US2004214815A1PendingUtilityA1
Therapeutic compounds
Est. expiryJul 5, 2021(expired)· nominal 20-yr term from priority
A61P 37/00A61P 9/00A61P 9/12A61P 43/00A61P 25/30A61P 25/22A61P 25/24A61P 25/14A61P 3/04A61P 25/18A61P 25/06A61P 25/00A61P 25/02A61P 25/20A61P 15/10A61P 1/00A61P 15/08C07D 491/04
47
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention provides compounds of formula (I): wherein: R 1 , R 2 , R 3 R 4 , R 5 , R 6 , X, - - - , m, and n have any of the values defined in the specification, as well as pharmaceutical compositions comprising the compounds or salts thereof. The invention also provides therapeutic methods as well as processes and intermediates useful for preparing compounds of formula (I). The compounds are useful as 5-HT ligands.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1 . A compound of formula (I):
wherein:
R 1 , R 2 , R 3 , and R 4 are independently hydrogen, halo, —CF 3 , —OCF 3 , —CN, —NO 2 , —C 1-8 alkyl, —C 3-8 cycloalkyl, —OR 8 , —NR 8 R 9 , —SR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl);
R 5 is hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 alkanoyl, haloC 1-8 alkanoyl, —C(═O)OR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl);
R 6 is hydrogen or C 1-4 alkyl;
each R 8 and R 9 is independently hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, —C 1-8 alkylene(heteroaryl) or R 8 and R 9 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
m is 0, 1, or 2;
n is 1 or 2; with the proviso that m and n cannot simultaneously be 1;
X is oxy (—O—), thio (—S—) —S(═O)— or —SO 2 —; and
the bond represented by - - - is absent or present;
wherein any C 1-8 alkyl, C 1-8 alkylene, C 1-8 alkoxy or C 3-8 cycloalkyl of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 and R 9 is optionally partially unsaturated; and
wherein any aryl or heteroaryl of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 or R 9 is optionally substituted with one or more substituents independently selected from halo, —CN, —NO 2 , —CF 3 , —OCF 3 , C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, aryl, heteroaryl, —OR c , —SR c , —C(═O)R c , —CO 2 R c , —C(═O)NR c R d , —NR c C(═O)R d , —C(═O)NR c R d , —NR c R d , —NR c C(═O)NR c R d , —SO 2 NR c R d or —SO 2 R c ;
wherein each R c and R d is independently hydrogen, C 1-8 alkyl, C 1-8 alkanoyl, C 1-8 alkoxycarbonyl, aryl, —C 1-8 alkylene(aryl), —C(═O)aryl, —C(═O)Oaryl, heteroaryl, —C 1-8 alkylene(heteroaryl),
—C(═O)heteroaryl, —C(═O)Oheteroaryl or R c and R d together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
or a pharmaceutically acceptable salt thereof.
2 . The compound of claim 1 , wherein the bond represented by - - - is absent.
3 . The compound of claim 1 , wherein the bond represented by - - - is present.
4 . The compound of claim 1 , wherein X is oxy.
5 . The compound of claim 1 , wherein X is thio.
6 . The compound of claim 1 , wherein R 2 is aryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , and —C(═O)NR c R d .
7 . The compound of claim 6 , wherein R 2 is phenyl, optionally substituted with one or more substituents independently selected from from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , and —C(═O)NR c R d .
8 . The compound of claim 7 , wherein R 2 is phenyl, optionally substituted with one or more substituents independently selected from halo, cyano, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy and thioC 1-6 alkyl.
9 . The compound of claim 8 , wherein R 2 is phenyl, substituted with one or more substituents independently selected from halo, cyano, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy and thioC 1-6 alkyl.
10 . The compound of claim 9 , wherein R 2 is phenyl, substituted with one or more substituents independently selected from fluoro, chloro, bromo, trifluoromethyl, trifluoromethoxy, methoxy, ethoxy, propoxy, isopropoxy and thiomethyl.
