Substituted azepino[4,5b]indole derivatives

1. A compound of Formula (I):

wherein

R 1 is selected from the group consisting of hydrogen, C 1-8 alkyl, and C 1-8 hydrocarbylene Ar;

each R 2 , independently, is selected from the group consisting of C 1-8 alkyl, and OH;

R 3 is Het, R 7 C(═O)—, R 7 OC(═O)—, R 5 R 6 NC(═O)—, R 7 C(═S)—, R 7 SC(═O)—, R 5 R 6 NC(═S)—, R 7 SO 2 —, R 5 R 6 NSO 2 —, R 7 S(═O)—, R 5 R 6 NS(═O)—, R c C 1-8 hydrocarbylene-, or R c C 1-8 hydrocarbyleneC(═O)—;

each R 4 , independently, is selected from the group consisting of Ar, C 1-8 alkyl, ArO—, C 1-8 alkoxy, Het, halo, OH, CN, NO 2 , CF 3 , CF 3 O, NR a R b , N═CR a R b , R 7 S, C 1-8 hydrocarbyleneAr, and C 1-8 hydrocarbyleneOR a ;

each R 5 and R 6 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr; or R 5 and R 6 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;

each R 7 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr;

R a and R b , independently, are selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het;

R c is R 7 CO 2 —, R 7 C(═O)—, R 7 OC(═O)—, R 7 O—, R 7 C 1-8 alkyleneO—, R 7 S—, R 7 C(═S)—, R 7 S(═O)—, R 7 S(═O) 2 —, R 7 SC(═O)—, R 7 C(═O)N(R 7 )—, R 7 (═S)N(R 7 )—, R 5 R 6 NC(═O)—, R 5 R 6 NC(═S)—, R 5 R 6 NS(═O)—, R 5 R 6 NSO 2 —, R 7 S(═O)N(R 7 )—, R 7 SO 2 N(R 7 )—, or R 7 N(R 7 )C(═O)N(R 7 )—;

each Ar is independently aryl or heteroaryl;

p is 0, 1, 2, 3, or 4; and

q is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

wherein any Ar of R 1 , R 4 -R 7 , R a , R b and R c is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR e , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR e , SO 2 R e , NR f R g , CONR f R g , COR e , R e , and C 1-8 hydrocarbyleneR d ;

each R d is independently hydroxy, C 1-8 alkoxy, cyano, SR h , or C(═O)R h ;

each R e is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; wherein any Ar of R e is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR d , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR f , SO 2 R f , NR f R g , CONR f R g , COR f , R f , and C 1-8 hydrocarbyleneR d ;

each R f and R g , is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; and

each R h is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, phenyl, or —C 1-8 hydrocarbylene(phenyl);

each Het is selected from the group consisting of 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-dioxane, 1,4-dithiane, 2H-pyran, 2-pyrazoline, 4H-pyran, chromanyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, morpholine, piperazinyl, piperidine, piperidyl, pyrazolidine, pyrazolidinyl, pyrazolinyl, pyrrolidine, pyrroline, quinuclidine, and thiomorpholino;

or a pharmaceutically acceptable salt thereof;

with the proviso that when

(a) R 3 is hydrogen, C 1-8 alkyl, or optionally substituted phenylC 1-8 hydrocarbylene-, and

(b) q is 0, and

(c) p is 1 or 2,

then

R 4 is other than halo, C 1-8 alkyl, or C 1-8 alkoxy;

and with the proviso that when

(a) R 3 is C 1-6 alkylenephenyl wherein the phenyl is optionally substituted with halo, C 1-8 alkyl, or OC 1-8 alkyl; then either

(i) p is 3 or 4; or

(ii) p is 2, one R 4 is halo, C 1-8 alkyl, or C 1-8 alkoxy, and the other R 4 is other than C 1-8 alkyl; or

(iii) at least one R 4 is present and is other than a halo, C 1-8 alkyl, or C 1-8 alkoxy.

