is recorded.
[0076] Following the assessment of baseline thermal sensitivity, thermal hypersensitivity
is produced by a 50 μL injection of 0.1 mg prostaglandin E2 (PGE2) into the terminal 1 cm of
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the tail. Temperature-effect curves are generated before (baseline) and after (15, 30, 60, 90
and 120 min) the PGE2 injection. Previous studies in other species (e.g., monkeys; Brandt et
al., J. Pharmacol. Exper. Titer. 296:939, 2001) have demonstrated that PGE2 produces a
dose- and time-dependent thermal hypersensitivity that peaks 15 min after injection and
dissipates after 2 hr.
[0077] Single compound studies. The ability of drugs to reverse PGE2-induced thermal
hypersensitivity is assessed using a single dose time-course procedure. Under this procedure,
a single dose of the compound to be tested is administered intraperitoneally (DP), orally (PO)
or intranasally (IN) 30 min before the injection of PGE2. Tactile sensitivity is assessed 30
min after PGE2 injection.
[0078] Combination compound studies. Combination studies with two or more potential
pain treatment agents can be conducted. A minimally effective dose of a first agent, e.g.,
morphine is administered alone and in combination with ineffective doses of one or more
compounds of formula I in the thermal warm-water tail withdrawal assay. Compounds are
administered IP at the same time 30 min before testing.
[0079] Combination studies can also be conducted in the PGE2-induced thermal
hypersensitivity assay. For example, a dose of morphine that completely reverses thermal
hypersensitivity (i.e., return to baseline) can be administered alone and in combination with
doses of one or more compounds of formula I in the PGE2-induced thermal warm-water tail
withdrawal assay. Compounds are administered P at the same time as PGE2, which is
administered 30 min before testing.
[0080] Test Method 1 Data Analysis - The temperature that produced a half-maximal
increase in the tail-withdrawal latency (i.e., T10) is calculated from each temperature-effect
curve. The T10 is determined by interpolation from a line drawn between the point above and
the point below 10 sec on the temperature-effect curve. For these studies, thermal
hypersensitivity is defined as a leftward shift in the temperature-effect curve and a decrease
in the Tjo value. Reversal of thermal hypersensitivity is defined as a return to baseline of the
temperature-effect curve and the T10 value and is calculated according to the following
equation:

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in which T10drug+PGE2 is the TJO after a drug in combination with PGE2, T10PGE2 is the T10 after
PGE2 alone, and T10baseline is the Ti0 under control conditions. A % MPE value of 100
indicates a complete return to the baseline thermal sensitivity observed without the PGE2
injection. A value of greater than 100% indicates that the compound tested reduced thermal
sensitivity more than the baseline thermal sensitivity without the PGE2 injection.
Test Method 2: Chronic Constriction Injury
[0081] Rats are anesthetized with 3.5% halothane in O2 at 1 L/min and maintained with
1.5% halothane in O2 during surgery. A modified chronic sciatic nerve constriction injury
(Mosconi & Kruger, 1996; Bennett & Xie, 1988) is produced by a cutaneous incision and a
blunt dissection through the biceps femoris to expose the sciatic nerve. A PE 90
Polyethylene tubing (Intramedic, Clay Adams; Becton Dickinson Co.) cuff (2mm length) is
placed around the sciatic nerve at the level of the mid-thigh. The wound is closed in layers
using 4-0 silk suture and wound clips. Testing was conducted 6-10 days after surgery.
[0082] Animals are placed in elevated wire cages and allowed 45-60 minutes to acclimate
to the testing room. Baseline tactile sensitivity is assessed using a series of calibrated von
Frey monofilaments (Stoelting; Wood Dale, EL) 0-3 days before surgery. Von Frey
monofilaments are applied to the mid-plantar hind paw in sequential ascending or descending
order, as necessary, to hover as closely as possible to the threshold of responses. The
threshold is indicated by the lowest force that evoked a brisk withdrawal response to the
stimuli. Thus, a withdrawal response leads to the presentation of the next lighter stimulus
and the lack of a withdrawal response leads to the presentation of the next stronger stimulus.
Rats with baseline thresholds < 4 g force are excluded from the study. Approximately one
week following CCI surgery, tactile sensitivities are reassessed and animals that exhibit
motor deficiency (i.e. paw dragging) or failure to exhibit subsequent tactile hypersensitivity
(threshold > lOg) are excluded from further testing. Under cumulative dosing conditions,
compounds are administered IP every 30 minutes with the cumulative dose increasing in Mi-
log unit increments. Tactile hypersensitivity is assessed 20-30 minutes following each drug
administration.
