Thienopyridine compounds, and methods of use thereof

1. A compound of formula Ib:

wherein

q is 0 or 1;

R 1 is selected from the group consisting of hydroxy, alkoxy, substituted alkoxy, acyloxy, cycloalkoxy, substituted cycloalkoxy, aryloxy, substituted aryloxy, mercapto, thioether, amino, substituted amino, and aminoacyl;

R 2 is selected from the group consisting of hydrogen, deuterium, and methyl;

R 3 is selected from the group consisting of hydrogen, deuterium, alkyl, and R 101 ;

R 4 is selected from the group consisting of hydrogen, alkyl, and R 101 ;

R 5 is selected from the group consisting of hydrogen, halo, alkyl, R 101 , alkenyl, R 111 , alkynyl, R 113 , alkoxy, substituted alkoxy, cycloalkyl, R 103 , cycloalkoxy, substituted cycloalkoxy, amino, substituted amino, aminoacyl, aryl, R 105 , aryloxy, substituted aryloxy, furanyl, thienyl, thioether, cyano, and acyl; and

R 6 and R 7 are independently selected from the group consisting of hydrogen, hydroxy, cyano, halo, nitro, acyl, amino, substituted amino, acylamino, sulfonyl, alkyl, R 101 , alkenyl, R 111 , alkynyl, R 113 , alkoxy, substituted alkoxy, aryl, R 105 , aryloxy, substituted aryloxy, thioether, arylthio, and substituted arylthio;

or a pharmaceutically acceptable salt, single stereoisomer, or mixture of stereoisomers thereof, or an ester or amide of the —COOH group on the glycine- or alanine-based substituent of the thienopyridine ring, which ester is selected from —C(O)O-alkyl, —C(O)O—R 101 , —C(O)O-alkenyl, —C(O)O—R 111 , —C(O)O-alkynyl, —C(O)O—R 113 , —C(O)O-aryl, and —C(O)O—R 105 ; and the amide is derived from amines of the formula HNR 20 R 21 , where R 20 and R 21 are independently hydrogen, alkyl, R 101 , aryl, or R 105 ; and further wherein

R 101 is substituted alkyl, wherein substituted alkyl is alkyl having from 1 to 5 substituents selected from the group consisting of R 200 , R 201 , R 202 , and R 203 ;

R 103 is substituted cycloalkyl, wherein substituted cycloalkyl is cycloalkyl having from 3 to 10 carbon atoms having single or multiple cyclic rings and from 1 to 5 substituents selected from the group consisting of oxo (═O), thioxo (═S), alkyl, R 101 , and R 201 ;

R 105 is substituted aryl, wherein substituted aryl is aryl having from 1 to 4 substituents selected from the group consisting of R 201 , alkyl, R 101 , alkenyl, R 111 , alkynyl, R 113 , R 202 , R 203 , amidino, aminocarbonyloxy, aminocarbonylamino, aminothiocarbonylamino, cycloalkoxy, substituted cycloalkoxy, thiol, alkylthio, substituted alkylthio, arylthio, substituted arylthio, cycloalkylthio, substituted cycloalkylthio, guanidino, oxycarbonylamino, oxythiocarbonylamino, —S(O) 2 -alkyl, —S(O) 2 —R 101 , —S(O) 2 -cycloalkyl, —S(O) 2 —R 103 , —S(O) 2 -alkenyl, —S(O) 2 —R 111 , —S(O) 2 -aryl, and —S(O) 2 —R 105 ;

R 111 is substituted alkenyl, wherein substituted alkenyl is alkenyl having from 1 to 3 R 201 ;

R 113 is substituted alkynyl, wherein substituted alkynyl is alkynyl having from 1 to 3 R 201 ;

R 200 is aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aryloxyaryl, substituted aryloxyaryl, oxo, thioxo, thiol, alkylthio, substituted alkylthio, arylthio, substituted arylthio, cycloalkylthio, substituted cycloalkylthio, cycloalkoxy, substituted cycloalkoxy, oxycarbonylamino, and oxythiocarbonylamino;

R 201 is alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, amino, substituted amino, aminoacyl, aryloxy, substituted aryloxy, cyano, halogen, hydroxyl, nitro, carboxyl, carboxyl esters, cycloalkyl, R 103 , aryl, and R 105 ;

