Fused cyclic modulators of nuclear hormone receptor function

A compound of the following formula (Ia) or (Ib):

• or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof;
• wherein the symbols have the following meanings and are, for each occurrence, independently selected:
• G is an aryl or heterocyclo group, where said group is mono- or polycyclic and is optionally substituted at one or more positions;
• A1 is CR7;
• A2 is CR7;
• Y is (CR7R7′)n and n=1 or 2;
• Q is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, —(C═O)OR1, —C(═O)R4, —C(═O)NR5R6, —C(R7R7′)—OH, nitro, —(C2)OR1, —OR1, —C(═O)SR1, —SO2R1, —NH2, or —NR4R5;
• L is a bond, (CR7R7′)n, NH, NR5 or N(CR7R7′)n, where n=0-2;
• R1 and R1′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, provided, however, that R1 and R1′ are not hydrogen when attached to —SO2O— or —SO2—;
• R2 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;
• R4 is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)OR1, —C(═O)NHR1, —SO2OR1, —SO2R1 or —SO2NR1R1′;
• R5 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)NHR1, —SO2OR1, —SO2R1 or —SO2NR1R1′;
• R6 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, —OR1, —C(═O)R1, —C(═O)NHR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• R7 and R7′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR1, nitro, hydroxylamine, hydroxylamide, NHR4, —NR2R5, —NHOR1, thiol, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —PO3R1R1′, —C(═O)NR1R1, —C(═O)SR1, —C(═O)NHSO2R1, —SOR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• or two groups R7 and R7′ attached to the same carbon atom may be joined to form a spiro ring, or groups R7 and R7′ attached to two adjacent carbon atoms may be joined to form a fused, optionally-substituted monocyclic or bicyclic heterocyclic or carbocyclic ring;
• R8 and R8′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR1, nitro, NHR4, —NR2R5, —NHOR1, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —PO3R1R1′, —C(═O)NR1R1, —C(═O)SR1, —C(═O)NHSO2R1, —SOR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• and
• or, groups R8 and R8′ may be joined to form a fused, optionally-substituted monocyclic or bicyclic heterocyclic or carbocyclic ring;
• with the provisos that:
• (a) when A1 and A2 are both CH, Q is H, CH3, or —CO2CH3, and R7, R7′, R8 and R8′ are at each occurrence hydrogen, then G—L considered together are not unsubstituted phenyl, 4-chlorophenyl, 4-methoxyphenyl, or benzyl;
• (b) when A1 and A2 are both CH, Q is H, and either or both of (i) R7 and R7′ of the group Y, and (ii) R8 and R8′, are taken together to form phenyl, then G—L is not 4-chlorophenyl or benzyl;
• and (c) when Q is H, Y is —CH2—CH2—, R7, R7′, R8 and R8′ are at each other occurrence hydrogen, then G—L— is not 4-chlorophenyl when (i) A1 and A2 are both C—CH3;
• and (ii) when A1 is C-isopropyl and A2 is C—CH3.

A compound having the formula (Ia*) or (Ib*),

• or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof;
• wherein the symbols have the following meanings and are, for each occurrence, independently selected:
• G is an aryl or heterocyclo group, where said group is mono- or polycyclic and is optionally substituted at one or more positions, provided that G is not 4-chlorophenyl;
• A1 is CR7;
• A2 is CR7;
• R1 and R1′ are each independently selected from H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, and aryl or substituted aryl;
• R2 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl;
• R4 is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkylalkyl or substituted cycloalkylalkyl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)OR1, —C(═O)NHR1, —SO2R1 or —SO2NR1R1′;
• R5 is alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, —C(═O)R1, —SO2R1, or —SO2NR1R1′;
• R6 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, or CN;
• R7 and R7′ are independently at each occurrence selected from H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, heterocycloalkyl or substituted heterocycloalkyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, halo, cyano, OR4, —NHR4, —NR2R5, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —C(═O)NR1R140, —SO2R1, and —SO2NR1R1′, provided, however, that every group R7, R7′ is not simultaneously hydrogen;
• R8 and R8′ are independently at each occurrence selected from H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, halo, CN, OR1, nitro, NHR4, —NR2R5, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —C(═O)NR1R1, SO2R1, and —SO2NR1R1′;
• and
• n=1 or 2.

