Heterocyclic cyclopamine analogs and methods of use thereof

A compound of formula 6a:

• or a tautomer, saturated derivative, or pharmaceutically acceptable salt thereof;
• wherein;
• R1 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, hydroxyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, —SR20, —OR20, —C(O)R20, —CO2R20, —OC(O)R20, —C(O)N(R20)(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)(R20), —[(W)—C(O)]pR20, —[(W)—C(O)O]pR20, —[(W)—OC(O)]pR20, —[(W)—SO2]pR20, —[(W)—N(R20)SO2]pR20, —[(W)—C(O)N(R20)]pR20, —[(W)—O]pR20, —[(W)—N(R20)]pR20, or —[(W)—S]pR20;
• each of R4 and R5 independently is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, nitrile, aralkyl, alkoxyl, aryloxy, acyloxy, halide, sulfhydryl, alkylthio, arylthio, aralkylthio, hydroxyl, amino, alkylamino, arylamino, acylamino, aralkylamino, heteroaryl, or heteroaralkyl;
• or R4 and R5 taken together form ═O or ═S;
• R20 independently for each occurrence is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, or —[C(R)2]q—R21;
• or any two occurrences of R20 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;
• R21 independently for each occurrence is H, cycloalkyl, aryl, heteroaryl, heterocycyl;
• alkoxyl, aryloxy, acyloxy, halide, sulfhydryl, alkylthio, arylthio, aralkylthio, hydroxyl, amino, acylamino, amido, or carbonyl-containing group;
• R22 independently for each occurrence is H, halide, ester, amide, or nitrile;
• R23 independently for each occurrence is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, perhaloalkyl, halide, nitro, nitrile, ═O, —SR20, —OR20—N(R20)(R20), —C(O)R20, —CO2R20, —OC(O)R20, —C(O)N(R20)(R20), —N(R20)C(O)R20, —N(R20)C(O)N(R20)(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)(R20), —N(R20)S(O)2R20, or —[C(R)2]q—R21;
• R24 independently for each occurrence is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, perhaloalkyl, halide, nitro, nitrile, —SR20, —OR20, —N(R20)(R20), —C(O)R20, —CO2R20, —OC(O)R20, —C(O)N(R20)(R20), —N(R20)C(O)R20, —N(R20)C(O)N(R20)(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)(R20), —N(R20)S(O)2R20, or —[C(R)2]qR21;
• p is 0, 1, 2, 3, 4, 5, or 6;
• q is 0, 1, 2, 3, 4, 5, or 6;
• R independently for each occurrence is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroarylalkyl;
• -T1-T2-T3- is Y-B-A, B-Y-A, or A-B-Y;
• each of A and B independently is N, S or C(R23);
• W is a diradical;
• X is a bond or —C(R22)2—;
• Y is —O—, —S—, or —N(R24)—;
• and
• and each alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, whether alone or part of another group, is optionally substituted.

A compound of formula 11b:

• or a tautomer, saturated derivative, or pharmaceutically acceptable salt thereof;
• wherein;
• R1 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, hydroxyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, —SR20, —OR20, —C(O)R20, —CO2R20, —OC(O)R20, —C(O)N(R20)(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)(R20), —[(W)—C(O)]pR20, —[(W)—C(O)O]pR20, —[(W)—OC(O)]pR20, —[(W)—SO2]pR20, —[(W)—N(R20)SO2]pR20, —[(W)—C(O)N(R20)]pR20, —[(W)—O]pR20, —[(W)—N(R20)]pR20, or —[(W)—S]pR20;
• each of R4 and R5 independently is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, nitrile, aralkyl, alkoxyl, aryloxy, acyloxy, halide, sulfhydryl, alkylthio, arylthio, aralkylthio, hydroxyl, amino, alkylamino, arylamino, acylamino, aralkylamino, heteroaryl, or heteroaralkyl;
• or R4 and R5 taken together form ═O or ═S;
• R20 independently for each occurrence is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, or —[C(R)2]q—R21;
• or any two occurrences of R20 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;
• R21 independently for each occurrence is H, cycloalkyl, aryl, heteroaryl, heterocycyl;
• alkoxyl, aryloxy, acyloxy, halide, sulfhydryl, alkylthio, arylthio, aralkylthio, hydroxyl, amino, acylamino, amido, or carbonyl-containing group;
• R22 independently for each occurrence is H, halide, ester, amide, or nitrile;
• R23 independently for each occurrence is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, perhaloalkyl, halide, nitro, nitrile, ═O, —SR20, —OR20—N(R20)(R20), —C(O)R20, —CO2R20, —OC(O)R20, —C(O)N(R20)(R20), —N(R20)C(O)R20, —N(R20)C(O)N(R20)(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)(R20), —N(R20)S(O) 20, or —[C(R)2]q—R21;
• R24 independently for each occurrence is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, perhaloalkyl, halide, nitro, nitrile, —SR20, —OR20, —N(R20)(R20), —C(O)R20, —CO2R20, —OC(O)R20, —C(O)N(R20)(R20), —N(R20)C(O)R20, —N(R20)C(O)N(R20)(R20), —S(O)R20, —S(O)2R20, —S(O)2N(R20)(R20), —N(R20)S(O)2R20, or —[C(R)2]q—R21;
• p is 0, 1, 2, 3, 4, 5, or 6;
• q is 0, 1, 2, 3, 4, 5, or 6;
• R independently for each occurrence is H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroarylalkyl;
• -T1-T2-T3- is Y-B-A, B-Y-A, or A-B-Y;
• each of A and B independently is N, S or C(R23);
• W is a diradical;
• X is a bond or —C(R22)2—;
• Y is —O—, —S—, or —N(R24)—;
• and
• and each alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, whether alone or part of another group, is optionally substituted.