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US 6,204,273 B1Granted
16-substituted-4-aza-androstane 5-α-reductase isozyme 1 inhibitors
AssigneeMerck & Co., Inc.
InventorsPhilippe L. Durette, William K. Hagmann, Thomas J. Lanza, Jr., Soumya P. Sahoo, Gary H. Rasmusson, Richard L. Tolman, Derek Von Langen
Life of this patent
Estimating the term…
Abstract
Compounds of the Formula I are inhibitors of the 5α-reductase 1 isozyme, and are useful alone, or in combination with a 5α-reductase 2 inhibitor, for the treatment of androgenic sensitive disorders such as acne vulgaris, seborrhea, female hirsutism, male pattern baldness, and benign prostatic hyperplasia.
Claims26
A method for treating the conditions of androgenic alopecia, female hirsutism, benign prostatic hyperplasia, and prostatitis comprising the step of administering to a mammal in need of such treatment a therapeutically effective amount of a compound of structural formula I:
- or a pharmaceutically acceptable salt or ester thereof wherein:
- the C1—C2 carbon-carbon bond may be a single bond, or a double bond as indicated by the dashed line;
- R1 is selected from the group consisting of hydrogen and C1-10 alkyl;
- R2 is selected from the group consisting of hydrogen and C1-10 alkyl;
- one of R3 and R4 is selected from the group consisting of hydrogen and methyl, and the other is selected from the group consisting of:
- (a) amino;
- (b) cyano;
- (c) fluoro;
- (d) OH;
- (e) —C(O)NRbRc, where Rb and Rc are independently H, C1-6 alkyl, aryl, or arylC1-6alkyl;
- wherein the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- and the aryl moiety can be substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy;
- and trifluoromethyl;
- (f) C1-10 alkyl-X—, with the proviso that X is not —CH(Re)—;
- (g) C2-10 alkenyl-X—, with the proviso that X is not —CH(Re)—;
- wherein the C1-10 alkyl in (f) and C2-10 alkenyl in (g) is unsubstituted or substituted with one to three of:
- i) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- oxo;
- hydroxysulfonyl;
- carboxy;
- ii) hydroxyC1-6alkyl;
- C1-6alkyloxy;
- C1-6 alkylthio;
- C1-6alkylsulfonyl;
- C1-6 alkyloxycarbonyl;
- in which the C1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4 alkoxy;
- and trifluoromethyl;
- iii) arylthio;
- aryl;
- aryloxy;
- arylsulfonyl;
- aryloxycarbonyl;
- in which the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4 alkyl;
- C1-4 alkoxy;
- and trifluoromethyl;
- iv) —C(O)NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- where Rb and Rc are defined above;
- (h) aryl-X—;
- (i) heteroaryl-X—, wherein heteroaryl is a 5, 6 or 7 membered heteroaromatic ring containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;
- wherein the aryl in (h) and heteroaryl in (i) is unsubstituted or substituted with one to three of;
- v) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- mono-, di- or trihalomethoxy;
- C2-6 alkenyl;
- C3-6 cycloalkyl;
- formyl;
- hydrosulfonyl;
- carboxy;
- ureido;
- vi) C1-6 alkyl;
- hydroxy C1-6 alkyl;
- C1-6 alkyloxy;
- C1-6 alkyloxy C1-6alkyl;
- C1-6 alkylcarbonyl;
- C1-6 alkylsulfonyl;
- C1-6 alkylthio;
- C1-6 alkylsulfinyl;
- C1-6 alkylsulfonamido;
- C1-6 alkylarylsulfonamido;
- C1-6 alkyloxy-carbonyl;
- C1-6 alkyloxycarbonyl C1-6alkyl;
- RbRcN—C(O)—C1-6alkyl;
- C1-6 alkanoylamino C1-6 alkyl;
- aroylamino C1-6 alkyl;
- wherein the C1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- vii) aryl;
- aryloxy;
- arylcarbonyl;
- arylthio;
- arylsulfonyl;
- arylsulfinyl;
- arylsulfonamido;
- aryloxycarbonyl;
- wherein the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4alkoxy;
- and trifluoromethyl;
- viii) —C(O)NRbRc;
