Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use

1. A compound represented by the formula:

wherein:

Y is —NH—, —O—, —S—, or —CH 2 —;

R 14 is a C 1 -C 6 alkyl, amino-C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl or methylureido group;

R 15 and R 17 are independently H, halo, or a C 1 -C 6 alkyl group unsubstituted or substituted by one or more R 5 groups;

R 11 is H, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —C(O)NR 12 R 13 , —C(O)(C 6 -C 10 aryl), —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t NR 12 R 13 , —SO 2 NR 12 R 13 or —CO 2 R 12 , wherein said C 1 -C 6 alkyl, —C(O)(C 6 -C 10 aryl), —(CH 2 ) t (C 6 -C 10 aryl), and —(CH 2 ) t (5 to 10 membered heterocyclic) moieties of the said R 11 groups are unsubstituted or substituted by one or more groups;

each R 5 is independently selected from halo, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, —C(O)R 8 , —C(O)OR 8 , —OC(O)R 8 , —OC(O)OR 8 , —NR 6 C(O)R 7 , —C(O)NR 6 R 7 , —NR 6 R 7 , —OR 9 , —SO 2 NR 6 R 7 , C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkylamino, —(CH 2 ) j O(CH 2 ) q NR 6 R 7 , —(CH 2 ) t O(CH 2 ) q OR 9 , —(CH 2 ) t OR 9 , —S(O) j (C 1 -C 6 alkyl), —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —C(O)(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t O(CH 2 ) j (C 6 -C 10 aryl), —(CH 2 ) t O(CH 2 ) q (5 to 10 membered heterocyclic), —C(O)(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) j NR 7 (CH 2 ) q NR 6 R 7 , —(CH 2 ) j NR 7 CH 2 C(O)NR 6 R 7 , —(CH 2 ) j NR 7 (CH 2 ) q NR 9 C(O)R 8 , (CH 2 ) j NR 7 (CH 2 ) t O(CH 2 ) q OR 9 , —(CH 2 ) j NR 7 (CH 2 ) q S(O) j (C 1 -C 6 alkyl), —(CH 2 ) j NR 7 (CH 2 ) t R 6 , —SO 2 (CH 2 ) t (C 6 -C 10 aryl), and —SO 2 (CH 2 ) t (5 to 10 membered heterocyclic), the —(CH 2 ) q — and —(CH 2 ) t — moieties of the said R 5 groups optionally include a carbon-carbon double or triple bond, and the alkyl, aryl and heterocyclic moieties of the said R 5 groups are unsubstituted or substituted with one or more substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, —OH, —C(O)R 8 , —C(O)OR 8 , —OC(O)R 8 , —OC(O)OR 8 , —NR 6 C(O)R 7 , —C(O)NR 6 R 7 , —(CH 2 ) t NR 6 R 7 , C 1 -C 6 alkyl, C 3 -C 10 cydoalkyl, —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , and —(CH 2 ) t OR 9 ;

each R 6 and R 7 is independently selected from H, OH, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , —(CH 2 ) t CN(CH 2 ) t OR 9 , —(CH 2 ) t CN(CH 2 ) t R 9 and —(CH 2 ) t OR 9 , and the alkyl, aryl and heterocyclic moieties of the said R 6 and R 7 groups are unsubstituted or substituted with one or more substituents independently selected from hydroxy, halo, cyano, nitro, trifluoromethyl, azido, —C(O)R 8 , —C(O)OR 8 , —CO(O)R 8 , —OC(O)OR 8 , —NR 9 C(O)R 10 , —C(O)NR 9 R 10 , —NR 9 R 10 , C 1 -C 6 alkyl, —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , and —(CH 2 ) t OR 9 , where when R 6 and R 7 are both attached to the same nitrogen, then R 6 and R 7 are not both bonded to the nitrogen directly through an oxygen;

each R 8 is independently selected from H, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 6 -C 10 aryl), and —(CH 2 ) t (5 to 10 membered heterocyclic);

t is an integer from 0 to 6; j is an integer from 0 to 2; q is an integer from 2 to 6;

each R 9 and R 10 is independently selected from H, —OR 6 , C 1 -C 6 alkyl, and C 3 -C 10 cycloalkyl; and

each R 12 and R 13 is independently selected from H, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 3 -C 10 cycloalkyl), —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , and —(CH 2 ) t OR 9 , and the alkyl, aryl and heterocyclic moieties of the said R 12 and R 13 groups are unsubstituted or substituted with one or more substituents independently selected from R 5 , or R 12 and R 13 are taken together with the nitrogen to which they are attached to form a C 5 -C 9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said C 5 -C 9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl rings are unsubstituted or substituted with one or more R 5 substituents, where R 12 and R 13 are not both bonded to the nitrogen directly through an oxygen;

or pharmaceutically acceptable salts or solvates thereof.

