US2008280873A1PendingUtilityA1
Biaryl Substituted Pyrazinones as Sodium Channel Blockers
Est. expiryMar 29, 2024(expired)· nominal 20-yr term from priority
Inventors:Jun LiangPrasun K. ChakravartyDeborah E. PanWilliam H. ParsonsPengcheng Patrick ShaoFeng YeeBishan Zhou
A61P 35/00A61P 3/10A61P 29/00C07D 403/06B05B 1/34B05B 1/02C07D 241/18C07D 241/24B05B 1/14C07D 405/04A61P 25/04C07D 413/06B65D 83/20
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Claims
Abstract
Biaryl substituted pyrazinone compounds represented by Formula I, or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, sodium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, urinary incontinence, itchiness, allergic dermatitis, epilepsy, irritable bowel syndrome, depression, anxiety, multiple sclerosis, and bipolar disorder, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds. A method of administering local anesthesia comprises administering an effective amount of a compound of the instant invention, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier.
Claims
exact text as granted — not AI-modified1 . A compound represented by Formula (I):
or pharmaceutically acceptable salts thereof, wherein
R 1 and R 2 each independently is
(a) H,
(b) C 1 -C 6 -alkyl, optionally substituted with one or more substituents selected from the group consisting of: F, CF 3 , OH, NR a R b , COOH, CONR a R b , SO 2 NR a R b , C(═NH)NH 2 , tetrazolyl, triazolyl, oxazolyl, oxadiazolyl, isooxazolyl, thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, phenyl, piperidinyl, morpholinyl, pyrrolidinyl and piperazinyl,
(c) —C(═O)R a , COOR a , CONR a R b ,
(d) —C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl,
(e) NR a R b , —N(COR a )R b , —N(SO 2 R a )R b , or
(f) tetrazolyl, triazolyl, oxazolyl, oxadiazolyl, isooxazolyl, thiazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, phenyl, piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl, any of which is optionally substituted with 1-3 substituents independently selected from the group consisting of: F, Cl, Br, I and CN;
R a is
(a) H,
(b) C 1 -C 6 -alkyl, optionally substituted with one or more substituents independently selected from the group consisting of CF 3 and O—(C 1 -C 4 )alkyl,
(c) C 0 -C 4 -alkyl-(C 1 -C 4 )-perfluoroalkyl,
(d) NH 2 ,
(e) C 1 -C 4 -alkyl-phenyl, C 1 -C 4 -alkyl-pyridyl, or
(f) C 3 -C 7 -cycloalkyl, optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, OH, —O—C 1 -C 4 -alkyl, and C 1 -C 4 -alkyl;
R b is
(a) H, or
(b) C 1 -C 6 -alkyl;
R is:
(a) H,
(b) —C 1 -C 4 -alkyl, optionally substituted with one or more substituents independently selected from the group consisting of: F, CF 3 , Cl, N, OH, O—(C 1 -C 4 )alkyl, S(O) 0-2 —(C 1 -C 4 )alkyl, O—CONR a R b , NR a R b , N(R a )CONR a R b , COOR a , CN, CONR a R b , SO 2 NR a R b , N(R a )SO 2 NR a R b , —C(═NH)NH 2 , tetrazolyl, triazolyl, imidazolyl, oxazolyl, oxadiazolyl, isooxazolyl, thiazolyl, furyl, thienyl, pyrazolyl, pyrrolyl, pyridyl, pyrimidinyl, pyrazinyl, phenyl, piperidinyl, morpholinyl, pyrrolidinyl and piperazinyl,
or R a and R b , together with N to which they are attached, may form a C 3 -C 7 -cycloalkyl or a C 3 -C 7 -heterocycloalkyl, wherein said cycloalkyl and heterocycloalkyl is optionally substituted with one or more substituents selected from the group consisting of: F, Cl, Br, OH, —O—C 1 -C 4 -alkyl, and C 1 -C 4 -alkyl,
(c) —C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl, or
(d) C 1 -C 4 -alkyl-C(═O)—R a , —C 1 -C 4 -alkyl-C(═O)—C 1 -C 4 -perfluoroalkyl, or