11 . The compound of claim 10 , wherein R 2 is phenyl substituted at the 2- or 6-position with fluoro, chloro or bromo.
12 . The compound of claim 10 , wherein R 2 is phenyl independently substituted at the 2- and 6-position with fluoro, chloro or bromo.
13 . The compound of claim 10 , wherein R 2 is phenyl substituted at the 2- or 4-position with fluoro, chloro or bromo.
14 . The compound of claim 10 , wherein R 2 is phenyl independently substituted at the 2- and 4-position with fluoro, chloro or bromo.
15 . The compound of claim 10 , wherein R 2 is phenyl independently substituted at the 2-, 4- and 6-position with fluoro, chloro or bromo.
16 . The compound of claim 10 , wherein R 2 is 2,4-dichlorophenyl, 2,4,6-trichlorophenyl or 2,6-difluoro-4-chlorophenyl.
17 . The compound of claim 1 , wherein R 2 is heteroaryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , and —C(═O)NR c R d .
18 . The compound of claim 17 , wherein R 2 is heteroaryl, optionally substituted with one or more substituents independently selected from halo, cyano, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c and —SR c .
19 . The compound of claim 18 , wherein R 2 is heteroaryl, optionally substituted with one or more substituents independently selected from fluoro, chloro, bromo, trifluoromethyl, trifluoromethoxy, methoxy, ethoxy, propoxy, and isopropoxy.
20 . The compound of claim 1 , wherein R 1 is hydrogen, C 1-3 alkyl, halo, haloC 1-3 alkyl, C 1-3 alkoxy, haloC 1-3 alkoxy, or —NR 8 R 9 .
21 . The compound of claim 20 , wherein R 1 is hydrogen or C 1-3 alkyl.
22 . The compound of claim 1 , wherein R 3 is hydrogen, C 1-3 alkyl, aryl, halo, haloC 1-3 alkyl, C 1-3 alkoxy, haloC 1-3 alkoxy or —NR 8 R 9 .
23 . The compound of claim 22 , wherein R 3 is hydrogen, C 1-3 alkyl, or aryl.
24 . The compound of claim 23 , wherein R 3 is hydrogen or C 1-3 alkyl.
25 . The compound of claim 1 , wherein R 4 is C 1-8 alkyl, —OR 8 , —SR 8 , —NR 8 R 9 , aryl or —C 1-8 alkylene(aryl), wherein the aryl groups are optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
26 . The compound of claim 25 , wherein R 4 is C 1-8 alkyl, —OR 8 , —SR 8 , —NR 8 R 9 or aryl, wherein the aryl group is substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
27 . The compound of claim 25 , wherein R 4 is methyl, ethyl, propyl, isopropyl, butyl, ethylpropyl, cyclohexyl, phenyl, benzyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, (ethylpropyl)oxy, (cyclohexyl)oxy, phenoxy, (benzyl)oxy, methylthio, ethylthio, propylthio, isopropylthio, butylthio, (ethylpropyl)thio, (cyclohexyl)thio, phenylthio, (benzyl)thio, or —NR 8 R 9 ,
wherein R 8 is hydrogen, methyl, ethyl, propyl or cyclohexyl; and R 9 is methyl, ethyl, propyl, cyclohexyl or phenyl; or R 8 and R 9 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring.
28 . The compound of claim 27 , wherein R 4 is —NR 8 R 9 , wherein R 8 is hydrogen, methyl, ethyl, propyl or cyclohexyl and R 9 is methyl, ethyl, propyl, cyclohexyl or phenyl.
29 . The compound of claim 28 , wherein R 4 is —NR 8 R 9 , wherein R 8 is hydrogen, methyl or ethyl and R 9 is methyl, ethyl, propyl, cyclohexyl or phenyl.
30 . The compound of claim 29 , wherein R 4 is —NR 8 R 9 , wherein R 8 is hydrogen, methyl or ethyl and R 9 is methyl, ethyl, cyclohexyl or phenyl.
