Modulators of 5-HT receptors and methods of use thereof
View Patent ↗The present application relates to aryl- and heteroaryl-fused decahydropyrroloazepine, octahydrooxepinopyrrole, octahydropyrrolothiazepine dioxide, decahydrocyclohepta[c]pyrrole, and octahydrocyclohepta[c]pyrrole derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , A, Y 1 , Y 2 , and Y 3 are as defined in the specification. The present application also relates to compositions comprising such compounds, processes for making such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.
1. A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
A is selected from the group consisting of
R 1 , R 3 , R 4 , and R 5 are independently selected from the group consisting of hydrogen, alkenyl, alkyl, haloalkyl, G 1 , G 2 , —(CR 4a R 5a ) m -G 1 , and —(CR 4a R 5a ) m -G 2 ;
R 4a and R 5a , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
G 1 , at each occurrence, is independently aryl or heteroaryl, wherein each G 1 is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, cyano, —NO 2 , OR 1b , —OC(O)R 1b , —OC(O)N(R b )(R 3b ), —SR 1b , —S(O)R 2b , —S(O) 2 R 2b , —S(O) 2 N(R b )(R 3b ), —C(O)R 1b , —C(O)OR 1b , —C(O)N(R b )(R 3b ), —N(R b )(R 3b ), —N(R a )C(O)R 1b , —N(R a )C(O)O(R 1b ), —N(R a )C(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —NO 2 , —N(R b )S(O) 2 (R 2b ), —(CR 4b R 5b ) m —OR 1b , —C(OH)[(CR 4b R 5b ) m —R 4b ] 2 , —(CR 4b R 5b ) m —OC(O)R 1b , —(CR 4b R 5b ) m —OC(O)N(R b )(R 3b ), —(CR 4b R 5b ) m SR 1b , —(CR 4b R 5b ) m S(O)R 2b , —(CR 4b R 5b ) m —S(O) 2 R 2b , —(CR 4b R 5b ) m —S(O) 2 N(R b )(R 3b ), —(CR 4b R 5b ) m —C(O)R 1b , —(CR 4b R 5b ) m —C(O)OR 1b , —(CR 4b R 5b ) m —C(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —N(R b )(R 3b ), —(CR 4b R 5b ) m —N(R a )C(O)R 1b , —(CR 4b R 5b ) m —N(R a )C(O)O(R 1b ), —(CR 4b R 5b ) m —N(R a )C(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —N(R b )S(O) 2 (R 2b ), cyanoalkyl, and haloalkyl;
G 2 is cycloalkyl, cycloalkenyl, or heterocycle unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, cyano, oxo, —SR 1b , —S(O)R 2b , —S(O) 2 R 2b , —S(O) 2 N(R b )(R 3b ), —C(O)R 1b , —C(O)OR 1b , —C(O)N(R b )(R 3b ), —N(R b )(R 3b ), —N(R a )C(O)R 1b , —N(R a )C(O)O(R 1b ), —N(R a )C(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —NO 2 , —N(R b )S(O) 2 (R 2b ), —(C R 4b R 5b ) m —OR 1b , —(CR 4b R 5b ) m —OC(O)R 1b , —(CR 4b R 5b ) m —OC(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —SR 1b , —(CR 4b R 5b ) m —S(O)R 2b , —(CR 4b R 5b ) m —S(O) 2 R 2b , —(CR 4b R 5b ) m —S(O) 2 N(R b ) (R 3b ), —(CR 4b R 5b ) m —C(O)R 1b , —(CR 4b R 5b ) m —C(O)OR 1b , —(CR 4b R 5b ) m C(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —N(R b )(R 3b ), —(CR 4b R 5b ) m —N(R a )C(O)R 1b , —(CR 4b R 5b ) m —N(R a )C(O)O(R 1b ), —(CR 4b R 5b ) m —N(R a )C(O)N(R b )(R 3b ), —(CR 4b R 5b ) m —N(R b )S(O) 2 (R 2b ), cyanoalkyl, and haloalkyl;
R a and R b , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
R 1b and R 3b , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
R 2b , at each occurrence, is independently alkyl or haloalkyl;
R 4b and R 5b , at each occurrence, are each independently hydrogen, halogen, alkyl, or haloalkyl;
m, at each occurrence, is independently 1, 2, 3, 4, or 5;