(e) —C 1 -C 4 -alkyl-C 3 -C 7 -cycloalkyl, wherein said cycloalkyl is optionally substituted with one or more substituents selected from the group consisting of: F, Cl, Br, OH, —O—C 1 -C 4 -alkyl, and C 1 -C 4 -alkyl;
R 4 and R 5 each independently is:
(a) H,
(b) —C 1 -C 6 -alkyl, optionally substituted with one or more substituents independently selected from the group consisting of: F, CF 3 and —O—(C 1 -C 4 )alkyl,
(c) —O—C 0 -C 6 -alkyl, —O-phenyl, —O—C 1 -C 4 -alkyl-phenyl, —O-pyridyl, —O—C 1 -C 4 -alkyl-pyridyl, wherein phenyl and pyridyl are optionally substituted with 1-3 substituents independently selected from the group consisting of: F, Cl, Br, I and CN,
(d) —C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl, —O—C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl, or
(e) F, Cl, Br, I; and
R 6 , R 7 and R 8 each independently is:
(a) H,
(b) C 1 -C 6 -alkyl,
(c) —O—C 1 -C 6 -alkyl, optionally substituted with one or more substituents independently selected from the group consisting of: F and CF 3 ,
(d) —C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl, —O—C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl,
(e) —O-phenyl, —O—C 1 -C 4 -alkyl-phenyl, —O-pyridyl, —O—C 1 -C 4 -alkyl-pyridyl, wherein phenyl and pyridyl are optionally substituted with 1-3 substituents independently selected from the group consisting of: F, Cl, Br, I, and CN, or
(f) F, Cl, Br, I, —OR a , phenyl or pyridyl, wherein phenyl and pyridyl are optionally substituted with one or more substituents independently selected from the group consisting of: F, Cl, Br, I and CN,
with the proviso that when R 6 and R 7 are present on adjacent carbon atoms, R 6 and R 7 , together with the benzene ring to which they are attached, may form a bicyclic aromatic ring selected from the group consisting of: naphthyl, quinolinyl and benzothiazolyl, any aromatic ring of which is optionally substituted with 1-4 substituents independently selected from F, Cl, Br, I and CN.
2 . The compound of claim 1 described by the chemical Formula (I), or a pharmaceutically acceptable salt thereof, wherein
R 6 is other than H and is attached at the ortho position, and all other variables are as previously defined.
3 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein
R 1 is H, COOR a or CONR a R b , and all other variables are as previously defined.
4 . The compound of claim 1 represented by Formula Ia:
or a pharmaceutically acceptable salt thereof, wherein
R 6 is OR a or C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl, and all other variables are as previously defined.
5 . The compound of claim 1 represented by Formula Ib:
or a pharmaceutically acceptable salt thereof, wherein
R 6 is OR a or C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl;
R 7 is H, F, Cl, Br or I; and all other variables are as previously defined.
6 . The compound of claim 1 represented by Formula Ic:
or a pharmaceutically acceptable salt thereof, wherein
R 4 and R 5 each independently is H, F, Cl, Br or I;
R 6 is OR a or C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl;
R 7 is H, F, Cl, Br or I; and all other variables are as previously defined.
7 . The compound of claim 1 represented by Formula Id:
or a pharmaceutically acceptable salt thereof, wherein
R 4 is F, Cl, Br or I;
R 6 is OR a or C 0 -C 4 -alkyl-C 1 -C 4 -perfluoroalkyl;
R 7 is H, F, Cl, Br or I; and all other variables are as previously defined.
8 . A compound selected from
and pharmaceutically acceptable salts thereof.