31 . The compound of claim 30 , wherein R 4 is —NR 8 R 9 , wherein R 8 is methyl or ethyl and R 9 is methyl, ethyl or cyclohexyl.
32 . The compound of claim 27 ,wherein R 4 is pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino.
33 . The compound of claim 1 , wherein R 5 is hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, aryl, —C 1-8 alkylene(aryl), heteroaryl, or —C 1-8 alkylene(heteroaryl).
34 . The compound of claim 33 , wherein R 5 is hydrogen or C 1-8 alkyl.
35 . The compound of claim 33 , wherein R 5 is hydrogen, methyl, ethyl, benzyl, or phenethyl.
36 . The compound of claim 33 , wherein R 5 is aryl, —C 1-8 alkylene(aryl), heteroaryl, or —C 1-8 alkylene(heteroaryl).
37 . The compound of claim 34 , wherein R 5 is hydrogen.
38 . The compound of claim 1 , wherein m is 1.
39 . The compound of claim 1 , wherein n is 1.
40 . The compound of claim 1 , wherein m is 0; n is 1; and X is oxy.
41 . The compound of claim 1 , wherein m is 2; n is 1; and X is oxy.
42 . The compound of claim 1 , wherein m is 0; n is 2; and X is oxy.
43 . The compound of claim 1 , wherein m is 1; n is 2; and X is oxy.
44 . The compound of claim 1 , wherein m is 2; n is 2; and X is oxy.
45 . The compound of claim 1 , wherein m is 0; n is 1; and X is thio.
46 . The compound of claim 1 , wherein m is 2; n is 1; and X is thio.
47 . The compound of claim 1 , wherein m is 0; n is 2; and X is thio.
48 . The compound of claim 1 , wherein m is 1; n is 2; and X is thio.
49 . The compound of claim 1 , wherein m is 2; n is 2; and X is thio.
50 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
51 . A method for treating a disease or condition in a mammal wherein the 5-HT receptor is implicated and modulation of 5-HT function is desired comprising administering a therapeutically effective amount of a compound of claim 1 to the mammal.
52 . A compound of formula (I):
wherein:
R 1 , R 3 , and R 4 are independently hydrogen, halo, —CF 3 , —OCF 3 , —CN, —NO 2 , —C 1-8 alkyl, —C 3-8 cycloalkyl, —OR 8 , —NR 8 R 9 , —SR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl);
R 2 is aryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , or —C(═O)NR c R d .
R 5 is hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 alkanoyl, haloC 1-8 alkanoyl, —C(═O)OR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl);
R 6 is hydrogen or C 1-4 alkyl;
each R 8 and R 9 is independently hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, —C 1-8 alkylene(heteroaryl) or R 8 and R 9 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
m is 0, 1, or 2;
n is 1 or 2; with the proviso that m and n cannot simultaneously be 1;
X is oxy (—O—), thio (—S—) —S(═O)— or —SO 2 —; and
the bond represented by - - - is absent or present;
wherein any C 1-8 alkyl, C 1-8 alkylene, C 1-8 alkoxy or C 3-8 cycloalkyl of R 1 , R 3 , R 4 , R 5 , R 6 , R 8 and R 9 is optionally partially unsaturated; and
wherein any aryl or heteroaryl of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 or R 9 is optionally substituted with one or more substituents independently selected from halo, —CN, —NO 2 , —CF 3 , —OCF 3 , C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, aryl, heteroaryl, —OR c , —SR c , —C(═O)R c , —CO 2 R c , —C(═O)NR c R d , —NR c C(═O)R d , —C(═O)NR c R d , —NR c R d , —NR c C(═O)NR c R d , —SO 2 NR c R d or —SO 2 R c ;
wherein each R c and R d is independently hydrogen, C 1-8 alkyl, C 1-8 alkanoyl, C 1-8 alkoxycarbonyl, aryl, —C 1-8 alkylene(aryl), —C(═O)aryl, —C(═O)Oaryl, heteroaryl, —C 1-8 alkylene(heteroaryl), —C(═O)heteroaryl, —C(═O)Oheteroaryl or R c and R d together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
or a pharmaceutically acceptable salt thereof.
