The compounds of the subject invention have a structure according to formula I: wherein each of the substituents is given the definition as set forth in the specification and claims, or a salt or hydrate form thereof.
1. A compound of formula I:
wherein
X is S or SO 2 ;
R 1 is (1C-6C)alkyl, (3C-6C)alkenyl, or (3C-6C)alkynyl, each optionally substituted with (3C-6C)cycloalkyl, OH, OC(O)(1C-4C)alkyl, (1C-4C)alkoxy, halogen, cyano, formyl, C(O)(1C-4C)alkyl, CO 2 H, CO 2 (1C-4C)alkyl, C(O)NR 5 R 6 , S(O)(1C-4C)alkyl or S(O) 2 (1C-4C)alkyl;
R 2 is hydrogen, (1C-4C)alkyl or C(O)(1C-4C)alkyl;
R 3 is pyridyl optionally substituted with (1C-4C)alkyl, (1C-4C)fluoroalkyl, (1C-4C)alkoxy, halogen or cyano;
R 4 is a phenyl group, substituted at the ortho position with 1-hydroxy(1C-4C)alkyl, (1C-4C)alkoxy, C(O)(1C-4C)alkyl, CO 2 (1C-4C)alkyl, C(O)NH 2 , cyano, nitro, or CH═NOR 7 , and optionally further substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen;
R 5 and R 6 are independently hydrogen or (1C-4C)alkyl;
R 7 is hydrogen or C(O)(1C-4C)alkyl;
R 8 , R 9 , R 10 are independently hydrogen, (1C-2C)alkyl, fluoro or chloro;
or a salt thereof.
2. A compound according to claim 1 , wherein R 8 , R 9 , R 10 are hydrogen.
3. A compound according to claim 2 , wherein
R 2 is hydrogen, (1C-2C)alkyl or C(O)CH 3 ;
R 3 is pyridyl optionally substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl, (1C-2C)alkoxy, halogen or cyano;
R 4 is a phenyl group, substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOR 7 , and optionally further substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen; and
R 7 is hydrogen or C(O)(1C-2C)alkyl.
4. A compound according to claim 3 , wherein
X is S;
R 1 is (1C-4C)alkyl, (3C-6C)alkenyl, or (3C-6C)alkynyl, each optionally substituted with (3C-6C)cycloalkyl, OH, OC(O)(1C-2C)alkyl, (1C-2C)alkoxy, halogen, cyano, formyl, C(O)(1C-2C)alkyl, CO 2 H or CO 2 (1C-2C)alkyl;
R 3 is pyridyl optionally substituted with methyl, CF 3 , methoxy, fluoro, chloro or cyano;
R 4 is a phenyl group, substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOH.
5. A compound according to claim 4 , wherein R 2 is hydrogen.
6. A compound according to claim 5 , wherein
R 3 is pyridyl optionally substituted with methyl, CF 3 , methoxy, fluoro, chloro or cyano.
7. A compound according to claim 6 , wherein
R 4 is a phenyl group substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOH.
8. A compound according to claim 7 , wherein
R 1 is (1C-4C)alkyl optionally substituted with OH, (1C-2C)alkoxy, cyano, C(O)(1C-2C)alkyl or CO 2 (1C-2C)alkyl;
R 3 is pyridyl optionally substituted with methyl, fluoro, chloro or cyano; and
R 4 is a phenyl group, substituted at the ortho position with hydroxymethyl, cyano or nitro.
9. A compound according to claim 8 , wherein
R 3 is selected from the group consisting of pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl, each optionally substituted with methyl, fluoro, chloro or cyano.
10. A compound according to claim 9 , wherein
R 1 is (1C-4C)alkyl optionally substituted with methoxy, cyano, C(O)CH 3 or CO 2 CH 3 ;
R 3 is selected from the group consisting of pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl; and
R 4 is a 2-nitrophenyl group.
11. A compound according to claim 10 which is methyl-[3-(2-nitro-phenylsulfanyl)-1-pyridin-2-ylmethyl-1H-indol-6-yl]-amine; or methyl-[3-(2-nitro-phenylsulfanyl)-1-pyridin-3-ylmethyl-1H-indol-6-yl]-amine.
12. A pharmaceutical composition comprising a compound according to claim 1 or a salt thereof and a pharmaceutically acceptable carrier.
13. A method of treating male hypogonadism comprising administering a pharmaceutically effective amount of a compound according to claim 1 or a salt thereof to a subject in need thereof.