9 . A compound according to claim 1 represented by
R 6
R 3
R 2
R 1
—OCF 3
H
H
—CONH 2
—OCF 3
CH 3
H
—COOH
—OCF 3
CH 3
—CONH 2
H
—CF 3
CH 3
—CONH 2
H
—CF 3
H
H
—COO-t-Bu
—CF 3
H
H
—CONH-t-Bu
—CF 3
H
H
—COOH
—OCH 2 CF 2 CF 3
H
H
—CONH 2
—OCH 2 CF 2 CF 3
H
H
—COOH
—OCH 2 CF 3
H
H
—CONH 2
—OCH 2 CF 3
CH 3
H
—CONH 2
—OCH 2 CF 3
H
—CONH 2
H
—OCH 2 CF 3
CH 3
—CONH 2
H
—OCH 2 CF 2 CF 3
CH 3
H
—CONH 2
—OCH 2 CF 3
H
H
—COOH
—CF 3
—CH 2 CF 3
H
—CONH 2
—CF 3
—C(CH 3 ) 3
H
—CONH 2
—CF 3
—CH(CH 3 ) 2
H
—CONH 2
—CF 3
—CH 2 CH 3
H
—CONH 2
—OCF 3
CH 3
—CONH 2
—CONH 2
or a pharmaceutically acceptable salt thereof.
10 . A compound according to claim 1 represented by
R 7
R 6
R 3
R 2
R 1
4-CF 3
—CF 3
—CH 3
H
—CONH 2
4-CF 3
—CF 3
—CH 3
—CONH 2
H
5-F
—OCF 3
—CH 3
H
—CONH 2
5-CF 3
—OCF 3
—CH 3
H
—CONH 2
5-F
—OCF 3
H
H
—CONH 2
5-F
—OCH 2 CF 2 CF 3
H
H
—CONH 2
5-F
—OCH 2 CF 3
H
H
—CONH 2
5-F
—OCH 2 CF 2 CF 3
—CH 3
H
—CONH 2
5-F
—OCH 2 CF 3
—CH 3
H
—CONH 2
6-F
—CF 3
H
H
—CONH 2
3-F
—CF 3
H
H
—CONH 2
6-F
—CF 3
—CH 3
H
—CONH 2
3-F
—CF 3
—CH 3
H
—CONH 2
5-F
—CF 3
—CH 3
H
—CONH 2
4-F
—CF 3
—CH 3
H
—CONH 2
4-F
—CF 3
H
H
—CONH 2
5-F
—CF 3
H
H
—CONH 2
5-CH 3
—CF 3
—CH 3
H
—CONH 2
4-CH 3
—CF 3
—CH 3
H
—CONH 2
or a pharmaceutically acceptable salt thereof.
11 . A compound according to claim 1 represented by
R 7
R 6
R 5
R 4
R 3
R 2
R 1
H
—OCF 3
F
H
—CH 3
—CONH 2
H
H
—OCF 3
F
H
—CH 3
H
—CONH 2
H
—OCF 3
H
F
—CH 3
H
H
H
—OCF 3
H
F
—CH 3
H
—CONH 2
H
—OCH 2 CF 3
H
F
—CH 3
H
—CONH 2
H
—OCF 3
H
F
—CH 3
H
—COOH
5-F
—OCF 3
F
H
—CH 3
H
—CONH 2
5-F
—OCF 3
H
F
—CH 3
H
—CONH 2
H
—CF 3
H
F
—CH 3
H
—CONH 2
H
—CF 3
F
H
—CH 3
H
—CONH 2
H
—OCF 3
H
F
H
H
—CONH 2
H
—OCF 3
F
H
H
H
—CONH 2
5-F
—OCF 3
F
H
H
H
—CONH 2
H
—CF 3
F
H
—CH 3
H
—COOH
5-F
—OCH 2 CF 2 CF 3
F
H
—CH 3
H
—CONH 2
H
—CF 3
H
F
—CH 3
H
—COOH
H
—OCF 3
F
H
—CH 3
H
—COOCH 3
H
—CF 3
F
H
—CH 3
H
—COOCH 3
H
—CF 3
F
H
—CH 3
H
—COOCH 3
5-F
—OCH 2 CH 3
F
H
—CH 3
H
—COOCH 3
5-F
—OCH 2 CF 3
F
H
—CH 3
H
—COOCH 3
H
—OCF 3
F
H
H
H
—COOH
H
—OCF 3
H
F
H
H
—COOH
5-F
—OCH 2 CF 2 CF 3
F
H
—CH 3
H
—COOH
H
—CF 3
H
F
H
H
—CONH 2
H
—CF 3
Br
H
—CH 3
H
—COOCH 3
H
—CF 3
F
H
H
H
—CONH 2
H
—CF 3
Br
H
—CH 3
H
—CONH 2
5-F
—CF 3
H
F
—CH 3
H
—CONH 2
H
—CF 3
Br
H
H
H
—COOCH 3
H
—CF 3
Br
H
H
H
—COOH
5-F
—OCH 2 CF 3
F
H
H
H
—CONH 2
3-F
—CF 3
F
H
—CH 3
H
—CONH 2
3-F
—CF 3
H
F
—CH 3
H
—CONH 2
5-F
—CF 3
F
H
—CH 3
H
—CONH 2
4-F
—CF 3
F
H
—CH 3
H
—CONH 2
4-F
—CF 3
H
F
H
H
—CONH 2
or a pharmaceutically acceptable salt thereof.
