Aryl sulfonamides useful for modulation of the progesterone receptor

1. A compound of the structure:

wherein:

R 1 and R 2 are independently selected from the group consisting of H, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 3 to C 8 cycloalkyl, substituted C 3 to C 8 cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, substituted heterocycle, C 3 to C 6 alkenyl, C 3 to C 6 substituted alkenyl, C 3 to C 6 alkynyl, substituted C 3 to C 6 alkynyl, —(CH m X n ) z CH p X q , O—C 1 to C 6 alkyl, O—C 1 to C 6 substituted alkyl, and O—(CH m X n ) z CH p X q ; or

R 1 and R 2 may be taken together to form a ring of 4 to 8 ring atoms containing in its backbone carbon atoms and 1 to 4 N, O, S, or SO 2 , and where any C-atom or N-atom of said ring is optionally substituted with C 1 to C 4 alkyl, F, or CF 3 ;

R 3 , R 4 , R 5 and R 6 are independently selected from the group consisting of H, halogen, CN, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, —(CH m X n ) z CH p X q , C 3 to C 6 cycloalkyl, substituted C 3 to C 6 cycloalkyl, O—C 1 to C 6 alkyl, O—C 1 to C 6 substituted alkyl, OH, NH 2 , NH—(CH m X n ) z CH p X q , O—(CH m X n ) z CH p X q , N—{(CH m X n ) z CH p X q } 2 , aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle, and substituted heterocycle;

X is halogen;

m and n are, independently, 0 to 2, provided that m+n=2;

p and q are, independently, 0 to 3, provided that p+q=3;

z is 0 to 10;

R 7 is selected from the group consisting of H, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, and substituted C 3 to C 6 cycloalkyl;

or a pharmaceutically acceptable salt or tautomer thereof.

2. The compound according to claim 1 , wherein R 7 is a branched C 3 to C 6 alkyl.

3. The compound according to claim 1 , wherein R 3 , R 4 , R 5 , and R 6 are H.

4. The compound according to claim 1 , wherein R 4 is H or halogen.

5. The compound according to claim 1 , wherein R 7 is C 1 to C 6 alkyl.

6. The compound according to claim 1 , wherein R 1 is H or C 1 to C 6 alkyl.

7. The compound according to claim 1 , wherein R 2 is H, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, CF 3 , or CH 2 —C 3 to C 8 cycloalkyl.

8. The compound according to claim 1 , wherein R 1 and R 2 are joined to form tetrahydropyrrole, pyrrolidine, piperidine, tetrahydropyran, or pyrrole.

9. The compound according to claim 1 , wherein R 3 is H or OCF 3 .

10. The compound according to claim 1 , wherein R 4 and R 6 are independently H or F.

11. The compound according to claim 1 , wherein R 5 is H, CF 3 , N(CH 3 ) 2 , or F.

12. The compound according to claim 1 , wherein:

R 1 is H or C 1 to C 6 alkyl;

R 2 is H, C 1 to C 6 alkyl, substituted C 1 to C 6 alkyl, C 3 to C 6 cycloalkyl, or CF 3 ; or

R 1 and R 2 are joined with the N-atom to form tetrahydropyrrole, piperidine, tetrahydropyran, or pyrrole;

R 3 is H or OCF 3 ;

R 4 and R 6 are independently H or F;

R 5 is H, CF 3 , N(CH 3 ) 2 , or F; or

R 7 is C 1 to C 6 alkyl.

13. The compound according to claim 1 which is selected from the group consisting of 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-methylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-dimethylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-ethylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-propylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-isopropylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-isobutylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-ethyl-N-methylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-diethylbenzenesulfonamide; N-(tert-butyl)-4-(5-cyano-1-methyl-1H-pyrrol-2-yl)benzenesulfonamide; 1-methyl-5-[4-(pyrrolidin-1-ylsulfonyl)phenyl]-1H-pyrrole-2-carbonitrile; 1-methyl-5-[4-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrrole-2-carbonitrile; 1-methyl-5-[4-(morpholin-4-ylsulfonyl)phenyl]-1H-pyrrole-2-carbonitrile; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclobutylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclopropylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclohexylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-(cyclopropylmethyl)benzenesulfonamide; 1-methyl-5-[4-(1H-pyrrol-1-ylsulfonyl)phenyl]-1H-pyrrole-2-carbonitrile; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-dimethyl-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-methyl-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-diethyl-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-isopropyl-2(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-ethyl-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-propyl-2-(trifluoromethyl)benzenesulfonamide; 1-methyl-5-[4-(pyrrolidin-1-ylsulfonyl)-3-(trifluoromethyl)phenyl]-1H-pyrrole-2-carbonitrile; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclopropyl-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-y1)-N-(cyclopropylmethyl)-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclobutyl-2-(trifluoromethyl)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-y1)-3-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluoro-N-methylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluoro-N,N-dimethylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-ethyl-3-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-diethyl-3-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluoro-N-isopropylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-3-fluoro-N-propylbenzenesulfonamide; 5-[2-fluoro-4-(pyrrolidin-1-ylsulfonyl)phenyl]-1-methyl-1H-pyrrole-2-carbonitrile; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclopropyl-3-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-(cyclopropylmethyl)-3-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclobutyl-3-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-diethyl-2-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-fluoro-N-isopropylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclopropyl-2-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-(cyclopropylmethyl)-2-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclobutyl-2-fluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-methyl-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-dimethyl-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-ethyl-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N,N-diethyl-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-isopropyl-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-propyl-2-(trifluoromethoxy)benzenesulfonamide; 1-methyl-5-[4-(pyrrolidin-1-ylsulfonyl)-3-(trifluoromethoxy)phenyl]-1H-pyrrole-2-carbonitrile; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclopropyl -2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-(cyclopropylmethyl)-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclobutyl-2-(trifluoromethoxy)benzenesulfonamide; N-tert-butyl-4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-(trifluoromethoxy)benzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-(dimethylamino)-N,N-dimethylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2,5-difluoro-N-methylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2,5-difluoro-N-isopropylbenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclopropyl-2,5-difluorobenzenesulfonamide; 4-(5-cyano-1-methyl-1H-pyrrol1-2-yl)-N-(cyclopropylmethyl)-2,5-difluorobenzenesulfonamide; and a pharmaceutically acceptable salt or tautomer thereof.