Androgen Receptor Modulator Compounds and Methods
First Claim
Patent Images
1. A compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI:
- wherein;
R1 and R2 each independently is selected from among 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 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
provided that if R1 is NO2 and R3a is F, then at least one of R2 and R4 and R5 is not hydrogen; and
provided that if R1 is NO2 and R3 is F, then Z is not O;
R6, R7, R10, and R11 each independently is selected from among hydrogen, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 alkenyl;
R6a and R7a each independently is selected from among hydrogen, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 alkenyl;
or R6a and R7a together form a carbonyl;
R8 and R9 each independently is selected from among 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 aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, and (CH2)mRC;
R12 and R13 each independently is selected from among 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 C2-C6 alkenyl, and (CH2)mRC;
R14 and R15 each independently is selected from among 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 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
R18 and R19 each independently is selected from among 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 each independently is selected from among 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 C, then at least one of R18, R20, and R21 is not hydrogen;
R22 is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, COR6, 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 among 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 each independently is selected from among 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;
R22 and R23 are optionally linked to form a ring;
R23 and R25 are optionally linked to form a ring;
X is selected from among O, S, CRARB, NRD, and a bond;
wherein if X is CRARB or a bond, then R25 and R26 each independently is selected from among 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 selected from among O, S, or NRD, then R25 and R26 each independently is selected from among 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;
RA and RB each independently is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
RC is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among 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 among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
Z is selected from among 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.
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Abstract
Provided herein are compounds having a structure selected from among Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V) and Formula (VI) that are androgen receptor modulators and/or androgen receptor binding agents. Also disclosed are methods of making and using such compounds, including, but not limited to, using such compounds for treating various conditions.
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Citations
82 Claims
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1. A compound of Formula I, Formula II, Formula III, Formula IV, Formula V, or Formula VI:
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wherein;
R1 and R2 each independently is selected from among 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 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
provided that if R1 is NO2 and R3a is F, then at least one of R2 and R4 and R5 is not hydrogen; and
provided that if R1 is NO2 and R3 is F, then Z is not O;
R6, R7, R10, and R11 each independently is selected from among hydrogen, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 alkenyl;
R6a and R7a each independently is selected from among hydrogen, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 haloalkyl, an optionally substituted C1-C6 heteroalkyl, an optionally substituted C2-C6 alkynyl, and an optionally substituted C2-C6 alkenyl;
or R6a and R7a together form a carbonyl;
R8 and R9 each independently is selected from among 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 aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, and (CH2)mRC;
R12 and R13 each independently is selected from among 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 C2-C6 alkenyl, and (CH2)mRC;
R14 and R15 each independently is selected from among 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 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
R18 and R19 each independently is selected from among 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 each independently is selected from among 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 C, then at least one of R18, R20, and R21 is not hydrogen;
R22 is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, COR6, 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 among 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 each independently is selected from among 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;
R22 and R23 are optionally linked to form a ring;
R23 and R25 are optionally linked to form a ring;
X is selected from among O, S, CRARB, NRD, and a bond;
wherein if X is CRARB or a bond, then R25 and R26 each independently is selected from among 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 selected from among O, S, or NRD, then R25 and R26 each independently is selected from among 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;
RA and RB each independently is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
RC is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among 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 among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
Z is selected from among 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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 82)
wherein;
R1 and R2 each independently is selected from among 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, R4, and R5 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
provided that if R1 is NO2 and R3 is F, then Z is not O;
R6, R7, and R10 each independently is selected from among 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 each independently is selected from among 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;
R9 is selected from among hydrogen, an optionally substituted C1-C8 alkyl, an optionally substituted C2-C8 alkenyl, an optionally substituted C1-C8 haloalkyl, an optionally substituted C1-C6 heterohaloalkyl, 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 C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, CORA, CO2RA and (CH2)mRC;
R12 and R13 each independently is selected from among 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 C1-C6 heterohaloalkyl, an optionally substituted C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted C2-C6 alkynyl, an optionally substituted C2-C6 alkenyl, and (CH2)mRC;
R14 and R15 each independently is selected from among 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 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
RA and RB each independently is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
RC is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among 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 among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
Z is selected from among O, S, CRARB, and NRD;
n is 0, 1, or 2; and
m is 1 or 2.
