Novel 4-phenyl substituted tetrahydroisoquinolines and therapeutic use thereof
The present invention relates to a method of treating disorders including cognition impairment, generalized anxiety disorder, acute stress disorder, social phobia, simple phobias, pre-menstrual dysphoric disorder, social anxiety disorder, major depressive disorder, eating disorders, obesity, anorexia nervosa, bulimia nervosa, binge eating disorder, substance abuse disorders, chemical dependencies, nicotine addiction, cocaine addiction, alcohol addiction, amphetamine addiction, Lesch-Nyhan syndrome, neurodegenerative diseases, late luteal phase syndrome, narcolepsy, psychiatric symptoms anger, rejection sensitivity, movement disorders, extrapyramidal syndrome, Tic disorder, restless leg syndrome, tardive dyskinesia, sleep related eating disorder, night eating syndrome, stress urinary incontinence, migraine, neuropathic pain, diabetic neuropathy, fibromyalgia syndrome, chronic fatigue syndrome, sexual dysfunction, premature ejaculation, and male impotence. This method involves administering to a patient in need of such treatment a therapeutically effective amount of a disclosed compound. Such compounds are 4-phenyl substituted tetrahydroisoquinolines having the Formula IA, IB, IIA, IIB, IIIA or IIIC as set forth herein.
1 . A method of treating a disorder selected from the group of disorders consisting of stress urinary incontinence, migraine, and neuropathic pain, wherein said method comprises:
administering to a patient in need of such treatment a therapeutically effective amount of a compound of the Formula IA, IB, IIA, IIB, IIIA or IIIB:
wherein:
R 1 is selected from the group consisting of C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl and benzyl, each of which is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 -C 3 alkyl, halogen, —CN, —OR 8 and —NR 8 R 9 ;
R 2 is selected from the group consisting of H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl and C 1 -C 6 haloalkyl;
R 3 is selected from the group consisting of H, halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 6 cycloalkyl, wherein C 1 -C 6 alkyl, C 1 -C 6 haloalkyl and C 3 -C 6 cycloalkyl are optionally substituted with I to 3 substituents selected independently at each occurrence from OR 8 and NR 8 R 9 ;
R 4 , R 5 and R 6 are each independently selected at each occurrence thereof from the group consisting of H, halogen, —OR 10 , —NO 2 , NR 10 R 11 , —NR 10 C(O)R 11 , —NR 10 C(O)NR 11 R 12 , —S(O) n R 11 , —CN, —C(O)R 11 , —C(O) 2 R 11 , —C(O)NR 11 R 12 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl and C 4 -C 7 cycloalkylalkyl, wherein each of the C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl and C 4 -C 7 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C 1 -C 3 alkyl, halogen, ═O, —CN, —OR 8 , —NR 8 R 9 and phenyl, and wherein phenyl is optionally substituted 1-3 substituents selected independently at each occurrence from halogen, —CN, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, —OR 8 and —NR 8 R 9 ;
alternatively R 5 and R 6 are —O—C(R 11 ) 2 —O—;
R 7 is selected from the group consisting of H, halogen and OR 10 ;
R 8 and R 9 are each independently selected from the group consisting of H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 4 alkoxyalkylalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 12 , phenyl and benzyl, wherein phenyl and benzyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy, or R 8 and R 9 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 10 is selected from the group consisting of H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, —C(O)R 12 , phenyl and benzyl, wherein phenyl and benzyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from halogen, —NH 2 , —OH, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy;
R 11 is selected from the group consisting of H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxyalkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, phenyl and benzyl, where phenyl and benzyl are optionally substituted with 1 to 3 substituents selected independently at each occurrence from halogen, —NH 2 , —OH, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy, or R 10 and R 11 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, N-methylpiperazine, morpholine, or thiomorpholine ring, with the proviso that only one of R 8 and R 9 or R 10 and R 11 are taken together with the nitrogen to which they are attached to form a piperidine, pyrrolidine, piperaine, N-methylpiperazine, morpholine, or thiomorpholine ring;
R 12 is selected from the group consisting of C 1 -C4 alkyl, C 1 -C 4 haloalkyl and phenyl;
X is selected from the group consisting of O, NR 13 and S, with the proviso that X is not NR 13 when a compound is of Formula (IA);
n is 0, 1, or2; and,
R 13 is selected from the group consisting of H, C 1 I-C 6 alkyl, benzyl and phenyl, wherein C 1 -C 6 alkyl, benzyl and phenyl are optionally substituted with 1-3 substituents independently at each occurrence from halogen, —NH 2 , —OH, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 haloalkoxy.