12 . A compound according to claim 1 represented by
R 7
R 6
R 4
R 3
R 2
R 1
H
—OCF 3
F
—CH 3
H
—CONH 2
H
—OCF 3
F
—CH 3
—CONH 2
H
H
—OCF 3
F
—CH 3
H
—COOH
H
—OCF 3
F
H
H
—CONH 2
H
—OCF 3
F
H
H
—COOH
H
—CF 3
F
—CH 3
H
—CONH 2
H
—CF 3
F
—CH 3
H
—COOH
5-F
—OCH 2 CF 2 CF 3
F
—CH 3
H
—CONH 2
5-F
—OCH 2 CF 3
F
—CH 3
H
—CONH 2
H
—OCF 3
F
—CH 3
H
—COOCH3
5-F
—CF 3
F
—CH 3
H
—CONH 2
H
—CF 3
F
H
H
—CONH 2
3-F
—CF 3
F
—CH 3
H
—CONH 2
or a pharmaceutically acceptable salt thereof.
13 . A compound according to claim 1 represented by
R 7
R 6
R 5
R 4
R 3
R 2
R 1
H
OCF 3
H
H
CH 2 CONH 2
H
CONH 2
H
CF 3
H
H
CH 2 CONH 2
H
CONH 2
H
OCF 3
H
H
CH 2 COOH
H
CONH 2
H
OCF 3
H
H
CH 2 COO-tBu
H
CONH 2
H
OCF 3
H
H
CH 2 CN
H
CONH 2
H
CF 3
H
H
CH 2 CN
H
CONH 2
H
CF 3
H
H
CH 2 COOH
H
CONH 2
H
CF 3
H
H
CH 2 COO-tBu
H
CONH 2
H
OCF 3
H
H
H
CONH 2
H
CF 3
H
H
H
CONH 2
H
CF 3
H
H
H
CONH 2
H
OCF 3
H
H
H
CONH 2
H
OCF 3
H
H
CH 2 CH 2 OH
H
CONH 2
H
CF 3
H
H
CH 2 CH 2 OH
H
CONH 2
H
OCF 3
H
H
CH 2 CH 2 NH 2
H
CONH 2
H
CF 3
H
H
CH 2 CH 2 NH 2
H
CONH 2
H
OCF 3
H
H
CH 2 CH 2 N(CH 3 ) 2
H
CONH 2
H
CF 3
H
H
CH 2 CH 2 N(CH 3 ) 2
H
CONH 2
4-F
CF 3
H
H
CH 2 CONH 2
H
CONH 2
5-F
CF 3
H
H
CH 2 CONH 2
H
CONH 2
H
CF 3
F
H
CH 2 CONH 2
H
CONH 2
H
CF 3
F
H
CH 2 CONH 2
H
CONH 2
4-F
CF 3
F
H
CH 2 CONH 2
H
CONH 2
5-F
CF 3
F
H
CH 2 CONH 2
H
CONH 2
or a pharmaceutically acceptable salt thereof.
14 . A compound selected from
and pharmaceutically acceptable salts thereof.
