WO 2006/116149 PCT/US2006/015191
NEW THERAPEUTIC COMBINATIONS FOR THE TREATMENT OR
PREVENTION OF DEPRESSION
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to United States Provisional Patent Application
serial number 60/674,048, filed April 22, 2005, the entirety of which is hereby incorporated
herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to therapeutic combinations of compounds useful for
the treatment or prophylaxis of depression, to pharmaceutical compositions containing such
combinations, and to their use in the treatment or prophylaxis of depression.
BACKGROUND OF THE INVENTION
[0003] Between 5-10% of adults worldwide suffer from depression Even more
experience depression-related mood disorders such as dysthymia, seasonal affective disorder,
and postpartum depression, bipolar disorder, anxiety disorder, posttraumatic stress disorder,
panic disorder, and obsessive-compulsive disorder.
[0004] The economic costs to society, and person costs to individuals and families,
associated with depression are enormous. Within a 15-month period after having been
diagnosed with depression, sufferers are four times more likely to die as those who do not
have depression. Almost 60% of suicides have their roots in major depression, and 15% of
those admitted to a psychiatric hospital for depression eventually kill themselves. See
Nierenberg, Am JManag Care 7(11 Suppl): S353-66, 2001. In the U.S. alone, the estimated
economic costs for depression exceeded $44 billion in 1990. The World Health Organization
estimates that major depression is the fourth most important cause worldwide of loss in
disability-adjusted life years, and will be the second most important cause by 2020.
[0005] A variety of pharmacologic agents are available for the treatment of depression.
Significant success has been achieved through the use of seratonin reuptake inhibitors (SRIs),
norepinephrine reuptake inhibitors (NERIs), combined serotonin-norepinephrine reuptake
inhibitors (SNRIs), monoamine oxidase inhibitors (MAQIs), phosphodiesterase-4 (PDE4)
inhibitors or other compounds. However, even with these options available, many patients
fail to respond, or respond only partially to treatment. Additionally, many of these agents
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show delayed onset of activity, so that patients are required to undergo treatment for weeks or
months before receiving benefits. Most currently available antidepressants take 2-3 weeks
or more to elicit a response.
[0006] Traditional therapies can also have significant side effects. For example, more
than a third of patients taking SRIs experience sexual dysfunction. Other problematic side
effects include gastrointestinal disturbances, often manifested as nausea and occasional
vomiting, agitation, insomnia, weight gain, onset of diabetes, prolongation of the heart rate
corrected interval (QTc), agranylocytosis, etc. Depressive patients who also suffer from
psychotic disorders (e.g., schizophrenia) also sometimes suffer extrapyramidal side effects.
These side effects often discourage patients from following their recommended therapeutic
regimen.
[0007] There remains a need for the development of improved therapies for the treatment
of depression and/or other mood disorders.
SUMMARY OF THE INVENTION
[0008] The present invention provides new combination therapies for the treatment of
depression. In particular, the present invention provides combinations of a 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-fiuoroethyl, 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,
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with one or more anti-depressive agents for treating patients suffering from or susceptible to
depression or related mood disorders. The present invention therefore provides, among other
things, certain drug combinations, pharmaceutical compositions containing such
combinations, and methods of treating patients suffering from or susceptible to depression or
related mood disorders with such combinations or compositions.
BRIEF DESCRIPTION OF THE DRAWING
[0009] Figure 1 shows the effects of Compound 1, alone or in combination with
paroxetine, in the tail suspension test.
DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION
[0010] The present invention encompasses the finding that certain 5-HT2C receptor
agonists can be usefully combined with one or more anti-depressive agents in the treatment or
prevention of depression or other mood disorders. In particular, the present invention
provides combinations of 5-HT2C receptor agonists, or partial agonists, 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,
with one or more anti-depressant drugs for the treatment of depression or other mood
disorders. In some embodiments, the inventive combinations allow treatment of refractory
depression (i.e., depression that is not responsive to traditional therapies). Alternatively or
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additionally, the inventive combinations may be employed to treat depression with more rapid
onset of benefit, and/or with fewer side effects.
1. 5-HT2C Receptor Agonists of Formula I
[0011] The present invention utilizes 5-HT2C receptor agonists of formula I:

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,
or pharmaceutically acceptable salts thereof, in combination with one or more anti-
depressants.
[0012] 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.
[0013] The term "alkoxy," as used herein, refers to the group -OR, wherein R is a lower
alkyl group.
[0014] The terms "halogen" or "halo," as used herein, refer to chlorine, bromine, fluorine
or iodine.
[0015] 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
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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.
[0016] The terms "effective amount" and "therapeutically effective amount," as used
herein, refer to the amount of a compound or combination that, when administered to an
individual, is effective to treat, prevent, delay, or reduce the severity of depression or another
mood disorder from which the individual suffers or to which the individual is susceptible, or
from one or more symptoms of depression or other mood disorder. Those of ordinary skill in
the art will appreciate that the amount of an individual active agent that is therapeutically
effective in the context of an inventive combination may well differ from the amount of that
agent that is therapeutically effective when the agent is delivered alone. In some
embodiments of the invention, a lower amount is required to therapeutic effectiveness in the
context of an inventive combination than is required to achieve therapeutic effectiveness
alone. Those of ordinary skill will further appreciate that a different amount of a particular
compound or combination may be required to achieve therapeutic effectiveness in the context
of different formulations, modes of delivery and/or administration regimen.
[0017] 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.
[0018] The term "patient," as used herein, refers to a mammal. In certain embodiments,
the term "patient" refers to a human.
[0019] The terms "administer," "administering," or "administration," as used herein, refer
to either directly administering a compound or composition to a patient, or administering a
prodrug derivative or analog of the compound to the patient, which will form an equivalent
amount of the active compound or substance within the patient's body.
[0020] The compounds of formula I, as defined above or in classes and subclasses as
described herein, have affinity for and agonist or partial agonist activity at the 2C subtype of
brain serotonin receptors.
[0021] 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
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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.
[0022] 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. In still other embodiments, y is 1 and R1 is
halogen.
[0023] According to another embodiment, y is 1 and R1 is at the 5-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] 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.
[0025] 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 substituents 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
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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 substituents on the phenyl moiety of the Ar group of formula I
include OMe, fluoro, chloro, methyl, and trifluoromethyl.
[0026] In certain embodiments, the present invention provides combinations including 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.
[0027] According to one embodiment, Ar is phenyl substituted with one Rx substituent in
the ortho-position, thus forming a compound of formula Ib, 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.
[0028] In certain embodiments, the Ar group of formula I is selected from the following:

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[0029] According to yet another embodiment, the present invention provides
combinations including a compound of formula Id or Ie:

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.
[0030] According to another embodiment, the present invention provides combinations
including a compound of formula If or Ig:

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.
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[0001] In certain embodiments, the present invention provides a compound of formula Ih
or Ii:
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.
[0031] In certain embodiments, the present invention provides combinations including a
compound of formula VIa or VIb:

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.
[0032] According to another embodiment, the present invention provides a compound of
formula VIc or VId:

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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.
[0033] Compounds of formula I for use in accordance with 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 a compound utilized in 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.
[0034] Where a particular 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, et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon
Compounds (McGraw-Hill, NY, 1962); Wilen, Tables of Resolving Agents and Optical
Resolutions p. 268 (EX. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972).
[0035] It is further recognized that atropisomers of the present compounds may exist.
The present invention thus encompasses atropisomeric forms of compounds of formula I as
defined above, and in classes and sublcasses described above and herein.
[0036] Also, 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
polymorphs, hydrates, etc. Also, compounds may be provided as pro-drugs or other forms
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converted into the active agent during manufacture, processing, formulation, delivery, or in
the body.
[0037] It will additionally be appreciated that the principles of the present invention apply
all radiolabelled forms of the compounds receited herein, including, for example, those where
the radiolabels are selected from as 3H, 11C, 14C, 18F, 123I and 125I. Such radiolabelled
compounds are useful as research and diagnostic tools in metabolism pharmacokinetics
studies and in binding assays in both animais and humans.