2 . The method according to claim 1 , wherein R 1 is C 1 -C 6 alkyl.
3 . The method according to claim 2 , wherein R 1 is CH 3 .
4 . The method according to claim 1 , wherein R 2 is H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, or C 1 -C 6 haloalkyl.
5 . The method according to claim 4 , wherein R 2 is H or C 1 -C 6 alkyl.
6 . The method according to claim 5 , wherein R 2 is H.
7 . The method according to claim 1 , wherein R 3 is at each occurrence thereof independently H, halogen, C 1 -C 6 alkyl, or C 1 -C 6 alkyl substituted with from 1 to 3 of OR 8 or NR 8 R 9 .
8 . The method according to claim 7 , wherein R 3 is H or C 1 -C 6 alkyl.
9 . The method according to claim 8 , wherein R 3 is H.
10 . The method according to claim 1 , wherein R 1 is CH 3 , R 2 is H and R 3 is H.
11 . The method according to claim 1 , wherein R 4 , R 5 and R 6 are each independently H, halogen, C 1 -C 6 alkyl or —OR 10 .
12 . The method according to claim 1 1 , wherein at least one of R 4 , R 5 and R 6 is H.
13 . The method according to claim 12 , wherein each of R 4 , R 5 and R 6 are H.
14 . The method according to claim 12 , wherein one of R 4 , R 5 and R 6 is halogen.
15 . The method according to claim 1 , wherein R 1 is CH 3 , R 2 and R 3 are each H, and at least one of R 4 , R 5 and R 6 is H.
16 . The method according to claim 1 , wherein the compound is a compound of Formula (10):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (10) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (10) wherein R 4 is H, R 5 is Me and R 6 is H;
a compound of Formula (10) wherein R 4 is Cl, R 5 is H and R 6 is H; and
a compound of Formula (10) wherein R 4 is H, R is F and R 6 is H.
17 . The method according to claim 1 , wherein the compound is a compound of Formula (20):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (20) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (20) wherein R 4 is H, R 5 is Me and R 6 is H;
a compound of Formula (20) wherein R 4 is H, R 5 is Cl and R 6 is H;
a compound of Formula (20) wherein R 4 is H, R 5 is F and R 6 is H; and
a compound of Formula (20) wherein R 4 is F, R 5 is H and R 6 is F.
18 . The method according to claim 1 , wherein the compound is a compound of Formula (30):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is F and R 6 is H;
a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is F;
a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is H;
a compound of Formula (30) wherein R 3 is H, R 4 is Cl,R 5 is H and R 6 is H;
a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is H;
a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is Cl;
a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is Cl;
a compound of Formula (30) wherein R 3 is H, R 4 is H, R 5 is OMe and R 6 is H; and
a compound of Formula (30) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is H.
19 . The method according to claim 1 , wherein the compound is a compound of Formula (40):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is F and R 6 is H;
a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is F;
a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is H;
a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is H;
a compound of Formula (40) wherein R 3 is H, R 4 is Cl, R 5 is H and R 6 is H;
a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is H;
a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (40) wherein R 3 is H, R 4 is H, R 5 is F and R 6 is Cl;
a compound of Formula (40) wherein R 3 is H, R 4 is F, R 5 is H and R 6 is Cl;
a compound of Formula (40) wherein R 4 is H, R 4 is H, R 5 is OMe and R 6 is H;
a compound of Formula (40) wherein R 3 is Me, R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (40) wherein R 3 is Et, R 4 is H, R 5 is H and R 6 is H; and
a compound of Formula (40) wherein R 3 is CH 2 OH, R 4 is H, R 5 is H and R 6 is H.
20 . The method according to claim 1 , wherein the compound is a compound of Formula (50):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (50) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H.
21 . The method according to claim 1 , wherein the compound is a compound of Formula (60):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is H and R 6 is H and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Me;
a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Et;
a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is Me;
a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is F and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is F and R 13 is Me;
a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is Me;
a compound of Formula (60) wherein R 3 is H, R 4 is F, R is H 5 R6 is H and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is H and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is H;
a compound of Formula (60) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is Me;
a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is H; and
a compound of Formula (60) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is Me.
