US2004127502A1PendingUtilityA1
Use of GAL3 antagonist for treatment of depression
Est. expiryJan 31, 2021(expired)· nominal 20-yr term from priority
Inventors:Thomas BlackburnMichael KonkelLakmal BotejuIan Jamie TalismanJohn WetzelMathivana PackiarajanHeidi ChenHermo Jimenez
C07D 401/06C07D 403/04C07D 409/04C07D 405/12C07D 409/12C07D 409/06A61P 25/22C07D 413/06A61P 25/24C07D 401/12C07D 405/04C07D 239/50C07D 409/14C07D 413/04A61K 31/404C07D 401/14C07D 417/12C07D 403/12C07D 401/04C07D 209/40A61K 31/407
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Claims
Abstract
This invention is directed to pyrimidine and indolone derivatives which are selective antagonists for the GAL3 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety. This invention also provides a method of treating depression and/or anxiety in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GAL3 receptor antagonist.
Claims
exact text as granted — not AI-modifiedWhat is claimed:
1 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is; NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z ;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
a pharmaceutically acceptable salt thereof.
2 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 )alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 15 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
3 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
4 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl(C 1 -C 6 )alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein q is an integer from 2 to 4 inclusive; or
a pharmaceutically acceptable salt thereof.
5 . The method of claim 1 , 2 , 3 or 4 , wherein the compound is enantiomerically and diasteriomerically pure.
6 . The method of claim 1 , 2 , 3 or 4 , wherein the compound is enantiomerically or diasteriomerically pure.
7 . The method of claim 1 , 2 , 3 or 4 , wherein the compound can be administered orally.
8 . The method of claim 1 , wherein X is:
9 . The method of claim 1 , wherein X is NR 11 R 12 and R 11 is H or straight chained or branched C 1 -C 7 alkyl.
10 . The method of claim 9 , wherein the compound has the structure:
11 . The. method of claim 8 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
12 . The method of claim 10 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
13 . The method of claim 11 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
14 . The method of claim 12 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
15 . The method of claim 13 , wherein the compound is selected from the group consisting of:
16 . The method of claim 11 , wherein Y is
17 . The method of claim 16 , wherein U is NR 16 .
18 . The method of claim 17 , wherein R 16 is (CH 2 ) m —Z.
19 . The method of claim 18 , wherein Z is aryl or heteroaryl.
20 . The method of claim 19 , wherein the compound is selected from the group consisting of:
21 . The method of claim 12 , wherein the compound is selected from the group consisting of:
22 . The method of claim 12 , wherein Y is
23 . The method of claim 22 , wherein U is NR 16 .
24 . The method of claim 23 , wherein the compound is
25 . The method of claim 19 , wherein the compound is
26 . The method of claim 23 , wherein the compound is selected from the group consisting of:
27 . The method of claim 23 , wherein the compound is selected from the group consisting of:
28 . The method of claim 3 , wherein X is N(CH 3 ) 2 .
29 . The method of claim 28 , wherein Y is
30 . The method of claim 29 , wherein R 13 is an aryl substituted with a C 1 -C 10 straight chained alkyl.
31 . The method of claim 30 , wherein the compound is selected from a group consisting of:
32 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is; NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m—Z;
wherein R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
a pharmaceutically acceptable salt thereof.
33 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl(C 1 -C 6 )alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m—CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
34 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
35 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 )alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein q is an integer from 2 to 4 inclusive; or
a pharmaceutically acceptable salt thereof.
36 . The method of claim 32 , 33 , 34 or 35 , wherein the compound is enantiomerically and diasteriomerically pure.
37 . The method of claim 32 , 33 , 34 or 35 , wherein the compound is enantiomerically or diasteriomerically pure.
38 . The method of claim 32 , 33 , 34 or 35 , wherein the compound can be administered orally.
39 . The method of claim 32 , wherein X is:
40 . The method of claim 32 , wherein X is NR 11 R 12 and R 11 is H or straight chained or branched C 1 -C 7 alkyl.
41 . The method of claim 40 , wherein the compound has the structure:
42 . The method of claim 39 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
43 . The method of claim 41 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
44 . The method of claim 42 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
45 . The method of claim 43 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
46 . The method of claim 44 , wherein the compound is selected from the group consisting of:
47 . The method of claim 42 , wherein Y is
48 . The method of claim 47 , wherein U is NR 16 .
49 . The method of claim 48 , wherein R 16 is (CH 2 ) m —Z.
50 . The method of claim 49 , wherein Z is aryl or heteroaryl.