R 2 is selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, haloalkyl, —(CR 4a R 5a ) m -G 1 , —(CR 4a R 5a ) p —O-G 1 , —C(O)-G 1 , —(CR 4a R 5a ) m -G 2 , —(CR 4a R 5a ) p —O-G 2 , —C(O)-G 2 , —S(O) 2 R 6 , and —C(O)NR 7 R 8 ;
p, at each occurrence, is independently 2, 3, 4, or 5;
R 6 and R 7 are independently selected from the group consisting of alkyl, haloalkyl, G 1 , —(CR 4a R 5a ) m -G 1 , G 2 and —(CR 4a R 5a ) m -G 2 ;
R 8 is selected from the group consisting of hydrogen, alkyl, and haloalkyl; or
R 7 and R 8 taken together with the nitrogen to which they are attached form a heterocycle;
X 1 is N or CR 9 ;
X 2 is N or CR 10 ;
X 3 is N or CR 11 ;
X 4 is N or CR 12 ;
provided that only one or two of X 1 , X 2 , X 3 , or X 4 can be N;
R 9 , R 10 , R 11 , and R 12 are each independently hydrogen, alkyl, alkenyl, alkynyl, halogen, cyano, -G 1 , -G 2 , —NO 2 , —OR 1a , —OC(O)R 1a , —OC(O)N(R b )(R 3a ), —SR 1a , —S(O)R 2a , —S(O) 2 R 2a , —S(O) 2 N(R b )(R 3a ), —C(O)R 1a , —C(O)G 3 , —C(O)OR 1a , —C(O)N(R b )(R 3a ), —N(R b )(R 3a ), —N(R a )C(O)R 1a , —N(R a )C(O)O(R 1a ), —N(R a )C(O)N(R b )(R 3a ), —N(R a )S(O) 2 (R 2a ), —(CR 4a R 5a ) m —NO 2 , —(CR 4a R 5a ) m —OR 1a , —(CR 4a R 5a ) m —OC(O)R 1a , —(CR 4a R 5a ) m —OC(O)N(R b )(R 3a ), —(CR 4a R 5a ) m —SR 1a , —(CR 4a R 5a ) m —S(O)R 2a , —(CR 4a R 5a ) m —S(O) 2 R 2a , —(CR 4a R 5a ) m —S(O) 2 N(R b )(R 3a ), —(CR 4a R 5a ) m —C(O)R 1a , —(CR 4a R 5a ) m —C(O)OR 1a , —(CR 4a R 5a ) m —C(O)N(R b )(R 3a ), —(CR 4a R 5a ) m —N(R b )(R 3a ), —(CR 4a R 5a ) m —N(R a )C(O)R 1a , —(CR 4a R 5a ) m —N(R a )C(O)O(R 1a ), —(CR 4a R 5a ) m —N(R)C(O)N(R b )(R 3a ), —(CR 4a R 5a ) m -G 1 , —CR 4a ═CR 5a -G 1 , —(CR 4a R 5a ) m -G 2 , —CR 4a ═CR 5a -G 2 , —CR 6a =C(R 7a ) 2 , cyanoalkyl, haloalkyl, (v), (vi), (vii) or (vi); wherein
R 1a and R 3a , at each occurrence, are each independently hydrogen, alkyl, haloalkyl, G 1 , —(CR 4a R 5a ) m -G 1 , G 2 , or —(CR 4a R 5a ) m -G 2 ;
R 2 , at each occurrence, is independently alkyl, haloalkyl, G 1 , or —(CR 4a R 5a ) m -G 1 ;
R 6a is alkyl or haloalkyl;
R 7a , at each occurrence, is independently hydrogen, alkyl, or haloalkyl;
G 3 is a heterocyclic ring attached to the adjacent carbonyl moiety through a nitrogen atom contained within the heterocycle;
q is 1 or 2; or
R 9 and R 10 , R 10 and R 11 , or R 11 and R 12 taken together with the carbon atoms to which they are attached form a substituted or unsubstituted phenyl, cycloalkyl, heterocycle, or heteroaryl ring;
Y 1 is O;
Y 2 is NR 20 , CR 18 R 19 , C(O), or S(O) n ;
Y 3 is NR 17 , CR 18 R 19 , C(O), or S(O) n ;
n is 1 or 2;
provided that Y 3 is other than NR 17 when Y 2 is NR 20 ; or only one of Y 2 , or Y 3 can be C(O) or S(O) n ; or Y 2 is other than NR 20 or S(O) n when Y 1 is O; or Y 3 is other than NR 17 when Y 1 is O;
R 17 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, haloalkyl, —C(O)-G 1 , —(CR 4a R 5a ) m -G 1 , —C(O)-G 2 , and —(CR 4a R 5a ) m -G 2 ;
R 18 and R 19 are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl; and
R 20 is selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, haloalkyl, —C(O)-G 1 , —C(O)NR a -G 1 , —S(O) n -G 1 , —(CR 4a R 5a ) m -G 1 , —C(O)-G 2 , —C(O)NR a -G 2 , —S(O) n -G 2 , and —(CR 4a R 5a ) m -G 2 .