22 . The method according to claim 1 , wherein the compound is a compound of Formula (70):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is H;
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Me;
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Et;
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is H, R 6 is H and R 13 is Bn;
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is H;
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is F and R 13 is Me;
a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is F and R 13 is Me;
a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is H;
a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is H, R 6 is H and R 13 is Me;
a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is H, R 6 is H and R 13 is H; is Me;
a compound of Formula (70) wherein R 3 is H, R 4 is H, R 5 is F, R 6 is H and R 13 is H;
a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is H;
a compound of Formula (70) wherein R 3 is H, R 4 is F, R 5 is Cl, R 6 is H and R 13 is Me;
a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is H; and
a compound of Formula (70) wherein R 3 is H, R 4 is Cl, R 5 is F, R 6 is H and R 13 is Me.
23 . The method according to claim 1 , wherein the compound is a compound of Formula (80):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (80) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (80) wherein R 4 is H, R 5 is F and R 6 is H; and
a compound of Formula (80) wherein R 4 is H, R 5 is F and R 6 is F.
24 . The method according to claim 1 , wherein the compound is a compound of Formula (90):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (90) wherein R 4 is H, R 5 is H and R 6 is H.
a compound of Formula (90) wherein R 4 is H, R 5 is F and R 6 is F; and
a compound of Formula (90) wherein R 4 is H, R 5 is F and R 6 is H.
25 . The method according to claim 1 , wherein the compound is a compound of Formula (100):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (100) wherein R 4 is H, R 5 is H, R 6 is H and R 3 is H.
26 . The method according to claim 1 , wherein the compound is a compound of Formula (110):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (110) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (110) wherein R 4 is H, R 5 is F and R 6 is F;
a compound of Formula (110) wherein R 4 is H, R 5 is F and R 6 is H;
a compound of Formula (110) wherein R 4 is H, R 5 is H and R 6 is Cl;
a compound of Formula (110) wherein R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (110) wherein R 4 is H, R 5 is F and R 6 is Cl; and
a compound of Formula (110) wherein R 4 is H, R 5 is OMe and R 6 is H.
27 . The method according to claim 1 , wherein the compound is a compound of Formula (120):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (120) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (120) wherein R 4 is H, R 5 is F and R 6 is F;
a compound of Formula (120) wherein R 4 is H, R 5 is F and R 6 is H;
a compound of Formula (120) wherein R 4 is H, R 5 is H and R 6 is Cl;
a compound of Formula (120) wherein R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (120) wherein R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (120) wherein R 4 is H, R 5 is OMe and R 6 is H; and
a compound of Formula (120) wherein R 4 is H, R 5 is F and R 6 is Cl.
28 . The method according to claim 1 , wherein the compound is a compound of Formula (130):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (130) wherein R 4 is H, R 5 is H and is R 6 is H; and
a compound of Formula (130) wherein R 4 is H, R 5 is Bn and R 6 is H.
29 . The method according to claim 1 , wherein the compound is a compound of Formula (140):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (140) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (140) wherein R 4 is H, R 5 is F and R 6 is H;
a compound of Formula (140) wherein R 4 is H, R 5 is F and R 6 is Cl;
a compound of Formula (140) wherein R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (140) wherein R 4 is H, R 5 is H and R 6 is Cl;
a compound of Formula (140) wherein R 4 is H, R 5 is OMe and R 6 is H;
a compound of Formula (140) wherein R 4 is H, R 5 is F and R 6 is F.
30 . The method according to claim 1 , wherein the compound is a compound of Formula (150):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (150) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (150) wherein R 4 is H, R 5 is F and R 6 is H;
a compound of Formula (150) wherein R 4 is H, R 5 is F and R 6 is Cl;
a compound of Formula (150) wherein R 4 is H, R 5 is Cl and R 6 is F;
a compound of Formula (150) wherein R 4 is H, R 5 is H and R 6 is Cl;
a compound of Formula (150) wherein R 4 is H, R 5 is OMe and R 6 is H; and
a compound of Formula (150) wherein R 4 is H, R 5 is F and R 6 is F.
31 . The method according to claim 1 , wherein the compound is a compound of Formula (160):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (160) wherein R 4 is H, R 5 is H and R 6 is H.