R 202 is —NR 40 S(O) 2 -alkyl, —NR 40 S(O) 2 —R 101 , —NR 40 S(O) 2 -aryl, —NR 40 S(O) 2 —R 105 , —NR 40 S(O) 2 —NR 40 -alkyl, —NR 40 S(O) 2 —NR 40 —R 101 , —NR 40 S(O) 2 —NR 40 -aryl, and —NR 40 S(O) 2 —NR 40 —R 105 , where each R 40 is hydrogen or alkyl; and

R 203 is —OS(O) 2 -alkyl, —OS(O) 2 —R 101 , —OS(O) 2 -aryl, —OS(O) 2 —R 105 , and —OSO 2 —NR 40 R 40 where each R 40 is hydrogen or alkyl;

and further wherein substituted alkoxy is —O—R 101 ;

substituted cycloalkoxy is —O—R 103 ;

substituted aryloxy is —O—R 105 ;

substituted amino is —NR 41 R 41 , where each R 41 group is independently selected from the group consisting of hydrogen, alkyl, R 101 , alkenyl, R 111 , alkynyl, R 113 , cycloalkyl, R 103 , aryl, R 105 , —S(O) 2 -alkyl, —S(O) 2 —R 101 , —S(O) 2 -cycloalkyl, —S(O) 2 —R 103 , —S(O) 2 -alkenyl, —S(O) 2 —R 111 , —S(O) 2 -aryl, and —S(O) 2 —R 105 , provided that both R 41 groups are not hydrogen;

substituted alkylthio is —S—R 101 ;

substituted arylthio is —S—R 105 ;

substituted cycloalkylthio is —S—R 103 ;

substituted aryloxyaryl is -aryl-O-aryl, wherein each aryl group is substituted on either or both aryl rings with from 1 to 3 substituents selected from the group consisting of R 201 , alkyl, R 101 , alkenyl, R 111 , alkynyl, R 113 , R 202 , R 203 , amidino, aminocarbonyloxy, aminocarbonylamino, aminothiocarbonylamino, cycloalkoxy, substituted cycloalkoxy, thiol, alkylthio, substituted alkylthio, arylthio, substituted arylthio, cycloalkylthio, substituted cycloalkylthio, guanidino, oxycarbonylamino, oxythiocarbonylamino, —S(O) 2 -alkyl, —S(O) 2 —R 101 , —S(O) 2 -cycloalkyl, —S(O) 2 —R 103 , —S(O) 2 -alkenyl, —S(O) 2 —R 111 , —S(O) 2 -aryl, and —S(O) 2 —R 105 ; and

acyl is H—C(O)—, alkyl-C(O)—, R 101 —C(O)—, alkenyl-C(O)—, R 111 -—C(O)—, alkynyl-C(O)—, R 113 —C(O)—, cycloalkyl-C(O)—, R 103 —C(O)—, aryl-C(O)—, or R 105 —C(O)—.

2. The compound of claim 1 , wherein q is 0.

3. The compound of claim 1 , wherein R 1 is hydroxy.

4. The compound of claim 3 , wherein R 2 , R 3 , and R 4 are all hydrogen.

5. The compound of claim 1 , wherein R 5 is selected from the group consisting of hydrogen, alkyl, halo, aryl, R 105 , cyano, alkynyl, furanyl and thienyl.

6. The compound of claim 5 , wherein R 5 is selected from the group consisting of hydrogen, methyl, bromo, chloro, phenyl, fluorophenyl, cyano, ethynyl, furanyl, and thienyl.

7. The compound of claim 1 , wherein R 6 is selected from the group consisting of hydrogen, halo, alkyl, R 101 , alkenyl, R 111 , aryl, R 105 , aryloxy, arylthio, and cyano.

8. The compound of claim 7 , wherein R 6 is selected from the group consisting of hydrogen, bromo, methyl, phenyl, trifluoromethylphenyl, phenoxyphenyl, fluorophenyl, phenylsulfanyl, phenethyl, phenylethenyl, phenoxy, and cyano.