[0038] Exemplary compounds for formula I useful for the practice 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,
(±)-1-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(3,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(+)-(l-(7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(-)-l -(7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]metlianamine,
(+)-1- [7-(3-methylphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-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,
(-)-1-(7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{7-[2-(trifluoromethyl)phenyl]-2,3 -dihydro-1-benzofuran-2-yl} methanamine,
(-)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
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(±)-l -[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran~2-yl]methanamine,
(±)-l -[7-(2-chlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-l -[7-(3-chlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(+)-1-[7-(3-cMorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(3-methoxyphenyl)-2,3-dihydro- i -benzofuran-2-yl]methanamine,
(±)-1-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzoluran-2-yl]methanamine,
(+)-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzoiuran-2-yl]methanamine,
(-)-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(4-fluoropheny])-2,3-dihydro-1-benzofuran-2-yl]methanainine,
(+)-1-[7-(4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-l -[7-(4-chlorophenyl)-2,3-dihydro-l -benzofiiran-2-yl]methanamine,
(+)-1-[7-(4-chlorophenyl)-2,3-dihydro-1-benzofiiran-2-yl]methanamine.
(-)-1-[7-(4-chlorophenyl)-2,3-dihydro-1-benzoiliran-2-yl]methanamine,
(±)-l-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1- { 7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl} methanamine,
(±)-1-[7-(2,4-dich]orophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(5-chloro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(+)-1-(5-chloro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(-)-1-(5-chloro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[5-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-chloro-7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine:,
(±)-(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(-)-(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(+)-(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine3
(+)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]-N-methylamine,
(-)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]-N-methylamine,
(±)-1-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
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(+)-1-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[5-chloro-7-(2-methylphenyl)-233-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(4-fluoro-7-phenyl-2,3-dihydro-l -benzofuran-2-yl)methanamine,
(±)-1-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(5-fluoro-7-phenyl-2,3 -dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-(4,5-difluoro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(±)-1-[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(5-chloro-2-methyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-(5-chloro-2-methyl-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(±)-(5-chloro-2-methy]-7-thien-2-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(+)-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-fluorophenyl)-2;3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1- [7-(3 -methoxyphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzoruran-2-yl}methanamine,
(+)-1-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)-1-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(-)-1-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,6-dichlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
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(-)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,4-dichlorophenyl)-2;3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,4-dichiorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)- {[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[(7-(2,3-dimethoxyphenyl)-2;3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(4-chloro-2-methylpheayl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine.
(±)-{[7-(2,5-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2J5-dimethoxyphenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl} amine,
(±)-{[7-(5-chloro-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-[(7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(+)- {[7-pyridin-3-yl-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-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,
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(±)-{[5-fluoro-7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-fluoro-7-(4-methoxyphenyl)-23-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-thien-3-yl-2,3-dihydro-1-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-1-benzofuran-2-yl)methyl]amine,
(±)- [(5 -fluoro-7-pyridin-3-yl-2,3 -dihydro-1-benzofuran-2-yl)methyl] amine,
(-)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(+)-{[5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-pyridin-4-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyrimidin-5-yl-2,3-dihydro-1-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-1-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-1-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-1-benzofuran-2-yl]methyl}amine.
(-)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{r5-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,6-difluorophenyl)-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-1-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,
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(±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}ethanamine,
(±)- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}dimethylamine,
(±)-{[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-1-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-1-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-1-benzofuran-2-y]]methyl}amine,
(+)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-y]]methyl}amine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-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-1-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-1-benzofuran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofiiran-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-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-233-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-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,
(-)- {[5 -chloro-7-(2,6-dichlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[(5-chloro-7-pyridin-3-yl-2:,3-dihydro-1-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-1-benzofuran-2-
yl]methyl}(cyclopropylmethyl)amine,
(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}ethanamine,
(±)-{[(5-methyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
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(±)-{[7-(2-methylphenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-1-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,
(±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(4-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-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-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,6-dichlorophenyl)-5 -methyl-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(+)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(3-methylphenyl)-2,3 -dihydro-1-benzofuran-2-yl]rnethyl} amine,
(±)-{[5-(trifluoromethyl)-7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
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(±)- {[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-(trifluoromethyl)-7-(4-fluorophenyl)-253-dihydro-1-benzofuran-2-yl] methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(4-chlorophenyl)-2:3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(4-methoxypheny])-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-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-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl] methyl} amine,
(±)-{[7-(2,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(i)- {[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-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(±)- {[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-4-[2-(aminomethyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-7-yl]benzonitrile
(±)-{[7-(3-furyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-thien-3-yl-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
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WO 2006/116149 PCT/US2006/015191
(±)- {[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(db)- {[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[5-methoxy-7-(3-thienyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5-difluorophenyl)-5-methoxy-2.3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl} amine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(±)-{ [7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-[(N-methyl-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(4-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
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WO 2006/116149 PCT/US2006/015191
(i)-[(N-methyl4-[7-(2,5-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-dich]orophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-[(N-methyl-1-[7-(5-chloro-2-methylphenyl)-233-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-N-methyl-1-(7-pyridin-3-yl-2.3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-[(N-methyl-1-[7-(2,3-difluorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(±)-{[5-fluoro-7-(2-fluorophenyl)-2J3-dihydro-1-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-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2-methylphenyl)-23-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl] methyl} methylamine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[7-(254-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzoftiran-2-yl]methyl}methylamine,
(+)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{ [7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]raethyl}methylamine,
(±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
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(±)-{[7-(5-chloro-2-methoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]methylamine,
(±)-[(5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-i-benzofuran-2-yl]methyl}methylamine;
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-1-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-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-chloro-7-(3.4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(4-methylphenyl)-5-methyl-2,3-dihydro-1-benzoforan-2-yl]methyl}methylamine,
(±)-{[7-(4-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-benzofuran-2-yl]methyl} methylamine,
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(±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)- {[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylarnine,
(±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(i)-{[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-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-1-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-1-benzofuran-2-
yl]methyl}methylamine,
(±)- {[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-N-methyl-1-[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-N-methyl-1-[7-(3,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-N-methyl-1-[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-N-methyl-1-[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
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(±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-N-methyl-1-[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(+){[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-){[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(R)-[7-(2-chloro-phenyl)-(5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl)methyl-amine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]ethylamine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]dimethylamine,
{[(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-1-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-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6 dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine,
(±)-{N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2;3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-{N-methyl-1-[(7-(2,4,6-tricbJorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)- {N-methyl-1- [(7-(2,4,6-trichlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl] methanamine,
(+)-{[7-(2,6-dimethy]phenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(+)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofluran-2-yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,6-dimethylphenyl)-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-methyl-2,3-dihydro-1-benzofuran-2-
yl] methyl} methylamine,
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(-)-{[7-(23-dimethoxyphenyl)-5-fluoro-2,3-dihydro4-benzofuran-2-yl]methyl}methylamine,
or
(+)-{[7-(23-dimethoxyphenyl)-5-fluoro-23-dihydro4-benzofuran-2-yl]methyl}methylamine;
or a pharmaceutically acceptable salt thereof.