2. The compound of claim 1 , wherein Y 1 is O, and Y 2 and Y 3 are independently CR 18 R 19 .
3. The compound of claim 1 , wherein R 2 is selected from the group consisting of hydrogen, alkyl, haloalkyl, —(CR 4a R 5a ) m -G 1 , and —S(O) 2 R 6 .
4. The compound of claim 1 , wherein R 9 , R 10 , R 11 , and R 12 are each hydrogen, or wherein R 10 and R 11 taken together with the carbon atoms to which they are attached form a substituted or unsubstituted phenyl or cycloalkyl ring, or wherein one or two of R 9 , R 10 , R 11 , and R 12 are each independently alkyl, alkenyl, alkynyl, halogen, cyano, -G 1 , -G 2 , —NO 2 , —OR 1a , —OC(O)R 1a , —OC(O)N(R b )(R 3a ), —SR 1a , —S(O)R 2a , —S(O) 2 R 2a , —S(O) 2 N(R b )(R 3a ), —C(O)R 1a , —C(O)G 3 , —C(O)OR 1a , —C(O)N(R b )(R 3a ), —N(R b )(R 3a ), —N(R a )C(O)R 1a , —N(R a )C(O)O(R 1a ), —N(R a )C(O)N(R b )(R 3a ), —N(R a )S(O) 2 (R 2a ), —(CR 4a R 5a ) m —NO 2 , —(CR 4a R 5a ) m —OR 1a , —(CR 4a R 5a ) m —OC(O)R 1a , —(CR 4a R 5a ) m —OC(O)N(R b )(R 3a ), —(CR 4a R 5a ) m —SR 1a , —(CR 4a R 5a ) m —S(O) 2 R 2a , —(CR 4a R 5a ) m —S(O) 2 R 2a , —(CR 4a R 5a ) m —S(O) 2 N(R b )(R 3a ), —(CR 4a R 5a ) m —C(O)R 1a , —(CR 4a R 5a ) m C(O)OR 1a , —(CR 4a R 5 ) m —C(O)N(R b )(R 3a ), —(CR 4a R 5a ) m —N(R b )(R 3a ), —(CR 4a R 5a ) m —N(R a )C(O)R 1a , —(CR 4a R 5a ) m —N(R a )C(O)O(R 1a ), —(CR 4a R 5a ) m —(R a )C(O)N (R b )(R 3a ), —(CR 4a R 5a ) m -G 1 , —CR 4a ═CR 5a -G 1 , —(CR 4a R 5a ) m -G 2 , —CR 4a =CR 5a -G 2 , cyanoalkyl, haloalkyl, (v), (vi), (vii) or (viii), and the others of R 9 , R 10 , R 11 , and R 12 are hydrogen
5. The compound of claim 1 , wherein the compound is selected from the group consisting of:
trans-2-benzyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2-benzyl-8-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-phenyl-2,3,3a,4,5,10 b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-phenyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aR,10bS)-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aR,10bS)-9-chloro-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aR,10bS)-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
2,3,3a-4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
trans-2-benzyl-2,3,3a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
trans-2,3,3a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
trans-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
(3aR,10bS)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aS,10 bR)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-methoxy-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-methoxy-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-methoxy-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-(trifluoromethoxy)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7,9-difluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-9-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(trifluoromethoxy)-2,3,3a,4,5,10-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7,10-difluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7,10-difluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-[3-(methylsulfonyl)phenyl]-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
1-{3-[trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-7-yl]phenyl}ethanone;
1-{3-[trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-7-yl]phenyl}ethanol;
trans-7-(pyridin-3-yl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(pyridin-4-yl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2-methyl-7-(pyridin-3-yl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
4-[trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-7-yl]-N-methylbenzamide;
trans-7-methoxy-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-10-ol;
trans-7-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7-bromo-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-bromo-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-phenyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-[(4-fluorobenzyl)oxy]-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(4-fluorophenyl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole; and
trans-7-(4-fluorophenyl)-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 1 of formula (Id):
or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 6 wherein
R 1 , R 3 , R 18 and R 19 are hydrogen; and
R 2 is hydrogen, alkyl, haloalkyl, —(CR 4a R 5a ) m -G 1 or —(CR 4a R 5a ) m -G 2 .
