Androgen receptor modulator compounds and methods

A method for modulating an activity of an androgen receptor comprising contacting an androgen receptor with a compound selected from Formula I, Formula II, Formula III, Formula IV, Formula V and Formula VI:

• wherein:
• R1 and R2 are each independently selected from hydrogen, F, Cl, Br, I, ORA, SRA, NO2, CN, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, CORA, CO2RA, CONRARB, SORA, SO2RA, and SO2NRARB, NHCORA, and NHCONRARB, provided that at least one of R1 and R2 is not hydrogen;
• R3, R3a, R4, and R5 are each independently selected from hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
• wherein if R1 is NO2 and R3a is F, then at least one of R2 and R4 and R5 is not hydrogen;
• and wherein if R1 is NO2 and R3 is F, then Z is not O;
• R6, R7, R10, and R11 are each independently selected from hydrogen, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C1-C6 heterohaloalkyl, an optionally substituted C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 alkenyl;
• R6a and R7a are each independently selected from hydrogen, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C1-C6 heterohaloalkyl, an optionally substituted C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 alkenyl;
• or R6a and R7a together form a carbonyl;
• R8 and R9 are each independently selected from hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 alkenyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C2-C8 haloalkenyl, C1-C8 heteroalkyl, an optionally substituted C2-C8 heteroalkenyl, an optionally substituted C2-C8 alkynyl, an optionally substituted C2-C8 haloalkynyl, an optionally substituted C2-C8 heteroalkynyl, an optionally substituted C1-C6 heterohaloalkyl, an optionally substituted C1-C6 heterohaloalkenyl, an optionally substituted C1-C6 heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, CORA, CO2RA and (CH2)mRC;
• R12 and R13 are each independently selected from hydrogen, F, Cl, ORA, NRARB, SRA, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C2-C6 alkynyl, an optionally substituted C1-C6 heterohaloalkyl, an optionally substituted C1-C6 heterohaloalkenyl, an optionally substituted C1-C6 heterohaloalkynyl, an optionally substituted C2-C6 alkenyl, and (CH2)mRC;
• R14 and R15 are each independently selected from hydrogen, F, Cl, Br, I, ORA, SRA, NO2, CN, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, NHCORA, NHCONRARB, CORA, CO2RA, CONRARB, SORA, SO2RA, and SO2NRARB;
• R16 and R17 are each independently selected from hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
• R18 and R19 are each independently selected from hydrogen, F, Cl, Br, I, ORA, SRA, NO2, CN, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, NHCORA, NHCONRARB, CORA, CO2RA, CONRARB, SORA, SO2RA, and SO2NRARB;
• R20 and R21 are each independently selected from hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
• wherein if R18 is NO2 and X is O, then at least one of R19, R20, and R21 is not hydrogen, and wherein if R19 is NO2 and X is O, then at least one of R19, R20, and R21 is not hydrogen;
• R22 is selected from hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, CORE, CO2RA, CONRARB, SO2RA, an optionally substituted aryl, an optionally substituted heteroaryl, CH2CH(RD)ORA, CH2CH(RD)NRARB, and (CH2)mRC, wherein the optionally substituted aryl or optionally substituted heteroaryl is optionally substituted with a substituent selected from F, Cl, Br, I, CN, ORA, NO2, NRARB, SRA, SORA, SO2RA, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
• R23 and R24 are each independently selected from hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 alkenyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C2-C8 haloalkenyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C2-C8 heteroalkenyl, an optionally substituted C2-C8 alkynyl, an optionally substituted C2-C8 haloalkynyl, an optionally substituted C2-C8 heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, and (CH2)mRC;
• or R23 and R24 together form a carbonyl group, provided that if R18 is NO2 and X is NH, then R23 and R24 do not together form a carbonyl group;
• or
• R22 and R23 are optionally linked to form a ring;
• or
• R23 and R25 are optionally linked to form a ring;
• X is selected from O, S, CRARB, NRD, and a bond;
• wherein if X is CRARB or a bond, then R25 and R26 are each independently selected from a halogen, ORA, NRARB, hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 alkenyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C2-C8 haloalkenyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C2-C8 heteroalkenyl, an optionally substituted C2-C8 alkynyl, an optionally substituted C2-C8 haloalkynyl, an optionally substituted C2-C8 heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH2)mRC;
• or R25 and R26 together form a carbonyl group;
• and wherein if X is O, S, or NRD, then R25 and R26 are each independently selected from hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 alkenyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C2-C8 haloalkenyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C2-C8 heteroalkenyl, an optionally substituted C2-C8 alkynyl, an optionally substituted C2-C8 haloalkynyl, an optionally substituted C2-C8 heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH2)mRC;
• or R25 and R26 together form a carbonyl group;
• R25 is selected from a halogen, ORA, NRARB, hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 alkenyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C2-C8 haloalkenyl, an optionally substituted C1-C8 heteroalkyl, an optionally substituted C2-C8 heteroalkenyl, an optionally substituted C2-C8 alkynyl, an optionally substituted C2-C8 haloalkynyl, an optionally substituted C2-C8 heterohaloalkenyl, an optionally substituted C2-C8 heterohaloalkynyl, an optionally substituted C2-C8 heteroalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH2)mRC;
• RA and RB are each independently selected from hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
• RC is selected from an optionally substituted aryl and an optionally substituted heteroaryl that is optionally with a substituent selected from F, Cl, Br, I, CN, ORA, NO2, NRARB, SRA, SORA, SO2RA, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
• RD is selected from hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
• Z is selected from O, S, CRARB, and NRD;
• n is 0, 1, or 2;
• and
• m is 1 or 2,
• or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.