53 . The compound of claim 52 , wherein - - - is absent.
54 . The compound of claim 53 , wherein m is 1.
55 . The compound of claim 54 , wherein n is 1.
56 . The compound of claim 55 , wherein R 2 is phenyl optionally substituted with one or more substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , or —C(═O)NR c R d .
57 . The compound of claim 56 , wherein R 2 is phenyl optionally substituted with one or more halo.
58 . The compound of claim 57 , wherein R 2 is phenyl substituted at the 2- or 6-position with fluoro, chloro, or bromo.
59 . The compound of claim 58 , wherein R 2 is phenyl substituted at the 2- and 6-position with halo independently selected from fluoro, chloro, and bromo.
60 . The compound of claim 57 , wherein R 2 is phenyl substituted at the 2- or 4-position with fluoro, chloro, or bromo.
61 . The compound of claim 57 , wherein R 2 is phenyl substituted at the 2- and 4-position with halo independently selected from fluoro, chloro, and bromo.
62 . The compound of claim 57 , wherein R 2 is phenyl substituted at the 2-, 4- and 6-position with halo independently selected from fluoro, chloro, and bromo.
63 . The compound of claim 57 , wherein R 2 is 2,4-dichlorophenyl, 2,4,6-trichlorophenyl, or 2,6-difluoro-4-chlorophenyl.
64 . The compound of claim 57 , wherein R 4 is halo, —CF 3 , C 1-8 alkyl, —OR 8 , —SR 8 , —NR 8 R 9 , aryl, or —C 1-8 alkylene(aryl), wherein aryl is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
65 . The compound of claim 64 , wherein R 4 is halo, —CF 3 , C 1-8 alkyl, —NR 8 R 9 , aryl, or —C 1-8 alkylene(aryl), wherein aryl is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
66 . The compound of claim 65 , wherein R 4 is aryl, —C 1-8 alkylene(aryl), wherein aryl is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d , or —NR 8 R 9 , wherein R 8 is hydrogen, methyl, ethyl, propyl or cyclohexyl and R 9 is methyl, ethyl, propyl, cyclohexyl or phenyl.
67 . The compound of claim 65 , wherein R 4 is halo, —CF 3 , or —CH 3 .
68 . A compound of formula (I):
wherein:
R 1 , R 3 , R 2 , and R 4 are independently hydrogen, halo, —CF 3 , —OCF 3 , —CN, —NO 2 , —C 1-8 alkyl, —C 3-8 cycloalkyl, —OR 8 , —NR 8 R 9 , —SR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl), provided that at least one of R 1 , R 3 , R 2 , and R 4 is aryl optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , or —C(═O)NR c R d ;
R 5 is hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 alkanoyl, haloC 1-8 alkanoyl, —C(═O)OR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl);
R 6 is hydrogen or C 1-4 alkyl;
each R 8 and R 9 is independently hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, —C 1-8 alkylene(heteroaryl) or R 8 and R 9 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
m is 0, 1, or 2;
n is 1 or 2; with the proviso that m and n cannot simultaneously be 1;
X is oxy (—O—), thio (—S—) —S(═O)— or —SO 2 —; and
the bond represented by - - - is absent or present;
wherein any C 1-8 alkyl, C 1-8 alkylene, C 1-8 alkoxy or C 3-8 cycloalkyl of R 1 , R 3 , R 4 , R 5 , R 6 , R 8 and R 9 is optionally partially unsaturated; and
wherein any aryl or heteroaryl of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 or R 9 is optionally substituted with one or more substituents independently selected from halo, —CN, —NO 2 , —CF 3 , —OCF 3 , C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, aryl, heteroaryl, —OR c , —SR c , —C(═O)R c , —CO 2 R c , —C(═O)NR c R d , —NR c C(═O)R d , —C(═O)NR c R d , —NR c R d , —NR c C(═O)NR c R d , —SO 2 NR c R d or —SO 2 R c ;
wherein each R c and R d is independently hydrogen, C 1-8 alkyl, C 1-8 alkanoyl, C 1-8 alkoxycarbonyl, aryl, —C 1-8 alkylene(aryl), —C(═O)aryl, —C(═O)Oaryl, heteroaryl, —C 1-8 alkylene(heteroaryl), —C(═O)heteroaryl, —C(═O)Oheteroaryl or R c and R d together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
or a pharmaceutically acceptable salt thereof.