A method of modulating the function of the androgen receptor in a mammal which comprises administering to the mammal in need thereof an effective androgen receptor modulating amount of a compound of the following formula (Ia) or (Ib):

• or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof;
• wherein the symbols have the following meanings and are, for each occurrence, independently selected:
• G is an aryl or heterocyclo group, where said group is mono- or polycyclic and is optionally substituted at one or more positions;
• A1 is CR7;
• A2 is CR7;
• Y is (CR7R1′)n and n=1 or 2;
• Q is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, —(C═O)OR1, —C(═O)R4, —C(═O)NR5R6, —C(R7R7′)—OH, nitro, —(CH2)OR1, —OR1, —C(═O)SR1, —SO2R1, —NH2, or —NR4R5;
• L is a bond, (CR7R7′)n, NH, NR5 or N(CR7R7′)n, where n=0-2;
• R1 and R1′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, provided, however, that R1 and R1′ are not hydrogen when attached to —SO2O— or —SO2—;
• R2 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;
• R4 is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)OR1, —C(═O)NHR1, —SO2OR1, —S2R1 or —SO2NR1R1′;
• R5 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)NHR1, —SO2OR1, —SO2R1 or —SO2NR1R1′;
• R6 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, —OR1, —C(═O)R1, —C(═O)NHR1, —SO2R1, —SO2OR1 or —SO2NR1R1′,
• R7 and R7′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR1, nitro, hydroxylamine, hydroxylamide, NHR4, —NR2R5, —NHOR1, thiol, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —PO3R1R1′, —C(═O)NR1R1, —C(═O)SR1, —C(═O)NHSO2R1, —SOR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• or two groups R7 and R7′ attached to the same carbon atom may be joined to form a spiro ring, or groups R7 and R7′ attached to two adjacent carbon atoms may be joined to form a fused, optionally-substituted monocyclic or bicyclic heterocyclic or carbocyclic ring;
• R8 and R8′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR1, nitro, NHR4, —NR2R5, —NHOR1, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —PO3R1R1′, —C(═O)NR1R1, —C(═O)SR1, —C(═O)NHSO2R1, —SOR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• or, groups R8 and R8′ may be joined to form a fused, optionally-substituted monocyclic or bicyclic heterocyclic or carbocyclic ring.

A method for treating a condition or disorder comprising administering to a mammalian species in need thereof a therapeutically effective amount of a compound of the following formula (Ia) or (Ib):

• or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof;
• wherein the symbols have the following meanings and are, for each occurrence, independently selected:
• G is an aryl or heterocyclo group, where said group is mono- or polycyclic and is optionally substituted at one or more positions;
• A1 is CR7;
• A2 is CR7;
• Y is (CR7R7′)n and n=1 or 2;
• Q is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, —(C═O)OR1, —C(═O)R4, —C(═O)NR5R6, —C(R7R7′)—OH, nitro, —(CH2)OR1, —OR1, —C(═O)SR1, —SO2R1, —NH2, or —NR4R5;
• L is a bond, (CR7R7′)n, NH, NR5 or N(CR7R7′)n, where n=0-2;
• R1 and R1′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, provided, however, that R1 and R1′ are not hydrogen when attached to —SO2O— or —SO2—;
• R2 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;
• R4 is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)OR1, —C(═O)NHR1, —SO2OR1, —SO2R1 or —SO2NR1R1′;
• R5 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, —C(═O)R1, —C(═O)NHR1, —SO2OR1, —SO2R1 or —SO2NR1R1′;
• R6 is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, —OR1, —C(═O)R1, —C(═O)NHR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• R7 and R1′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR1, nitro, hydroxylamine, hydroxylamide, NHR4, —NR2R5, —NHOR1, thiol, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —PO3R1R1′, —C(═O)NR1R1, —C(═O)SR1, —C(═O)NHSO2R1, —SOR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• or two groups R7 and R7′ attached to the same carbon atom may be joined to form a spiro ring, or groups R7 and R7′ attached to two adjacent carbon atoms may be joined to form a fused, optionally-substituted monocyclic or bicyclic heterocyclic or carbocyclic ring;
• R8 and R8′ are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR1, nitro, NHR4, —NR2R5, —NHOR4, alkylthio or substituted alkylthio, —C(═O)R1, —OC(═O)R1, —C(═O)OR1, —PO3R1R1′, —C(═O)NR1R1, —C(═O)SR1, —C(═O)NHSO2R1, —SOR1, —SO2R1, —SO2OR1 or —SO2NR1R1′;
• or, groups R8 and R8′ may be joined to form a fused, optionally-substituted monocyclic or bicyclic heterocyclic or carbocyclic ring;
• wherein said condition or disorder is selected from the group consisting of benign prostate hypertrophia, hirsutism, ance, hyperpilosity, seborrhea, endometriosis, polycystic ovary syndrome, androgenic alopecia, hypogonadism, osteoporosis, suppressing spermatogenesis, libido, cachexia, anorexia, androgen supplementation for age related decreased testosterone levels in men, prostate cancer, breast cancer, endometrial cancer, and hot flashes.