[0083] Test Method 2 Data Analysis. The 50% threshold values (in gm force) estimated
by the Dixon non-parametric test (Ghaplan et al, 1994) are calculated and fifteen-grams of
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force is used as the maximal force. Dose-effect curves are generated for each experimental
condition for each rat. Individual tactile hypersensitivity threshold values are averaged to
provide a mean (± 1 SEM). Reversal of tactile hypersensitivity was defined as a return to
baseline tactile sensitivity and was calculated according to the following equation:

in which 50%drug+CCI is the 50% value after compound in animals approximately one week
after CCI surgery, 50%CCI is the 50% value approximately one week after CCI surgery alone,
and 50%baseIine is the 50% value before CCI surgery. Maximal effect of 100 % reversal
represents a return to the mean pre-operative threshold value for subjects in that experimental
condition.
Test Method 3: Scheduled-controlled responding.
[0084] Rats are trained under a multiple-cycle procedure during experimental sessions
conducted five days each week. Each training cycle consists of a 10-min pretreatment period
followed by a 10-min response period. During the pretreatment period, stimulus lights are
not illuminated, and responding has no scheduled consequences. During the response period,
the left or right stimulus lights are illuminated (counterbalanced among subjects), the
response lever is extended and subjects can respond under a fixed ratio 30 schedule of food
presentation. Training sessions consist of 3 consecutive cycles. Testing sessions are
identical to training sessions except that a single dose of drug is administered at the start of
the first cycle.
[0085] Test Method 3 Data analysis. Operant response rates from individual animals
are averaged for the three cycles during test sessions and are converted to percent of control
response rates using the average rate from the previous training day as the control value (i.e.,
average of three cycles). Data are presented as the mean (± 1 SEM) response rate as a
percent of control. Thus, for example, a test value of 100% would indicate the response rate
after administration of the compound to be tested is the same as the control response rate and
there is no adverse effect of the compound tested.
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Example 2
Assessment of Effectiveness in Chronic Neuropathic Pain Model
[0086] Compound 1, (7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydrobenzofuran-2-
yl)methanamine, was obtained from Wyeth compound repository and gabapentin was
purchased from Toronto Research Chemicals (Ontario, Canada) and were purchased from
Sigma Chemical Company (St. Louis, MO). Compound 1 was dissolved in sterile saline and
gabapentin was suspended in 2% Tween 80 in 0.5% methylcellulose and sterile water. All
compounds were administered intraperitoneally (i.p.).
[0087] Male Sprague-Dawley rats (125 - 150 g, Harlan; Indianapolis, IN) were
individually housed on bedding. For all studies animals were maintained in climate-
controlled rooms on a 12-hour light/dark cycle (lights on at 0630) with food and water
available ad libitum.
[0088] All surgical procedures were performed under 4% isofiurane/02 anesthesia,
delivered via nose cone and maintained at 2.5% for the duration of the surgery.
[0089] L5 Spinal Nerve Ligation (SNL): Surgery was performed as previously
described (Kim and Chung) with the exception that nerve injury was produced by tight
ligation of the left L5 spinal nerve.
[0090] Assessment of Tactile Allodynia (Tactile Sensitivity): Tactile thresholds were
assessed using a series of calibrated von Frey monofilaments (Stoelting; Wood Dale, IL).
The threshold that produced a 50% likelihood of a withdrawal was determined using the up-
down method, as previously described (Chaplan et al., 1994).
[0091] Animals were placed in elevated wire cages and allowed 45-60 minutes to
acclimate to the testing room. Von Frey monofilaments were applied to the mid-plantar left
hind paw in sequential ascending or descending order, as necessary, to hover as closely as
possible to the threshold of responses. The lowest force that evoked a brisk withdrawal
response to the stimuli determined the pain threshold. Tactile thresholds were determined on
the day prior to surgery and rats with baseline thresholds < 10g force were excluded from
studies. Three weeks after SNL surgery tactile thresholds were reassessed and animals that
failed to exhibit subsequent tactile allodynia (threshold > 5g) were excluded from further
testing. Subjects were pseudo-randomly divided into test groups (n=8-10) so that average
baseline and post-surgery sensitivities were similar among groups. For all compound testing,
rats were administered Compound 1 (0:3, 1 or 3 mg/kg, i.p), gabapentin (100 mg/kg, i.p.,
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postivie control) or vehicle and tactile thresholds were assessed up to 60, 180 and 300
minutes after dosing.