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3. The compound of claim 1, wherein R1 is NO2 or CN.
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4. The compound of claim 1, wherein R1 is NO2.
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5. The compound of claim 1, wherein R1 is CN.
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6. The compound of claim 1, wherein R2 is an optionally substituted C1-C4 alkyl or an optionally substituted C1-C4 haloalkyl.
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7. The compound of claim 1, wherein R2 is C1-C4 alkyl or trifluoromethyl.
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8. The compound of claim 1, wherein R3, R4, and R5 each independently is selected from among hydrogen, F, Cl, and an optionally substituted C1-C4 alkyl.
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9. The compound of claim 1, wherein R3 is hydrogen.
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10. The compound of claim 1, wherein R4 is hydrogen.
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11. The compound of claim 1, wherein R5 is hydrogen.
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12. The compound of claim 1, wherein R6a and R7a each independently is selected from among hydrogen, an optionally substituted C1-C6 alkyl, and an optionally substituted C1-C6 heterohaloalkyl or R6a and R7a together form a carbonyl.
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13. The compound of claim 1, wherein R6a is hydrogen.
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14. The compound of claim 1, wherein R7a is hydrogen or an optionally substituted C1-C6 alkyl.
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15. The compound of claim 1, wherein R7a is hydrogen or methyl.
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16. The compound of claim 1, wherein R7a is hydrogen.
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17. The compound of claim 1, wherein R7a is methyl.
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18. The compound of claim 1, wherein R6a and R7a together form a carbonyl.
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19. The compound of claim 1, wherein R10 is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 heterohaloalkyl and (CH2)mRC.
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20. The compound of claim 1, wherein R10 is hydrogen.
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21. The compound of claim 1, wherein R9 is selected from among hydrogen, F, Cl, Br, I, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C6 heterohaloalkyl, CORA, CO2RA, CH(RD)ORA, and CH(RD)NRARB.
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22. The compound of claim 1, wherein R9 is hydrogen, formyl, hydroxy C1-C6alkyl, hydroxyhalo C1-C6alkyl, C1-C6alkylsilyloxy C1-C6alkyl, C1-C6alkoxycarbonyl, amino C1-C6alkyl, carboxy, or C1-C6alkylcarbonyloxyC1-C6alkyl.
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23. The compound of claim 1, wherein R9 is hydrogen, formyl, hydroxymethyl, 1-hydroxy-2,2,2-trifluoromethyl, tributylsilyloxymethyl, ethoxycarbonyl, aminomethyl, carboxy, or acetyoxymethyl.
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24. The compound of claim 1, wherein R12 and R13 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 heterohaloalkyl and (CH2)mRC.
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25. The compound of claim 1, wherein R13 is hydrogen, F, OH or benzyl.
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26. The compound of claim 1 of formula IIA:
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27. The compound of claim 1 of formula IIB:
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28. The compound of claim 1, wherein R1 is NO2 or CN;
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R2 is hydrogen, optionally substituted C1-C4 alkyl or an optionally substituted C1-C4 haloalkyl;
R3, R4, and R5 each independently is selected from among hydrogen, F, Cl, and an optionally substituted C1-C4 alkyl;
R6a and R7a each independently is selected from among hydrogen and an optionally substituted C1-C6 alkyl;
an optionally substituted C1-C6 heterohaloalkyl, or R6a and R7a together form a carbonyl;
R9 is selected from among hydrogen, F, Cl, Br, I, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C6 heterohaloalkyl, CORA, CO2RA, CH(RD)ORA, and CH(RD)NRARB;
R10 is hydrogen; and
R12 and R13 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C6 alkyl, an optionally substituted C1-C6 heterohaloalkyl and (CH2)mRC.
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29. The compound of claim 1, wherein R1 is NO2 or CN;
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R2 is hydrogen or trifluoromethyl;
R3, R4, and R5 each is hydrogen;
R7a is hydrogen or methyl and R6a is hydrogen;
or R6a and R7a together form a carbonyl;
R9 is selected from among hydrogen, formyl, hydroxymethyl, 1-hydroxy-2,2,2-trifluoromethyl, tributylsilyloxymethyl, ethoxycarbonyl, aminomethyl, carboxy, and acetyloxymethyl;
R10 is hydrogen;
R12 is hydrogen; and
R13 is selected from among hydrogen, F, OH and benzyl.