15 . A compound according to claim 1 represented by
R 7
R 6
R 3
R 1
4-F
—CF 3
—CH 3
—CONH 2
5-F
—CF 3
H
—CONH 2
H
CF 3
—CH 2 CH 2 OH
—CONH 2
H
—CF 3
—CH 2 CH 2 F
—CONH 2
H
—OCF 3
—CH 2 CH 2 OH
—CONH 2
H
—OCF 3
—CH 2 CH 2 CH 2 OH
—CONH 2
H
—OCF 3
—CH 2 CONH 2
—CONH 2
H
—OCF 3
—CH(CH 3 )CONH 2
—CONH 2
H
—OCF 3
—CH 2 CH 3
—CONH 2
H
—OCF 3
—CH 2 CH 2 F
—CONH 2
H
—CF 3
—CH 2 CONH 2
—CONH 2
H
—OCF 3
—CH 2 SO 2 NH 2
—CONH 2
3-F
—CF 3
—CH 2 SO 2 NH 2
—CONH 2
H
—CF 3
—CH 2 CH 3
—CONH 2
H
—CF 3
—CH 2 CH 2 CH 2 OH
—CONH 2
H
—OCF 3
—CH 2 CH 2 Cl
—CONH 2
H
—OCF 3
—CH 2 CH 2 N 3
—CONH 2
H
—OCF 3
—CH 2 CH 2 NH 2
—CONH 2
H
—CF 3
—CH(CH 3 )CONH 2
—CONH 2
H
—OCF 3
—CH 2 CONHCH 3
—CONH 2
4-F
—CF 3
—CH 2 CONH 2
—CONH 2
4-F
—CF 3
—CH 2 CH 2 OH
—CONH 2
4-F
—CF 3
—CH 2 CH 3
—CONH 2
4-F
—CF 3
H
—CONH 2
5-F
—CF 3
—CH 2 CH 2 OH
—CONH 2
5-F
—CF 3
—CH 2 CONH 2
—CONH 2
H
—OCF 3
—CH 2 C(═O)CH 3
—CONH 2
or a pharmaceutically acceptable salt thereof.
16 . A compound according to claim 1 represented by
R 4
R 3
F
H
F
CH 2 CONH 2
F
CH 2 CH 2 OH
F
CH 3
H
H
H
CH 2 CONH 2
H
CH 3
or a pharmaceutically acceptable salt thereof.
17 . A compound according to claim 1 represented by
R 6
R 3
OCF3
CH 2 CONH 2
OCF3
CH(CH 3 )CONH 2
OCF3
CH 2 CH 2 OH
OCF3
CH 2 CH 2 CH 2 OH
OCF3
CH 2 CH 3
CF3
CH 2 CONH 2
CF3
CH(CH 3 )CONH 2
CF3
CH 2 CH 2 OH
CF3
CH 2 CH 2 CH 2 OH
CF3
CH 2 CH 3
or a pharmaceutically acceptable salt thereof.
18 . A compound according to claim 1 represented by
R 3
H
CH 2 CONH 2
CH 2 CH 2 OH
CH(CH 3 )CONH 2
CH 2 CH 2 CH 2 OH
CH 2 CH 3
CH 2 CONHCH 3
CH 2 CON(CH 3 ) 2
CH 2 CO 2 CH 3
or a pharmaceutically acceptable salt thereof.