[0092] Analysis of Results: Statistical analysis was done using a repeated measures
analysis of variance (ANOVA) using a customized SAS-excel application (SAS Institute,
Cary, NC). Significant main effects were analyzed further by subsequent least significant
difference analysis. The criterion for significant differences was p < 0.05. Reversal of tactile
allodynia was calculated according to the following equation:

In which 50% thresholddrug + post surgeiy is the 50% threshold in g force after drug in nerve
injured subjects, 50% thresholdpost surgery is the 50% threshold in g force in nerve injured
subjects, and 50% threshold1"6 surgery is the 50% threshold in g force before nerve injury.
Maximal effect of 100 % reversal represents a return to the mean pre-operative threshold
value for subjects in that experimental condition. See Figure 1.
Example 3
Assessment of Effectiveness in Chronic Inflammatory Pain
[0093] Compound 1 was dissolved in sterile saline and administered intraperitoneally
(i.p.). Celecoxib was used as a positive control and was suspended in 2% Tween 80 in 0.5%
methylcellulose and administered orally (p.o.).
[0094] Male Sprague-Dawley rats (125 - 150 g, Harlan; Indianapolis, IN) were housed
3/cage on bedding and. animals were maintained in climate-controlled rooms on a 12-hour
light/dark cycle (lights on at 0630) with food and water available ad libitum.
[0095] Freund's complete adjuvant (FCA') of mechanical hyperalgesia: The hind paw
withdrawal thresholds (PWTs) to a noxious mechanical stimulus were determined using an
analgesimeter (model 7200; Ugo Basile). Cutoff was set at 250 g, and the endpoint taken was
complete paw withdrawal. PWT was determined once for each rat at each time point
(n=10/group). Baseline PWT was determined, and the rats were anesthetized with isofluorane
(2% in oxygen) and received an intraplantar injection of 50% FCA (50 ul, diluted in saline) to
the left hind paw. Twenty-four hours after FCA injection, pre-drug PWTs were measured,
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and the rats were administered vehicle or compound and assessed on PWTs 1, 3, 5, and 24 h
post-drug administration.
[0096] Analysis of Results: Statistical analysis was done using a one way analysis of
variance (ANOVA) using a customized SAS-excel application (SAS Institute, Cary, NC).
Significant main effects are analyzed further by subsequent least significant difference
analysis. The criterion for significant differences is p < 0.05 from vehicle-treated FCA rats.
Data is presented as percent reversal according to the following equation: percent reversal =
[(post-dose threshold) - pre-dose threshold))/(baseline threshold-pre-dose threshold)] X 100.
See Figure 2.
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CLAIMS
We claim:
1. A method of treating pain in a mammal comprising administering to a
mammal in need thereof, an effective amount of at least one compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
n is one or two;
each of R2 and R3 is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl
or cyclopropyl;
each R1 is independently hydrogen, halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl,
lower haloalkoxy, or CN;
Ar is thienyl, furyl, pyridyl, or phenyl, wherein Ar is optionally substituted with one or more
Rx substituents;
each Rx is independently selected from halogen, OH, lower alkyl, lower alkoxy, lower
haloalkyl, lower haloalkoxy, or CN; and
y is 0-3.
2. The method according to claim 1, wherein one of R2 and R3 is hydrogen and
the other R2 and R3 group is hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl or
cyclopropyl.
3. The method according to claim 2, wherein both of R2 and R3 are hydrogen.
4. The method according to claim 1, wherein neither R2 and R3 is hydrogen.
5. The method according to any one of claims 1 to 4, wherein y is zero.
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6. The method according to any one of claims 1 to 4, wherein y is other than zero
and at least one R1 group is halogen.
7. The method according to any one of claims 1 to 4, wherein y is one and R1 is
halogen, OH, lower alkyl, lower alkoxy, trifluoromethyl, trifluoromethoxy, or CN.
8. The method according to claim 7, wherein y is one and R1 is fhioro or chloro.
9. The method according to claim 7, wherein said compound is of formula la or
Ia':
or a pharmaceutically acceptable salt thereof.