2. A compound, salt, or solvate according to claim 1 , wherein R 11 is —(CH 2 ) t (5 to 10 membered heterocyclic), —C(O)NR 12 R 13 , —(CH 2 ) t NR 12 R 13 , —SO 2 NR 12 R 13 or —CO 2 R 12 .

3. A compound of claim 2 , wherein R 11 is —(CH 2 ) t (5 to 10 membered heterocyclic), —C(O)NR 12 R 13 , —SO 2 NR 12 R 13 or —CO 2 R 12 .

4. A compound of claim 3 , wherein R 11 is —(CH 2 ) t (5 to 10 membered heterocyclic) or —C(O)NR 12 R 13 .

5. A compound of claim 4 , wherein R 11 is —C(O)NR 12 R 13 , wherein R 12 and R 13 are independently selected from H, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 3 -C 10 cycloalkyl), —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , and —(CH 2 ) t OR 9 .

6. A compound of claim 5 , wherein R 11 is —C(O)NR 12 R 13 , and wherein R 12 and R 13 are taken together with the nitrogen to which they are attached to form a C 5 -C 9 azabicyclic, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said C 5 -C 9 azabicyclic, azindinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring is unsubstituted or substituted by 1 to 5 R 5 substituents.

7. A compound of claim 6 , wherein R 12 and R 13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring, wherein said pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, isoquinolinyl, or dihydroisoquinolinyl ring is unsubstituted or substituted with 1 to 5 R 5 substituents.

8. A compound of claim 7 , wherein R 12 and R 13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, pipendinyl, piperazinyl, morpholinyl, or thiomorpholinyl ring, wherein said pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiomorpholinyl ring is unsubstituted or substituted with 1 to 5 R 5 substituents.

9. A compound of claim 8 , wherein R 12 and R 13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl ring is unsubstituted or substituted with 1 to 5 R 5 substituents.

10. A compound of claim 9 , wherein R 12 and R 13 are taken together with the nitrogen to which they are attached to form a pyrrolidinyl ring, wherein said pyrrolidinyl is unsubstituted or substituted with 1 to 5 R 5 substituents.

11. A compound of claim 10 , wherein R 12 and R 13 are taken together with the nitrogen to which they are attached to form a pyrrolidin-1-yl ring, wherein said pyrrolidin-1-yl ring is unsubstituted or substituted with 1 to 5 R 5 substituents.

12. A compound of claim 4 , wherein R 11 is a —(CH 2 ) t (5 to 10 membered heterocyclic) group unsubstituted or substituted with 1 to 5 R 5 groups.

13. A compound of claim 12 , wherein R 11 is a —(CH 2 ) t (5-8 membered heterocyclic) group unsubstituted or substituted with 1 to 5 R 5 groups.

14. A compound of claim 13 , wherein R 11 is a —(CH 2 ) t (5 or 6 membered heterocyclic) group is unsubstituted or substituted with 1 to 5 R 5 groups.

15. A compound of claim 14 , wherein R 11 is a —(CH 2 ) t (5 membered heterocyclic) group unsubstituted or substituted with 1 to 5 R 5 groups.

16. A compound of claim 15 , wherein R 11 is a thiazolyl, unsubstituted or substituted by 1 to 5 R 5 groups.

17. A compound of claim 15 , wherein R 11 is an imidazolyl, unsubstituted or substituted by 1 to 5 R 5 groups.

18. A compound of claim 1 , wherein R 14 is methyl.

19. A compound represented by the formula:

wherein:

R 14 is a C 1 -C 6 alkyl, amino-C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl or methylureido group;

R 15 and R 17 are independently H, halo, or a C 1 -C 6 alkyl group;