19 . A compound according to claim 1 represented by
R 7
R 6
R 5
R 4
R 3
H
OCF 3
H
H
C(CH 3 ) 2 CONH 2
5-Cl
Cl
H
H
CH 2 CONH 2
4-CF 3
CF 3
H
H
CH 2 COOH
4-CF 3
CF 3
H
H
CH 2 CONH 2
H
Cl
H
H
CH 2 CONH 2
3-Cl
Cl
H
H
CH 2 CONH 2
5-CF 3
CF 3
H
H
CH 2 CONH 2
H
OCF 3
H
H
CH(CH 3 )COOH
H
OCF 3
H
H
CH(CH 3 )CONH 2
H
CF 3
H
H
CH(CH 3 )CONH 2
H
OCF 3
H
H
H
OCF 3
H
H
CH(CH 3 )COCH 3
H
OCF 3
H
F
CH 2 CONH 2
6-F
CF 3
H
H
CH 2 CONH 2
H
OCF 3
F
H
CH 2 CONH 2
6-F
CF 3
H
H
CH(CH 3 )CONH 2
H
OCF 3
F
H
CH(CH 3 )CONH 2
4-F
OCF 3
F
H
CH 2 CONH 2
4-F
OCF 3
F
H
CH(CH 3 )CONH 2
H
CF 3
H
F
CH 2 CONH 2
3-F
CF 3
H
H
CH 2 CONH 2
4-Cl
CF 3
H
H
CH 2 CONH 2
H
OCF 3
H
F
CH(CH 3 )CONH 2
6-F
CF 3
H
H
CH 2 CONHCH 3
6-F
CF 3
H
H
CH 2 CON(CH 3 ) 2
H
CF 3
H
H
CH(CONH 2 ) 2
H
OCF 3
H
H
CH(CONH 2 ) 2
6-F
CF 3
H
H
CH(CONH 2 ) 2
H
CF 3
H
H
CH 2 CONHCH 3
H
CF 3
H
H
CH 2 CON(CH 3 ) 2
4-CF 3
CF 3
H
F
CH 2 CONH 2
H
OCF 3
H
H
CH 2 CON(CH 3 ) 2
H
OCF 3
H
H
CH 2 CONHCH 3
H
OCF 3
F
H
CH 2 CONHCH 3
H
OCF 3
H
F
CH 2 CONHCH 3
6-F
CF 3
H
H
CH 2 CONH(CH 2 ) 2 OH
H
CF 3
H
F
CH 2 CONHCH 3
H
OCH 2 CF 3
H
H
CH 2 CONH 2
H
OCH 2 CF 2 CF 3
H
H
CH 2 CONH 2
6-F
CF 3
H
H
H
CF 3
H
H
6-F
CF 3
H
H
CH 2 CONHCH(CH 3 ) 2
6-F
CF 3
H
H
CH 2 CONHC(CH 3 ) 3
H
CF 3
H
H
CH 2 CONHC(CH 3 ) 3
4-F
OCF 3
H
H
CH 2 CONH 2
H
CF 3
H
H
CH 2 CONHCH 2 CH 3
H
CF 3
H
F
CH 2 CONHCH 2 CH 3
6-F
CF 3
H
H
6-F
OCF 3
H
H
CH 2 CONH 2
6-F
CF 3
H
H
5-F
OCF 3
H
H
CH 2 CONH 2
6-F
OCF 3
H
H
CH 2 COOH
H
OCF 3
H
OCH 2 Ph
CH 2 CONH 2
H
OCF 3
H
OCH 2 Ph
CH(CH 3 )CONH 2
H
CF 3
H
H
5-I
OCF 3
H
H
CH 2 CONH 2
6-F
CF 3
H
H
CH 2 COCH 3
H
CF 3
H
H
CH 2 COCH 3
H
CF 3
H
H
H
CF 3
I
I
CH 2 CONH 2
5-F
OCF 3
H
F
CH 2 CONH 2
4-F
CF 3
H
F
CH 2 CONH 2
H
OCF 3
H
H
CH 2 COCH 3
H
CF 3
H
H
H
OCF 3
Br
H
CH 2 CONH 2
H
OCF 3
H
F
CH 2 COCH 3
5-F
CF 3
H
H
CH 2 COCH 3
5-F
CF 3
H
H
H
OCF 3
F
H
CH 2 COCH 3
or a pharmaceutically acceptable salt thereof.
20 . A compound according to claim 1 represented by
R 7
R 6
R 5
R 4
4-F
CF 3
H
H
6-F
CF 3
H
H
3-F
CF 3
H
H
H
CF 3
F
H
H
CF 3
H
F
5-CF 3
OCF 3
H
H
4-F
OCF 3
H
H
H
OCF 3
F
H
H
OCF 3
H
F
4-F
CF 3
H
F
3-F
CF 3
H
F
H
OCH 2 CF 2 CF 3
F
H
4-F
OCF 3
F
H
4-CF 3
CF 3
H
H
5-Cl
Cl
H
H
5-CF 3
CF 3
H
H
5-F
CF 3
H
H
4-F
OCF 3
H
H
5-F
OCF 3
H
H
H
OCF 3
H
OCH 2 Ph
H
OCF 3
Br
H
4-Cl
CF 3
H
H
or a pharmaceutically acceptable salt thereof.