- —O—C(O)—NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- Rb—C(O)—N(Rc)—;
- where Rb and Rc are defined in (e) above;
- and —N(Rb)—C(O)—ORg, wherein Rg is C1-6alkyl or aryl, in which the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy, and trifluoromethyl, and the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy, and trifluoromethyl;
- —N(Rb)—C(O)NRcRd, wherein Rd is selected from H, C1-6 alkyl, and aryl;
- in which said C1-6alkyl and aryl is unsubstituted or substituted as described above in (e) for Rb and Rc;
- ix) a heterocyclic group, which is a 5, 6 or 7 membered ring, containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heterocyclic ring is aromatic, unsaturated, or saturated, wherein the heterocyclic ring is optionally fused with a benzo ring, and
- wherein said heterocyclic ring is unsubstituted or substituted with one to three substituents, as defined above for v), vi), vii) and viii), excluding ix) a heterocyclic group;
- and
- (j) R3 and R4 taken together are carbonyl oxygen;
- (k) R3 and R4 taken together are ═CH—Rg, wherein Rg is defined in viii);
- and wherein:
- X is selected from the group consisting of:
- —O—;
- —S(O)n—;
- —C(O)—;
- —CH(Re)—;
- —C(O)—O—*;
- —C(O)—N(Re)—*;
- —N(Re)—C(O)—O—*;
- —O—C(O)—N(Re)—*;
- —N(Re)C(O)—N(Re)—;
- —O—CH(Re)—*;
- —N(Re)—;
- wherein Re is H, C1-3 alkyl, aryl, aryl-C1-3 alkyl, or unsubstituted or substituted heteroaryl, as defined above in (i);
- wherein the asterisk (*) denotes the bond which is attached to the 16-position in structural formula I;
- and n is zero, 1 or 2;
- or a therapeutically effective amount of a compound of structural formula I in combination with an inhibitor of 5α-reductase 2.
137 more elements
A method of arresting and reversing androgenic alopecia and promoting hair growth in a mammal in need of such treatment comprising the step of administering to said mammal a therapeutically effective amount of a compound of structural formula I:
- or a pharmaceutically acceptable salt or ester thereof wherein:
- the C1—C2 carbon-carbon bond may be a single bond, or a double bond as indicated by the dashed line;
- R1 is selected from the group consisting of hydrogen and C1-10 alkyl;
- R2 is selected from the group consisting of hydrogen and C1-10 alkyl;
- one of R3 and R4 is selected from the group consisting of hydrogen and methyl, and the other is selected from the group consisting of:
- (a) amino;
- (b) cyano;
- (c) fluoro;
- (d) OH;
- (e) —C(O)NRbRc, where Rb and Rc are independently H, C1-6 alkyl, aryl, or arylC1-6alkyl;
- wherein the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- and the aryl moiety can be substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy, and trifluoromethyl;
- (f) C1-10 alkyl-X—, with the proviso that is not —CH(Re)—;
- (g) C2-10 alkenyl-X—, with the proviso that is not —CH(Re)—,
- wherein the C1-10 alkyl in (f) and C2-10 alkenyl in (g) is unsubstituted or substituted with one to three of:
- i) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- oxo;
- hydroxysulfonyl;
- carboxy;
- ii) hydroxyC1-6alkyl;
- C1-6alkyloxy;
- C1-6 alkylthio;
- C1-6alkylsulfonyl;
- C1-6 alkyloxycarbonyl;
- in which the C1-6 alkyl moiety is unsubstitute or substituted with 1-3 substituents selected from:
- halo;
- C1-4 alkoxyl;
- and trifluoromethyl;
- iii) arylthio;
- aryl;
- aryloxy;
- arylsulfonyl;
- aryloxycarbonyl;
- in which the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4 alkyl;
- C1-4 alkoxy;
- and trifluoromethyl;
- iv) —C(O)NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- where Rb and Rc are defined above;
- (h) aryl-X—;
- (i) heteroaryl-X—, wherein heteroaryl is a 5, 6 or 7 membered heteroaromatic ring containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;