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30. The compound of claim 1, wherein the compound is selected from among:
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31. The compound of claim 30, wherein R7a is an optionally substituted C1-C6 heterohaloalkyl.
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32. The compound of claim 30, wherein R9 is an optionally substituted C1-C6 heterohaloalkyl.
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33. The compound of claim 30, wherein R13 is an optionally substituted C1-C6 heterohaloalkyl.
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34. The compound of claim 30, wherein the compound is:
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35. The compound of claim 30, wherein the compound is:
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36. The compound of claim 1 of Formula IIC or Formula IID:
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37. The compound of claim 36, wherein R1 is NO2;
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R2 is hydrogen or haloalkyl;
R3, R4, R5, R6a, R7a, R9, R12, and R13 each is hydrogen; and
R9 is selected from among CO2RA, CH(RD)ORA, and CH(RD)NRARB.
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38. The compound of claim 36, wherein R1 is NO2;
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R2 is hydrogen or trifluoromethyl;
R3, R4, R5, R6a, R7a, R9, R12, and R13 each is hydrogen; and
R9 is selected from among hydroxymethyl, ethoxycarbonyl and acetyoxymethyl.
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39. The compound of claim 1, wherein the compound is:
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40. The compound of claim 1, wherein the compound is:
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41. The compound of claim 1, wherein the compound is:
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42. The compound of claim 1 of Formula V or Formula VI:
wherein R18 and R19 each independently is selected from among 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 each independently is selected from among 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 C, then at least one of R18, R20, and R21 is not hydrogen;
R22 is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, an optionally substituted C1-C4 heteroalkyl, an optionally substituted C1-C4 heterohaloalkyl, an optionally substituted C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, COR6, 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 among 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 each independently is selected from among 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 C2-C8 heterohaloalkenyl, an optionally substituted C2-C8 heterohaloalkynyl, 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;
orR22 and R23 are optionally linked to form a ring;
orR23 and R25 are optionally linked to form a ring;
R25 is selected from among 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;
X is selected from among O, S, CRARB, NRD, and a bond;
wherein if X is CRARB or a bond, then R25 and R26 each independently is selected from among 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 C1-C6 heterohaloalkyl, an optionally substituted C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, 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 each independently is selected from among 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 C1-C6 heterohaloalkyl, an optionally substituted C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, and (CH2)mRC;
or R25 and R26 together form a carbonyl group;
RA and RB each independently is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
RC is selected from among an optionally substituted aryl and an optionally substituted heteroaryl that is optionally substituted with a substituent selected from among 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 among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
Z is selected from among O, S, CRARB, and NRD;
n is 0, 1, or 2; and
m is 1 or 2.
-
43. The compound of claim 1 of Formula V, wherein n is 1:
-
44. The compound of claim 1 of Formula V, wherein X is CRARB, and RA and RB each is hydrogen:
-
45. The compound of claim 1 of Formula V, wherein X is O:
-
46. The compound of claim 1, wherein R18 and R19 each independently is selected from among hydrogen, NO2, and an optionally substituted C1-C4 alkyl;
-
R22 is hydrogen, an optionally substituted C1-C4 alkyl and an optionally substituted C1-C4 haloalkyl;
R23 and R24 each independently is hydrogen or an optionally substituted C1-C4 alkyl; and
R25 and R26 each is hydrogen.
-
-
47. The compound of claim 1, wherein R18 is NO2.
-
48. The compound of claim 1, wherein R19 is NO2.
-
49. The compound of claim 1, wherein R22 is hydrogen, heterohaloalkyl or haloalkyl.
-
50. The compound of claim 1, wherein R22 is hydrogen or trifluoroethyl.
-
51. The compound of claim 1, wherein R23 and R24 each independently is hydrogen or methyl.
-
52. The compound of claim 1 of Formula VI:
-
53. The compound of claim 52, wherein R18 is NO2.
-
54. The compound of claim 53, wherein R19 is NO2.
-
55. The compound of claim 52, wherein R22 is hydrogen, haloalkyl, an optionally substituted C1-C4 heteroalkyl or an optionally substituted C1-C4 heterohaloalkyl.