21 . A compound according to claim 1 represented by
R 7
R 6
R 5
R 4
R 3
H
OCF 3
H
H
CH 3
H
CF 3
H
H
CH 3
H
CF 3
H
H
H
H
OCF 3
H
H
H
4-F
CF 3
H
H
H
4-F
CF 3
H
H
CH 3
4-F
CF 3
H
H
CH 2 CH 2 OH
3-F
CF 3
H
H
H
3-F
CF 3
H
H
CH 3
3-F
CF 3
H
H
CH 2 CH 2 OH
4-Cl
CF 3
H
H
CH 3
5-CF 3
CF 3
H
H
CH 3
4-Cl
CF 3
H
H
H
5-CF 3
CF 3
H
H
H
4-F
OCF 3
H
H
H
4-F
OCF 3
H
H
CH 3
4-F
OCF 3
H
H
CH 2 CH 2 OH
4-Cl
CF 3
H
H
CH 2 CH 2 OH
5-CF 3
CF 3
H
H
CH 2 CH 2 OH
H
OCH 2 CF 2 CF 3
H
H
H
H
OCH 2 CF 2 CF 3
H
H
CH 3
H
OCH 2 CF 2 CF 3
H
H
CH 2 CH 2 OH
H
OCH 2 CF 3
H
H
H
H
OCF 3
F
H
H
H
CF 3
F
H
H
H
OCH 2 CF 3
H
H
CH 3
H
OCF 3
F
H
CH 3
H
CF 3
F
H
CH 3
H
OCF 3
F
H
CH 2 CH 2 OH
H
CF 3
F
H
CH 2 CH═CH 2
H
OCF 3
F
H
CH 2 CH═CH 2
H
CF 3
F
H
CH 2 CH═CH 2
H
CF 3
F
H
CH 2 CH 2 OCH 3
or a pharmaceutically acceptable salt thereof.
22 . A compound according to claim 1 represented by
R 7
R 6
R 5
R 4
R 3
H
OCF 3
H
H
CH 2 CH 2 OCH 3
6-F
CF 3
H
H
CH 2 CH 2 OCH 3
6-F
CF 3
H
H
CH 2 CH 2 OCH 2 CH 3
H
OCF 3
H
H
CH 2 CH 2 CH 3
H
OCF 3
H
H
CH(CH 2 OH)CH 2 OH
H
CF 3
H
H
CH(CH 2 OH)CH 2 OH
H
OCF 3
H
H
6-F
OCF 3
H
H
CH(CH 2 OH)CH 2 OH
H
CF 3
H
F
CH(CH 2 OH)CH 2 OH
H
CF 3
H
F
CH 2 CH(OH)CH 2 OH
H
OCF 3
H
H
CH 2 CH 2 CH 2 CH 3
H
CF 3
H
H
CH 2 CH(OH)CH 3
6-F
CF 3
H
H
CH 2 CH(OH)CH 3
6-F
OCF 3
H
H
CH 2 CH(OH)CH 2 OH
H
OCF 3
H
H
H
OCF 3
H
H
CH 2 CH 2 CH 2 CH 2 CH 3
6-F
CF 3
H
H
H
OCF 3
H
H
CH 2 C(CH 3 ) 2 CH 2 OH
H
OCF 3
H
H
CH 2 CH 2 CONH 2
H
OCF 3
H
H
CH 2 CH 2 SCH 3
6-F
CF 3
H
H
CH 2 CH 2 SCH 3
H
OCF 3
H
H
H
OCF 3
H
H
CH 2 CH 2 SO 2 CH 3
6-F
CF 3
H
H
CH 2 CH 2 SO 2 CH 3
6-F
CF 3
H
H
6-F
CF 3
H
H
CH 2 CH 2 CH 2 OH
6-F
CF 3
H
H
CH 2 SCH 3
6-F
CF 3
H
H
CH 2 CH 2 CH 2 SCH 3
6-F
CF 3
H
H
CH 2 CH 2 CH 2 SO 2 CH 3
H
OCF 3
H
H
CH 2 CH 2 NHCONH 2
6-F
CF 3
H
H
H
OCF 3
H
H
CH 2 CF 3
H
OCF 3
H
H
CH 2 CF 2 CF 3
H
CF 3
H
H
CH 2 CH 2 CH 2 OH
H
CF 3
H
H
H
OCF 3
H
H
H
CF 3
H
H
CH 2 SCH 3
H
OCF 3
H
H
CH 2 SCH 3
H
OCF 3
H
H
CH 2 SO 2 CH 3
6-F
CF 3
H
H
CH 2 SO 2 CH 3