[0001] 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:
(±)-1-(7-phenyl-2,3 -dihydro-1-benzofuran-2-yl)methanamine,
(+)-(1 -(7-phenyl-2,3 -dihydro-1-benzofuran-2-yl)methanamine,
(-)-1-(7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1- [7-(2-fluorophenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(-)-1- { 7- [2-(trifluoromethyl)phenyl] -2,3 -dihydro-1-benzofuran-2-yl} methanamine,
(+)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(rt)-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1- [7-(2-chlorophenyl)-2.3-dihydro-1-benzofuran-2-yl] methanamine,
(±)-1-[7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1- [5-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl] methanamine,
(±)-1- [5 -chloro-7-(2-methylphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
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(+)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(5-chloro-2-methyl-7-phenyl-2,3 -dihydro-1-benzofuran-2-yl)methanamine,
(+)-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1- [7-(2-chlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl] methanamine,
(±)-1-[7-(2,6-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,6-dichlorophenyl)-233-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,6-dichloropheny])-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-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,
(-)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)- {[7-(2,3 -dimethoxyphenyl)-2,3 -dihydro-1-benzofuran-2-yl] methyl} amine,
(-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-y]]methyl}amine,
(+)- {[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(+)- {[7-(4-chloro-2-methylphenyl)-2,3-dihydro-1-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-1-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-1-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-1-benzofuran-2-yl]methyl}amine,
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WO 2006/116149 PCT/US2006/015191
(-)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-1-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-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-1-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-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-1-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-1-benzofuran-2-yl]methyl}amine,
(-)- {[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(+)-{[5-fluoro-7-(2,4-dichloropheny])-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,4-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-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-1-benzofuran-2- yl]methyl} amine,
(±)-{[7-(2,6-difluorophenyl)-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-1-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-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}ethanamine,
(±)- {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-y]]methyl} dimethylamine,
(±)-{[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)- {[5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
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WO 2006/116149 PCT/US2006/015191
(±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-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-1-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-1-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-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-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-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,
(-)-{[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-1-benzofuran-2-
yl]methyl} cyclopropanamine,
(±)-N- {[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} (cyclopropylmethyl)amine,
(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}ethanamine,
(±)- {[7-(2-methylphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dib.ydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-1-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,
(±)- {[7-(2,3 -dimethoxyphenyl)-5-methyl-2,3 -dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
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WO 2006/116149 PCT/US2006/015191
(-)-{[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-dichloroph6nyl)-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-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(-)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[5-(trifluoromethyl)-7-(2-(trifluoromethyl)pb.enyl)-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-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amme,
(±)-{[7-(2,3-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(±)- {[7-(2,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
((233-)-{[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,6-dimethylphenyl)-5-(trijEluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
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WO 2006/116149 PCT/US2006/015191
(±)-{[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzojEuran-2-yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2:,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,4-dichlorophenyl)-5-methoxy-2,3 -dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1-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]meth.yl}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-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-[(N-methyl-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)- [(N-methyl-1- [7-(2,3 -dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2;4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,6-dichIorophenyl)-2,3-dihydro-1-benzofuran-2-y]]methanamine,
(-)-{[7-(2,6-dichloropheny])-2,3-dib.ydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[(N-methyl-1-[7-(2,3-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-{[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-chlorophenyl)-2,3-dihydro-1-benzoniran-2-yl]methyl}methylamine,
(±)-{ [5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
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WO 2006/116149 PCT/US2006/015191
(-)- {[5 -fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} methylamine,
(+)-{[5-fluoro-7-(2-methylphenyl)-23-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxyphenyl)-23-dihydro-1-benzofuran-2-yl]me1iiyl}methylamine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,5 -dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-berLzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-[(5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl}methylamine,
(±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2)3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(db)-{[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-1-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-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
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WO 2006/116149 PCT/US2006/015191
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2-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-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dichlorophenyl)-5-raethyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,5-dichlorophenyl)-5-methyl-2.3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,6-dimethy]phenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-methyl-2>3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl} methylamine,
(±)-{[7-(2-methylphenyl)-5-methoxy-23-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}mcthylamine,
(±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-1-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-1-benzofuran-2-
yl]methyl} methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)- {[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
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WO 2006/116149 PCT/US2006/015191
(±)-N-methyl-1-[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yljmethanamine,
(±)-N-methyl-1-[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yljmethanamine,
(±)-N-methyl-1-[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yljmethanamine,
(+){[7-(2,6-dichloropheny])-5-fIuoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-){[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(R)-[7-(2-chloro-phenyl)-(5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl)methyl-amine,
(R)~ [7-(2,6-dichloro-phenyl)-5 -Fluoro-2,3 -dihydro-benzofuran-2-ylmethyl] ethylamine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]dimethylamine,
{[(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-1-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-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)- {[7-(2,6 dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dib.ydro-1-benzofuran-2-yl]ethyl}amine,
(±)-{2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine,
(±)- {N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)- {N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-{N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)- {[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl} methylamine,
(+)- {[7-(2,6-dimethylphenyl)-5-methoxy-2,3 -dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} methylamine,
(+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
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WO 2006/116149 PCT/US2006/015191
(.).{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-
yl]methyl} methylamine,
(-)-{[7-(23-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
or
(+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine;
or a pharmaceutically acceptable salt thereof.
[0039] 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.
2. Antidepressant Agents
[0040] In certain embodiments, compounds of the present invention are administered in
combination with one or more antidepressive agents. Suitable antidepressant agents include,
for example, serotonin reuptake inhibitors (SRIs), norepinephrine reuptake inhibitors (NRIs),
combined serotonin- norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase
inhibitors (MAOIs), reversible inhibitors of monoamine oxidase (RIMAs),
phosphodiesterase-4 (PDE4) inhibitors, corticotropin releasing factor (CRF) antagonists,
alpha.-adrenoreceptor antagonists or other compounds including atypical antidepressants.
Additional antidepressants for administering in combination with compounds of the present
invention include triple uptake inhibitors such as DOV 216303 and DOV 21947...; melatonin
agonists such as agomelotine, super neurotransmitter uptake blockers (SNUBs: e.g., NS-2389
from GlaxoSmithKline and Neurosearch; (R)-DDMA from Sepracor), and/or substance
P/neurokinin receptor antagonists (e.g., aprepitant/MK-869 from Merck; NKP-608 from
Novartis; CPI-122721 from Pfizer; R673 from Roche; TAK637 from Takeda; and GW-97599
from GlaxoSmithKline).
[0041] Another class of antidepressant agents that may be used in the present invention
are noradrenergic and specific serotonergic antidepressants (NaSSAs), such as mirtazepine
(see, for example, United States Patent 5,178,878, the entire contents of which are
incorporated herein by reference).
[0042] Suitable NRIs that may be used in the present invention include tertiary amine
tricyclics and secondary amine tricyclics. Suitable examples of tertiary amine tricyclics
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WO 2006/116149 PCT/US2006/015191
include: amitriptyline, clomipramine, doxepin, imipramine (See United States Patent
2,554,736, incorporated herein by reference in its entirety) and trimipramine, and
pharmaceutically acceptable salts thereof. Suitable examples of secondary amine tricyclics
include: amoxapine, desipramine, maprotiline, nortriptyline and protriptyline, and
pharmaceutically acceptable salts thereof.
[0043] Another NRI that may be used in the present invention is reboxetine (Edronax™;
2-[.alpha.-(2~ethoxy)phenoxy-benzyl]rnorpholine, usually administered as the racemate; See
United States Patent. 4,229,449, incorporated herein by reference in its entirety).
[0044] Suitable SSRIs that may be used in the present invention include: citalopram (1-
[3-(dimethylamino)propyl]-(4-fluorophenyl)-l,3-dihydr-o-5-isobenzofurancarbonitrile; See
United States Patent 4,136,193; Christensen et al., Eur. J. Pharmacol. 41:153, 1977; Dufour
et al., Int. Clin. Psychopharmacol. 2:225, 1987; Timmerman et al., ibid., 239, each of which
is incorporated herein by reference in its entirety); fluoxetine (N-methyl-3-(p-
trifluoromethylphenoxy)-3-phenylpropylamine, marketed in the hydrochloride salt form and
as the racemic mixture of its two isoforms; see, for example, United States Patent 4,314,081;
Robertson et al., J. Med. Chem. 31:1412, 1988, each of which is incorporated herein by
reference); fluoxetine/olanzapine in combination; fluvoxamine (5-methoxy-1-[4-
(trifluoromethyl)phenyl]-1-pentanone O-(2-aminoethyl)oxime; See United States Patent
4,085,225; Claassen et al., Brit. J. Pharmacol. 60:505, 1977; De Wilde et al., J. Affective
Disord. 4:249, 1982; Benfield et al., Drugs 32:313, 1986, each of which is incorporated
herein by reference in its entirety); paroxetine (trans-(-)-3-[(l,3-benzodioxol-5-yloxy)methyl]-
4-(4-fluo- rophenyl)piperidine; See United States Patent 3,912,743; United States Patent
4,007,196; Lassen, Eur. J. Pharmacol. 47:351, 1978; Hassan et al., Brit. J. Clin. Pharmacol.
19:705, 1985; Laursen et al., Acta Psychiat. Scand. 71:249, 1985; Battegay et al.,
Neuropsychobiology 13:31, 1985, each of which is incorporated herein by reference in its
entirety); sertraline, (lS-cis)-4-(3,4-dichlorophenyl)-l,2,3,4-tetrahydro-N-methyl-1-
naphthylamine hydrochloride; See United States Patent 4,536,518, incorporated herein by
reference in its entirety); escitalopram (see United States Patent RE34/712); new 5HT1A
agonists variza, alnespirone, gepirone, sunepitron, MKC242, vilazodone, eptapirone, and
ORG12962 from Organon; and pharmaceutically acceptable salts thereof.
[0045] Suitable MAOIs that may be used in the present invention include: isocarboxazid,
phenelzine, selegiline and tranylcypromine, and pharmaceutically acceptable salts thereof.
[0046] Suitable reversible MAOIs that may be used in the present invention include:
moclobemide (4-chloro-N-[2~(4-morpholinyl)-ethyl]benzamide; See United States Patent
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WO 2006/116149 PCT/US2006/015191
4,210,754, incorporated herein by reference in its entirety), selegiline, and pharmaceutically
acceptable salts thereof.