-
56. The compound of claim 52, wherein R22 is hydrogen or trifluoroethyl.
-
57. The compound of claim 52, wherein R23 is hydrogen, an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted C1-C4 alkyl.
-
58. The compound of claim 1, wherein R25 is hydrogen, methyl or methoxyphenyl.
-
59. The compound of claim 1 of Formula III:
wherein;
R1 and R2 each independently is selected from among 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;
R3a, R4, and R5 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
provided that if R1 is NO2 and R3a is F, then at least one of R2 and R4 and R5 is not hydrogen;
R6, R7, R10, and R11 each independently is selected from among 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;
R8 and R9 each independently is selected from among 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 C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, and (CH2)mRC;
R14 and R15 each independently is selected from among 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 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
RA and RB each independently is selected from among hydrogen, an optionally substituted C1-C4 alkyl an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
RC is selected from among an optionally substituted aryl and a heteroaryl that is optionally substituted with a substituent selected from among 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 among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl; and
m is 1 or 2;
provided that at least one of R6, R7, R10, and R11 is other than hydrogen and at least one of R8 and R9 is other than hydrogen, alkyl, haloalkyl, alkenyl, and alkynyl.
-
60. The compound of claim 59, wherein at least one of R6, R7, R10, and R11 is other than hydrogen and at least one of R8 and R9 is heterohaloalkyl.
-
61. The compound of claim 1 of Formula I:
wherein;
R1 and R2 each independently is selected from among 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;
R3a, R4, and R5 each independently is selected from among hydrogen, F, Cl, ORA, an optionally substituted C1-C4 alkyl, and an optionally substituted C1-C4 haloalkyl;
provided that if R1 is NO2 and R3a is F, then at least one of R2 and R4 and R5 is not hydrogen;
R6, R7, R10, and R11 each independently is selected from among 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;
R8 and R9 each independently is selected from among 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 C2-C6 heterohaloalkenyl, an optionally substituted C2-C6 heterohaloalkynyl, an optionally substituted aryl, an optionally substituted heteroaryl, CH(RD)ORA, CH(RD)NRARB, and (CH2)mRC;
RA and RB each independently is selected from among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl;
RC is selected from among an optionally substituted aryl and a heteroaryl that is optionally substituted with a substituent selected from among 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 among hydrogen, an optionally substituted C1-C4 alkyl, an optionally substituted C1-C4 haloalkyl, and an optionally substituted C1-C4 heteroalkyl; and
m is 1 or 2;
provided that at least one of R6, R7, R10, and R11 is other than hydrogen and at least one of R8 and R9 is heterohaloalkyl.
-
62. A compound of claim 1, wherein the compound is selected from among:
-
N,N-bis(2,2,2-trifluoroethyl)-3-methyl-4-nitroaniline (compound
101);
N,N-bis(2,2,2-trifluoroethyl)-4-nitroaniline (compound
102);
4-(Bis(2,2,2-trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile (compound
103);
(5R)—
N-(4-nitrophenyl)-5-(dimethyl-tert-butylsilyloxymethyl)-2-pyrrolidone (compound
104);
(5R)—
N-(4-nitrophenyl)-5-(hydroxymethyl)-2-pyrrolidone (compound