10. The method according to any one of claims 1 to 9, wherein Ar is unsubstituted
phenyl.
11. The method according to any one of claims 1 to 9, wherein Ar is phenyl with
at least one substituent in the ortho position.
12. The method according to claim 11, wherein Ar is phenyl with at least one
substituent in the ortho position selected from halogen, lower alkyl, lower alkoxy, or
trifluoromethyl.
13 The method according to claim 11, wherein said compound is of formula lb or
Ic:
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or a pharmaceutical^ acceptable salt thereof.
14. The composition according to claim 13, wherein said compound is of formula
Id, Ie, If, Ig, Ih, orli:

or a pharmaceutically acceptable salt thereof.
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15. The method according to any one of claims 1 to 9, wherein Ar is selected
from:

16. The method according to claim 1, wherein said compound is selected from:
(±)-l-{7-[3,5-bis(Mfluorometiiyl)phenyl]-23-dmydro-l-benzoiuran-2-yl}methanamine,
(±)-l-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(3,5-dichlorophenyl)-253-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-(7-phenyl-2,3-dmydro-l-benzofuran-2-yl)methanamine,
(+)-(l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(-)-l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(±)-l-[7-(3-methylphenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-(7-thien-3-yl-253-dihydro-l-benzofuran-2-yl)methanamine,
(+)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(-)-1 -(7-thien-3-yl-2,3-dihydro-1 -benzofuran-2-yl)methanamine,
(±)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-1 - [7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine5
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(-)4-[7-(2-methylphenyl)-2,3-dihydro-l-benzoforan-2-yl]methanamine5
(±)-l-[7-(2-fluorophenyl)-233-dihydro-l-benzofuran-2-yl]methanamine,
(+)-1 - [7-(2-fluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanarnine,
(-)-1 -[7-(2-fluorophenyl)-2,3-dihydro-l -benzofhran-2-yl]methanamine,
(±)-l-{7-[2-(trifluorome1iiyl)phenyl]-23-dihydro-l-benzofuran-2-yl}methanatnine,
(-)-1 - {7-[2-(trifluoromethyl)phenyl]-2,3 -dihydro-1 -benzofuran-2-yl} methanamine,
(+)-l-{7-[2-(trifluoromethyl)phenyl]-23-dihydro-l-beiizofuran-2-yl}methanamine5
(±)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(2,6-dimethylphenyl)-23-dihydro-l-beiKofuran-2-yl]methanamine,
(+)-1 -[7-(2,6-dimethylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-1 - [7-(2-methoxyphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]raethanamine,
(±)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine>
(+)-1 -[7-(3-chlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 - [7-(3 -methoxyphenyl)-2,3 -dihydro-1 -benzofuran-2-yl] methanamine,
(±)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine3
(±)-1 -[7-(4-methylphenyl)-2,3-dihydro-1 -benzoruran-2-yl]methanamine,
(+)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamines
(-)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(±)-l -[7-(4-fluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(+)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzoturan-2-yl]methanamine,
(-)-l -[7-(4-fluorophenyl)-2,3-dihydro-1 -benzoruran-2-yl]methanamine,
(±)-l-[7-(4-chlorophenyI)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(-)-l-[7-(4-clilorophenyl)-2,3-dihydro-l-benzoturan-2-yl]methanamine5
(±)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(+)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzoturan-2-yl}methanamine,
(±)-l-[7-(234-dichlorophenyl)-253-dihydro-l-benzoruran-2-yl]methanamine,
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(±)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(+)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(-)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(±)-l-[5-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 -[5-chloro-7-(3-methylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-l -[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-(5-cWoro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylamine,
(-)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylamine,
(+)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylambe,
(+)-7^-[(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]-Ar-methylamm^
(-)-A^-[(5-chloro-74hien-3-yl-23-dihydro-l-benzoftiran-2-yl)methyl]-//-methylamine,
(±)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-1 - [5-chloro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[5-chloro-7-(2-methylphenyl)-23-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-(4-fluoro-7-phenyl-2,3-dihydro-l-benzoftiran-2-yl)meihanamine,
(±)-l -[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-[7-(2-chlorophenyl)-5-fluoro-23-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofbran-2-yl]methanamine,