2. The compound of claim 1 wherein R 1 is hydrogen.

3. A compound of Formula (I):

wherein R 1 is selected from the group consisting of hydrogen, C 1-8 alkyl, and C 1-8 hydrocarbylene Ar;

each R 2 , independently, is selected from the group consisting of C 1-8 alkyl, and OH;

R 3 is hydrogen, C 1-8 alkyl, Het, R 7 C(═O)—, R 7 OC(═O)—, R 5 R 6 NC(═O)—, R 7 C(═S)—, R 7 SC(═O)—, R 5 R 6 NC(═S)—, R 7 SO 2 —, R 5 R 6 NSO 2 —, R 7 S(═O)—, R 5 R 6 NS(═O)—, R c C 1-8 hydrocarbylene-, or R c C 1-8 hydrocarbyleneC(═O)—;

each R 4 , independently, is selected from the group consisting of Ar, C 1-8 alkyl, ArO—, C 1-8 alkoxy, Het, halo, OH, CN, NO 2 , CF 3 , CF 3 O, NR a AR b , N═CR a R b , R 7 S, C 1-8 hydrocarbylener, and C 1-8 hydrocarbyleneOR a ;

each R 5 and R 6 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr; or R 5 and R 6 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;

each R 7 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr;

R a and R b , independently, are selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het;

R c is Ar, Het, R 7 CO 2 —, R 7 C(═O)—, R 7 OC(═O)—, R 7 O—, R 7 C 1-8 alkyleneO—, R 7 S—, R 7 C(═S)—, R 7 S(═O)—, R 7 S(═O) 2 —, R 7 SC(═O)—, R 7 C(═O)N(R 7 )—, R 7 C(═S)N(R 7 )—, R 5 R 6 N—, R 5 R 6 NC(═O)—, R 5 R 6 NC(═S)—, R 5 R 6 NS(═O)—, R 5 R 6 NSO 2 —, R 7 S(═O)N(R 7 )—, R 7 SO 2 N(R 7 )—, or R 7 N(R 7 )C(═O)N(R 7 )—;

each Ar is independently aryl or heteroaryl;

p is 0, 1, 2, 3, or 4; and

q is 0, 1, 2, 3, or 4;

wherein any Ar of R 1 , R 4 -R 7 , R a , R b and R c is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR e , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR e , SO 2 R e , NR f R g , CONR f R g , COR e , R e , and C 1-8 hydrocarbyleneR d ;

each R d is independently hydroxy, C 1-8 alkoxy, cyano, SR h , or C(═O)R h ;

each R e is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; wherein any Ar of R e is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR d , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR f , SO 2 R f , NR f R g , CONR f R g , COR f , R f , and C 1-8 hydrocarbyleneR d ;

each R f and R g , is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; and

each R h is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, phenyl, or —C 1-8 hydrocarbylene(phenyl);

each Het is selected from the group consisting of 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-dioxane, 1,4-dithiane, 2H-pyran, 2-pyrazoline, 4H-pyran, chromanyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, morpholine, piperazinyl, piperidine, piperidyl, pyrazolidine, pyrazolidinyl, pyrazolinyl, pyrrolidine, pyrroline, quinuclidine, and thiomorpholino;

or a pharmaceutically acceptable salt thereof;

with the proviso that when

(a) R 3 is hydrogen, C 1-8 alkyl, or optionally substituted phenylC 1-8 hydrocarbylene-, and

(b) p is 1 or 2,

then

R 4 is other than halo, C 1-8 alkyl, or C 1-8 alkoxy;

and with the proviso that when

(a) R 3 is hydrogen or alkyl, and

(b) q is at least 1, and at least one R 2 is hydroxy substituted at the 5-position of Formula (I),

then either

(i) p is 2, 3, or 4, or

(ii) p is 1 and R 4 is other than halo, hydroxy, C 1-8 alkyl, CF 3 , CF 3 O, C 1-8 alkoxy, or C 1-8 hydrocarbyleneOR a , wherein R a is hydrogen or C 1-6 alkyl;

and with the proviso that when

(a) R 3 is phenyl or phenyl substituted with one halo, trifluoromethyl, C 1-8 alkyl, hydroxy, or OC 1-8 alkyl; then either

(i) p is 3, or 4, or

(ii) p is 2 and R 4 is halo, C 1-8 alkyl, C 1-8 alkoxy, and the other R 4 is other than C 1-8 alkyl; or

(iii) at least one R 4 is present and is other than a halo, C 1-8 alkyl, or C 1-8 alkoxy.

