Patent EA-000362-B1 (EA)
Title: Phenylsubstituted 4-azasteroid fluoroderivatives and the use thereof
Inventor: PANZERI ACHILLE
IPC: A61K31/58
Filed: 1996-08-09
Abstract: 1. A compound of formula (I)   wherein: the symbol ---- represents a single or a double bond; R is a hydrogen atom or a C1-C4 alkyl group; Rf and R'f, each independently, are C1-C4 alkyl groups substituted by one or more fluorine atoms; R1 and R2 each independently, are selected from: a hydrogen atom; a phenyl group; a C1-C4 alkyl group unsubstituted or substituted by one or more fluorine atoms; a halogen atom; a cyano (CN) group; a group OR4, wherein R4 is a hydrogen atom or a C1-C4 alkyl group; a group SR5, wherein R5 is a hydrogen atom or a C1-C4 alkyl group; and a group COR6, wherein R6 is a group OR4 in which R4 is as defined above or a C1-C4 alkyl group unsubstituted or substituted by one or more fluorine atoms. 2. A compound of formula (I) according to Claim 1, wherein: the symbol ---- is a single or a double bond; R is hydrogen or methyl; R1 is hydrogen, p-fluoro, m-fluoro, o-fluoro, p-chloro, m- chloro, o-chloro, p-methyl, m-methyl, o-methyl, p-trifluoromethyl, m-trifluoromethyl, o-trifluoromethyl, o-methoxy, p-methoxy, or p-trifluoroacetyl; R2 is hydrogen. 3. A compound of formula (I) according to Claim 1, wherein: the symbol ---- is a single or a double bond; R is hydrogen or methyl; Rf and R'f are trifluoromethyl groups; R1 is hydrogen, p-fluoro, p-chloro, p-methyl, or p-trifluoromethyl; R2 is hydrogen. 4. A compound of formula (I) according to Claim 1, selected from the group consisting of: N-(1,1,1,3,3,3-hexafluorophenylpropyl) -3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide; N-(1,1,1,3,3,3-hexafluorophenylpropyl)-3-oxo-4-aza-5α-androstane-17β-carboxamide; N-(1,1,1,3,3,3-hexafluorophenylpropyl)-4-methyl-3-oxo-4-aza-5α-androst-l-ene-17β-carboxamide; N-(1,1,1,3,3,3-hexafluorophenylpropyl)-4-methyl-3-oxo-4-aza-5α-androstane-17β-carboxamide; N-[l,1,1,3,3,3-hexafluoro-(4'-methylphenyl)propyl]-3-oxo-4-aza-5α-androst-l-ene-17β-carboxamide; N-[1,1,1,3,3,3-hexafluoro-(4'-fluorophenyl)propyl]-3-oxo-4-aza-5α- androst -1-ene-17β-carboxamide; N- [1,1,1,3,3,3-hexafluoro- (4'-chlorophenyl)propyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide; N-[1,1,1,3,3,3-hexafluoro-(4'-trifluoromethylphenyl)propyl]-3-oxo-4-aza-5α-androst-l-ene-17β-carboxamide; N-[1,1,1,3,3,3-hexafluoro-(2',4'-dimethylphenyl)propyl]-3-oxo-4-aza-5α-androst-l-ene-17β-carboxamide; N-[1,1,1,3,3,3-hexafluoro-(4'-phenylphenyl)propyl]-3-oxo-4-aza-5α-androst-l-ene-17β-carboxamide; and N-[1,1,1,3,3,3-hexafluoro-(4'-cyanophenyl)propyi]-3-oxo-4-aza-5α-androst-l-ene-17β-carboxamide. 5. A process for preparing a compound of formula (I) as defined in Claim 1, which comprises: a) reacting a compound of formula (II)   wherein the symbol ---- and R are as defined in Claim 1, and X is OH or an activating group of the carboxy function, with a compound of formula (III)   wherein Rf, R'f, R1 and R2 are as defined in Claim 1, thus obtaining a compound of formula (I); or b) reducing a compound of formula (IV)   wherein R, Rf, R'f, R1, and R2 are as defined in Claim 1, thus obtaining a compound of formula (I), wherein the symbol ---- is a single bond, and R, Rf, R'f, R1, and R2, are as defined in Claim 1, and, if desired, dehydrogenating the resulting compound of formula (I) to obtain another compound of formula (I) wherein the symbol ---- is a double bond, and R, Rf, R'f, R1, and R2, are as defined in Claim 1, and, if desired, alkylating a compound of formula (I) wherein the symbol ---- is a single or double bond, R is an hydrogen atom, R1, R2, Rf and R'f are as defined in Claim 1, so obtaining a compound of formula (I) wherein the symbol ---- is a single or double bond, R is a C1-C4 alkyl group, R1, R2, Rf and R'f are as defined in Claim 1, and, if desired, hydrogenating a compound of formula (I) wherein the symbol ---- is a double bond, R is a C1-C4 alkyl group, R1, R2, Rf, and R'f are as defined in Claim 1 to obtain a compound of formula (I) wherein the symbol ---- is a single bond, R is a C1-C4 alkyl group, R1, R2 Rf and R'f are as defined in Claim 1. 6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or diluent and, as an active principle, a compound of formula (I) as defined in Claim 1. 7. Use of a compound of formula (I) according to Claim 1 as a testosterone 5α-reductase inhibitor for use in the treatment of acne, seborrhoea, female hirsutism, male pattern baldness, policistic ovary disease and breast cancer, or for use in the treatment and/or chemoprevention of benign prostatic hyperplasia or of prostatic cancer.