(-)-1 -[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-l -(S-fltioro^-phenyl^jS-dihydro-l -benzofuran-2-yl)methanamine,
(±)-1 -[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine3
(+)-l -[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-l-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine5
(±)-1 - {5-fluoro-7- [2-(tri£luoromethyl)phenyl] -2,3 -dihydro-1 -benzofuran-2-yl} methanamine,
(±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methylamine,
(±)-1 -[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-l-(5-chloro-2-methyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine,
(±)-(5-cMoro-2-methyl-7-tMen-3-yl-2,3-dihydro-l-benzofuran-2-yl)inethylamine5
(±)-(5-chloro-2-methyl-7-thien-2-yl-2,3-dihydro-l-benzofuran-2-yl)methylamine,
(+)-1 -[7-(2-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(+)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(-)-l-[7-(3-fluorophenyl)-253-dihydro-l-benzofuran-2-yl]methanamine,
(+)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzof\n^n-2-yl]methanamine5
(-)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofoan-2-yl]methanamine,
(-)-l-{7-[3-(1xifluoromethyl)phenyl]-23-dihydro-l-benzofuran-2-yl}methanamine,
(+)-l-{7-[3-(trifluoromethyl)phenyl]-23-dihydro-l-benzofuran-2-yl}methanamine,
(+)-l-{7-[4-(trifluoromethyl)phenyl]-23-dihydro-l-benzofuran-2-yl}methanamine,
(-)-l-{7-[4-(trifluoromethyl)phenyl]-23^ihydro-l-benzofiHan-2-yl}methanamine,
(±)-l-[7-(2,6-difluoroplienyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-1 - [7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(-)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamiQe,
(+)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methananiine,
(±)-l-[7-(2,4-dimethoxyphenyl)-253-dihydro-l-benzofuran-2-yl]methanamine,
(-)-1 - [7-(2,4-dimethoxyphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methanamine,
(+)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-beiizof\nmi-2-yl]methanamine,
(±)-l-[7-(2,4-difluorophenyl)-23-dihydro-l-beiizofuran-2-yl]methanamine,
(+)-l-[7-(2,4-difluorophenyl)-23-dihydro-l-benzofuran-2-yl]methanamineJ
(-)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzoforan-2-yl]methanamine,
(-)-1 -[7-(2,4-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(+)-1 -[7-(2,4-dichlorophenyl)-2,3~dihydro-1 -benzofuran-2-yl]methanamine,
(-)4-{5-fluoro-7-[2-(trifluorome1iiyl)pte^
(+)-l-{5-fluoro-7-[2-(1rifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methanamine,
(±)-l-[7-(23-dimethylphenyl)-2,3-dib.ydro-l-benzofuran-2-yl]methanamine,
(±)- {[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(+)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)- {[7-(4-chloro-2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{ [7-(2,5-dimethoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
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(±)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-beiizofean-2-yl]methyl}ainine,
(+)- {[7-(2,5-dichlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(-)-{[7-(2,5-dicWorophenyl)-2}3-dihydro-l-benzofuran--yl]methyl}amine,
(±)- {[7-(2,4,6-trichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(5 -chloro-2-methylphenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(5-cWoro-2-methoxyphenyl)-2,3-dihydio-l-benzofuran-2-yl]methyl}aniine,
(±)- [(7-pyridin-3-yl-2,3 -dihydro-1 -benzofuran-2-yl)methyl] amine,
(+)- {[7-pyridin-3-yl-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(-)- {[7-pyridin-3-yl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(3-methoxyphenyl)-2,3-dihydro-l-benzofijran-2-yl]methyl}amine,
(±)- {[5-fluoro-7-(3-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-fluoro-7-(4-fluorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-fluoro-7-(4-chlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-fluoro-7-(4-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-fluoro-7-(4-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yI]methyl}amine,
(±)-[(5-fluoro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)- {[5 -fluoro-7-(3 -furyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-[(5-fluoro-7-pyridin-2-yl-2,3-dihydro-l-benzonoran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyI]amine,
(-)-[(5-fluoro-7-pyridin-3 -yl-2,3 -dihydro-1 -benzofuran-2-yI)methyl]amine,
(+)-{[5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-[(5-£luoro-7-pyridin-4-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyrimidin-5-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-{[7-(2,3-dichlorophenyl)-5-fluoro-253-dihydro-l-benzofixran-2-yl]methyl}amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,3 -dimethoxyphenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,4-difluorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(-)-{[5-fluoro-7<2,4-dicMorophenyl)-253-dihy(ko4-benzofm,an-2-yl]methyl}amine,