4. The compound of claim 1 wherein q is 1.

5. The compound of claim 1 wherein q is 0.

6. The compound of claim 1 wherein R 3 is hydrogen, R 7 SC 1-8 alkylene.

7. The compound of claim 1 wherein R 3 is C 1-8 alkyl, R 5 R 6 NC(═O)CH 2 — or aryloxy(CH 2 ) 2 —.

8. The compound of claim 1 wherein R 3 is: 2-(3-methoxyphenoxy)ethyl, 2-(3-nitrophenoxy)ethyl, 2-(3-isopropylphenoxy)ethyl, 2-(4-pyridyloxy)ethyl, 3-phenoxypropyl, 3-(3-chlorophenoxy)propyl, 3-(4-fluorophenoxy)propyl, 2-phenoxyethyl, N-(2,3-dimethylphenyl)aminocarbonylmethyl, N-(3-methylphenyl)aminocarbonylmethyl, N-(2-fluoro-4-methylphenyl)aminocarbonylmethyl, N-mesitylaminocarbonylmethyl, N-(4-methoxyphenyl)aminocarbonylmethyl, N-(phenyl)aminocarbonylmethyl, N-(4-fluorophenyl)aminocarbonylmethyl, N-(3-nitrophenyl)aminocarbonylmethyl, N-(3-methoxyphenyl)aminocarbonylmethyl, N-(4-cyanophenyl)aminocarbonylmethyl, N-(3,5-dimethoxyphenyl)aminocarbonylmethyl, N-(2,4-dimethoxyphenyl)aminocarbonylmethyl, N-(3-chloro-4-fluorophenyl)aminocarbonylmethyl, 2-anilinoethyl, 1H-benzimidazol-2-ylmethyl, isobutoxycarbonylmethyl, carboxymethyl, N,N-dimethylaminocarbonylmethyl, aminocarbonylmethyl, 2-(phenylsulfinyl)ethyl, 2-(phenylsulfonyl)ethyl, 2-hydroxyethyl, 2-(4-chlorophenoxy)ethyl, 2-(4-fluorophenoxy)ethyl, 2-(phenylthio)ethyl, 2-aminoethyl, 2-(anilinocarbonylamino)-ethyl, 2-(benzoylamino)ethyl, 2-(phenylsulfonylamino)ethyl, N-(4-methoxyphenyl)aminocarbonylethyl, N-phenylaminocarbonylmethyl, N-(2-pyridyl)aminocarbonylmethyl, N-(4-methoxyphenyl)aminocarbonylmethyl, N-(2,3-dimethylphenyl)aminocarbonylmethyl, N-(5,6,7,8-tetrahydro-1-naphthalenyl)aminocarbonylmethyl, 3-ethylanilinocarbonylmethyl, 3-isopropylanilinocarbonylmethyl, N-(3-tert-butylphenyl)aminocarbonylmethyl, N-(1,3-benzothiazol-2-yl)aminocarbonylmethyl, N-(4-methyl-1,3-thiazol-2-yl)aminocarbonylmethyl, N-(5-methyl-1,3-thiazol-2-yl)aminocarbonylmethyl, N-(4-tert-butyl-1,3-thiazol-2-yl)aminocarbonylmethyl, N-(4-phenyl-1,3-thiazol-2-yl)aminocarbonylmethyl, 3-phenylpropyl, 2-phenoxyethyl, 2-(4-chlorophenoxy)ethyl, 2-(4-fluorophenoxy)ethyl, 2-(5,7-dibromo-8-quinolinyloxy)ethyl, 2-(8-quinolinyloxy)ethyl, 2-(5-isoquinolinyloxy)ethyl, 2-(5-quinolinyloxy)ethyl, 2-(5,6,7,8-tetrahydro-1-naphthalenyloxy)ethyl, 2-(1,3-benzodioxol-5-yloxy)ethyl, 2-(1H-indol-4-yloxy)ethyl, 2-(5,6,7,8-tetrahydro-2-naphthalenyloxy)ethyl, 2-(7-quinolinyloxy)ethyl, 2-[(5,5-dimethyl-5,6,7,8-tetrahydronaphthalen-1-yl)oxy]ethyl, N-(3-chloro-2-methylphenyl)aminocarbonylmethyl, N-[2-methyl-3-(trifluoromethyl)phenyl]aminocarbonylmethyl, N-(5,6,7,8-tetrahydronaphthalen-1-yl)aminocarbonylmethyl, N-(4-methyl-1,3-thiazol-2-yl)aminocarbonylmethyl, N-(1,3-dihydro-2-benzofuran-4-yl)aminocarbonylmethyl, N-(4-methoxyphenyl)aminocarbonylmethyl, N-(3-pyridyl)aminocarbonylmethyl, N-(4-methyl-1,3-thiazol-2-yl)aminocarbonylmethyl, or 2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl.

9. A compound of Formula (I):

wherein

R 1 is selected from the group consisting of hydrogen, C 1-8 alkyl, and C 1-8 hydrocarbylene Ar;

each R 2 , independently, is selected from the group consisting of C 1-8 alkyl, and OH;

R 3 is hydrogen, C 1-8 alkyl, Het, R 7 C(═O)—, R 7 OC(═O)—, R 5 R 6 NC(═O)—, R 7 C(═S)—, R 7 SC(═O)—, R 5 R 6 NC(═S)—, R 7 SO 2 —, R 5 R 6 NSO 2 —, R 7 S(═O)—, R 5 R 6 NS(═O)—, R c C 1-8 hydrocarbylene-, or R c C 1-8 hydrocarbyleneC(═O)—;

each R 4 is phenyl, optionally substituted at the 2-position of the phenyl;

each R 5 and R 6 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr; or R 5 and R 6 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;

each R 7 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr;

R a and R b , independently, are selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het;

R c is Ar, Het, R 7 CO 2 —, R 7 C(═O)—, R 7 OC(═O)—, R 7 O—, R 7 C 1-8 alkyleneO—, R 7 S—, R 7 C(═S)—, R 7 S(═O)—, R 7 S(═O) 2 —, R 7 SC(═O)—, R 7 C(═O)N(R 7 )—, R 7 C(═S)N(R 7 )—, R 5 R 6 N—, R 5 R 6 NC(═O)—, R 5 R 6 NC(═S)—, R 5 R 6 NS(═O)—, R 5 R 6 NSO 2 —, R 7 S(═O)N(R 7 )—, R 7 SO 2 N(R 7 )—, or R 7 N(R 7 )C(═O)N(R 7 )—;

each Ar is independently aryl or heteroaryl;

p is 0, 1, 2, 3, or 4; and

q is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

wherein any Ar of R 1 , R 4 -R 7 , R a , R b and R c is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR e , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR e , SO 2 R e , NR f R g , CONR f R g , COR e , R e , and C 1-8 hydrocarbyleneR d ;

each R d is independently hydroxy, C 1-8 alkoxy, cyano, SR h , or C(═O)R h ;

each R e is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; wherein any Ar of R e is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR d , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR f , SO 2 R f , NR f R g , CONR f R g , COR f , R f , and C 1-8 hydrocarbyleneR d ;

each R f and R g , is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; and

each R h is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, phenyl, or —C 1-8 hydrocarbylene(phenyl);

each Het is selected from the group consisting of 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-dioxane, 1,4-dithiane, 2H-pyran, 2-pyrazoline, 4H-pyran, chromanyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, morpholine, piperazinyl, piperidine, piperidyl, pyrazolidine, pyrazolidinyl, pyrazolinyl, pyrrolidine, pyrroline, quinuclidine, and thiomorpholino;

or a pharmaceutically acceptable salt thereof;

with the proviso that when

(a) R 3 is hydrogen, C 1-8 alkyl, or optionally substituted phenylC 1-8 hydrocarbylene-, and

(b) p is 0, and

(c) q is 1 or 2,

then

R 4 is other than halo, C 1-8 alkyl, or C 1-8 alkoxy;

and with the proviso that when

(a) R 3 is hydrogen or alkyl, and

(b) q is at least 1, and at least one R 2 is hydroxy substituted at the 5-position of Formula (I),

then either

(i) p is 2, 3, or 4, or

(ii) p is 1 and R 4 is other than halo, hydroxy, C 1-8 alkyl, CF 3 , CF 3 O, C 1-8 alkoxy, or C 1-8 hydrocarbyleneOR a , wherein R a is hydrogen or C 1-6 alkyl;

and with the proviso that when

(a) R 3 is phenyl or phenyl substituted with one halo, trifluoromethyl, C 1-8 alkyl, hydroxy, or OC 1-8 alkyl; then either

(i) p is 3, or 4, or

(ii) p is 2 and R 4 is halo, C 1-8 alkyl, C 1-8 alkoxy, and the other R 4 is other than C 1-8 alkyl; or

(iii) at least one R 4 is present and is other than a halo, C 1-8 alkyl, or C 1-8 alkoxy.

