Cyclopamine analogues and methods of use thereof

A compound of Formula 2:

• or a pharmaceutically acceptable salt thereof;
• wherein each R1 and R8 is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, halide, sulfhydryl, alkylthio, arylthio, aralkylthio, hydroxyl, alkoxyl, aryloxy, acyloxy, amino, alkylamino, arylamino, acylamino, aralkylamino, nitro, acylthio, carboxamide, sulfonamide, sulfate, —OP(L)(OR20)2, —X—C(L)-R21 or —X—C(L)-X—R21;
• wherein R1 may also be a sugar;
• each X is independently O or NR wherein R is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl or aralkyl;
• L is O or S;
• R2 and R9 are independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, nitrile, aralkyl, alkoxyl, aryloxy, acyloxy, carboxyl, halide, sulfhydryl, alkylthio, arylthio, aralkylthio, hydroxyl, amino, alkylamino, arylamino, acylamino, aralkylamino, heteroaryl, or heteroaralkyl;
• each R5 and R11 is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, alkoxyl, aryloxy, acyloxy, halide, hydroxyl, amino, alkylamino, arylamino, acylamino, aralkylamino, alkylseleno, aralkylseleno, arylseleno, alkylthio, aralkylthio, arylthio, heteroaryl, or heteroaralkyl;
• each R3, R4, R6, R7, R13 and R14 is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, alkoxyl, aryloxy, acyloxy, halide, hydroxyl, amino, alkylamino, arylamino, acylamino, aralkylamino, heteroaryl, or heteroaralkyl;
• or R1 and R2 taken together and/or R8 and R9 taken together, along with the carbon to which they are bonded, form —(C═O)—, —(C═S)—, —(C═N(OR20))—, —(C═N(R20))—, —(C═N(N(R20)(R20))), or form an optionally substituted 3-8 membered ring containing up to two heteroatoms selected from N, O, and S;
• or
• R4 and R5 taken together and/or R5 and R6 taken together and/or R10 and R11 taken together form a double bond or form a group represented by 1b
• wherein Z is NR21, O, or C(R23)(R23);
• R12 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, hydroxyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, alkoxyl, —C(O)R21, —CO2R21, —SO2R21, —C(O)N(R21)(R21), —[C(R21)2]q—R21, —[(W)—N(R21)C(O)]qR21, —[(W)—C(O)]qR21, —[(W)—C(O)O]qR21, —[(W)—OC(O)]qR21, —[(W)—SO2]qR21, —[(W)—N(R2)SO2]qR21, —[(W)—C(O)N(R21)]qR21, —[(W)—O]qR21, —[(W)—N(R21)]qR21, or [(W)—S]qR21;
• wherein each W is independently a diradical, and q is 1, 2, 3, 4, 5, or 6;
• R15, R16, and R17 are independently H, alkoxyl, aryloxy, acyloxy, halide, hydroxyl, amino, alkylamino, arylamino, acylamino, aralkylamino;
• or R15 and R16 taken together, along with the carbon to which they are bonded, form —C(O)— or —C(S)—;
• R18 and R19 are independently H, alkyl, araalkyl, halide, amido, or ester;
• each R20 is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, or heteroaralkyl;
• or any two occurrences of R20 on the same substitutent can be taken together to form a 4-8 membered optionally substituted ring;
• each R21 is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl or —[C(R20)2]p—R25 wherein p is 0-6;
• or any two occurrences of R21 on the same substitutent can be taken together to form a 4-8 membered optionally substituted ring which contains up two heteroatoms selected from N, O, S, and P;
• each R23 is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, halide, alkoxyl, aryloxy, acyloxy, silyloxy, nitrile, —C(O)R21, —CO2R21, —SO2R21, and —C(O)N(R21)2;
• each R25 is independently H, hydroxyl, acylamino, —N(R20)COR20, —N(R20)C(O)OR20, —N(R20)SO2(R20), —COR20N(R20)2, —OC(O)R20N(R20)(R20), —SO2N(R20)(R20), —N(R20)(R20), —COOR20, —C(O)N(OH)(R21), —OS(O)2OR21, —S(O)2OR20, —OP(L)(OR20)(OR20), —NP(O)(OR20)(OR20), or —P(O)(OR20)(OR20).
• provided that there is at least one group represented by formula 1b on said compound of formula 2.