[0047] Suitable SNRIs that may be used in the present invention include venlafaxine (see
United States Patent 4,535,186, incorporated herein by reference in its entirety; see also
United States Patents 5,916,923, 6,274,171, 6,403,120, 6,419,958, 6,444,708, each of which
is incorporated herein by reference in its entirety), and pharmaceutically acceptable salts and
analogs, including the O-desmethylvenlafaxine succinate salt; milnacipran (N,N-diethyl-2-
aminomethyl-1-phenylcyclopropanecarboxamide; see United States Patent 4,478,836; Moret
et al., Neuropharmacology 24:1211-19, 1985, each of which is incorporated herein by
reference in its entirety); nefazodone (available from Bristol Myers Squibb and Dr. Reddy
Labs Inc.); duloxetine; and pharmaceutically acceptable salts thereof.
[0048] Suitable CRF antagonists that may be used in the present invention include those
compounds described in International Patent Specification Nos. WO 94/13643, WO
94/13644, WO 94/13661, WO 94/13676 and WO 94/13677.
[0049] Suitable atypical antidepressants that may be used in the present invention include:
buproprion (Wellbutrin™; (.+-.)-1-(3-chlorophenyl)-2-[(l,l-dim- ethylethyl)amino]-1-
propanone), lithium, nefazodone, trazodone and viloxazine, and pharmaceutically acceptable
salts thereof. Another suitable atypical antidepressant is sibutramine.
[0050] Particular antidepressants that may be used in the present invention include, but
are not limited to, adinazolam, alaproclate, alnespirone, amineptine, amitriptyline,
amitriptyline/chlordiazepoxide combination, amoxapine, aprepitant, atipamezole,
azamianserin, bazinaprine, befuraline, bifemelane, binodaline, bipenamol, brofaromine,
buproprion, caroxazone, cericlamine, cianopramine, cimoxatone, citalopram, clemeprol,
clomipramine, clovoxamine, dazepinil, deanol, demexiptiline, desipramine, O-
desmethylvenlafaxine, dibenzepin, dothiepin, doxepin, droxidopa, duloxetine, elzasonan,
enefexine, eptapirone, escitalopram, estazolam, etoperidone, femoxetine, fengabine,
fezolamine, fluotracen, fluoxetine, fluvoxamine, gepirone, idazoxan, imipramine, indalpine,
indeloxazine, iprindole, isocarboxazid, levoprotiline, litoxetine, lofepramine, maprotiline,
medifoxamine, metapramine, metralindole, mianserin, milnacipran, minaprine, mirtazapine,
moclobemide, montirelin, nebracetam, nefopam, nefozodine, nemititide, nialamide,
nomifensine, norfluoxetine, nortriptyline, orotirelin, oxaflozane, paroxetine, pheneizine,
pinazepam, pirlindone, pizotyline, protryptiline, reboxetine, ritanserin, robalzotan, rolipram,
selegiline, sercloremine, sertraline, setiptiline, sibutramine, sulbutiamine, sulpiride,
sunepitron, teniloxazine, thozalinone, thymoliberin, tianeptine, tiflucarbine, tofenacin,
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WO 2006/116149 PCT/US2006/015191
tofisopam, toloxatone, tomoxetine, tranylcypromine, trazodone, trimiprimine, venlafaxine,
veralipride, vilazodone, viloxazine, viqualine, zimelidine and zometrapine, and
pharmaceutically acceptable salts thereof, and St. John's wort herb, or Hypencuin perforatum,
or extracts thereof.
[0051] Suitable classes of anti-anxiety agents for administering in combination with
compounds of the present invention include 5-HTIA agonists or antagonists, especially 5-HTIA
partial agonists, neurokinin recepter (NK) antagonists (e.g., saredutant and osanetant) and
corticotropin releasing factor (CRF) antagonists. Suitable 5-HTIA receptor agonists or
antagonists that may be used in the present invention include, in particular, the 5-HTIA
receptor partial agonists buspirone, flesinoxan, gepirone and ipsapirone, and pharmaceutically
acceptable salts thereof. An example of a compound with 5-HTIA receptor antagonist/partial
agonist activity is pindolol. new 5HTIA agonists variza, alnespirone, gepirone, sunepitron,
MKC242, vilazodone, eptapirone, and ORG12962 from Organon; new 5HTIA antagonists
such as robalzotan; new 5-HTIB agonists such as elzasonan; new 5HT2 antagonists such as
YM-992 (from Yamanouchi Pharmaceuticals) and nemifitide.
[0052] Antidepressant agents for use in accordance with the present invention may be
obtained or produced according to any available means.
3. Other Agents
[0053] Inventive combinations may further include one or more additional
pharmaceutically active agents. For example, according to the present invention, the
inventive combinations may be administered in conjunction with one or more other agents
that is useful in treating depression or other mood disorders. Alternatively or additionally,
inventive combinations 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 depression or mood disorder 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, pain-relieving agents, anti-
psychotic agents, gastrointestinal agents, etc., or combinations thereof. Other pharmaceutical
agents useful in the practice of the present invention include, for example, adjunctive
therapies typically used to enhance the effects of an antidepressant. Such adjunctive agents
may include, for instance, mood stabilizers (e.g., lithium, valproic acid, carbamazepine, etc.);
pindolol, stimulants (e.g., methylphenidate, dextroamphetamine, etc.); or thyroid augmenting
agents (e.g., T3); antipsychotics, anti-anxiety agents (e.g., benzodiazepines), and/or agents
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WO 2006/116149 PCT/US2006/015191
that relieve sexual dysfunction (e.g., buspirone, which also has anti-anxiety effects;
dopaminergic agents such as amantadine, pramipexole, etc.).
[0054] A more complete list of pharmaceutically active 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
compounds 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.
[0055] Particular pharmaceutical agents useful in conjunction with the inventive
combinations are those discussed, for example, in United States Patent Application
2003/0092770, United States Patent Application 2004/0029972, United States Patent
Application 2004/00220274, United States Patent Application 2005/0054676, or United
States Patent Application 2005/0069936, each of which is incorporated herein by reference in
its entirety.
4. Pharmaceutical Compositions
[0056] While it is possible for the active ingredients of the inventive combination to be
administered as raw chemicals, it is often desirable to present them in the context of one or
more pharmaceutical formulations. Pharmaceutical formulations according to the present
invention comprise a combination according to the invention together with one or more
pharmaceutically acceptable carriers or excipients and optionally other therapeutic agents.
[0057] The present invention thus provides a pharmaceutical composition comprising one
or more 5-HT2C receptor agonists of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
n is one or two;
each of R2 andR3 is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl
or cyclopropyl;
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WO 2006/116149 PCT/US2006/015191
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
n is one or two,
or pharmaceutically acceptable salts thereof, and one or more antidepressant agents as a
combined preparation for simultaneous, separate or sequential administration to treat a patient
suffering from or susceptible to depression or other mood disorder.
[0058] Agents used in inventive combinations or compositions may be administered
simultaneously, in the same or different pharmaceutical formulation, or sequentially. The
timing of the sequential administration may desirably be selected to preserve the
advantageous effects of the combination and said timing can be determined by a skilled
practitioner. In other embodiments, the combinations are combined in a single unit dosage
form.
[0059] A therapeutically effective amount of the combination will be understood to be an
amount which treats, inhibits, prevents or ameliorates one or more symptoms of the
depression or mood disorder in question. In certain embodiments of the invention, the
combination will show improved efficacy as compared with that achieved by administration
of the same amount of either the compound of formula I or the antidepressant agent alone.
Furthermore, in certain embodiments, the effective amount of the combination produces
fewer side effects than are observed when the antidepressant agent is administered alone at a
dose that achieves substantially similar therapeutic efficacy.
[0060] The dosages of each of the drugs in the inventive combination may be determined
by a physician and will often depend upon the specific circumstances of the depression or
mood disorder, as well as the size, age and response pattern of the patient. Dosage guidelines
are provided here. For the combination, the dosage guideline for each of the drugs of the
combination would be considered.
[0061] In general, suitable doses of compound of formula I from about 0.5 mg per day to
about 500 mg per day; in some embodiments from about 1 to about 500 mg per day.