6-F
CF 3
H
H
CH 2 CH 3
6-F
CF 3
H
H
CH 2 CH 2 CH 3
H
OCF 3
H
H
CH 2 SO 2 NHC(CH 3 ) 3
H
OCF 3
H
H
CH 2 SO 2 NH 2
H
OCF 3
H
H
4-F
CF 3
H
H
CH 2 SO 2 NH 2
H
CF 3
H
H
CH 2 SO 2 NH 2
4-F
OCF 3
H
H
CH 2 SO 2 NH 2
6-F
CF 3
H
H
CH 2 SO 2 NH 2
H
CF 3
H
H
CH 2 SO 2 CH 3
H
OCF 3
F
H
CH 2 SO 2 CH 3
4-F
CF 3
H
H
CH 2 CH 3
4-F
OCF 3
H
H
CH 2 CH 2 CH 2 OH
4-Cl
CF 3
H
H
CH 2 SO 2 NH 2
3-F
CF 3
H
H
CH 2 SO 2 NH 2
4-F
CF 3
H
H
CH 2 SO 2 NHCH 3
H
CF 3
H
F
CH 2 CH 2 CH 2 OH
H
OCF 3
F
H
CH 2 CH 2 F
H
OCF 3
H
F
CH 2 CH 2 F
4-F
OCF 3
F
H
CH 2 CH 2 F
6-F
CF 3
H
H
CH 2 CH 2 F
H
CF 3
H
F
CH 2 CH 2 F
4-CF 3
CF 3
H
H
CH 2 SO 2 NH 2
H
OCF 3
H
F
CH 2 SO 2 NH 2
H
CF 3
H
F
CH 2 SO 2 NH 2
H
OCF 3
H
F
CH 2 SO 2 NHCH 3
H
CF 3
H
F
CH 2 SO 2 NHCH 3
H
CF 3
H
H
CH 2 CH 2 F
H
OCF 3
H
H
CH 2 CH 2 F
3-F
CF 3
H
H
CH 2 CH 2 F
4-Cl
CF 3
H
H
CH 2 CH 2 F
5-CF 3
CF 3
H
H
CH 2 CH 2 F
H
OCF 3
F
H
H
OCF 3
H
F
CH 2 CH 2 F
H
OCF 3
F
H
CH 2 CH 2 F
5-F
CF 3
H
H
CH 2 CH 3
5-F
CF 3
H
H
CH 2 CH 2 F
H
CF 3
H
H
CH(CONH 2 ) 2
H
OCF 3
H
H
CH(CONH 2 ) 2
6-F
CF 3
H
H
CH(CONH 2 ) 2
6-F
CF 3
H
H
CH 2 CONHCH 2 CH 2 OH
or a pharmaceutically acceptable salt thereof.
23 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
24 . (canceled)
25 . A method of treatment or prevention of pain comprising the step of administering to a patient in need thereof a therapeutically effective amount, or a prophylactically effective amount, of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
26 - 37 . (canceled)
38 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
39 . (canceled)
40 . A method of treatment or prevention of pain comprising the step of administering to a patient in need thereof a therapeutically effective amount, or a prophylactically effective amount, of a compound according to claim 2 , or a pharmaceutically acceptable salt thereof.
41 - 52 . (canceled)Join the waitlist — get patent alerts
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