10. The compound of claim 9 wherein R 4 is 2-ethoxyphenyl, 2-(C 3-8 cycloalkyloxy)phenyl, or 2-chlorophenyl.

11. The compound of claim 1 wherein each R 4 is aryl, substituted at the 10-position of formula (I).

12. A compound of Formula (I):

wherein

R 1 is selected from the group consisting of hydrogen, C 1-8 alkyl, and C 1-8 hydrocarbylene Ar;

each R 2 , independently, is selected from the group consisting of C 1-8 alkyl, and OH;

each R 3 is hydrogen, C 1-8 alkyl, Het, R 7 C(═O)—, R 7 OC(═O)—, R 5 R 6 NC(═O)—, R 7 C(═S)—, R 7 SC(═O)—, R 5 R 6 NC(═S)—, R 7 SO 2 —, R 5 R 6 NSO 2 —, R 7 S(═O)—, R 5 R 6 NS(═O)—, R c C 1-8 hydrocarbylene-, or R c C 1-8 hydrocarbyleneC(═O)—;

wherein R 4 is: 5-pyrimidinyl, 3,4-dimethoxyphenyl, 3,5-difluorophenyl, 4-n-butyloxyphenyl, 4-trifluoromethoxyphenyl, 3,4-dichlorophenyl, 2-naphthyl, 4-pyridinyl, bromo, benzhydrilideneamino, amino, N-(phenylsulfonyl)amino, phenoxy, 3-(phenoxy)propyl, 3-(2-naphthyloxy)propyl, 3-(1-naphthyloxy)propyl, 3-([1,1′-biphenyl]-4-yloxy)propyl, 3-(3-methoxyphonoxy)propyl, 3-(4-methoxyphenoxy)propyl, 3-(4-chlorophenoxy)propyl, 3-(3-chlorophenoxy)propyl, 3-(2-chlorophenoxy)propyl, 3-(2,4-dichlorophenoxy)propyl, 3-(2,5-dichlorophenoxy)propyl, 3-(4-fluorophenoxy)propyl, 3-(4-methylphenoxy)propyl, 3-(4-cyanophenoxy)propyl, 3-(pyridin-2-yloxy)propyl, 3-(2-bromophenoxy)propyl, 3-(2-iodophenoxy)propyl, 3-(2-ethylphenoxy)propyl, 3-(2-isopropylphenoxy)propyl, 3-(2-cyanophenoxy)propyl, 3-(pyridin-3-yloxy)-propyl, 3-(3-fluorophenoxy)propyl, 3-(3-bromophenoxy)propyl, 3-(3-iodophenoxy)propyl, 3-(3-isopropylphenoxy)propyl, 3-[3-(trifluoromethyl)phenoxy]propyl, 3-[3-(trifluoromethoxy)phenoxy]propyl, 3-(3-ethylphenoxy)propyl, 3-(3-tert-butylphenoxy)propyl, 3-(pyridin-4yloxy)propyl, 3-(4-methoxyphenoxy)propyl, 3-[4-(benzyloxy)phenoxy]propyl, 3-(4-bromophenoxy)propyl, 3-(4-iodophenoxy)propyl, 3-(4-ethylphenoxy)propyl, 3-(4-tert-butylphenoxy)propyl, 3-[4′-(bromo[1,1′-biphenyl]-4-yl)oxy]propyl, 3-(2,3-difluorophenoxy)propyl, 3-(2,4-dibromophenoxy)propyl, 3-(2,4-difluorophenoxy)propyl, 3-(2-methoxy-4-methylphenoxy)propyl, 3-(4-iodo-2-methylphenoxy)propyl, 3-(2,5-difluorophenoxy)propyl, 3-(2-chloro-5-methylphenoxy)propyl, 3-(2-isopropyl-5-methylphenoxy)propyl, 3-(2,6-difluorophenoxy)propyl, 3-(2,6-dichlorophenoxy)propyl, 3-(2,6-dimethylphenoxy)propyl, 3-(2-fluoro-6-methylphenoxy)propyl, 3-hydroxypropyl, 3-(2,3,6-trimethylphenoxy)propyl, 3-(mesityloxy)propyl, 3-(2,6-dibromo-4-fluorophenoxy)propyl, 3-(4-chloro-3-fluorophenoxy)propyl, 3-(4-chloro-3-methylphenoxy)propyl, 3-(3-chloro-4-fluorophenoxy)propyl, 3-(1,3-benzodioxol-5-yloxy)propyl, 3-(3,5-dichlorophenoxy)propyl, 3-(3,5-dimethylphenoxy)propyl, 3-(3,5-dimethoxyphenoxy)propyl, 3-(5,6,7,8-tetrahydro-1-naphthalenyloxy)propyl, 3-[(2,4-dichloro-1-naphthyl)oxy]propyl, 3-[4-methoxy-1-naphthyl)oxy]propyl, 3-[4-chloro-1-naphthyl)oxy]propyl, 3-[1,6-dibromo-2-naphthyl)oxy]propyl, 3-[1-bromo-2-naphthyl)oxy]propyl, 3-(2,3,4,5,6-pentafluorophenoxy)propyl, 3-(5-isoquinolinyloxy)propyl, 2-methyl-4-methoxyphenyl, 2-ethoxyphenyl, phenyl, phenoxy, 4-pyridinyl, 4-methoxyphenyl, 3,5-difluorophenyl, 3-[1,1′-biphenyl]-2-yloxypropyl, chloro, 2,6-difluorophenyl, bromo, 2-methylphenyl, 2-methoxyphenyl, 2-propoxyphenyl, 2-fluorophenyl, 2,4-dichlorophenyl, 3-(2,4-dibromophenoxy)propyl, 3-(5-chloro-8-quinolinyloxy)propyl, fluoro, 2,6-difluorophenyl, 4-methoxy-2-methylphenyl, or 2,4-dichlorophenyl.