105);
(2R)—
N-(4-nitro-3-trifluoromethylphenyl)-2-(dimethyl-tert-butylsilyloxymethyl)pyrrolidine (compound
106);
(2R)—
N-(4-nitro-3-trifluoromethylphenyl)-2-(hydroxymethyl)pyrrolidine (compound
108);
(2R)—
N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine (compound
109);
(2R)—
N-(3-Trifluoromethyl-4-nitrophenyl)-2-formylpyrrolidine (compound
110);
(2R)—
N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound
111);
(2R)—
N-(3-Trifluoromethyl-4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound
112);
(2S)—
N-(4-nitrophenyl)-2-(hydroxymethyl)pyrrolidine (compound
113);
(2R)—
N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound
114);
(2R)—
N-(4-nitrophenyl)-2-(R)-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound
115);
(2S)—
N-(4-nitrophenyl)-2-(1-(S)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound
116);
(2S)—
N-(4-nitrophenyl)-2-(1-(R)-hydroxy-2,2,2-trifluoroethyl)pyrrolidine (compound
117);
3-(3-Methoxyphenyl)-6-nitro-2,7-dimethyl-1H-indole (compound
118);
4-[Bis-(2,2,2-trifluoroethyl)amino]-2-chloro-3-methyl-benzonitrile (compound
119);
cis-2,5-Dimethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine (compound
120);
trans-2,5-dimethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine (compound
121);
1-(4-Nitro-3-trifluoromethylphenyl)-piperidine-2-carboxylic acid ethyl ester (compound
122);
1-(4-Nitro-3-trifluoromethylphenyl)-4-(hydroxymethyl)-piperidine (compound
123);
(1-(3-trifluoromethyl-4-nitrophenyl)piperidin-2-yl)methyl acetate (compound
124);
4-(2-Hydroxymethyl-pyrrolidin-1-yl)-benzonitrile (compound
125);
4-Benzyl-2-hydroxymethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine (compound
126);
2-Fluoro-4-(2-hydroxymethyl-pyrrolidin-1-yl)-benzonitrile (compound
127);
4-Hydroxy-1-(4-nitrophenyl)-pyrrolidine-2-carboxylic acid ethyl ester (compound
128);
4-Hydroxy-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine-2-carboxylic acid ethyl ester (compound
129);
5-Hydroxymethyl-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidin-3-ol (compound
130);
2-(Aminomethyl)-1-(4-Nitro-3-trifluoromethylphenyl)-pyrrolidine (compound
131);
4-Hydroxy-1-(4-nitrophenyl)-pyrrolidine-2-carboxylic acid (compound
132); and
4-Hydroxy-1-(4-nitro-3-trifluoromethylphenyl)-pyrrolidine-2-carboxylic acid (compound
133);
and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
-
-
63. The compound of claim 1, wherein the compound is a selective androgen receptor modulator.
-
64. The selective androgen receptor modulator of claim 63, wherein the compound is an androgen receptor agonist.
-
65. The selective androgen receptor modulator of claim 63, wherein the compound is an androgen receptor antagonist.
-
66. The selective androgen receptor modulator of claim 63, wherein the compound is an androgen receptor partial agonist.
-
67. The selective androgen receptor modulator of claim 63, wherein the compound is a tissue-specific modulator.
-
68. The compound of claim 1, wherein the compound is a selective androgen binding compound.
-
69. A method for modulating an activity of an androgen receptor, comprising contacting an androgen receptor with a compound of claim 1.
-
70. The method of claim 68, wherein the androgen receptor is in a cell.
-
71. A method for identifying a compound that modulates an activity of an androgen receptor comprising:
-
contacting a cell expressing an androgen receptor with a compound of claim 1;
andmonitoring an effect of the compound upon the cell.
-
-
72. A method for treating a patient having a condition susceptible to treatment with an androgen receptor modulator, comprising administering to the patient a pharmaceutical agent comprising a compound of claim 1.
