Inhibitor of apoptosis protein (IAP) antagonists

A compound having the structure of Formula C-I, pharmaceutically acceptable salt, N-oxide, racemate, or stereoisomer thereof:

• wherein,
• R1 is H, C1-C6alkyl, C3-C6cycloalkyl, —C1-C6alkyl-(substituted or unsubstituted C3-C6cycloalkyl), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C1-C6alkyl-(substituted or unsubstituted aryl), or —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• X1 is N—RA;
• X2 is CR2cR2d;
• X3 is CR2aR2b;
• RA is H, C1-C6alkyl, —C(═O)C1-C6alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• W1 is O, S, N—Ra, or C(R8a)(R8b);
• W2 is O, S, N—Ra, or C(R8c)(R8d);
• provided that W1 and W2 are not both O, or both S;
• R2a, R2b, R2c, and R2d are independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C5heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C1-C6alkyl-(substituted or unsubstituted C3-C6cycloalkyl), —C1-C6alkyl-(substituted or unsubstituted C2-C5heterocycloalkyl), —C1-C6alkyl-(substituted or unsubstituted aryl), —C1-C6alkyl-(substituted or unsubstituted heteroaryl), and —C(═O)RB;
• RB is substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C5heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C1-C6alkyl-(substituted or unsubstituted C3-C6cycloalkyl), —C1-C6alkyl-(substituted or unsubstituted C2-C5heterocycloalkyl), —C1-C6alkyl-(substituted or unsubstituted aryl), —C1-C6alkyl-(substituted or unsubstituted heteroaryl), or —NRDRE;
• RD and RE are independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C5heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C1-C6alkyl-(substituted or unsubstituted C3-C6cycloalkyl), —C1-C6alkyl-(substituted or unsubstituted C2-C5heterocycloalkyl), —C1-C6alkyl-(substituted or unsubstituted aryl), and —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• m is 0, 1, or 2;
• —U— is —NHC(═O)—, —C(═O)NH—, —NHS(═O)2—, —S(═O)2NH-, —NHC(═O)NH—, —NH(C═O)O-, —O(C═O)NH-, or —NHS(═O)2NH-;
• R3 is C1-C3alkyl or C1-C3fluoroalkyl;
• R4 is —NHR5, —N(R5)2, —N+(R5)3, or —OR5;
• each R5 is independently selected from H, C1-C3alkyl, C1-C3haloalkyl, and —C1-C3alkyl-(C3-C5cycloalkyl);
• or:
• R3 and R5 together with the atoms to which they are attached form a substituted or unsubstituted 5-7 membered ring;
• or:
• R3 is bonded to a nitrogen atom of U to form a substituted or unsubstituted 5-7 membered ring;
• R6 is —NHC(═O)R7, —C(═O)NHR7, —NHS(═O)2R7, —S(═O)2NHR7;
• —NHC(═O)NHR7, —NHS(═O)2NHR7, -(C1-C3alkyl)-NHC(═O)R7, -(C1-C3alkyl)-C(═O)NHR5, -(C1-C3alkyl)-NHS(═O)2R7, -(C1-C3alkyl)-S(═O)2NHR7;
• -(C1-C3alkyl)-NHC(═O)NHR7, -(C1-C3alkyl)-NHS(═O)2NHR7, substituted or unsubstituted C2-C10heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• each R7 is independently selected from C1-C6alkyl, C1-C6haloalkyl, a substituted or unsubstituted C3-C10cycloalkyl, a substituted or unsubstituted C2-C10heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C1-C6alkyl-(substituted or unsubstituted C3-C10cycloalkyl), —C1-C6alkyl-(substituted or unsubstituted C2-C10heterocycloalkyl, —C1-C6alkyl-(substituted or unsubstituted aryl), —C1-C6alkyl-(substituted or unsubstituted heteroaryl), —(CH2)P—CH(substituted or unsubstituted aryl)2, —(CH2)P—CH(substituted or unsubstituted heteroaryl)2, —(CH2)P—CH(substituted or unsubstituted aryl)(substituted or unsubstituted heteroaryl), -(substituted or unsubstituted aryl)-(substituted or unsubstituted aryl), -(substituted or unsubstituted aryl)-(substituted or unsubstituted heteroaryl), -(substituted or unsubstituted heteroaryl)-(substituted or unsubstituted aryl), and -(substituted or unsubstituted heteroaryl)-(substituted or unsubstituted heteroaryl);
• p is 0, 1, or 2;
• R8a, R8b, R8c, and R8d are independently selected from H, C1-C6alkyl, C1-C6fluoroalkyl, C1-C6 alkoxy, and substituted or unsubstituted aryl;
• or:
• R8a and R8d are as defined above, and R8b and R8c together form a bond;
• or:
• R8a and R8d are as defined above, and R8b and R8c together with the atoms to which they are attached form a substituted or unsubstituted fused 5-7 membered saturated, or partially saturated carbocyclic ring or heterocyclic ring comprising 1-3 heteroatoms selected from S, O, and N, a substituted or unsubstituted fused 5-10 membered aryl ring, or a substituted or unsubstituted fused 5-10 membered heteroaryl ring comprising 1-3 heteroatoms selected from S, O, and N;
• or:
• R8c and R8d are as defined above, and R8a and R8b together with the atoms to which they are attached form a substituted or unsubstituted saturated, or partially saturated 3-7 membered spirocycle or heterospirocycle comprising 1-3 heteroatoms selected from S, O, and N;
• or:
• R8a and R8b are as defined above, and R8c and R8d together with the atoms to which they are attached form a substituted or unsubstituted saturated, or partially saturated 3-7 membered spirocycle or heterospirocycle comprising 1-3 heteroatoms selected from S, O, and N;
• where each substituted alkyl, fused ring, spirocycle, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is substituted with 1-3 R9;
• each R9 is independently selected from halogen, —OH, —SH, (C═O), CN, C1-C4alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C1-C4fluoroalkoxy, —NH2, —NH(C1-C4alkyl), —NH(C1-C4alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)C1-C3alkyl, —S(═O)2CH3, —NH(C1-C4alkyl)-OH, —NH(C1-C4alkyl)-O—(C1-C4alkyl), —O(C1-C4alkyl)-NH2, —O(C1-C4alkyl)-NH—(C1-C4alkyl), and —O(C1-C4alkyl)-N—(C1-C4alkyl)2;
• or two R9 together with the atoms to which they are attached form a methylene dioxy or ethylene dioxy ring substituted or unsubstituted with halogen, —OH, or C1-C3alkyl;
• where each heterocycloalkyl is independently selected from a monocyclic, fused bicyclic, and bridged bicyclic ring, where the heterocycloalkyl has from 2 to 10 carbons in the ring and heteroatoms selected from O, N, or S;
• and
• where each heteroaryl is independently selected from a monocyclic and fused bicyclic ring, where the heteroaryl is a 5- to 14-membered ring system comprising one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of O, N, or S.