[0062] A suitable dose of antidepressant agent may be in the range recommended by the
manufacturer or reported in the literature. In some embodiments of the invention, the
antidepressant agent is used at the low end of the range recommended by the manufacturer, or
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WO 2006/116149 PCT/US2006/015191
even below the range, in light of synergistic benefits that can be achieved according to the
present invention. The following guidelines are provided for certain antidepressants useful in
the practice of the present invention:
Amitryptiline: typically about 100-300 mg/day maintenance dose;
Buproprion: from about 100 to about 300 mg/day;
Citalopram: from about 5 to about 50 mg once/day; preferred, from about 10 to
about 30 mg once/day;
Clomipramine: typically about 100-250 mg/day maintenance dose;
Duloxetine: from about 1 to about 30 mg once/day; preferred, from about 5 to
about 20 mg once/day;
Fluoxetine: from about 1 to about 80 mg, once/day; preferred, from about 10 to
about 40 mg once/day;
Fluvoxamine: from about 20 to about 500 mg once/day; preferred, from about 50
to about 300 mg once/day;
Imipramine: typically about 100-300 mg/day maintenance dose;
Isocarboxazid: typically about 10-20 mg/day maintenance dose;
Maprotiline: typically about 100-200 mg/day maintenance dose;
Mianserin: typically about 30-90 mg/day maintenance dose;
Milnacipran: from about 10 to about 100 mg once-twice/day; preferred, from
about 25 to about 50 mg twice/day;
Mirtazapine: typically about 14-45 mg/day maintenance dose;
Moclobemide: typically about 300-600 mg/day maintenance dose;
Nefazodone: typically about 150-300 mg/day maintenance dose;
Nortriptyline: typically about 50-200 mg/day maintenance dose;
Paroxetine: from about 20 to about 50 mg once/day; preferred, from about 20 to
about 30 mg once/day;
Phenelzine: typically about 15-60 mg/day maintenance dose;
Reboxetine: from about 1 to about 30 mg, once to four times/day; preferred, from
about 5 to about 30 mg once/day;
Sertraline: from about 20 to about 500 mg once/day; preferred, from about 50 to
about 200 mg once/day;
Tranylcypromine: typically about 30-60 mg/day maintenance dose;
Trazodone: typically about 75-300 mg/day maintenance dose;
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WO 2006/116149 PCT/US2006/015191
Venlafaxine: from about 10 to about 150 mg once-thrice/day; preferred, from
about 25 to about 125 mg thrice/day or about 30 to about 200 mg once a day, for example
37.5 mg, 75 mg, or 150 mg once a day;
[0063] Useful carriers for use in inventive pharmaceutical formulations are compatible
with the other ingredients in the composition. According to the present invention,
compounds of formula I may be administered with antidepressant agents in a single
pharmaceutical formulation, or in multiple formulations. Where multiple formulations are
employed, each may include both the compound of formula I and the antidepressant agent, or
alternatively, each may include only one.
[0064] An inventive combination of one or more compounds of formula I and one or
more antidepressant agents may conveniently be presented as a pharmaceutical formulation in
a unitary dosage form. A convenient unitary dosage formulation contains the active
ingredients in amounts from 0.1 mg to 1 g each, for example 1 mg to 500 mg. Typical unit
doses may, for example, contain about 0.5 to about 500 mg, or about 1 mg to about 500 mg,
of a compound of formula I.
[0065] According to the present invention, pharmaceutical formulations may be prepared
as "patient packs" containing the whole course of treatment in a single package, for example a
blister pack. Patient packs have an advantage over traditional prescriptions, where a
pharmacist divides a patient's supply of a pharmaceutical from a bulk supply, in that the
patient always has access to the package insert contained in the patient pack, normally
missing in traditional prescriptions. The inclusion of a package insert has been shown to
improve patient compliance with the physician's instructions.
[0066] It will be understood that the administration of the inventive combination by
means of a single patient pack, or patient packs of each formulation, with a package insert
directing the patient to the correct use of the invention is a desirable additional feature of this
invention.
[0067] According to a further aspect of the invention, there is provided a patient pack
comprising at least one active ingredient of the combination of the invention and an
information insert containing directions on the use of the combination of the invention. In
other embodiments, the present invention provides a patient pack comprising both active
ingredients of the combination of the invention for simultaneous or sequential administration
to a patient, and further comprising an information insert containing directions on the use of
the combination of the invention. In certain embodiments, the present invention provides a
patient pack comprising both active ingredients of the combination of the invention
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WO 2006/116149 PCT/US2006/015191
formulated into a single unit dosage form for administration to a patient, and further
comprising an information insert containing directions on the use of the combination of the
invention.
[0068] According to the present invention, combinations of one or more compounds of
formula I and one or more antidepressant agents may be formulated for any mode of delivery
including, for example, oral, rectal, nasal, topical (including transdermal, buccal and
sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous and
intradermal) administration. The formulations may be prepared by any methods well known
in the art of pharmacy, for example, using methods such as those described in Gennaro et al.,
Remington's Pharmaceutical Sciences (18th ed., Mack Publishing Company, 1990, see
especially Part 8: Pharmaceutical Preparations and their Manufacture). Such methods
typically include a step of bringing into association the active ingredient(s) with the carrier
which constitutes one or more accessory ingredients. Such accessory ingredients include, for
example, fillers, binders, diluents, disintegrants, lubricants, colorants, flavouring agents and
wetting agents.
[0069] Formulations suitable for oral administration may be presented, for example, as
discrete units such as pills, tablets or capsules each containing a predetermined amount of
active ingredient; as a powder or granules; as a solution or suspension. The active
ingredient(s) may also be present as a bolus or paste, or may be contained within liposomes.
[0070] For oral administration, tablets containing various excipients such as
microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and
glycine may be employed along with various disintegrants such as starch (and preferably corn,
potato or tapioca starch), alginic acid and certain complex silicates, together with granulation
binders like polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents
such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting
purposes. Solid compositions of a similar type may also be employed as fillers in gelatin
capsules; preferred materials in this connection also include lactose or milk sugar as well as
high molecular weight polyethylene glycols.
[0071] Formulations suitable for oral administration may alternatively be presented, for
example, as liquids. When aqueous suspensions and/or elixirs are desired for oral
administration, the active ingredient(s) may be combined with various sweetening or
flavoring agents, coloring matter or dyes, and, if so desired, emulsifying and/or suspending
agents as well, together with such diluents as water, ethanol, propylene glycol, glycerin and
various like combinations thereof. Liquid formulations may be particularly useful for
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WO 2006/116149 PCT/US2006/015191
administration to children. In general, when preparing liquid formulations for administration
to children, it is desirable to avoid or minimize use of alcohol in the formulation.
[0072] Formulations for rectal administration may be presented, for example, as a
suppository or enema.
[0073] For parenteral administration, solutions of therapeutic agent(s) in either sesame or
peanut oil or in aqueous propylene glycol may be employed. Aqueous solutions may be
suitably buffered if necessary, and the liquid diluent may be rendered isotonic. Aqueous
solutions are suitable for intravenous injection purposes. Oily solutions are suitable for intra-
articular, intramuscular and subcutaneous injection purposes. The preparation of all these
solutions under sterile conditions is readily accomplished by standard pharmaceutical
techniques well known to those skilled in the art, Parenteral formulations may be presented
in unit-dose or multi-dose containers, for example, sealed vials and ampoules, and may be
stored in a freeze dried (lyophilized) condition requiring only the addition of the sterile liquid
carrier, for example, water prior to use.
[0074] Preferred compositions for administration of inventive combinations by injection
include those comprising the therapeutic agent(s) in association with a surface-active agent
(or wetting agent or surfactant) or in the form of an emulsion (as a water-in-oil or oil-in-water
emulsion). Suitable surface-active agents include, in particular, non-ionic agents, such as
polyoxyethylenesorbitans (e.g., Tween.TM. 20, 40, 60, 80 or 85) and other sorbitans (e.g.,
Span.TM. 20, 40, 60, 80 or 85). Compositions with a surface-active agent will conveniently
comprise between 0.05 and 5% surface-active agent, and preferably between 0.1 and 2.5%. It
will be appreciated that other ingredients may be added, for example mannitol or other
pharmaceutically acceptable vehicles, if necessary.
[0075] Suitable emulsions may be prepared using commercially available fat emulsions,
such as Intralipid™, Liposyn™, Infonutrol™, Lipofundin™ and Lipiphysan™. The
therapeutic agent(s) may be either dissolved in a pre-mixed emulsion composition or
alternatively may be dissolved in an oil (e.g., soybean oil, safflower oil, cottonseed oil,
sesame oil, corn oil or almond oil) and an emulsion formed upon mixing with a phospholipid
(e.g., eggs phospholipids, soybean phospholipids or soybean lecithin) and water. It will be
appreciated that other ingredients may be added, for example glycerol or glucose, to adjust the
tonicity of the emulsion. Suitable emulsions will typically contain up to 20% oil, for example,
between 5 and 20%. The fat emulsion will preferably comprise fat droplets between 0.1 and
1.0 .mu.m, particularly 0.1 and 0.5 .mu.m, and have a pH in the range of 5.5 to 8.0.