51 . The method of claim 50 , wherein the compound is selected from the group consisting of:
52 . The method of claim 43 , wherein the compound is selected from the group consisting of:
53 . The method of claim 43 , wherein Y is
54 . The method of claim 53 , wherein U is NR 16 .
55 . The method of claim 54 , wherein the compound is
56 . The method of claim 50 , wherein the compound is
57 . The method of claim 54 , wherein the compound is selected from the group consisting of:
58 . The method of claim 54 , wherein the compound is selected from the group consisting of:
59 . The method of claim 34 , wherein X is N(CH 3 ) 2 .
60 . The method of claim 59 , wherein Y is
61 . The method of claim 60 , wherein R 13 is an aryl substituted with a C 1 -C 10 straight chained alkyl.
62 . The method of claim 61 , wherein the compound is selected from a group consisting of:
63 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is; NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q—O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
a pharmaceutically acceptable salt thereof.
64 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CONR( 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 - 6 ) alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
65 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
66 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein q is an integer from 2 to 4 inclusive; or a pharmaceutically acceptable salt thereof.
67 . The pharmaceutical composition of claim 63 , 64 , 65 or 66 , wherein the compound is enantiomerically and diasteriomerically pure.
68 . The pharmaceutical composition of claim 63 , 64 , 65 or 66 , wherein the compound is enantiomerically or diasteriomerically pure.
69 . The pharmaceutical composition of claim 63 , 64 , 65 or 66 , wherein the compound can be administered orally.
70 . The pharmaceutical composition of claim 63 , wherein X is:
71 . The pharmaceutical composition of claim 63 , wherein X is NR 11 R 12 and R 11 is H or straight chained or branched C 1 -C 7 alkyl.
72 . The pharmaceutical composition of claim 71 , wherein the compound has the structure:
73 . The pharmaceutical composition of claim 70 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
74 . The pharmaceutical composition of claim 72 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
75 . The pharmaceutical composition of claim 73 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
76 . The pharmaceutical composition of claim 74 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
77 . The pharmaceutical composition of claim 73 , wherein Y is
78 . The pharmaceutical composition of claim 77 , wherein U is NR 16 .
79 . The pharmaceutical composition of claim 78 , wherein R 16 is (CH 2 ) m —Z.
80 . The pharmaceutical composition of claim 79 , wherein Z is aryl or heteroaryl.
81 . The pharmaceutical composition of claim 74 , wherein Y is
82 . The pharmaceutical composition of claim 81 , wherein U is NR 16 .
83 . The pharmaceutical composition of claim 82 , wherein the compound is selected from the group consisting of:
84 . The pharmaceutical composition of claim 82 , wherein the compound is selected from the group consisting of:
85 . The pharmaceutical composition of claim 65 , wherein X is N(CH 3 ) 2 .
86 . The pharmaceutical composition of claim 85 , wherein Y is
87 . The pharmaceutical composition of claim 86 , wherein R 13 is an aryl substituted with a C 1 -C 10 straight chained alkyl.
88 . The pharmaceutical composition of claim 87 , wherein the compound is selected from a group consisting of:
89 . A compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is; NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
a pharmaceutically acceptable salt thereof.
90 . A compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is NR 11 R 12 ;
wherein R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
wherein R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl(C 1 -C 6 )alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z ;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched -C 1 -7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
91 . A compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
wherein aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
wherein Q 1 is
wherein Q 2 is
wherein each J is independently O, S, C(R 22 ) 2 or NR 4 ;
wherein R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , CON(R 2 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein p is an integer from 0 to 2 inclusive;
wherein q is an integer from 2 to 4 inclusive;
wherein t is 1 or 2; or
a pharmaceutically acceptable salt thereof.
92 . A compound having the structure:
wherein W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
wherein X is N(CH 3 ) 2 or
wherein R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
wherein Y is NR 14 R 15 ;
wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
wherein R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
wherein Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein q is an integer from 2 to 4 inclusive; or
a pharmaceutically acceptable salt thereof.
93 . An enantiomerically and diasteriomerically pure compound of claim 89 , 90 , 91 , or 92 .
94 . An enantiomerically or diasteriomerically pure compound of claim 89 , 90 , 91 , or 92 .
95 . The compound of claim 89 , wherein X is:
96 . The compound of claim 88 , wherein X is NR 11 R 12 and R 11 is H or straight chained or branched C 1 -C 7 alkyl.