69 . The compound of claim 68 , wherein - - - is absent.
70 . The compound of claim 69 , wherein m is 1.
71 . The compound of claim 70 , wherein n is 1.
72 . The compound of claim 71 , wherein R 2 is phenyl optionally substituted with one or more substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , or —C(═O)NR c R d .
73 . The compound of claim 72 , wherein R 2 is phenyl optionally substituted with one or more halo.
74 . The compound of claim 73 , wherein R 2 is phenyl substituted at the 2- or 6-position with fluoro, chloro, or bromo.
75 . The compound of claim 73 , wherein R 2 is phenyl substituted at the 2- and 6-position with halo independently selected from fluoro, chloro, and bromo.
76 . The compound of claim 73 , wherein R 2 is phenyl substituted at the 2- or 4-position with fluoro, chloro, or bromo.
77 . The compound of claim 73 , wherein R 2 is phenyl substituted at the 2- and 4-position with halo independently selected from fluoro, chloro, and bromo.
78 . The compound of claim 73 , wherein R 2 is phenyl substituted at the 2-, 4- and 6-position with halo independently selected from fluoro, chloro, and bromo.
79 . The compound of claim 73 , wherein R 2 is 2,4-dichlorophenyl, 2,4,6-trichlorophenyl or 2,6-difluoro-4-chlorophenyl.
80 . The compound of claim 73 , wherein R 4 is halo, —CF 3 , C 1-8 alkyl, —OR 8 , —SR 8 , —NR 8 R 9 , aryl, or —C 1-8 alkylene(aryl), wherein the aryl groups are optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
81 . The compound of claim 80 , wherein R 4 is halo, —CF 3 , C 1-8 alkyl, —NR 8 R 9 , aryl, or —C 1-8 alkylene(aryl), wherein the aryl groups are optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
82 . The compound of claim 81 , wherein R 4 is aryl, —C 1-8 alkylene(aryl), wherein aryl is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d , or —NR 8 R 9 , wherein R 8 is hydrogen, methyl, ethyl, propyl or cyclohexyl and R 9 is methyl, ethyl, propyl, cyclohexyl or phenyl.
83 . The compound of claim 81 , wherein R 4 is halo, —CF 3 , or —CH 3 .