- wherein the aryl in (h) and heteroaryl in (i) is unsubstituted or substituted with one to three of:
- v) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- mono-, di- or trihalomethoxy;
- C2-6 alkenyl;
- C3-6 cycloalkyl;
- formyl;
- hydrosulfonyl;
- carboxy ureido;
- vi) C1-6 alkyl;
- hydroxy C1-6 alkyl;
- C1-6 alkyloxy;
- C1-6 alkyloxy C1-6alkyl;
- C1-6 alkylcarbonyl;
- C1-6 alkylsulfonyl;
- C1-6 alkylthio;
- C1-6 alkylsulfinyl;
- C1-6 alkylsulfonamido;
- C1-6 alkylarylsulfonamido;
- C1-6 alkyloxy-carbonyl;
- C1-6 alkyloxycarbonyl C1-6 alkyl;
- RbRcN—C(O)—C1-6alkyl;
- C1-6 alkanoylamino C1-6 alkyl;
- aroylamino C1-6 alkyl;
- wherein the C1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- vii) aryl;
- aryloxy;
- arylcarbonyl;
- arylthio;
- arylsulfonyl;
- arylsulfinyl;
- arylsulfonamido;
- aryloxycarbonyl;
- wherein the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4alkoxy;
- and trifluoromethyl;
- viii) —C(O)NRbRc;
- —O—C(O)—NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- Rb—C(O)—N(Rc)—;
- where Rb and Rc are defined in (e) above;
- and —N(Rb)—C(O)—ORg, wherein Rg is C1-6alkyl or aryl, in which the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl, and the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy, and trifluoromethyl;
- —N(Rb)—C(O)NRcRd, wherein Rd is selected from H, C1-6 alkyl, and aryl;
- in which said C1-6alkyl and aryl is unsubstituted or substituted as described above in (e) for Rb and Rc;
- ix) a heterocyclic group, which is a 5, 6 or 7 membered ring, containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heterocyclic ring is aromatic, unsaturated, or saturated, wherein the heterocyclic ring is optionally fused with a benzo ring, and
- wherein said heterocyclic ring is unsubstituted or substituted with one to three substituents, as defined above for v), vi), vii) and viii), excluding ix) a heterocyclic group;
- and
- (j) R3 and R4 taken together are carbonyl oxygen;
- (k) R3 and R4 taken together are ═CH—Rg, wherein Rg is defined in viii);
- and
- wherein:
- X is selected from the group consisting of:
- —O—;
- —S(O)n—;
- —C(O)—;
- —CH(Re)—;
- —C(O)—O—*;
- —C(O)—N(Re)—*;
- —N(Re)—C(O)—O—*;
- —O—C(O)—N(Re)—*;
- —N(Re)C(O)—N(Re)—;
- —O—CH(Re)—*;
- —N(Re)—;
- wherein Re is H, C1-3 alkyl, aryl, aryl-C1-3 alkyl, or unsubstituted or substituted heteroaryl, as defined above in (i);
- wherein the asterisk (*) denotes the bond which is attached to the 16-position in structural formula I;
- and n is zero, 1 or 2;
- or a therapeutically effective amount of a compound of structural formula I in combination with an inhibitor of 5α-reductase 2.
137 more elements
A method of inhibiting the biosynthetic conversion of testosterone to dihydrotesterone in a mammal in need of such treatment comprising the step of administering to said mammal a therapeutically effective amount of a compound of structural formula I:
- or a pharmaceutically acceptable salt or ester thereof wherein:
- the C1—C2 carbon-carbon bond may be a single bond, or a double bond as indicated by the dashed line;
- R1 is selected from the group consisting of hydrogen and C1-10 alkyl;
- R2 is selected from the group consisting of hydrogen and C1-10 alkyl;
- one of R3 and R4 is selected from the group consisting of hydrogen and methyl, and the other is selected from the group consisting of:
- (a) amino;
- (b) cyano;
- (c) fluoro;
- (d) OH;
- (e) —C(O)NRbRc, where Rb and Rc are independently H, C1-6 alkyl, aryl, or arylC1-6alkyl;
- wherein the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- and the aryl moiety can be substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy;
- and trifluoroethyl;