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WO 2006/116149 PCT/US2006/015191
[0076] Compositions for inhalation or insufflation include solutions and suspensions in
pharmaceutically acceptable, aqueous or organic solvents or mixtures thereof, and powders.
The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients
as set out above. Preferably the compositions are administered by the oral or nasal respiratory
route for local or systemic effect. Compositions in preferably sterile pharmaceutically
acceptable solvents may be nebulised by use of inert gases. Nebulised solutions may be
breathed directly from the nebulising device or the nebulising devise may be attached to a
face mask, tent or intermittent positive pressure breathing machine. Solution, suspension, or
powder compositions may be administered, preferably orally or nasally, from devices which
deliver the formulation in an appropriate manner.
[0077] Compositions of the present invention may also be presented for administration in
the form of transdermal patches using conventional technology. The compositions may also
be administered via the buccal cavity using, for example, absorption wafers.
5. Uses
[0078] Administration of the inventive combinations is useful to treat, prevent, delay, or
reduce the severity of depression or another mood disorder from which the individual suffers
or to which the individual is susceptible, or from one or more symptoms of depression or
other mood disorder. For example, according to the present invention, combinations of one
or more compounds of formula I and one or more antidepressive are useful in the treatment of
disorders, for example, single episodic or recurrent major depressive disorders, dysthymic
disorders, depressive neurosis, and neurotic depression; melancholic depression including
anorexia, weight loss, insomnia and early morning waking, and psychomotor retardation;
atypical depression (or reactive depression) including increased appetite, hypersomnia,
psychomotor agitation or irritability, anxiety and phobias, seasonal affective disorder, or
bipolar disorders or manic depression, for example, bipolar I disorder, bipolar II disorder and
cyclothymic disorder. In some embodiments, inventive combinations are used to treat
depression. In some embodiments, inventive combinations are used to treat bipolar disorder.
[0079] In other embodiments, compounds of the present invention are useful for treating
one or more depressive disorders such as major depressive disorder, seasonal affective
disorder, dysthymic disorder, substance-induced mood disorder, depressive disorder not
otherwise specified, and treatment resistant depression.
[0080] Another aspect of the present invention provides a method for treating one or more
mood episodes such as major depressive episode, manic episode, mixed episode, and
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hypomanic episode; and adjustment disorders such as adjustment disorders with anxiety
and/or depressed mood.
[0081] Combinations of the present invention are also useful for treating symptoms
related to depressive disorders including somatic symptoms such as neuropathic pain and
sexual dysfunction. Other somatic symptoms include hopelessness, helplessness, anxiety and
worries, memory complaints with or without objective signs of cognitive impairment, loss of
feeling of pleasure (anhedonia), slowed movement, irritability, and lack of interest in personal
care, such as poor adherence to medical or dietary regimens.
[0082] In certain embodiments, the present invention provides a method of treating sexual
dysfunction related to depression. In other embodiments, the present invention provides a
method of treating sexual dysfunction associated with administering a serotonin reuptake
inhibitor (SRI) for treating a depressive or other disorder.
[0083] Combinations of the present invention are useful for treating sexual dysfunction in
the male (e.g. male erectile dysfunction - MED) and in the female - female sexual dysfunction
(FSD), e.g. female sexual arousal disorder (FSAD).
[0084] In other embodiments, the present invention provides a method for treating one or
more disorders associated with sexual dysfunction including: HSDD, characterized by a
deficiency, or absence of, sexual fantasies and desire for sexual activity; FSAD, characterized
by a persistent or recurrent inability to attain, or to maintain until completion of the sexual
activity, an adequate lubrication-swelling response of sexual excitement; FOD characterized
by persistent or recurrent delay in, or absence of, orgasm following a normal sexual
excitement phase; Sexual Pain Disorders such as dyspareunia and vaginismus; and/or HSDD
characterized by a woman who has no or little desire to be sexual, and has no or few sexual
thoughts or fantasies.
[0085] It was surprisingly found that compounds of the present invention provide a rapid
onset of action as compared with other therapeutic agents typically used for treating
depression and depressive disorders.
[0086] Alternatively or additionally, inventive combinations may be useful in the
treatment of other mood disorders such as dysthymic disorder with early or late onset and
with or without atypical features; dementia of the Alzheimer's type, with early or late onset,
with depressed mood; vascular dementia with depressed mood, disorders induced by alcohol,
amphetamines, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives,
hypnotics, anxiolytics and other substances; schizoaffective disorder of the depressed type;
and adjustment disorder with depressed mood.
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[0087] The term "treatment", as used herein, refers to reversing, alleviating, delaying the
onset of, inhibiting the progress of, or preventing depression or another mood disorder, or one
or more symptoms thereof, as described herein. In some embodiments, treatment may be
applied after one or more symptoms have developed. In other embodiments, treatment may
be administered in the absence of symptoms. For example, treatment may be administered
prior to symptoms (e.g., in light of a history of symptoms and/or one or more other
susceptibility factors), or after symptoms have resolved, for example to prevent or delay their
reoccurrence.
[0088] Individuals to be treated in accordance with the present invention include those
suffering from depression or a mood disorder, and those susceptible to depression or a mood
disorder. In general, a patient is considered to be suffering from depression or a mood
disorder if that patient shows an appropriate collection of accepted symptoms. A patient is
considered to be susceptible to depression or a mood disorder o if, for example, that patient
has a familial history of depression or of the mood disorder, or carries a known genetic
susceptibility trait. A patient may also be considered to be susceptible if the patient has
shown one or more symptoms of depression, or of the mood disorder, or has experienced an
episode of depression or of the mood disorder, in the past.
[0089] In some embodiments the inventive cmbinations are useful for treatment-resistant
depression. In other embodiments, the inventive combinations, when administered to treat
depression or other mood disorders, show fewer undesirable side effects than are observed
upon administration of the antidepressant alone in an amount that achieves comparabale relief
of depression. Alternatively or additionally, the inventive combinations show more rapid
onset of activity than do the antidepressants alone.
[0090] Those of ordinary skill in the art will also appreciate that, particularly given the
high comorbidity of depression and psychotic disorders, inventive combinations may also be
used to treat one or more psychotic disorders, or symptoms thereof. For example, in some
embodiments, inventive combinations may be used in the treatment of psychotic disorders or
episodes. For example, according to the present invention, combinations of one or more
compounds of formula I and one or more anti-psychotic agents may be used in the treatment
of schizophrenia including paranoid type, disorganized type, catatonic type, and
undifferentiated type, schizophreniform disorder, schizoaffective disorder, delusional
disorder, substance-induced psychotic disorder, and psychotic disorder not otherwise
specified; L-DOPA-induced psychosis; psychosis associated with Alzheimer's dementia;
psychosis associated with Parkinson's disease; psychosis associated with Lewy body disease;
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bipolar disorders such as bipolar I disorder, bipolar II disorder, and cyclothymic disorder;
dementia, and depression with psychotic features. In some embodiments, inventive
combinations are useful in the treatment of bipolar disorder. A more complete description of
the aforementioned mental disorders can be found in the Diagnostic and Statistical Manual of
Mental Disorders, 4th edition, Washington, DC, American Psychiatric Association (1994),
incorporated herein by reference in its entirety. In some embodiments, the inventive
combinations are used to treat schizophrenia. In some embodiments, the inventive
combinations are used to treat bipolar disorder.
EXAMPLES
Assessment of Effectiveness in Tail Suspension Test
[0091] Compound 1, (7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydrobenzofuran-2-
yl)methanamine, was used to exemplify the effectiveness of compounds of the present
invention in the tail suspension test. While not a direct model of depression, the tail
suspension test is an assay that can evaluate antidepressant-like effects of drugs. Clinically
effective drugs such as Prozac (fluoxetine) are effective in this assay. Specifically, they
decrease the amount of time the mice spend immobile after being hung upside down by their
tails during the test. It is impossible to determine if a mouse is indeed depressed. However,
the fact that clinically effective antidepressants reduce immobility lends predictive validity to
the model.
[0092] Male Swiss Webster mice (Charles River) weighing 20-35 g were used throughout
this study. They were housed in groups of five per cage in an AALAC-accredited facility that
was maintained on a 12-h light dark cycle (lights on at 0600 h) and had free access to food
and water. Experimental groups consisted of 12 mice, randomly assigned to treatment
groups. All experiments were performed between 9:00 AM and noon in accordance to the
Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the
National Institutes of Health (Pub. 85-23,1985).