9. The compound of claim 1 , wherein R 7 is selected from the group consisting of hydrogen, aryl, and R 105 .

10. The compound of claim 1 , wherein R 7 is selected from the group consisting of hydrogen, phenyl, and fluorophenyl.

11. The compound of claim 1 wherein

R 1 is hydroxy;

R 2 , R 3 , and R 4 are hydrogen;

R 5 is hydrogen, halo, alkyl, or aryl;

R 6 is halo, alkyl, aryl, R 105 , or arylthio; and

R 7 is hydrogen or R 105 ;

or a pharmaceutically acceptable salt, single stereoisomer, or mixture of stereoisomers thereof, or an ester or amide of the —COOH group on the glycine- or alanine-based substituent of the thienopyridine ring, which ester is selected from —C(O)O-alkyl, —C(O)O—R 101 , —C(O)O-alkenyl, —C(O)O—R 111 , C(O)O-alkynyl, —C(O)O—R 113 , —C(O)O-aryl, and —C(O)O—R 105 ; and the amide is derived from amines of the formula HNR 20 R 21 , where R 20 where and R 21 are independently hydrogen, alkyl, R 101 , aryl, or R 105 .

12. The compound of claim 1 wherein

R 1 is hydroxy;

R 2 , R 3 , and R 4 are hydrogen;

R 5 is hydrogen, halo, alkyl, aryl, R 105 , furanyl, thienyl, alkynyl, or cyano;

R 6 is hydrogen, halo, alkyl, R 105 , arylthio, or cyano; and

R 7 is hydrogen or R 105 ;

or a pharmaceutically acceptable salt, single stereoisomer, or mixture of stereoisomers thereof, or an ester or amide of the —COOH group on the glycine- or alanine-based substituent of the thienopyridine ring, which ester is selected from —C(O)O-alkyl, —C(O)O—R 101 , —C(O)O-alkenyl, —C(O)O—R 111 , C(O)O-alkynyl, —C(O)O—R 113 , —C(O)O-aryl, and —C(O)O—R 105 ; and the amide is derived from amines of the formula HNR 20 R 21 , where R 20 and R 21 are independently hydrogen, alkyl, R 101 , aryl, or R 105 .

13. A compound of claim 1 selected from the group consisting of:

[(2-Bromo-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

{[4-Hydroxy-2-(4-methoxy-phenyl)-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

[(4-Hydroxy-2,7-dimethyl-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

{[4-Hydroxy-2-(4-phenoxy-phenyl)-7-methyl-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

{[4-Hydroxy-2-(4-phenoxy-phenyl)-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

[(2,7-Dibromo-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(2-Bromo-7-chloro-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(4-Hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(4-Hydroxy-2-phenylsulfanyl-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(4-Hydroxy-2,7-diphenyl-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

{[7-Bromo-3-(4-fluoro-phenyl)-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

{[3-(4-Fluoro-phenyl)-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

{[2-(4-Fluoro-phenyl)-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

{[2-(4-Fluoro-phenyl)-4-hydroxy-7-methyl-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

[(7-Chloro-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(7-Bromo-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(4-Hydroxy-7-phenyl-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

{[7-(4-Fluoro-phenyl)-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl]-amino}-acetic acid;

2-(7-(furan-2-yl)-4-hydroxythieno[2,3-c]pyridine-5-carboxamido)acetic acid;

[(7-Furan-3-yl-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

2-(4-hydroxy-7-(thiophen-2-yl)thieno[2,3-c]pyridine-5-carboxamido)acetic acid;

[(4-Hydroxy-7-thiophen-3-yl-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(4-Hydroxy-7-methyl-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

[(7-Ethynyl-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid; and

[(7-Cyano-4-hydroxy-thieno[2,3-c]pyridine-5-carbonyl)-amino]-acetic acid;

or a pharmaceutically acceptable salt, single stereoisomer, or mixture of stereoisomers thereof, or an ester or amide of the —COOH group on the glycine- or alanine-based substituent of the thienopyridine ring, which ester is selected from —C(O)O-alkyl, —C(O)O—R 101 , —C(O)O-alkenyl, —C(O)O—R 111 , —C(O)O-alkynyl, —C(O)O—R 113 , —C(O)O-aryl, and —C(O)O—R 105 ; and the amide is derived from amines of the formula HNR 20 R 21 , where R 20 and R 21 are independently hydrogen, alkyl, R 101 , aryl, or R 105 .

14. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier, and a therapeutically effective amount of at least one compound as claimed in claim 1 .