- (f) C1-10 alkyl-X—, with the proviso that when X is —CH(Re)—, Re cannot be H or C1-3 alkyl;
- C2-10 alkenyl-X—, with the proviso that when X is —CH(Re)—, Re cannot be H or C1-3 alkyl;
- wherein the C1-10 alkyl in (g) and C2-10 alkenyl in (g) is unsubstituted or substituted with one to three of:
- i) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- oxo;
- hydroxysulfonyl;
- carboxy;
- ii) hydroxyC1-6alkyl;
- C1-6alkyloxy;
- C1-6 alkylthio;
- C1-6alkylsulfonyl;
- C1-6 alkyloxycarbonyl;
- in which the C1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4 alkoxy;
- and trifluoromethyl;
- iii) arylthio;
- aryl;
- aryloxy;
- arylsulfonyl;
- aryloxycarbonyl;
- in which the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4 alkyl;
- C1-4 alkoxy;
- and trifluoromethyl;
- iv) —C(O)NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- where Rb and Rc are defined above;
- (h) aryl-X—;
- (i) heteroaryl-X—, wherein heteroaryl is a 5, 6 or 7 membered heteroaromatic ring containing at least one member select from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;
- wherein the aryl in (h) and heteroaryl in (i) is unsubstituted or substituted with one to three of:
- v) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- mono-, di- or trihalomethoxy;
- C2-6 alkenyl;
- C3-6 cycloalkyl;
- formyl;
- hydrosulfonyl;
- carboxyl ureido;
- vi) C1-6 alkyl;
- hydroxy C1-6 alkyl;
- C1-6 alkyloxy;
- C1-6 alkyloxy C1-6alkyl;
- C1-6 alkylcarbonyl;
- C1-6 alkylsulfonyl;
- C1-6 alkylthio;
- C1-6 alkylsulfinyl;
- C1-6 alkylsulfonamido;
- C1-6 alkylarylsulfonamido;
- C1-6 alkyloxy-carbonyl;
- C1-6 alkyloxycarbonyl C1-6alkyl;
- RbRcN—C(O)—C1-6alkyl;
- C1-6 alkanoylamino C1-6 alkyl;
- aroylamino C1-6 alkyl;
- wherein the C1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- vii) aryl;
- aryloxy;
- arylcarbonyl;
- acylthio;
- arylsulfonyl;
- arylsulfinyl;
- arylsulfonamido;
- aryloxycarbonyl;
- wherein the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4alkoxy;
- and trifluoromethyl;
- viii) —C(O)NRbRc;
- —O—C(O)—NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- Rb—C(O)—N(Rc)—;
- where Rb and Rc are defined in (e) above;
- and —N(Rb)—C(O)—ORg, wherein Rg is C1-6alkyl or aryl, in which the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl, and the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy, and trifluoromethyl;
- —N(Rb)—C(O)NRcRd, wherein Rd is selected from H, C1-6 alkyl, and aryl;
- in which said C1-6alkyl and aryl is unsubstituted or substituted as described above in (e) for Rb and Rc;
- ix) a heterocyclic group, which is a 5, 6 or 7 membered ring, containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heterocyclic ring is aromatic, unsaturated, or saturated, wherein the heterocyclic ring is optionally fused with a benzo ring, and
- wherein said heterocyclic ring is unsubstituted or substituted with one to three substituents, as defined above for v), vi), vii) and vii), excluding ix) a heterocyclic group;
- and p1 (i) R3 and R4 taken together are carbonyl oxygen;
- (k) R3 and R4 taken together are ═CH—Rg wherein Rg is defined in viii);
- and
- wherein:
- X is selected from the group consisting of:
- —O—;
- —S(O)n—;
- —C(O)—;
- —CH(Re)—;
- —C(O)—O—*;
- —(O)—N(Re)—*;
- —N(Re)—C(O)—O—*;
- —O—C(O)—N(Re)—*;
- —N(Re)C(O)—N(Re)—;
- —O—CH(Re)—*;
- —N(Re)—;
- wherein Re is H, C1-3 alkyl, aryl, aryl-C1-3 alkyl, or unsubstituted or substituted heteroaryl, as defined above in (i);
- wherein the asterisk (*) denotes the bond which is attached to the 16-position in structural formula I;
- and n is zero, 1 or 2;
- or a therapeutically effective amount of a compound of structural formula I in combination with an inhibitor of 5α-reductase 2.
