Cyclopamine analogs

1. A compound represented by the following structure:

or a pharmaceutically acceptable salt thereof;

wherein:

R 1 is H, alkyl, —OR, amino, sulfonamido, sulfamido, —OC(O)R 5 , —N(R 5 )C(O)R 5 or a sugar;

R 2 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, nitrile, or 3-7 membered heterocycloalkyl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

or R 1 and R 2 taken together form ═O, ═S, ═N(OR), ═N(R), ═N(NR 2 ), or ═C(R) 2 ;

R 3 is H, alkyl, alkenyl, or alkynyl;

R 4 is H; alkyl; alkenyl; alkynyl; aryl; cycloalkyl; 3-7 membered heterocycloalkyl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; aralkyl; 5-6 membered heteroaryl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; heteroaralkyl, wherein the heteroaryl portion is a 5-6 membered heteroaryl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; haloalkyl; —OR; —C(O)R 5 ; —CO 2 R 5 ; —SO 2 R 5 ; —C(O)N(R 5 )(R 5 ); —[C(R) 2 ] q —R 5 ; —[(W)—N(R)C(O)] q R 5 ; —[(W)—C(O)] q R 5 ; —[(W)—C(O)O] q R 5 ; —[(W)—OC(O)] q R 5 ; —[(W)—SO 2 ] q R 5 ; —[(W)—N(R 5 )SO 2 ] q R 5 ; —[(W)—C(O)N(R 5 )] q R 5 ; —[(W)—O] q R 5 ; —[(W)—N(R)] q R 5 ; —W—NR 3 + X − ; or —[(W)—S] q R 5 ;

wherein each W is, independently, a diradical;

each q is independently for each occurrence 1, 2, 3, 4, 5, or 6;

X − is a halide;

each R 5 is, independently, H; alkyl; alkenyl; alkynyl; aryl; cycloalkyl; 3-7 membered heterocycloalkyl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; aralkyl; 5-6 membered heteroaryl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; heteroaralkyl, wherein the heteroaryl portion is a 5-6 membered heteroaryl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or —[C(R) 2 ] p —R 6 ; wherein p is 0-6; or any two occurrences of R 5 on the same substituent can be taken together to form a 4-8 membered optionally substituted ring which contains 0-3 heteroatoms selected from N, O, S, and P;

each R 6 is independently hydroxyl, —N(R)COR, —N(R)C(O)OR, —N(R)SO 2 (R), —C(O)N(R) 2 , —OC(O)N(R)(R), —SO 2 N(R)(R), —N(R)(R), —COOR, —C(O)N(OH)(R), —OS(O) 2 OR, —S(O) 2 OR, —OP(O)(OR)(OR), —NP(O)(OR)(OR), or —P(O)(OR)(OR);

each R is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl or aralkyl;

provided that when R 2 , R 3 , and R 4 are H; R 1 is not hydroxyl or a sugar; further

provided that when R 4 is hydroxyl, then R 1 is not a sugar or hydroxyl; further

provided that when R 4 is hydroxyl, then R 1 and R 2 together are not C═O.

2. The compound of claim 1 , wherein R 1 is H, —OR, amino, sulfonamido, sulfamido, —OC(O)R 5 or —N(R 5 )C(O)R 5 .

3. The compound of claim 2 , wherein R 1 is sulfonamido.

4. The compound of claim 1 , wherein R 2 is H or 3-7 membered heterocycloalkyl that includes from 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

5. The compound of claim 4 , wherein R 2 is H.

6. The compound of claim 1 , wherein R 1 and R 2 taken together along with the carbon to which they are bonded form ═O, ═N(OR), or ═S.

7. The compound of claim 6 , wherein R 1 and R 2 taken together along with the carbon to which they are bonded form ═O.

8. The compound of claim 1 , wherein R 3 is H.

9. The compound of claim 1 , wherein R 4 is H, alkyl, hydroxyl, aralkyl, —[C(R) 2 ] q —R 5 , —[(W)—N(R)C(O)] q R 5 , —[(W)—N(R)SO 2 ] q R 5 , —[(W)—C(O)N(R)] q R 5 , —[(W)—O] q R 5 , —[(W)—C(O)] q R 5 or —[(W)—C(O)O] q R 5 .

10. The compound of claim 9 , wherein R 4 is H, alkyl, aralkyl, —[(W)—C(O)N(R)] q R 5 or —[(W)—N(R)C(O)] q R 5 .

11. The compound of claim 10 , wherein R 4 is H.

12. The compound of claim 1 , wherein R 1 is sulfonamido, R 2 is H and R 3 is H.

13. The compound of claim 1 , wherein R 1 is sulfonamido, R 3 is H and R 4 is H.

14. The compound of claim 1 , wherein R 1 is sulfonamido, R 2 is H and R 4 is H.

15. The compound of claim 1 , wherein R 2 is H, R 3 is H and R 4 is H.

16. The compound of claim 1 , wherein said compound is isolated.

17. The compound of claim 1 , wherein said compound is epimerically pure.

18. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

19. A composition comprising a mixture of

or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

21. An isolated compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

22. The compound of claim 21 , wherein said compound is epimerically pure.

23. A pharmaceutical composition comprising a compound of claim 21 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

24. The compound of claim 1 , wherein each R 5 is, independently, alkyl or aralkyl.

25. The compound of claim 1 , wherein:

R 1 is H, alkyl, —OR, amino, sulfonamido, sulfamido, —OC(O)R 5 , —N(R 5 )C(O)R 5 or a sugar;

R 2 is H;

R 1 and R 2 taken together form ═O, ═S, ═N(OR);

R 3 is H;

R 4 is H, alkyl, hydroxyl, aralkyl, —[C(R) 2 ] q —R 5 , —[(W)—N(R)C(O)] q R 5 , —[(W)—N(R)SO 2 ] q R 5 , —[(W)—C(O)N(R)] q R 5 , —[(W)—O] q R 5 , —[(W)—C(O)] q R 5 or —[(W)—C(O)O] q R 5 ; and

each R 5 is, independently, alkyl or aralkyl.

26. The compound of claim 25 , wherein R 1 is H, alkyl, —OR, amino, sulfonamido, sulfamido, —OC(O)R 5 , —N(R 5 )C(O)R 5 or a sugar.

27. The compound of claim 25 , wherein R 1 is —OR, amino, sulfonamido, —OC(O)R 5 , or —N(R 5 )C(O)R 5 .

28. The compound of claim 25 , wherein R 1 is sulfonamido.

29. The compound of claim 25 , wherein R 1 and R 2 taken together along with the carbon to which they are bonded form ═O.

30. The compound of claim 25 , wherein R 4 is H, alkyl, aralkyl, —[(W)—C(O)N(R)] q R 5 or —[(W)—N(R)C(O)] q R 5 .

31. The compound of claim 26 , wherein R 4 is H, alkyl, aralkyl, —[(W)—C(O)N(R)] q R 5 or —[(W)—N(R)C(O)] q R 5 .

32. The compound of claim 27 , wherein R 4 is H, alkyl, aralkyl, —[(W)—C(O)N(R)] q R 5 or —[(W)—N(R)C(O)] q R 5 .

33. The compound of claim 28 , wherein R 4 is H, alkyl, aralkyl, —[(W)—C(O)N(R)] q R 5 or —[(W)—N(R)C(O)] q R 5 .

34. The compound of claim 25 , wherein R 4 is H.

35. The compound of claim 26 , wherein R 4 is H.

36. The compound of claim 27 , wherein R 4 is H.

37. The compound of claim 28 , wherein R 4 is H.

38. The compound of claim 25 , wherein R 5 is aralkyl.