97 . The compound of claim 96 , wherein the compound has the structure:
98 . The compound of claim 95 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
99 . The compound of claim 97 , wherein R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
100 . The compound of claim 98 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
101 . The compound of claim 99 , wherein R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
102 . The compound of claim 98 , wherein Y is
103 . The compound of claim 102 , wherein U is NR 16 .
104 . The compound of claim 103 , wherein R 16 is (CH 2 ) m —Z.
105 . The compound of claim 104 , wherein Z is aryl or heteroaryl.
106 . The compound of claim 99 , wherein Y is
107 . The compound of claim 106 , wherein U is NR 16 .
108 . The compound of claim 107 , wherein the compound is selected from the group consisting of:
109 . The compound of claim 107 , wherein the compound is selected from the group consisting of:
110 . The compound of claim 89 , wherein X is N(CH 3 ) 2 .
111 . The compound of claim 110 , wherein Y is
112 . The compound of claim 111 , wherein the compound is selected from a group consisting of:
113 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 89 , 90 , 91 , or 92 and a pharmaceutically acceptable carrier.
114 . A pharmaceutical composition made by combining a therapeutically effective amount of the compound of claim 89 , 90 , 91 , or 92 and a pharmaceutically acceptable carrier.
115 . A process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of claim 89 , 90 , 91 , or 92 and a pharmaceutically acceptable carrier.
116 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of the compound of claim 89 , 90 , 91 , or 92 effective to treat the subject's depression.
117 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of the compound of claim 89 , 90 , 91 , or 92 effective to treat the subject's anxiety.
118 . A method of treating a subject suffering from depression and anxiety which comprises administering to the subject an amount of the compound of claim 89 , 90 , 91 , or 92 effective to treat the subject's depression and anxiety.
119 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
wherein A′ is
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on-adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein q is an integer from 2 to 4 inclusive;
wherein B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
120 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl (C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 ) alkyl;
wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR O or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein n is an integer from 1 to 4 inclusive;
or a pharmaceutically acceptable salt thereof.
121 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 ) alkyl;
wherein A′ is
wherein B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
wherein a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein n is an integer from 1 to 4 inclusive;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
122 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) m —Z;
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
wherein q is an integer from 2 to 4 inclusive;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
or a pharmaceutically acceptable salt thereof.
123 . The method of claim 119 , 120 , 121 , or 122 , wherein the compound is enantiomerically and diastereomerically pure.
124 . The method of claim 119 , 120 , 121 , or 122 , wherein the compound is enantiomerically or diastereomerically pure.
125 . The method of claim 119 , 120 , 121 , or 122 , wherein the compound is a pure Z imine isomer or a pure Z alkene isomer.
126 . The method of claim 119 , 120 , 121 , or 122 , wherein the compound is a pure E imine isomer or a pure E alkene isomer.
127 . The method of claim 119 , 120 , 121 , or 122 , wherein the compound is administered orally.
128 . The method of claim 119 or 120 , wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , —F, —Cl, —Br, —I, —OR 4 , —N(R 4 ) 2 , or —CON(R 4 ) 2 ;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , or phenyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; and
wherein A′ is
129 . The method of claim 119 , 120 or 122 , wherein B is heteroaryl.
130 . The method of claim 119 or 120 , wherein B is aryl.
131 . The method of claim 130 , wherein B is phenyl and the phenyl is optionally substituted with one or more of the following: —F, —Cl, —Br, —CF 3 , straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 .
132 . The method of claim 131 , wherein A is aryl.
133 . The method of claim 131 , wherein A is heteroaryl.
134 . The method of claim 133 , wherein the compound is selected from the group consisting of:
135 . The method of claim 132 , wherein the compound is selected from the group consisting of:
136 . The method of claim 130 , wherein A is A′ and A′ is
137 . The method of claim 136 , wherein the compound is:
138 . The method of claim 121 , wherein B is Q 6 .
139 . The method of claim 138 , wherein A is aryl.
140 . The method of claim 139 , wherein the compound has the structure:
141 . The method of claim 140 , wherein the compound is:
142 . The method of claim 122 , wherein B is aryl.
143 . The method of claim 142 , wherein A is (CHR 17 )—(CHR 17 ) n —Z.
144 . The method of claim 143 , wherein the compound is:
145 . The method of claim 119 , wherein the compound has the structure:
wherein each R 24 is independently one or more of the following: H, F, Cl, Br, I, CF 3 , OCH 3 or NO 2 ; and
wherein R 25 is methyl, ethyl, allyl, phenyl and the phenyl is optionally substituted with a F, Cl, Br, CF 3 , NO 2 .