32 . The method according to claim 1 , wherein the compound is a compound of Formula (170):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (170) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (170) wherein R 4 is H, R 5 is F and R 6 is H; and
a compound of Formula (170) wherein R 4 is H, R 5 is F and R 6 is F.
33 . The method according to claim 1 , wherein the compound is a compound of Formula (180):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (180) wherein R 4 is H, R 5 is H and R 6 is H;
a compound of Formula (180) wherein R 4 is H, R 5 is F and R 6 is H; and
a compound of Formula (180) wherein R 4 is H, R 5 is F and R 6 is F.
34 . The method according to claim 1 , wherein the compound is a compound of Formula (190):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (190) wherein R 4 is H, R 5 is H and R 6 is H.
35 . The method according to claim 1 , wherein the compound is a compound of Formula (200):
or a pharmaceutically acceptable salt form thereof selected from the group consisting of:
a compound of Formula (200) wherein R 4 is H, R 5 is H, R 6 is H and R 13 is H; and
a compound of Formula (200) wherein R 4 is H, R 5 is H, R 6 is H and R 13 is Me.
36 . The method according to claim 1 , wherein the compound is a compound selected from the group consisting of:
(R)-2-methyl-4-phenyl- 1,2,3,4,8,9-hexahydro-furo[2,3-h]isoquinoline;
(S)-2-methyl-4-phenyl- 1,2,3,4,8,9-hexahydro-furo[2,3 -h]isoquinoline;
(R)-7-methyl-5-phenyl-5,6,7,8-tetrahydro-furo[3,2-g]isoquinoline;
(S)-7-methyl-5-phenyl-5,6,7,8-tetrahydro-furo[3,2-g]isoquinoline;
(R)-4-(4-fluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3 -h]isoquinoline;
(S)-4-(4-fluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(R)-4-(3,4-difluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(S)-4-(3,4-difluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(R)-2-methyl-4-phenyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(S)-2-methyl-4-phenyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(R)-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(S)-4-(4-chloro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(R)-8-methyl-6-phenyl-2,3,6,7,8,9-hexahydro-furo[3,2-h]isoquinoline;
(S)-8-methyl-6-phenyl-2,3,6,7,8,9-hexahydro-furo[3,2-h]isoquinoline;
(R)-4-(4-fluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(S)-4-(4-fluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(R)-4-(3,5-difluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(S)-4-(3,5-difluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(R)-2-methyl-4-phenyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h]isoquinoline; and
(S)-2-methyl-4-phenyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h]isoquinoline.
37 . The method according to claim 1 , wherein the compound is a compound selected from the group consisting of:
(+)-2-methyl-4-phenyl- 1,2,3,4,8,9-hexahydro-furo[2,3-h]isoquinoline;
(−)-2-methyl-4-phenyl- 1,2,3,4,8,9-hexahydro-furo[2,3-h]isoquinoline;
(+)-7-methyl-5-phenyl-5,6,7,8-tetrahydro-furo[3,2-g]isoquinoline;
(−)-7-methyl-5-phenyl-5,6,7,8-tetrahydro-furo[3,2-g]isoquinoline;
(+)-4-(4-fluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(−)-4-(4-fluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(+)-4-(3,4-difluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(−)-4-(3,4-difluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(+)-2-methyl-4-phenyl-1,2,3,4-tetrahydro-furo[2,3 -h]isoquinoline;
(−)-2-methyl-4-phenyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(+)-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3 -h]isoquinoline;
(−)-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(+)-8-methyl-6-phenyl-2,3,6,7,8,9-hexahydro-furo[3,2-h]isoquinoline;
(−)-8-methyl-6-phenyl-2,3,6,7,8,9-hexahydro-furo[3,2-h]isoquinoline;
(+)-4-(4-fluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(−)-4-(4-fluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(+)-4-(3,5-difluoro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(−)-4-(3,5-difluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-furo[2,3-h]isoquinoline;
(+)-2-methyl-4-phenyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h]isoquinoline; and
(−)-2-methyl-4-phenyl-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-h]isoquinoline.
38 . The method according to claim 1 , wherein the compound is administered with a pharmaceutically acceptable carrier.
39 - 70 . (canceled)
71 . The method according to claim 1 , wherein the disorder is stress urinary incontinence.
72 . The method according to claim 1 , wherein the disorder is migraine.
73 . The method according to claim 1 , wherein the disorder is neuropathic pain.
74 - 79 . (canceled)