137 more elements
A method for treating the conditions of androgenic alopecia, female hirsutism, benign prostatic hyperplasia, and prostatitis, comprising the step of administering to a human in need of such treatment a therapeutically effective amount of a compound of structural formula I:
- or a pharmaceutically acceptable salt or ester thereof wherein:
- the C1—C2 carbon-carbon bond may be a single bond, or a double bond as indicated by the dashed line;
- R1 is selected from the group consisting of hydrogen and C1-10 alkyl;
- R2 is selected from the group consisting of hydrogen and C1-10 alkyl;
- one of R3 and R4 is selected from the group consisting of hydrogen and methyl, and the other is selected from the group consisting of:
- (i) aryl-X—;
- (j) heteroaryl-X—, wherein heteroaryl is a 5, 6 or 7 membered heteroaromatic ring containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heteroaromatic ring can also be fused with one benzo or heteroaromatic ring;
- wherein the aryl in (i) and heteroaryl in (j) is unsubstituted or substituted with one to three of:
- v) halo;
- hydroxy;
- cyano;
- nitro;
- mono-, di- or trihalomethyl;
- mono-, di- or trihalomethoxy;
- C2-6 alkenyl;
- C3-6 cycloalkyl;
- formyl;
- hydrosulfonyl;
- carboxy;
- ureido;
- vi) C1-6 alkyl;
- hydroxy C1-6 alkyl;
- C1-6 alkyloxy;
- C1-6 alkyloxy C1-6alkyl;
- C1-6 alkylcarbonyl;
- C1-6 alkylsulfonyl;
- C1-6 alkylthio;
- C1-6 alkylsulfinyl;
- C1-6 alkylsulfonamido;
- C1-6 alkylarylsulfonamido;
- C1-6 alkyloxy-carbonyl;
- C1-6 alkyloxycarbonyl C1-6alkyl;
- RbRcN—C(O)—C1-6alkyl;
- C1-6 alkanoylamino C1-6 alkyl;
- aroylamino C1-6 alkyl;
- wherein the C1-6 alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl;
- vii) aryl;
- aryloxy;
- arylcarbonyl;
- arylthio;
- arylsulfonyl;
- arylsulfinyl;
- arylsulfonamido;
- aryloxycarbonyl;
- wherein the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4alkoxy;
- and trifluoromethyl;
- viii) —C(O)NRbRc;
- —O—C(O)—NRbRc;
- —N(Rb)—C(O)—Rc;
- —NRbRc;
- Rb—C(O)—N(Rc)—;
- where Rb and Rc are independently H, C1-6 alkyl, aryl, or arylC1-6alkyl;
- wherein the alkyl moiety can be substituted with 1-3 of:
- halo;
- C1-4alkoxy;
- or trifluoromethyl;
- and the aryl moiety can be substituted with 1-3 of:
- halo;
- C1-4alkyl;
- C1-4 alkoxy:
- or trifluoromethyl;
- and —N(Rb)—C(O)—ORg, wherein Rg is C1-6alkyl or aryl, in which the alkyl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkoxy;
- and trifluoromethyl, and the aryl moiety is unsubstituted or substituted with 1-3 substituents selected from:
- halo;
- C1-4alkyl;
- C1-4 alkoxy, and trifluoromethyl;
- —N(Rb)—C(O) NRcRd, wherein Rd is selected from H, C1-6 alkyl, and aryl;
- in which said C1-6alkyl and aryl is unsubstituted or substituted as described above for Rb and Rc;
- ix) a heterocyclic group, which is a 5, 6 or 7 membered ring, containing at least one member selected from the group consisting of:
- one ring oxygen atom, one ring sulfur atom, 1-4 ring nitrogen atoms, or combinations thereof;
- in which the heterocyclic ring is aromatic, unsaturated, or saturated, wherein the heterocyclic ring is optionally fused with a benzo ring, and
- wherein said heterocyclic ring is unsubstituted or substituted with one to three substituents, as defined above for v), vi), vii) and viii), excluding ix) a heterocyclic group;
- and
- and wherein:
- X is selected from the group consisting of:
- —O—;
- —S(O)n—;
- —C(O)—;
- —CH(Re)—;
- —C(O)—O—*;
- —C(O)—N(Re)—*;
- —N(Re)—C(O)—O—*;
- —O—C(O)—N(Re)—*;
- —N(Re)C(O)—N(Re)—;
- —O—CH(Re)—*;
- —N(Re)—;
- wherein Re is H, C1-3 alkyl, aryl, aryl-C1-3 alkyl, or unsubstituted or substituted heteroaryl, as defined above in (j);
- wherein the asterisk (*) denotes the bond which is attached to the 16-position in structural formula I;
- and n is zero, 1 or 2;
- or a therapeutically effective amount of a compound of structural formula I in combination with an inhibitor of 5α-reductase 2.
97 more elements
Dependencies are inferred from the claim text.