146 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl (C 1 -C 6 )alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) m —Z;
wherein A′ is
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein q is an integer from 2 to 4 inclusive;
wherein B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
147 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein n is an integer from 1 to 4 inclusive;
or a pharmaceutically acceptable salt thereof.
148 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
wherein A′ is
wherein B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
wherein a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein n is an integer from 1 to 4 inclusive;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
149 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 )n—Z;
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
wherein q is an integer from 2 to 4 inclusive;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
or a pharmaceutically acceptable salt thereof.
150 . The method of claim 146 , 147 , 148 , or 149 , wherein the compound is enantiomerically and diastereomerically pure.
151 . The method of claim 146 , 147 , 148 , or 149 , wherein the compound is enantiomerically or diastereomerically pure compound.
152 . The method of claim 146 , 147 , 148 , or 149 , wherein the compound is a pure Z imine isomer or a pure Z alkene isomer.
153 . The method of claim 146 , 147 , 148 , or 149 , wherein the compound is a pure E imine isomer or a pure E alkene isomer.
154 . The method of claim 146 or 147 , wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , —F, —Cl, —Br, —I, —OR 4 , —N(R 4 ) 2 , or —CON(R 4 ) 2 ;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , or phenyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; and
wherein A′ is
155 . The method of claim 146 or 147 , wherein B is heteroaryl.
156 . The method of claim 146 or 147 , wherein B is aryl.
157 . The method of claim 156 , wherein B is phenyl and the phenyl is optionally substituted with one or more of the following: —F, —Cl, —Br, —CF 3 , straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 .
158 . The method of claim 157 , wherein A is aryl.
159 . The method of claim 157 , wherein A is heteroaryl.
160 . The method of claim 159 , wherein the compound is selected from the group consisting of:
161 . The method of claim 158 , wherein the compound is selected from the group consisting of:
162 . The method of claim 156 , wherein A is A′, and A′ is
163 . The method of claim 162 , wherein the compound is:
164 . The method of claim 148 , wherein B is Q 6 .
165 . The method of claim 164 , wherein A is aryl.
166 . The method of claim 165 , wherein the compound has the structure:
167 . The method of claim 166 , wherein the compound is:
168 . The method of claim 149 , wherein B is aryl.
169 . The method of claim 168 , wherein A is (CHR 17 )—(CHR 17 ) n 13 Z.
170 . The method of claim 169 , wherein the compound is:
171 . The method of claim 146 , wherein the compound has the structure:
wherein each R 24 is independently one or more of the following: H, F, Cl, Br, I, CF 3 , OCH 3 or NO 2 ; and
wherein R 25 is methyl, ethyl, allyl, phenyl and the phenyl is optionally substituted with a F, Cl, Br, CF 3 , NO 2 .
172 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 ) alkyl, heteroaryl(C 1 -C 6 )alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
wherein A′ is
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein q is an integer from 2 to 4 inclusive;
wherein B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
173 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein n is an integer from 1 to 4 inclusive;
or a pharmaceutically acceptable salt thereof.
174 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
wherein A′ is
wherein B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
wherein a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein n is an integer from 1 to 4 inclusive;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
175 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or. alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) n —Z;
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
wherein q is an integer from 2 to 4 inclusive;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m CH 3 ;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
or a pharmaceutically acceptable salt thereof.
176 . The pharmaceutical composition of claim 172 , 173 , 174 , or 175 , wherein the compound is an enantiomerically and diastereomerically pure compound.
177 . The pharmaceutical composition of claim 172 , 173 , 174 , or 175 , wherein the compound is an enantiomerically or diastereomerically pure compound.
178 . The pharmaceutical composition of claim 172 , 173 , 174 , or 175 , wherein the compound is a pure Z imine isomer or a pure Z alkene isomer.
179 . The pharmaceutical composition of claim 172 , 173 , 174 , or 175 , wherein the compound is a pure E imine isomer or a pure E alkene isomer.
180 . The pharmaceutical composition of claim 172 , 173 , 174 , or 175 , wherein the composition can be administered orally.
181 . The pharmaceutical composition of claim 172 or 173 , wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , —F, —Cl, —Br, —I, —OR 4 , —N(R 4 ) 2 , or —CON(R 4 ) 2 ;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , or phenyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; and
wherein A′ is
182 . The pharmaceutical composition of claim 172 , 173 or 175 , wherein B is heteroaryl.
183 . The pharmaceutical composition of claim 172 or 173 ,
wherein B is aryl.