(4-)-{[5-fluoro-7-(2,4-dichlorophenyl)-23-dihydro-l-benzofuran-2-yl]methyl}anime,
(±)-{[7-(254-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofoi:an-2-yl]methyl}amine,
(±)^[7<2,5-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dicWorophenyl)-5-fluoro-23-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-dimethylpb.enyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzoftiran-2-yl]methyl}ambe,
(±)- {[5-fluoro-7-(5-methoxy-2-memylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2,6-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3 -dihydro-1 -benzofuran-2-yl] methyl} amine,
(±)-N- {[7-(2,6-dichlorophenyl)-5 -fluoro-2,3 -dihydro-1 -benzofuran-2-
yl]methyl}cyclopropanamine,
(±)-1 -cyclopropyl-N- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3 -dihydro-1 -benzofuran-2-
yl]methyl}methanamine,
(±)-N-{[7-(2,6-dicUorophenyl)-5-fluoro-2,3-dihydro-l-benzoruran-2-yl]metliyl}ethanamine,
(±)- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1 -benzofuran-2-yl]methyl }dimethylamine,
(±)-{[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(3-furyl)-2)3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(±)- {[5-chloro-7-(2,3 -dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(-)-{[5-chloro-7-(2,4-dicUorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yI]methyl}amine,
(±)-{[5-chloro-7-(2,4-dimethoxyphenyl)-23-dihydro4-benzoforan-2-yl]methyl} amine,
(±)-{[5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,5-dicUorophenyl)-23-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{ [5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l -benzofuran-2- yl]methyl}amine,
(±)-{[5-chloro-7-(3,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzoflu,an-2-yl]methyl}amirie,
(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(256-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{ [5-cMoro-7-(2,6-dichlorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl }amine,
(+)-{[5-chIoro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[5-cMoro-7-(2,6-dicMorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amineJ
(±)-{[(5-cWoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-N- {[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1 -benzofuran-2-
yljmethyl} cyclopropanamine,
(±)-N- {[5-chloro-7-(2,6-dimethylpb.enyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl}(cyclopropylmethyl)amine>
(±)-N-{[5-chloro-7-(236-dimethylphenyl)-2,3-dihydro-l-benzofliran-2-yl]methyl}ethanamine,
(±)-{[(5-methyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl]amine,
(±)-{[7-(2-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yI]methyl}amine,
(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-({5-methyl-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofiiran-2-yl}methyl)amine,
(±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(4-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(±)- {[7-(4-fluorophenyl)-5 -methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(4-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(±)- {[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(-)- {[7-(2,3 -dimethoxyphenyl)-5-methyl-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2;4-dicWorophenyl)-5-methyI-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,4-dichlorophenyl)-5-methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,4-dicMorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dmydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,6-dimethylphenyl)-5 -methyl-2,3 -dihydro-1 -benzofuran-2-yl]methyI} amine,
(±)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,6-dichlorophenyl)-5-methyI-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzojEuran-2-yl]methyl}amine,
(±)- {[5-ethyl-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-ethyl-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-fluorophenyl)-2,3-dihydro-l-benzofiiran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(2-methylphenyl)-253-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-methoxyphenyI)-2,3-dihydro-l-benzofuran-2-
yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(2-(trifluoromethyl)phenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(3-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(3-fluorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)"{[5-(trifluoromethyl)-7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{ [5-(trifluoromethyl)-7-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(4-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[5-(tri£luoromethyl)-7-(4-fluorophenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluorometb.yl)-7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl} amine,
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(±)-{[5-(Mfluoromethyl)-7-(4-(trifluoromethyl)phenyl)-23-dihydro-l-benzoftiran-2-
yl]methyl}amine,
(±)-{[7-(23-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzoftiran-2-
yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)- {[7-(2,3 -dichlorophenyl)-5-(trifluoromethyl)-2,3-dihy dro-1 -benzofuran-2-
yljmethyl) amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yljmethyl} amine,
(±)-{[7-(2,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzoftiran-2-
yl]methyl} amine,
(±)-{[7-(3,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofliran-2-
yl]methyl} amine,
(±)- {[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1 -benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzoftjran-2-
yl]methyl}amine,
(±)-{[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3-dib.ydro-l-benzofuran-2-
yl]methyl}amine,
(±)-4-[2-(aminomethyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-7-yl]benzonitrile
(±)- {[7-(3-furyl)-5-(trifluoromethyl)-2,3-dihydro-1 -benzofbran-2-yl]methyl} amine,
(±)- {[7-thien-3-yl-5-(trifluoromethyl)-2,3-dihydro-1 -benzofttran-2-yl]methyl} amine,
(±)- {[7-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amme,
(±)-{[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
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(±)-{[5-methoxy-7-(3-tMenyl)-23-diiiydro-l-benzofliran-2-yl]methyl}amine,
(±)-{[7-(23-difluorophenyl)-5-methoxy-23-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,3-dicUorophenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{[7-(23-dimetiaylphenyl)-5-methoxy-2,3-dmydro-l-benzofuran-2-yl]me1hyl}amine,
(±)-{[7-(2)4-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,4-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzoftiran-2-yl]methyl}amine,
(±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,5~dichlorophenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)- {[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-{['7-(2,5-dimethoxylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}amine,
(±)- {[7-(5-chloro-2-methoxyphenyl)-5 -methoxy-2,3 -dihydro-1 -benzofuian-2-
yl]methyl} amine,
(±)- {[7-(3-chloro-4-fiuorophenyl)-5-methoxy-2,3 -dihydro-1 -benzomran-2-yl]methyl} amine,
(±)- {[7-(2,6-dimethylphenyl)-5-methoxy-2,3 -dihydro-1 -benzofuran-2-yl]methyl} amine,
(±)-[(N-methyl-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzoftiran-2-yl]methanamme,
(±)-[(N-methyl-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzoJEuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-m ethyl-1 -[7-(2,3 -dimethoxyphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzoruran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-l-[7-(2,5-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
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(±)-(N-methyl-l-[7-(2,5-dicMoropte^^
(±)-[(N-methyl-l-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methanamine,
(±)-[(N-methyl-l-[7-(5-chloro-2-methylphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methanamine,
(±)-[(N-methyl-l-[7-(2,6-dime%lphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine,
(±)-[(N-me1hyl-l-[7-(2,6-dicWorophenyl)-2,3-dftyd
(-)-{[7-(2,6-dicUorophenyl)-2,3-dihydro4-benzofuran-2-yl]methyl}methylamine,
(+)- {[7-(2,6-dichlorophenyl)-2,3 -dihydro-1 -benzofuran-2-yl]methyl} methylamine,
(±)-N-methyl-l -(7-pyridin-3-yl~2,3-dihydro-1 -benzofuran-2-yl)methanamine,
(±)-[(N-metliyl-l-[7-(2,3-difluorophenyl)-23-dihydro-l-benzof\iran-2-yl]methanamine,
(±)-{[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-fluoro-7-(2-chlorophenyl)-2,3-dihydro~ 1 -benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2-methylphenyl)-23-dihydro-l-benzofean-2-yl]methyl}methylamine,
(+)- {[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1 -benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}inethylamine,
(±)- {[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1 -benzoniran-2-
yl]methyl}methylamine,
(±)-[7-(2,4-dicMoTophenyl)-5-fluoro-2,3-dihydro-l-benzoforan-2-yl]methyl}methylamine5
(-)-[7-(254-dicUorophenyl)-5-fluoro-2^-dihydro-l-benzofiran-2-yl]methyl}methylamine,
(+)-[7-(2,4-dicMorophenyl)-5-fluoro-23-dihydro-l-beiizofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-1 -berizofuran-2-yl]methyl} methylamine,
(±)- {[7-(2,5 -dichlorophenyl)-5 -fluoro-2,3 -dihydro-1 -benzofiiran-2-yl] methyl} methylamine,
(+)-{[5-fluoro-7-(235-dichlorophenyl)-2,3-dihydro-l-benzoftiran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2,5-dichlorophenyl)-253-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzoftiran-2-yl]methyl}methylamme,
(±)-{[7-(2J6-dimethylphenyl)-5-fluoro-253-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-253-dihydro-l-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l-benzofuran-2-
yl]methyl}methylamine,
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(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l-benzofuran-2-
y 1] methyl} methylamine,
(±)- {[7-(5-chloro-2-methoxyphenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2-
yl]methyl}methylamine,
(±)-[(5-fluoro-7-pyridin-3-yl-23-