Inhibitor of apoptosis protein (iap) antagonists

A compound having the structure of Formula B-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), —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• when X1 is selected from N—RA, then X2 is C═O, or CR2cR2d, and X3 is CR2aR2b;
• or
• when X1 is selected from S, S(O) and S(O)2, then X2 is CR2cR2d, and X3 is CR2aR2b;
• or
• when X1 is O, then X2 is selected from CR2cR2d and N—RA, and X3 is CR2aR2b;
• or:
• when X1 is CH2, then X2 is selected from O, N—RA, S, S(O), and S(O)2, and X3 is CR2aR2b;
• or:
• X1 is CR2eR2f and X2 is CR2cR2d, and R2e and R2c together form a bond, and X3 is CR2aR2b;
• or:
• X1 and X3 are both CH2 and X2 is C═O, C═C(RC)2, or C═NRC;
• where each RC is independently selected from H, —CN, —OH, alkoxy, 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), or —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• or:
• X1 and X2 are independently selected from C and N, and are members of a fused substituted or unsubstituted saturated or partially saturated 3-10 membered cycloalkyl ring, a fused substituted or unsubstituted saturated or partially saturated 3-10 membered heterocycloalkyl ring, a fused substituted or unsubstituted 5-10 membered aryl ring, or a fused substituted or unsubstituted 5-10 membered heteroaryl ring, and X3 is CR2aR2b;
• or:
• X2 and X3 are independently selected from C and N, and are members of a fused substituted or unsubstituted saturated or partially saturated 3-10 membered cycloalkyl ring, a fused substituted or unsubstituted saturated or partially saturated 3-10 membered heterocycloalkyl ring, a fused substituted or unsubstituted 5-10 membered aryl ring, or a fused substituted or unsubstituted 5-10 membered heteroaryl ring, and X1 is CR2eR2f;
• 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(R8a)(R8d);
• provided that W1 and W2 are not both O, or both S;
• R2a, R2b, R2c, R2d R2e, and R2f are independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, 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), or —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, C1-C3heteroalkyl 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, C1-C6heteroalkyl, 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), or -(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, C1-C6heteroalkyl, 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, heteroalkyl, fused ring, spirocycle, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is substituted with 1-3 R9;
• and
• each R9 is independently selected from halogen, —OH, —SH, (C═O), CN, C1-C4alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C1-C4 fluoroalkoxy, —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.

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), —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• when X1 is selected from N—RA, S, S(O) and S(O)2, then X2 is CR2cR2d, and X3 is CR2aR2b;
• or
• when X1 is O, then X2 is selected from CR2cR2d and N—RA, and X3 is CR2aR2b;
• or:
• when X1 is CH2, then X2 is selected from O, N—RA, S, S(O), and S(O)2, and X3 is CR2aR2b;
• or:
• X1 is CR2eR2f and X2 is CR2cR2d, and R2e and R2c together form a bond, and X3 is CR2aR2b;
• or:
• X1 and X2 are independently selected from C and N, and are members of a fused substituted or unsubstituted saturated or partially saturated 3-10 membered cycloalkyl ring, a fused substituted or unsubstituted saturated or partially saturated 3-10 membered heterocycloalkyl ring, a fused substituted or unsubstituted 5-10 membered aryl ring, or a fused substituted or unsubstituted 5-10 membered heteroaryl ring, and X3 is CR2aR2b;
• or:
• X2 and X3 are independently selected from C and N, and are members of a fused substituted or unsubstituted saturated or partially saturated 3-10 membered cycloalkyl ring, a fused substituted or unsubstituted saturated or partially saturated 3-10 membered heterocycloalkyl ring, a fused substituted or unsubstituted 5-10 membered aryl ring, or a fused substituted or unsubstituted 5-10 membered heteroaryl ring, and X1 is CR2eR2f;
• 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(R8s)(R8d);
• provided that W1 and W2 are not both O, or both S;
• R2a, R2b, R2c, R2d R2e, and R2f are independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, 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), or —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, C1-C3heteroalkyl 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, C1-C6heteroalkyl, 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), -(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, C1-C6heteroalkyl, 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, heteroalkyl, fused ring, spirocycle, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is substituted with 1-3 R9;
• and
• each R9 is independently selected from halogen, —OH, —SH, (C═O), CN, C1-C4alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C1-C4 fluoroalkoxy, —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.

A compound having the structure of Formula D-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), —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• when X1 is selected from N—RA, S, S(O) and S(O)2, then X2 is CR2cR2d, and X3 is CR2aR2b;
• or
• when X1 is O, then X2 is selected from CR2cR2d and N—RA, and X3 is CR2aR2b;
• or:
• when X1 is CH2, then X2 is selected from O, N—RA, S, S(O), and S(O)2, and X3 is CR2aR2b;
• or:
• X1 is CR2eR2f and X2 is CR2cR2d, and R2e and R2c together form a bond, and X3 is CR2aR2b;
• or:
• X1 and X3 are both CH2 and X2 is C═O, C═C(RC)2, or C═NRC;
• where each RC is independently selected from H, —CN, —OH, alkoxy, 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), or —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• or:
• X1 and X2 are independently selected from C and N, and are members of a fused substituted or unsubstituted saturated or partially saturated 3-10 membered cycloalkyl ring, a fused substituted or unsubstituted saturated or partially saturated 3-10 membered heterocycloalkyl ring, a fused substituted or unsubstituted 5-10 membered aryl ring, or a fused substituted or unsubstituted 5-10 membered heteroaryl ring, and X3 is CR2aR2b;
• or:
• X2 and X3 are independently selected from C and N, and are members of a fused substituted or unsubstituted saturated or partially saturated 3-10 membered cycloalkyl ring, a fused substituted or unsubstituted saturated or partially saturated 3-10 membered heterocycloalkyl ring, a fused substituted or unsubstituted 5-10 membered aryl ring, or a fused substituted or unsubstituted 5-10 membered heteroaryl ring, and X1 is CR2eR2f;
• W1 is O, S, N—RA, or C(R8a)(R8b);
• W2 is O, S, N—RA, or C(R8c)(R8d);
• W3 is O, S, N—RA, or C(R8e)(R8f);
• provided that the ring comprising W1, W2 and W3 does not comprise two adjacent oxygen atoms or sulfur atoms;
• RA is H, C1-C6alkyl, —C(═O)C1-C6alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• 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), —C1-C6alkyl-(substituted or unsubstituted heteroaryl);
• R2a, R2b, R2c, R2d R2e, and R2f are independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, 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), or —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, C1-C3heteroalkyl 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, C1-C6heteroalkyl, 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), -(substituted or unsubstituted heteroaryl)-(substituted or unsubstituted heteroaryl);
• p is 0, 1 or 2;
• R8a, R8b, R8c, R8d, R8e and R8f are independently selected from H, C1-C6alkyl, C1-C6fluoroalkyl, C1-C6 alkoxy, C1-C6heteroalkyl, and substituted or unsubstituted aryl;
• or:
• R8a, R8d, R8e and R8f are as defined above, and R8b and R8c together form a bond;
• or:
• R8a, R8b, R8d, and R8f are as defined above, and R8c and R8e together form a bond;
• or:
• R8a, R8d, R8e and R8f 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:
• R8a, R8b, R8d, and R8f are as defined above, and R8c and R8e 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, R8d, R8e and R8f 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, R8b, R8e and R8f 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;
• or:
• R8a, R8b, R8c, and R8d are as defined above, and R8e and R8f 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, heteroalkyl, fused ring, spirocycle, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is substituted with 1-3 R9;
• and
• each R9 is independently selected from halogen, —OH, —SH, (C═O), CN, C1-C4alkyl, C1-C4 fluoroalkyl, C1-C4 alkoxy, C1-C4 fluoroalkoxy, —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.