184 . The pharmaceutical composition of claim 183 , wherein B is phenyl and the phenyl is optionally substituted with one or more of the following: —F, —Cl, —Br, —CF 3 , straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 .
185 . The pharmaceutical composition of claim 184 , wherein A is aryl.
186 . The pharmaceutical composition of claim 184 , wherein A is heteroaryl.
187 . The pharmaceutical composition of claim 186 , wherein the compound is selected from the group consisting of:
188 . The pharmaceutical composition of claim 174 , wherein B is Q 6 .
189 . The pharmaceutical composition of claim 188 , wherein A is aryl.
190 . The pharmaceutical composition of claim 189 , wherein the compound has the structure:
191 . The pharmaceutical composition of claim 190 , wherein the compound is:
192 . The pharmaceutical composition of claim 175 , wherein B is aryl.
193 . The pharmaceutical composition of claim 192 , wherein A is (CHR 17 )—(CHR 17 ) n —Z.
194 . The pharmaceutical composition of claim 193 , wherein the compound is:
195 . A compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
wherein A′ is
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein q is an integer from 2 to 4 inclusive;
wherein B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
196 . A compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
wherein A′ is
wherein R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
wherein R 3 is H, straight chaired or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
wherein R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
wherein R 6 is straight chained or branched C 1 -C 7 alkyl or aryl;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
wherein n is an integer from 1 to 4 inclusive;
or a pharmaceutically acceptable salt thereof.
197 . A compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
wherein A′ is
wherein B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
wherein a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
wherein Q 6 is
wherein n is an integer from 1 to 4 inclusive;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
or a pharmaceutically acceptable salt thereof.
198 . A compound having the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a methylenedioxy group;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
wherein A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) n —Z;
wherein Q 3 is
wherein Q 4 is
wherein Q 5 is
wherein each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
wherein each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
wherein each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
wherein each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
wherein q is an integer from 2 to-4 inclusive;
wherein each m is an integer from 0 to 4 inclusive;
wherein each n is an integer from 1 to 4 inclusive;
wherein each p is an integer from 0 to 2 inclusive;
wherein U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
wherein Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
wherein R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
wherein B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
or a pharmaceutically acceptable salt thereof.
199 . An enantiomerically and diastereomerically pure compound of claim 195 , 196 , 197 , or 198 .
200 . An enantiomerically or diastereomerically pure compound of claim 195 , 196 , 197 , or 198 .
201 . A pure Z imine isomer or a pure Z alkene isomer of the compound of claim 195 , 196 , 197 , or 198 .
202 . A pure E imine isomer or a pure E alkene isomer of the compound of claim 195 , 196 , 197 , or 198 .
203 . The compound of claim 195 , 196 , 197 , or 198 , wherein the compound can be administered orally.
204 . The compound of claim 195 or 196 , wherein the compound has the structure:
wherein each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , —F, —Cl, —Br, —I, —OR 4 , —N(R 4 ) 2 , or —CON(R 4 ) 2 ;
wherein each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, —CF 3 , or phenyl;
wherein A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl; and
wherein A′ is
205 . The compound of claim 195 , 196 or 198 , wherein B is heteroaryl.
206 . The compound of claim 195 or 196 , wherein B is aryl.
207 . The compound of claim 206 , wherein B is phenyl and the phenyl is optionally substituted with one or more of the following: —F, —Cl, —Br, —CF 3 , straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 .
208 . The compound of claim 207 , wherein A is aryl.
209 . The compound of claim 207 , wherein A is heteroaryl.
210 . The compound of claim 209 , wherein the compound is selected from the group consisting of:
211 . The compound of claim 197 , wherein B is Q 6 .
212 . The compound of claim 211 , wherein A is aryl.
213 . The compound of claim 212 , wherein the compound has the structure:
214 . The compound of claim 213 , wherein the compound is:
215 . The compound of claim 198 , wherein B is aryl.
216 . The compound of claim 215 , wherein A is (CHR 17 )—(CHR 17 ) n —Z.
217 . The compound of claim 215 , wherein the compound is:
218 . A pure Z imine isomer of the compound of claim 195 , 196 , 197 or 198 .
219 . A pure E imine isomer of the compound of claim 195 , 196 , 197 or 198 .
220 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 195 , 196 , 197 or 198 , and a pharmaceutically acceptable carrier.
221 . A pharmaceutical composition made by combining a therapeutically effective amount of the compound of claim 195 , 196 , 197 or 198 , and a pharmaceutically acceptable carrier.