[0093] Solutions of Compound 1 and paroxetine were freshly prepared. Compound 1
was dissolved in saline and paroxetine was dissolved in distilled water. All drugs were
injected i.p. at a volume of 10 ml/kg body weight. Combination treatments were cotreated,
30 minutes prior to the test.
[0094] The procedure followed in this study was a variant of the one originally described
by Steru et al. (1985). 30 minutes following treatment, the mice were suspended upside down
by the tail using adhesive laboratory tape (VWR International), to a flat metal bar connected
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to a strain gauge within a tail suspension chamber (Med Associates). The time spent
immobile during a 6-minute test session was automatically recorded. 8 mice were
simultaneously tested within separate chambers. Data collected were expressed as a mean of
immobility time and statistical analysis was performed using a one-way ANOVA with least
significant difference (LSD) post-hoc test.
[0095] Neither Compound 1 (0.1 mg/kg) nor either dose of paroxetine (10 or 30 mg/kg)
produced antidepressant-like effects alone. 10 and 30 mg/kg of paroxetine produced 5% and
4% decreases in immobility time respectively when dosed alone. The combination of 10 and
30 mg/kg of paroxetine with 0.1 mg/kg of Compound 1 produced decreases in immobility
time of 31% and 23% respectively, indicating an enhancement of the antidepressant-like
effects of paroxetine. See Figure 1.
[0096] The entire disclosure of each patent, patent application, and publication cited or
described in this document is hereby incorporated by reference.
[0097] While we have presented a number of embodiments of this invention, it is
apparent that our basic construction can be altered to provide other embodiments which
utilize the compounds and methods of this invention. Therefore, it will be appreciated that
the scope of this invention is to be defined by the appended claims rather than by the specific
embodiments which have been represented by way of example.
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CLAIMS
What is claimed is:
1. A composition comprising:
(a) a 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,
and
(b) an antidepressant,
2. The composition 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 composition according to claim 2, wherein both of R2 and R3 are
hydrogen.
4. The composition according to claim 1, wherein neither R2 and R3 is hydrogen.
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5. The composition according to any one of claims 1 to 4, wherein y is zero.
6. The composition 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 composition according to any one of claims 1 to 4, wherein y is one and
R! is halogen, OH, lower alkyl, lower alkoxy, trifiuoromethyl, trifluoromethoxy, or CN.
8. The composition according to claim 7, wherein y is one and R1 is fluoro or
chloro.
9. The composition according to claim 7, wherein said compound is of formula
Ia or Ia':
or a pharmaceutically acceptable salt thereof.
10. The composition according to any one of claims 1 to 9, wherein Ar is
unsubstituted phenyl.
11. The composition according to any one of claims 1 to 9, wherein Ar is phenyl
with at least one substituent in the ortho position.
12. The composition 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
trifiuoromethyl.
13 The composition according to claim 11, wherein said compound is of formula
Ib or Ic:
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WO 2006/116149 PCT/US2006/015191

or a pharmaceutically acceptable salt thereof.
14. The composition according to claim 13, wherein said compound is of formula
Id, Ie, If, Ig, Ih,or Ii:

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

16. The composition according to claim 1, wherein said compound is selected
from:
(±)-1-{7-[3,5-bis(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(3,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(7-phenyl-2,3 -dihydro-1-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,
(±)-1-[7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1- [7-(3 -methylphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-methylphenyl)-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-thien-3 -yl-2,3 -dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1- [7-(2-methylphenyl) -2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzoruran-2-yl]methanamine,
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(+)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(-)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)-1-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,6-dimethylphenyl)-2,3 -dihydro-1-benzofuran-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,
(±)-1-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl] methanamine,
(±)-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1- [7-(3-chlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{7-[3-(trifluoromethyl)phenyl] -2,3 -dihydro-1-benzofuran-2-yl} methanamine,
(±)-1- [7-(4-methylphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzoruran-2-yl]methanamine,
(-)-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(4-fluorophenyl)-2,3-dihydro-1-benzoruran-2-yl]methanamine,
(±)-1-[7-(4-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(4-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(4-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-1-[7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuxan-2-yl]methanamine,
(±)-1-(5-chloro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(+)-1-(5-chloro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(-)-1-(5-chloro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[5-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
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WO 2006/116149 PCT/US2006/015191
(±)-1-[5-chloro-7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(-)-(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(+)-(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(+)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]-N-methylamine,
(-)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)mcthyl]-N-methylarnine,
(±)-1-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[5 -chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(4-fluoro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-ylmethanamine,
(-)-1-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(5 -fluoro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[5-fluoro-7-(2-methylphenyl)-2,3-dih.ydro-1-benzofuran-2-yl]methanamine,
(±)-1-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine ,
(±)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(±)-(4,5-difluoro-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(±)-1-[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-(5-chloro-2-raethyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-(5-chloro-2-methyl-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(±)-(5-chloro-2-methyl-7-thien-2-yl-2,3-dihydro-1-benzofuran-2-yl)methylamine,
(+)-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(3-methoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine,
(-)-1-{7-[3-(trifluoromethyl)phenyl] -2,3 -dihydro-1-benzofuran-2-yl}methanamine,
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(+)-1-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)4-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(-)-1-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl} methanamine,
(±)-1- [7-(2,6-difluorophenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(±)-l -[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1- [ 7-(2,6-dichlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine)
(+)-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-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,
(-)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine,
(+)-1-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-1-benzofuran-2-yl}methanamine:,
(±)-1-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine)
(±)-{[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)- {[(7-(2,3 -dimethoxyphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methyl} amine,
(+)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-1-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-1-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-1-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-1-benzofuran-2-yl]methyl}amine,
(-)- {[7-(2,5-dichlorophenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(5-chloro-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- [(7-pyridin-3 -yl-2,3 -dihydro-1-benzofuran-2-yl)methyl] amine,
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(+)- {[7-pyridin-3-yl-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)- {[5-fluoro-7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)- {[5-fluoro-7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[5-fluoro-7-(3-methylpb.enyl)-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-benzoJfuran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-thien-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]aniine,
(±)-{[5-fluoro-7-(3-furyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-[(5-fluoro-7-pyridin-2-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(-)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(+)- {[5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-[(5-fluoro-7-pyridin-4-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(±)-[(5-fluoro-7-pyrimidin-5-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine,
(±)- {[7-(2,3-dichlorophenyl)-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-1-benzofuran-2-yl]methyl}amine,
(+)- {[7-(2,3 -dimethoxyphenyl)-5-fluoro-2,3 -dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(-)- {[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(+)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,6-difluorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
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(±)- {[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-1-benzofuxan-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-benzoftuan-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-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}ethanamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}dimethylamine,
(±)- {[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-1-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-1-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-1-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-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine3
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-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-1-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-1-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-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-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-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-1-benzofuran-27yl]methyl}amine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)- {[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-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,
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(-)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[(5-chloro-7-pyridin-3-yl-2,3-dihydro-1-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-1-benzofuran-2-
yl]methyl}(cyclopropylmethyl)amine,
(±)-N-{[5-chloro-7-(2,6-dimethylphcnyl)-23-dihydro-1-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-1-benzofuran-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-1-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,
(±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(4-chlorophenyl)-5 -methyl-2,3 -dihydro-1-benzofuran-2-yl] methyl} amine,
(±)- {[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-1-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-]-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,3-dimethoxyphenyl)-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-(2,4-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-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(-)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-1-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-1-benzofuran-2-yl]methyl}amine,
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(±)-{[5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(2-methoxyphenyl)-23-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}amine,
(±)- {[5-(trifluoromethyl)-7-(3 -chlorophenyl)-2.3 -dihydro-1-benzofuran-2-yl]methyl} amine,
(±)- {[5 -(trifluoromethyl)-7-(3 -methoxyphenyl)-2,3 -dihydro-1-benzofuran-2-yl] methyl} 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-(trifluoromethyl)-7-(4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(4-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[5-(trifluoromethyl)-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-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,3-dimethoxyphenyl)-5-(txifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl] methyl} amine,
(±)-{[7-(234-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-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-1-benzofuran-2-
yl]methyl} amine,
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(±)- {[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-{[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}amine,
(±)-4-[2-(aminomethyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-7-yl]benzonitrile
(±)- {[7-(3-furyl)-5-(trifluoromethyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} amine,
(±)-{[7-thien-3-yl-5-(trifluoromethyl)-2,3-dihydro-1-benzofluarn-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-1-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-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl} amine,
(±)-{[5-methoxy-7-(3-tbienyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2;3-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amineJ
(±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(2,4-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {[7-(2,5 -difluorophenyl)-5 -methoxy-2,3-dihydro-1-benzofuran-2-yl] methyl} amine,
(±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)- {[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-1-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-(235-dimethoxylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl} amine,
(±)-{[7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-{[7-(256-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)-[(N-methyl-1-[7-(2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(3-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)- [(N-methyl-1-[7-(3-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(4-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
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(±)-[(N-methyl-1-[7-(4-fluorophenyl)-2,3-dihydro4-benzofuran-2-yl]methanamine,
(±)-[(N-methyl4-[7-(4-chlorophenyl)-23-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(4-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine3
(±)-[(N-methyl-1-[7-(2,3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(i)-[(N-methyl4-[7-(2,4-dichlorophenyl)-2>3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-difluorophenyl)-23-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-[(N-methyl-1-[7-(5-chloro-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-[(N-methyl-1-[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)- {[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-N-methyl-1-(7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methanamine,
(±)-[(N-methyl-1-[7-(2,3-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(±)-{[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-1-benzofuran-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-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,3 -dimethoxyphenyl)-5 -fluoro-2,3 -dihydro-1-benzofuran-2-yl]methyl} methylamine,
(±)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-beiizofuran-2-yl]methyl}methylamine,
(-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
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WO 2006/116149 PCT/US2006/015191
(±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]metliyl}methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} methylamine,
(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-fluoro-2:,3-dihydro-1-benzofuran-2-
yl]methyl} methylamine,
(±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-1-benzofuran-2-yl)methyl]methylamine,
(±)- [(5 -chloro-7-(2-methoxyphenyl)-2,3 -dihydro-1-benzofuran-2-yl]methyl} methylamine,
(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[5-chloro-7-(2.3-dimethoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-1-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-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl} methylamine,
(±)-{[5-chloro-7-(3.4-difluorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
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(±)-{[7-(4-methylphenyl)-5-methyl-2,3-dihydro4-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(4-chlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-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-23-dihydro-1-benzofuran-2-yl]methyl}methylamine.