-
73. The method of claim 72, wherein the condition is selected from among maintenance of muscle strength and function;
- reversal or prevention of frailty or age-related functional decline in the elderly;
treatment of catabolic side effects of glucocorticoids;
treatment of reduced bone mass, density or growth;
treatment of chronic fatigue syndrome;
chronic myalgia;
treatment of acute fatigue syndrome and muscle loss;
accelerating of wound healing;
accelerating bone fracture repair;
accelerating healing of complicated fractures;
in joint replacement;
prevention of post-surgical adhesion formation;
acceleration of tooth repair or growth;
maintenance of sensory function;
treatment of periodontal disease;
treatment of wasting secondary to fractures and treatment of wasting in connection with chronic obstructive pulmonary disease, treatment of wasting in connection with chronic liver disease, treatment of wasting in connection with AIDS, cancer cachexia, burn and trauma recovery, chronic catabolic state, eating disorders and chemotherapy;
treatment of cardiomyopathy;
treatment of thrombocytopenia;
treatment of growth retardation in connection with Crohn'"'"'s disease;
treatment of short bowel syndrome;
treatment of irritable bowel syndrome;
treatment of inflammatory bowel disease;
treatment of Crohn'"'"'s disease and ulcerative colitis;
treatment of complications associated with transplantation;
treatment of physiological short stature including growth hormone deficient children and short stature associated with chronic illness;
treatment of obesity and growth retardation associated with obesity;
treatment of anorexia;
treatment of hypercortisolism and Cushing'"'"'s syndrome;
Paget'"'"'s disease;
treatment of osteoarthritis;
induction of pulsatile growth hormone release;
treatment of osteochondro-dysplasias;
treatment of depression, nervousness, irritability and stress;
treatment of reduced mental energy and low self-esteem;
improvement of cognitive function;
treatment of catabolism in connection with pulmonary dysfunction and ventilator dependency;
treatment of cardiac dysfunction;
lowering blood pressure;
protection against ventricular dysfunction or prevention of reperfusion events;
treatment of adults in chronic dialysis;
reversal or slowing of the catabolic state of aging;
attenuation or reversal of protein catabolic responses following trauma;
reducing cachexia and protein loss due to chronic illness;
treatment of hyper-insulinemia;
treatment of immunosuppressed patients;
treatment of wasting in connection with multiple sclerosis or other neurodegenerative disorders;
promotion of myelin repair;
maintenance of skin thickness;
treatment of metabolic homeostasis and renal homeostasis;
stimulation of osteoblasts, bone remodeling and cartilage growth;
regulation of food intake;
treatment of insulin resistance;
treatment of insulin resistance in the heart;
treatment of hypothermia;
treatment of congestive heart failure;
treatment of lipodystrophy;
treatment of muscular atrophy;
treatment of musculoskeletal impairment;
improvement of the overall pulmonary function;
treatment of sleep disorders; and
the treatment of the catabolic state of prolonged critical illness;
treatment of hirsutism, acne, seborrhea, androgenic alopecia, anemia, hyperpilosity, benign prostate hypertrophy, adenomas and neoplasies of the prostate and malignant tumor cells containing the androgen receptor;
osteosarcoma;
hypercalcemia of malignancy;
metastatic bone disease;
treatment of spermatogenesis, endometriosis and polycystic ovary syndrome;
counteracting preeclampsia, eclampsia of pregnancy and preterm labor;
treatment of premenstrual syndrome;
treatment of vaginal dryness;
age related decreased testosterone levels in men, male menopause, hypogonadism, male hormone replacement, male and female sexual dysfunction, male and female contraception, hair loss, Reaven'"'"'s Syndrome and the enhancement of bone and muscle strength.
- reversal or prevention of frailty or age-related functional decline in the elderly;
-
74. A method according to claim 72, wherein the patient has a condition selected from among acne, male-pattern baldness, wasting diseases, hirsutism, hypogonadism, osteoporoses, infertility, impotence and cancer.
-
75. A method for stimulating hematopoiesis in a patient, comprising administering to the patient a pharmaceutical agent comprising a compound of claim 1.
-
76. A method of contraception, comprising administering to a patient a pharmaceutical agent comprising a compound of claim 1.
-
77. A method of improving athletic performance in an athlete, comprising administering to the athlete a pharmaceutical agent comprising a compound of claim 1.
-
78. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
-
82. An article of manufacture, comprising:
-
packaging material;
a compound of claim 1 that is effective for modulating the activity of androgen receptor, or for treatment, prevention or amelioration of one or more symptoms of androgen receptor mediated diseases or disorders, or diseases or disorders in which androgen receptor activity is implicated, within the packaging material; and
a label that indicates that the compound or composition, or pharmaceutically acceptable derivative thereof, is used for modulating the activity of androgen receptor or for treatment, prevention or amelioration of one or more symptoms of androgen receptor mediated diseases or disorders, or diseases or disorders in which androgen receptor activity is implicated.
-
-
79-81. -81. (canceled)
Specification