84 . A compound of formula (I):
wherein:
R 1 , R 3 , R 2 , and R 4 are independently hydrogen, halo, —CF 3 , —OCF 3 , —CN, —NO 2 , —C 1-8 alkyl, —C 3-8 cycloalkyl, —OR 8 , —NR 8 R 9 , —SR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl), provided that at least one of R 1 , R 3 , R 2 , and R 4 is aryl optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , or —C(═O)NR c R d , and further provided that at least two of R 1 , R 3 , R 2 , and R 4 are other than hydrogen;
R 5 is hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, C 1-8 alkanoyl, haloC 1-8 alkanoyl, —C(═O)OR 8 , —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, or —C 1-8 alkylene(heteroaryl);
R 6 is hydrogen or C 1-4 alkyl;
each R 8 and R 9 is independently hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 3-8 cycloalkyl, —C(═O)aryl, aryl, —C 1-8 alkylene(aryl), —C(═O)heteroaryl, heteroaryl, —C 1-8 alkylene(heteroaryl) or R 8 and R 9 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
m is 1 or 2;
n is 1 or 2; with the proviso that m and n cannot simultaneously be 1;
X is oxy (—O—), thio (—S—) —S(═O)— or —SO 2 —; and
the bond represented by - - - is absent or present;
wherein any C 1-8 alkyl, C 1-8 alkylene, C 1-8 alkoxy or C 3-8 cycloalkyl of R 1 , R 3 , R 4 , R 5 , R 6 , R 8 and R 9 is optionally partially unsaturated; and
wherein any aryl or heteroaryl of R 1 , R 2 , R 3 , R 4 , R 5 , R 8 or R 9 is optionally substituted with one or more substituents independently selected from halo, —CN, —NO 2 , —CF 3 , —OCF 3 , C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, aryl, heteroaryl, —OR c , —SR c , —C(═O)R c , —CO 2 R c , —C(═O)NR c R d , —NR c C(═O)R d , —C(═O)NR c R d , —NR c R d , —NR c C(═O)NR c R d , —SO 2 NR c R d or —SO 2 R c ;
wherein each R c and R d is independently hydrogen, C 1-8 alkyl, C 1-8 alkanoyl, C 1-8 alkoxycarbonyl, aryl, —C 1-8 alkylene(aryl), —C(═O)aryl, —C(═O)Oaryl, heteroaryl, —C 1-8 alkylene(heteroaryl), —C(═O)heteroaryl, —C(═O)Oheteroaryl or R c and R d together with the nitrogen to which they are attached form a pyrrolidino, piperidino, azepano, piperazino, morpholino, or thiomorpholino ring;
or a pharmaceutically acceptable salt thereof.
85 . The compound of claim 84 , wherein m is 1.
86 . The compound of claim 85 , wherein n is 1.
87 . The compound of claim 86 , wherein R 2 is phenyl optionally substituted with one or more substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, —OR c , —SR c , phenyl, —NR c R d , or —C(═O)NR c R d .
88 . The compound of claim 87 , wherein R 2 is phenyl optionally substituted with one or more halo.
89 . The compound of claim 88 , wherein R 2 is phenyl substituted at the 2- or 6-position with fluoro, chloro, or bromo.
90 . The compound of claim 88 , wherein R 2 is phenyl substituted at the 2- and 6-position with halo independently selected from fluoro, chloro, and bromo.
91 . The compound of claim 88 , wherein R 2 is phenyl substituted at the 2- or 4-position with fluoro, chloro, or bromo.
92 . The compound of claim 88 , wherein R 2 is phenyl substituted at the 2- and 4-position with halo independently selected from fluoro, chloro, and bromo.
93 . The compound of claim 88 , wherein R 2 is phenyl substituted at the 2-, 4- and 6-position with halo independently selected from fluoro, chloro, and bromo.
94 . The compound of claim 88 , wherein R 2 is 2,4-dichlorophenyl, 2,4,6-trichlorophenyl or 2,6-difluoro-4-chlorophenyl.
95 . The compound of claim 88 , wherein R 4 is halo, —CF 3 , C 1-8 alkyl, —OR 8 , —SR 8 , —NR 8 R 9 , aryl or —C 1-8 alkylene(aryl), wherein the aryl groups are optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
96 . The compound of claim 95 , wherein R 4 is halo, —CF 3 , C 1-8 alkyl, —NR 8 R 9 , aryl, or —C 1-8 alkylene(aryl), wherein aryl is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d .
97 . The compound of claim 96 , wherein R 4 is aryl, —C 1-8 alkylene(aryl), wherein aryl is optionally substituted with one or more substituents independently selected from halo, hydroxy, cyano, nitro, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, phenyl, —NR c R d , and —C(═O)NR c R d , or —NR 8 R 9 , wherein R 8 is hydrogen, methyl, ethyl, propyl or cyclohexyl and R 9 is methyl, ethyl, propyl, cyclohexyl or phenyl.
98 . The compound of claim 96 , wherein R 4 is halo, —CF 3 , or —CH 3 .Join the waitlist — get patent alerts
Track US2004214815A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.