8. The compound according to claim 7 wherein R 2 is hydrogen or methyl.
9. The compound according to claim 6 wherein the compound is:
trans-2-benzyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2-benzyl-8-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-phenyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-phenyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aR,10bS)-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aR,10bS)-9-chloro-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aR,10bS)-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
2,3,3a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
trans-2-benzyl-2,3,3a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
trans-2,3,3a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
trans-2-methyl-2,3,3 a,4,5,10b-hexahydro-1H-pyrrolo[3′,4′:4,5]oxepino[2,3-b]pyridine;
(3aR,10bS)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
(3aS,10bR)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-methoxy-2,3,3a,4,5,100b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole; or
trans-10-methoxy-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-methoxy-2,3,3a,4,5,1b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-(trifluoromethoxy)-2,3,3a,4,5,10 b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7,9-difluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-9-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(trifluoromethoxy)-2,3,3a,4,5,10 b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-fluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7,10-difluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7,10-difluoro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-9-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-[3-(methylsulfonyl)phenyl]-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
1-{3-[trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-7-yl]phenyl}ethanone;
1-{3-[trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-7-yl]phenyl}ethanol;
trans-7-(pyridin-3-yl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(pyridin-4-yl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2-methyl-7-(pyridin-3-yl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
4-[trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-7-yl]-N-methylbenzamide;
trans-7-methoxy-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-8-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrol-10-ol;
trans-7-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-10-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-bromo-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
cis-7-bromo-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-bromo-9-chloro-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-phenyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-[(4-fluorobenzyl) oxy]-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(4-fluorophenyl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(4-fluorophenyl)-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-phenyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-[(4-fluorobenzyl) oxy]-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
trans-7-(4-fluorophenyl)-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole; or
trans-7-(4-fluorophenyl)-2-methyl-2,3,3a,4,5,10b-hexahydro-1H-[1]benzoxepino[4,5-c]pyrrole;
or a pharmaceutically acceptable salt thereof.
10. A method for treating conditions, disorders or deficits modulated by a 5-HT 2C receptor, a 5-HT 6 receptor or both 5-HT 2C and 5-HT 6 receptors wherein the condition, disorder or deficit is selected from the group consisting of a cognitive dysfunction, attention deficit/hyperactivity syndrome, personality disorders, affective disorders, motion or motor disorders, migraine, sleep disorders, feeding disorders, gastrointestinal disorders, diseases associated with neurodegeneration, addiction diseases, obesity, diabetes, and psoriasis, and ocular hypertension comprising administration of a therapeutically effective amount of the compound of claim 5 , or a pharmaceutically acceptable salt thereof.
11. A method for treating a disorder or condition modulated by the 5-HT 2C receptor selected from the group consisting of bipolar disorder, depression, anxiety, schizophrenia, cognitive deficits of schizophrenia, obsessive compulsive disorder, migraine, epilepsy, substance abuse, eating disorders, obesity, diabetes, sexual dysfunction/erectile dysfunction, sleep disorders, psoriasis, Parkinson's disease, pain and spinal cord injury, pain, bladder dysfunction/urinary incontinence, smoking cessation, ocular hypertension and Alzheimer's disease, said method comprising the step of administering to a subject in need thereof the compound of claim 5 , or a pharmaceutically acceptable salt thereof.
12. The method according to claim 11 wherein the disorder modulated by the 5-HT 2C receptor is schizophrenia or cognitive deficits of schizophrenia, said method comprising the step of administering to a subject in need thereof the compound of claim 5 , or a pharmaceutically acceptable salt thereof.
13. A method for treating a disorder modulated by the 5-HT 6 receptor selected form the group consisting of deficits in memory and cognition and learning, Alzheimer's disease, age-related cognitive decline, mild cognitive impairment, attention deficit/hyperactivity syndrome, schizophrenia, cognitive deficits of schizophrenia, depression, anxiety, obsessive compulsive disorders, Parkinson's disease, epilepsy, migraine, sleep disorders, anorexia, bulimia, irritable bowel syndrome, stroke, spinal or head trauma and head injuries, drug addiction, and obesity, said method comprising the step of administering to a subject in need thereof the compound of claim 5 , or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 , or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers.