Androgen receptor modulators and methods for their use

A compound having the structure (I-A):

• or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein:
• A and B are each independently aryl or heteroaryl;
• X is a bond, —(CR8R9)t—, —O—, —C(═O)—, —S(O)p—, —NR10—, —CONR10—, —SO2NR10—, or —NR10SO2—;
• Y and Z are each independently a bond, —(CR8R9)t—, —O—, —S(O)p—, —NR10—, —CONR10—, —NR10CO—, —SO2NR10—, or —NR10SO2—;
• V is a bond, optionally substituted —(CR11R12)m—, —C(═O)—, —N(R10)CO—, —CONR10—, or —NSO2R10—;
• R is —(CR4aR4b)—(CR5aR5b)—W or W;
• W is hydrogen, halogen, —CF3, —CF2R10, —CN, —OR13, —NR13R14, optionally substituted —CONR13R14, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• D is —(CR1aR1b)q—, —O—, or —NR10—;
• L is —(CR2aR2b)—R3 or -E-R3;
• E is —(CR2aR2b)g—, —O—, —NR10—, or —NR10—(CR2aR2b)g—;
• R1a, R1b, R2a, and R2b are each independently hydrogen, halogen, hydroxy, optionally substituted C1-6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-6 alkoxy, optionally substituted —OCO(C1-C6 alkyl), —NR13R14, optionally substituted —(C1-C6 alkyl)-NR13R14, NR14COR16, optionally substituted —(C1-C6 alkyl)-NR14COR16, —CONR14R15, optionally substituted —(C1-C6 alkyl-CONR14R15, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R1a and R1b taken together form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R2a and R2b taken together form a CO, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R1a, R1b, R2a and R2b taken together form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R4a, R4b, R5a, and R5b are each independently hydrogen, halogen, hydroxy, optionally substituted C1-6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-6 alkoxy, optionally substituted —OCO(C1-C6 alkyl), —NR13R14, optionally substituted —(C1-C6 alkyl)-NR13R14, NR14COR16, optionally substituted —(C1-C6 alkyl)-NR14COR16, —CONR14R15, optionally substituted —(C1-C6 alkyl-CONR14R15, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R4a and R4b taken together form a CO, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R4a, R4b, R5a and R5b taken together form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R3 is absent, hydrogen, —CN, —CF3, —OH, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted —OR15, optionally substituted C1-C6 alkoxy, —NH2, —NR16R17, —NR16COR18, NR16S(O)pR18, —CONR14R15, —SONR14R15, —SO2NR14R15, optionally substituted —S(O)pR18, —N3, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R2a, R2b and R3 taken together form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R2a and R10 taken together form an optionally substituted heterocyclyl;
• R6 and R7 are each independently H, methyl, methoxy, —CN, F, Cl, Br, I, 123I, —CF3, —OH, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted —(C1-C6 alkyl)-(C1-C6 alkoxy), optionally substituted —(C1-C6 alkyl)-OH, —NR13R14, optionally substituted —(C1-C6 alkyl-NR13R14, —NR14SO2R16, optionally substituted —(C1-C6 alkyl)NR14SO2R16, —NR14COR16, optionally substituted —(C1-C6 alkyl)-NR14COR16, —CONR14R15, optionally substituted —(C1-C6 alkyl)-CONR14R15, —SO2NR14R15, optionally substituted —(C1-C6 alkyl)-SO2NR14R15, optionally substituted —SO2R16, or optionally substituted —(C1-C6 alkyl)-SO2R16, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R8, R9, R11 and R12 are each independently hydrogen, —OH, halogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkylamino, optionally substituted —OCO(C1-C6 alkyl), —NR13R14, optionally substituted —(C1-C6 alkyl)-NR13R14, —NR14COR16, optionally substituted —(C1-C6 alkyl)-NR14COR16, —CONR14R15, optionally substituted —(C1-C6 alkyl-CONR14R15, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R8 and R9 taken together form an optionally substituted carbocyclyl or optionally substituted heterocyclyl;
• or alternatively, R11 and R12, on a same carbon atom or a different carbon atom, taken together form an optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R10 is hydrogen, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, —CO(C1-C6 alkyl), optionally substituted C1-C6 alkylamino, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• R13, R14, R15, R16, R17 and R18 are each independently hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl;
• or alternatively, R14 and R15 are taken together to form an optionally substituted heterocyclyl, or optionally substituted heteroaryl;
• or alternatively, R16 and R17 are taken together to form an optionally substituted heterocyclyl, or optionally substituted heteroaryl;
• m is 0, 1, 2, 3, or 4;
• each n is independently 0, 1 or 2;
• each p is independently 0, 1 or 2;
• q is 0, 1 or 2;
• each g is independently 0, 1, 2, 3, or 4;
• and
• each t is independently 1 or 2.