R 11 is a heteroaryl group unsubstituted or substituted by one or more halo, cyano, nitro, trifluoromethoxy, trifluoromethyl, azido, —C(O)R 8 , —C(O)OR 8 , —OC(O)R 8 , —OC(O)OR 8 , —NR 6 C(O)R 7 , —C(O)NR 6 R 7 , —NR 6 R 7 , —OR 9 , —SO 2 NR 6 R 7 , C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) j O(CH 2 ) q NR 6 R 7 , —(CH 2 ) t O(CH 2 ) q OR 9 , —(CH 2 ) t OR 9 , —S(O) j (C 1 -C 6 alkyl), —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —C(O)(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t O(CH 2 ) j (C 6 -C 10 aryl), —(CH 2 ) t O(CH 2 ) q (5 to 10 membered heterocyclic), —C(O)(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) j NR 7 (CH 2 ) q NR 6 R 7 , —(CH 2 ) j NR 7 CH 2 C(O)NR 6 R 7 , —(CH 2 ) j NR 7 (CH 2 ) q NR 9 C(O)R 8 , —(CH 2 ) j NR 7 (CH 2 ) t O(CH 2 ) q OR 9 , —(CH 2 ) j NR 7 (CH 2 ) q S(O) j (C 1 -C 6 alkyl), —(CH 2 ) j NR 7 —(CH 2 ) t R 6 , —SO 2 (CH 2 ) t (C 6 -C 10 aryl), and —SO 2 (CH 2 ) t (5 to 10 membered heterocyclic), the —(CH 2 ) q — and —(CH 2 ) t — moieties of the said R 5 groups optionally include a carbon-carbon double or triple bond, and the alkyl, aryl and heterocyclic moieties of the said R 5 groups are unsubstituted or substituted with one or more substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, —OH, —C(O)R 8 , —C(O)OR 8 , —OC(O)R 8 , —OC(O)OR 8 , —NR 6 C(O)R 7 , —C(O)NR 6 R 7 , —(CH 2 ) t NR 6 R 7 , C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , and —(CH 2) t OR 9 ;

each R 6 and R 7 is independently selected from H, OH, C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , —(CH 2 ) t CN(CH 2 ) t OR 9 , —(CH 2 ) t CN(CH 2 ) t R 9 and —(CH 2 ) t OR 9 , and the alkyl, aryl and heterocyclic moieties of the said R 6 and R 7 groups are unsubstituted or substituted with one or more substituents independently selected from hydroxy, halo, cyano, nitro, trifluoromethyl, azido, —C(O)R 8 , —C(O)OR 8 , —CO(O)R 8 , —OC(O)OR 8 , —NR 9 C(O)R 10 , —C(O)NR 9 R 10 , —NR 9 R 10 , C 1 -C 6 alkyl, —(CH 2 ) t (C 6 -C 10 aryl), —(CH 2 ) t (5 to 10 membered heterocyclic), —(CH 2 ) t O(CH 2 ) q OR 9 , and —(CH 2 ) t OR 9 , where when R 6 and R 7 are both attached to the same nitrogen, then R 6 and R 7 are not both bonded to the nitrogen directly through an oxygen;

each R 8 is independently selected from H, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 6 -C 10 aryl), and —(CH 2 ) t (5 to 10 membered heterocyclic);

each R 9 and R 10 is independently selected from H, C 1 -C 6 alkyl, and C 3 -C 10 cycloalkyl;

t is an integer from 0 to 6; j is an integer from 0 to 2; q is an integer from 2 to 6;

or pharmaceutically acceptable salts or solvates of said compounds.

20. A compound of claim 19 , wherein R 14 is methyl.

21. A compound represented by the formula III:

wherein:

R 14 is a C 1 -C 6 alkyl, amino-C 1 -C 6 alkyl, hydroxy C 1 -C 6 alkyl, C 3 -C 10 cycloalkyl or methylureido group;

R 15 and R 17 are independently H, halo, or a C 1 -C 6 alkyl group; and

R 11 is a heterocyclic or a heteroaryl group unsubstituted or substituted by one or more groups selected from —C(O)OR 8 , C 1 -C 6 alkyl, and —(CH 2 ) t OR 9 ;

each R 8 is independently selected from H, C 1 -C 10 alkyl, C 3 -C 10 cycloalkyl, —(CH 2 ) t (C 6 -C 10 aryl), and —(CH 2 ) t (5 to 10 membered heterocyclic);

each R 9 is independently selected from H, C 1 -C 6 alkyl, and C 3 -C 10 cycloalkyl; and

t is an integer from 0 to 6; j is an integer from 0 to 2; q is an integer from 2 to 6;

or pharmaceutically acceptable salts or solvates of said compounds.

22. A compound of claim 21 , wherein R 14 is methyl.

23. A compound of claim 1 , wherein R 14 is cyclopropyl.

24. A compound of claim 19 , wherein R 14 is cyclopropyl.

25. A compound of claim 21 , wherein R 14 is cyclopropyl.

26. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or solvate thereof.