222 . A process for making a pharmaceutical composition comprising combining a therapeutically effective amount of the compound of claim 195 , 196 , 197 or 198 , and a pharmaceutically acceptable carrier.
223 . A method of treating a subject suffering from depression which comprises administering to the subject an amount of the compound of claim 195 , 196 , 197 or 198 effective to treat the subject's depression.
224 . A method of treating a subject suffering from anxiety which comprises administering to the subject an amount of the compound of claim 195 , 196 , 197 or 198 effective to treat the subject's anxiety.
225 . A method of treating a subject suffering from depression and anxiety which comprises administering to the subject an amount of the compound of claim 195 , 196 , 197 or 198 effective to treat the subject's depression and anxiety.
226 . A method of treating depression in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GAL3 receptor antagonist, wherein:
(a) the GAL3 receptor antagonist binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human GAL1 receptor; (b) (1), the GAL3 receptor antagonist does not inhibit the activity of central monoamine oxidase A greater than 50 percent, at a concentration of 10 μM; and
(2) the GAL3 receptor antagonist does not inhibit the activity of central monoamine oxidase B greater than 50 percent, at a concentration of 10 μM; and
(c) the GAL3 receptor antagonist binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to each of the following transporters: serotonin transporter, norepinephrine transporter, and dopamine transporter.
227 . The method of claim 226 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 30-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
228 . The method of claim 227 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 50-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
229 . The method of claim 228 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 100-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
230 . The method of claim 229 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 200-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
231 . The method of claim 226 , wherein the receptor antagonist additionally binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human GAL2 receptor.
232 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to each of the human 5HT 1B , human 5HT 1D , human 5HT 1E , human 5HT 1F , human 5HT 2A , rat 5HT 2C , human 5HT 6 and human 5HT 7 receptors.
233 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human histamine H 1 receptor.
234 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human dopamine D 1 , D 2 , D 3 , D 4 and D 5 receptors.
235 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human α 1A adrenoceptor, the human α 1B adrenoceptor and the human α 1D adrenoceptor.
236 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human α 2A adrenoceptor, the human α 2B adrenoceptor and the human α 2C adrenoceptor.
237 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a. binding affinity less than ten-fold higher than the binding affinity with which it binds to the human 5HT 4 receptor.
238 . The method of claim 226 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity less than ten-fold higher than the binding affinity with which it binds to the human 5HT 1A receptor.
239 . The method of claim 226 , wherein the receptor antagonist does not inhibit the activity of central monoamine oxidase A greater than 30 percent.
240 . The method of claim 226 , wherein the receptor antagonist does not inhibit the activity of central monoamine oxidase B greater than 30 percent.
241 . The method of claim 226 , wherein the receptor antagonist does not inhibit the activity of central monoamine oxidase A greater than 15 percent.
242 . The method of claim 226 , wherein the receptor antagonist does not inhibit the activity of central monoamine oxidase B greater than 15 percent.
243 . A method of treating anxiety in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GAL3 receptor antagonist, wherein:
(a) the GAL3 receptor antagonist binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human GAL1 receptor; and (b) the GAL3 receptor antagonist binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to each of the following transporters: serotonin transporter, norepinephrine transporter, and dopamine transporter.
244 . The method of claim 243 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 30-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
245 . The method of claim 244 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 50-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
246 . The method of claim 245 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 100-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
247 . The method of claim 246 , wherein the receptor antagonist binds to the human GAL3 receptor with a binding affinity at least 200-fold higher than the binding affinity with which it binds to the human GAL1 receptor.
248 . The method of claim 243 , wherein the receptor antagonist additionally binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human GAL2 receptor.
249 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to each of the human 5HT 1B , human 5HT 1D , human 5HT 1E , human 5HT 1F , human 5HT 2A , rat 5HT 2C , human 5HT 6 and human 5HT 7 receptors.
250 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human histamine H 1 receptor.
251 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human dopamine D 1 , D 2 , D 3 , D 4 and D5 receptors.
252 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human α 1A adrenoceptor, the human α 1B adrenoceptor and the human α 1D adrenoceptor.
253 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to the human α 2A adrenoceptor, the human α 2B adrenoceptor and the human α 2C adrenoceptor.
254 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity less than ten-fold higher than the binding affinity with which it binds to the human 5HT 4 receptor.
255 . The method of claim 243 , wherein the receptor antagonist also binds to the human GAL3 receptor with a binding affinity less than ten-fold higher than the binding affinity with which it binds to the human 5HT 1A receptor.Cited by (0)
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