Inhibitors for testosterone 5.alpha.-reductase activity
AssigneeEndorecherche, Inc.
InventorsFernand Labrie, Yves M. Merand, Shankar M. Singh
Life of this patent
Estimating the term…
Abstract
Inhibitors of testosterone 5.alpha.-reductase activity, for example those of formula: ##STR1## wherein novel substituents are provided at the R.sup.4, R.sup.6, R.sup.7, R.sup.17.alpha. and/or R.sup.17.beta. positions are useful for the treatment of diseases whose progress is aided by activation of androgen receptors, e.g., prostate cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, androgenic alopecia and the like.
Claims38
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR20## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a hydrogen or C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is hydrogen or lower alkyl;
- and
- wherein R.sup.17.beta. is tertiary amino or tertiary amido.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR21## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a hydrogen or C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalky, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- and
- wherein R.sup.17.beta. is hydrogen, hydroxy or a moiety converted to hydroxy in vivo.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR22## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is hydrogen or lower alkyl;
- and
- wherein R.sup.17.beta. is selected from the group consisting of acyl, carboxamide, tertiary amino and tertiary amido.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR23## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a hydrogen or a C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of a C.sub.2 -C.sub.6 hydroxyalkyl, C.sub.2 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is hydrogen or lower alkyl;
- and
- wherein R.sup.17.beta. is selected from the group consisting of acyl, carboxamide, tertiary amino and tertiary amido.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase of the formula:
- ##STR24## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is hydrogen or a C.sub.1 -C.sub.3 hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sub.a is selected from the group consisting of lower alkyl, and cycloalkyl;
- wherein R.sub.b is selected from the group consisting of --COR.sub.c, --CONR.sub.c R.sub.d, --CSNR.sub.c R.sub.d, --SO.sub.2 R.sub.c, --PO.sub.3 R.sub.c R.sub.d (R.sub.c and R.sub.d being hydrogen, lower alkyl or lower haloalkyl).
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of at least one inhibitor of testosterone 5.alpha.-reductase having the molecular structure:
- ##STR25## 1.beta. -(N-n-Amyl-N-formamido)-4-methyl-4-aza-5.alpha.-androstan-3-one, and ##STR26## 1.beta. -(N-n-butyl-N-formamido)-4-methyl-4-aza-5.alpha.-androstan-3-one.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of at least one inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR27## 1.beta. -(N-n-hexyl-N-formamido)-4-methyl-4-aza-5.alpha.-androstan-3-one.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of at least one inhibitor of testosterone 5.alpha.-reductase selected from the group consisting of:
- ##STR28## 1.beta. -allyl-17.beta.-hydroxy-4-methyl-4-aza-5.alpha.-androstan-3-one and ##STR29## 1.alpha. -propyl-17.beta.- hydroxy-4-methyl-4-aza-5.alpha.-androstan-3-one.
A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a therapeutically effective amount of at least one inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR30## 1.alpha. -(4-iodo-butynyl)-17.beta.-hydroxy-4-methyl-4-aza-5.alpha.-andros t ane-3-one.
A method of inhibiting testosterone 5.alpha.-reductase activity in a patient in need of such inhibition, said method comprising administering to said patient a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR31## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a hydrogen or C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.2 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is hydrogen or lower alkyl;
- and
- wherein R.sup.17.beta. is tertiary amino or tertiary amido.
A method of inhibiting testosterone 5.alpha.-reductase activity in a patient in need of such inhibition, said method comprising administering to said patient a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR32## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a hydrogen or C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalky, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- and
- wherein R.sup.17.beta. is hydrogen, hydroxy or a moiety converted to hydroxy in vivo.
A method of inhibiting testosterone 5.alpha.-reductase activity in a patient in need of such inhibition, said method comprising administering to said patient a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR33## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1-C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.alpha. is hydrogen or lower alkyl;
- and
- wherein R.sup.17.beta. is selected from the group consisting of acyl, carboxamide, tertiary amino and tertiary amido.
A method of inhibiting testosterone 5.alpha.-reductase activity in a patient in need of such inhibition, said method comprising administering to said patient a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR34## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is a hydrogen or a C.sub.1 -C.sub.3 saturated or unsaturated hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of a C.sub.2 -C.sub.6 alkyl, C.sub.2 -C.sub.6 hydroxyalkyl, C.sub.2 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sup.17.beta. is hydrogen or lower alkyl;
- and
- wherein R.sup.17.beta. is selected from the group consisting of acyl, carboxamide, tertiary amino and tertiary amido.
A method of inhibiting testosterone 5.alpha.-reductase activity in a patient in need of such inhibition, said method comprising administering to said patient a therapeutically effective amount of an inhibitor of testosterone 5.alpha.-reductase having the molecular formula:
- ##STR35## wherein the dotted line is an optional pi bond;
- wherein R.sup.4 is hydrogen or methyl;
- wherein R.sup.6 is hydrogen or a C.sub.1 -C.sub.3 hydrocarbon;
- wherein R.sup.7 is selected from the group consisting of hydrogen, a C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 hydroxyalkyl, C.sub.1 -C.sub.6 haloalkyl, C.sub.2 -C.sub.6 carbonylalkyl, C.sub.3 -C.sub.6 cyclopropylalkyl, C.sub.3 -C.sub.6 epoxyalkyl and unsaturated analogs of the foregoing;
- wherein R.sub.a is selected from the group consisting of lower alkyl, and cycloalkyl;
- and
- wherein R.sub.b is selected from the group consisting of --COR.sub.c, --CONR.sub.c R.sub.d, --CSNR.sub.c R.sub.d, --SO.sub.2 R.sub.c, --PO.sub.3 R.sub.c R.sub.d (R.sub.c and R.sub.d being hydrogen, lower alkyl or lower haloalkyl).
Dependencies are inferred from the claim text.