(±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(+)- {[7-(2,5 -dichlorophenyl)-5 -methyl-2,3 -dihydro-1-benzofuran-2-yl] methyl} methylamine,
(-)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl] methyl} methylamine,
(±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-1-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-1-benzofuran-2-yl]methyl}methylamine,
(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(±)- {[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-l -benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)- {[7-(2,4-difluorophenyl)-5-methoxy-2,3 -dihydro-1-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-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(2,5-dimethoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl} methylamine,
(±)- {[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(±)-N-methyl-1-[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
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(±)-N-methyl-1-[7-(3,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-N-methyl-1-[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-N-methyl-1-[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl]methanamine,
(±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-
yl] methyl} methylamine,
(±)-N-methyl-1-[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2;3-dihydro-1-benzofuran-2-
yl] methanamine,
(+){[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-benzofuran-2-ylmethyl)methyl-amine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]ethylamine,
(R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran-2-ylmethyl]dimethylamine,
{[(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-1-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-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(+)-{[7-(2,6 dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine,
(±)- {2- [6-chloro-7-(2-chlorophenyl)-2,3 -dihydro-1-benzofuran-2-yl] ethyl} amine,
(±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]ethyl}amine,
(±)- {2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-yl]ethyl} amine,
(±)- {N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)- {N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(-)- {N-methyl-1-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine,
(+)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(+)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(+)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine,
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(+)-{[5-chloro-7-(2,6-dimethylphenyl)-23-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-methyl-2,3-dihydro-1-benzofuran-2-
yl]methyl}methylamine,
(-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]xnethyl}methylamine,
or
(+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}methylamine;
or a pharmaceutically acceptable salt thereof.
17. A method of treating a patient suffering from a depression or a mood disorder
comprising administering to said patient an effective amount of a composition according to
any one of claims 1 to 16.
18. A method of treating a patient suffering from anxiety comprising
administering to said patent an anxiety-reducing effective amount of or composition
according to any one of claims 1 to 16.
19. A method of treating a patient suffering from a psychotic disorder comprising
administering to said patient an effective amount of a composition according to any one of
claims 1 to 16.
20. The method of claim 19 wherein the patient is suffering from schizophrenia.
21. The method of claim 19 wherein the patient is suffering from bipolar disorder.
22. The method according to any one of claims 17 to 21, wherein the
antidepressant is selected from the group consisting of seratonin reuptake inhibitors (SRIs),
norepinephrine reuptake inhibitors (NERIs), combined serotonin-norepinephrine reuptake
inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of
monoamine oxidase (RIMAs), phosphodiesterase-4 (PDE4) inhibitors, corticotropin releasing
factor (CRF) antagonists, alpha.-adrenoreceptor antagonists, and combinations therof.
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23. The method according to claim 22, wherein the antidepressant is selected
from the group consisting of adinazolam, alaproclate, amineptine, amitriptyline,
amitriptyline/chlordiazepoxide combination, amoxapine, atipamezole, azamianserin,
bazinaprine, befuraline, bifemelane, binodaline, bipenamol, brofaromine, buproprion,
caroxazone, cericlamine, cianopramine, cimoxatone, citalopram, clemeprol, clomipramine,
clovoxamine, dazepinil, deanol, demexiptiline, desipramine, O-desmethylvenlafaxine,
dibenzepin, dothiepin, doxepin, droxidopa, duloxetine, enefexine, escitalopiam, estazolarn,
etoperidone, femoxetine, fengabine, fezolamine, fluotracen, fluoxetine, fluvoxamine,
idazoxan, imipramine, indalpine, indeloxazine, iprindole, isocarboxazid, levoprotiline,
lithium, litoxetine, lofepramine, maprotiline, medifoxamine, metapramine, metralindole,
mianserin, milnacipran, minaprine, mirtazapine, moclobemide, montirelin, nebracetam,
nefazodone, nefopam, netazodane, nialamide, nomifensine, norfluoxetine, nortriptyline,
orotirelin, oxaflozane, paroxetine, phenelzine, pinazepam, pirlindone, pizotyline,
protriptyline, reboxetine, ritanserin, rolipram, selegiline, sercloremine, sertraline, setiptiline,
sibutramine, sulbutiamine, sulpiride, teniloxazine, thozalinone, thymoliberin, tianeptine,
tiflucarbine, tofenacin, tofisopam, toloxatone, tomoxetine, tranylcypromine, trazodone,
trimipramine, venlafaxine, veralipride, viloxazine, viqualine, zimelidine, zometrapine,
pharmaceutically acceptable salts thereof, and combinations thereof.
24. The method according to any one of claims 17 to 23, wherein administration
of the compounds is oral.
25. The method according to claim 17, wherein the patient is suffering from
depression.
26. The method according to claim 17, wherein the patient is suffering from
anxiety.
27. The method according to claim 17, wherein the patient is further suffering
from a psychotic disorder.
28. The method according to claim 27, wherein the patient is suffering from
schizophrenia.
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29 The method of claim 27 wherein the patient is suffering from bipolar disorder.
30. The method according to claim 17, wherein the patient is suffering from a
mood disorder selected from the group consisting of dysthymic disorder with early or late
onset and with or without atypical features; dementia of the Alzheimer's type, with early or
late onset, with depressed mood; vascular dementia with depressed mood, disorders induced
by alcohol, amphetamines, cocaine, hallucinogens, inhalants, opioids, phencyclidine,
sedatives, hypnotics, anxiolytics; schizoaffective disorder of the depressed type; adjustment
disorder with depressed mood; and combinations thereof.
31. A product comprising a compound as claimed in any one of claims 1 to 16 and
an antidepressant as a combined preparation for simultaneous, separate or sequential use in
treating a patient suffering from a depression or a mood disorder, anxiety, schizophrenia or
bipolar disorder.
32. Use of a compound as claimed in any one of claims 1 to 16 and an
antidepressant in the preparation of a medicament for treating a patient suffering from a
depression or a mood disorder, anxiety, schizophrenia or bipolar disorder.
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Effect of Compound 1 (ip, 30 min pre) in the mouse tail suspension test.

Effect of Compound 1 (0.1 mg/kg ip) + paroxetine (10 or 30 mg/kg) in the mouse tail
suspension test.

* p < 0.05 vs. veh/veh
FIGURE 1
1/1

Therapeutic combinations useful in the treatment or prevention of depression or other mood disorders, to pharmaceutical compositions containing said combinations, and to their use in the treatment or prophylaxis of depression or
other mood disorders are provided. Such compounds are of formula (I) or a pharmaceutically acceptable salt thereof, wherein each of R1, R2, R3, n, y, and Ar are
as defined and described herein.