each R 5 and R 6 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr; or R 5 and R 6 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, or thiomorpholino ring;

each R 7 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr;

R a and R b , independently, are selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het;

R c is Ar, Het, R 7 CO 2 —, R 7 C(═O)—, R 7 OC(═O)—, R 7 O—, R 7 C 1-8 alkyleneO—, R 7 S—, R 7 C(═S)—, R 7 S(═O)—, R 7 S(═O) 2 —, R 7 SC(═O)—, R 7 C(═O)N(R 7 )—, R 7 C(═S)N(R 7 )—, R 5 R 6 N—, R 5 R 6 NC(═O)—, R 5 R 6 NC(═S)—, R 5 R 6 NS(═O)—, R 5 R 6 NSO 2 —, R 7 S(═O)N(R 7 )—, R 7 SO 2 N(R 7 )—, or R 7 N(R 7 )C(═O)N(R 7 )—;

each Ar is independently aryl or heteroaryl;

p is 0, 1, 2, 3, or 4; and

q is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

wherein any Ar of R 1 , R 4 -R 7 , R a , R b and R c is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR e , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR e , SO 2 R e , NR f R g , CONR f R g , COR e , R e , and C 1-8 hydrocarbyleneR d ;

each R d is independently hydroxy, C 1-8 alkoxy, cyano, SR h , or C(═O)R h ;

each R e is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; wherein any Ar of R e is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR d , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR f , SO 2 R f , NR f R g , CONR f R g , COR f , R f , and C 1-8 hydrocarbyleneR d ;

each R f and R g , is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; and

each R h is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, phenyl, or —C 1-8 hydrocarbylene(phenyl);

each Het is selected from the group consisting of 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-dioxane, 1,4-dithiane, 2H-pyran, 2-pyrazoline, 4H-pyran, chromanyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, morpholine, piperazinyl, piperidine, piperidyl, pyrazolidine, pyrazolidinyl, pyrazolinyl, pyrrolidine, pyrroline, quinuclidine, and thiomorpholino;

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 1 wherein R 4 is 10-(2-ethoxyphenyl).

14. The compound of Formula (II):

wherein

each R 2 , independently, is selected from the group consisting of C 1-8 alkyl, and OH;

each R 4 , independently, is selected from the group consisting of Ar, C 1-8 alkyl, ArO—, C 1-8 alkoxy, Het, halo, OH, CN, NO 2 , CF 3 , CF 3 O, NR a R b , N═CR a R b , R 7 S, C 1-8 hydrocarbyleneAr, and C 1-8 hydrocarbyleneOR a ;

each R 7 is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, Ar, or —C 1-8 hydrocarbyleneAr;

R a and R b , independently, are selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het;

R c is Ar, Het, R 7 CO 2 —, R 7 C(═O)—, R 7 OC(═O)—, R 7 O—, R 7 C 1-8 alkyleneO—, R 7 S—, R 7 C(═S)—, R 7 S(═O)—, R 7 S(═O) 2 —, R 7 SC(═O)—, R 7 C(═O)N(R 7 )—, R 7 C(═S)N(R 7 )—, R 5 R 6 N—, R 5 R 6 NC(═O)—, R 5 R 6 NC(═S)—, R 5 R 6 NS(═O)—, R 5 R 6 NSO 2 —, R 7 S(═O)N(R 7 )—, R 7 SO 2 N(R 7 )—, or R 7 N(R 7 )C(═O)N(R 7 )—;

each Ar is independently aryl or heteroaryl;

p is 0, 1, 2, 3, or 4; and

q is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

wherein any Ar of R 1 , R 4 -R 7 , R a , R b and R c is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR e , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR e , SO 2 R e , NR f R g , CONR f R g , COR e , R e , and C 1-8 hydrocarbyleneR d ;

each R d is independently hydroxy, C 1-8 alkoxy, cyano, SR h , or C(═O)R h ;

each R e is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; wherein any Ar of R e is optionally substituted with one or more substituents independently selected from halo, CN, NO 2 , OR d , methylenedioxy, ethylenedioxy, CF 3 , OCF 3 , SR f , SO 2 R f , NR f R g , CONR f R g , COR f , R f , and C 1-8 hydrocarbyleneR d ;

each R f and R g , is independently selected from the group consisting of hydrogen, C 1-8 alkyl, Ar, C 1-3 hydrocarbyleneAr, SO 2 Ar, SO 2 C 1-4 alkyl, (C 3-8 cycloalkyl)C 1-8 alkyl, and Het; and

each R h is independently hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, haloC 1-8 alkyl, C 3-8 cycloalkenyl, phenyl, or —C 1-8 hydrocarbylene(phenyl);

each Het is selected from the group consisting of 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-dioxane, 1,4-dithiane, 2H-pyran, 2-pyrazoline, 4H-pyran, chromanyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanyl, isoindolinyl, morpholine, piperazinyl, piperidine, piperidyl, pyrazolidine, pyrazolidinyl, pyrazolinyl, pyrrolidine, pyrroline, quinuclidine, and thiomorpholino;

or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising a compound as described in claim 1 and a pharmaceutically acceptable carrier.

16. A method of treating anxiety, depression, epilepsy, migraine, or obesity in a mammal comprising administering to the mammal a pharmaceutically effective amount of a compound as described in claim 1 .

17. The method of claim 45 wherein the disease or disorder is anxiety or depression.

18. A method of treating anxiety, depression, epilepsy, migraine, or obesity in a mammal comprising administering to the mammal a pharmaceutically effective amount of a compound as described in claim 3 .

19. A method of treating anxiety, depression, epilepsy, migraine, or obesity in a mammal comprising administering to the mammal a pharmaceutically effective amount of a compound as described in claim 9 .

20. A method of treating anxiety, depression, epilepsy, migraine, or obesity in a mammal comprising administering to the mammal a pharmaceutically effective amount of a compound as described in claim 14 .

21. The compound N-[2-(2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)ethyl]aniline or 2-(2,3,4,5-tetrahydroazepino[4,5-b]indole-6(1H)-yl)ethanamine dihydrochloride or a pharmaceutically acceptable salt thereof.