Patent EA-001868-B1 (EA)
Title: Steroids, substituted in position 11, method of preparation, application as medicines and pharmaceutical compositions containing same
Inventor: BOUALI YAMINA
IPC: C07J41/00
Filed: 1997-12-22
Abstract: 1. Compounds of general formula (I):   in which: n is an integer equal to 2 or 3, either R1 and R2 which may be identical or different, represent a hydrogen atom or an alkyl radical containing from 1 to 4 carbon atoms, either R1 and R2 form together with the nitrogen atom to which they are bound, a mono or polycyclic heterocycle, having from 5 to 15 units, aromatic or non-aromatic, optionally containing from 1 to 3 additional heteroatoms selected from oxygen, sulphur and nitrogen, substituted or unsubstituted. X represents a hydroxyl radical, optionally esterified, and Y represents a substituted or unsubstituted alkyl radical containing from 1 to 4 carbon atoms, , as well as their pharmaceutically acceptable salts of addition with acids. 2. Compounds of general formula (I) as defined in Claim 1, in which n is equal to 2, as well as their pharmaceutically acceptable salts of addition with acids. 3. Compounds of general formula (I) as defined in Claim 1 or 2 in which n is equal to 2, either R1 and R2, which may be identical or different, represent an alkyl radical containing from 1 to 4 carbon atoms, or R1 and R2 form, together with the nitrogen atom to which they are bound, a piperidino, pyrrolidino or 2-azabicyclo(2.2.1)hept-2-yl group, X represents a hydroxyl radical and Y represents a methyl or ethyl radical, as well as their pharmaceutically acceptable salts of addition with acids. 4. Compounds of general formula (I) as defined in any one of the Claims 1 to 3 as well as their pharmaceutically acceptable salts of addition with acids, the names of which are given below: -11β-[4-[2-(1-piperidinyl)ethoxy]phenyl]-19-nor-17α-pregna-1,3,5(10)-triene-3,17β-diol, -17α-methyl-11β-[4-[2-(1-piperidinyl)ethoxy]phenyl]-oestra-1,3,5(10)-triene-3,17β-diol, -17α-methyl-11β-[4-[2-(diethylamino)ethoxy]phenyl]-oestra-1,3,5(10)-triene-3,17β-diol, -17α-methyl-11β-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-oestra-1,3,5(10)-triene-3,17β-diol, -17α-methyl-11β-[4-[2-(2-aza-bicyclo(2.2.1)hept-2-yl)ethoxy]phenyl]-oestra-1,3,5(10)-triene-3,17β-diol, -11β-[4-[2-(2-aza-bicyclo(2.2.1)hept-2-yl)ethoxy]phenyl]-19-nor-17α-pregna-1,3,5(10)-triene-3,17β-diol, -17α-(trifluoromethyl)-11β-[4-[2-(1-piperidinyl)ethoxy]phenyl]-oestra-1,3,5(10)-triene-3,17β-diol. 5. A method of preparation of the compounds of general formula (I) as defined in Claim 1, characterized in that a compound of general formula (II):   in which n, R1 and R2 are as defined in Claim 1, is submitted to the action of an organometallic compound derived from an alkyl radical, containing from 1 to 4 carbon atoms so as to form the compounds of formula (I) in which X is a hydroxyl group and Y is an alkyl group containing from 1 to 4 carbon atoms, this obtained compound being submitted if necessary to a reaction of esterification of the 17-OH group or to a reaction of salification. 6. A method of preparation of the compounds of general formula (I) as defined in Claim 1, with Y representing an alkyl radical containing from 2 to 4 carbon atoms, characterized in that a compound of general formula (III):   in which n, R1 and R2 are as defined previously and in which Y' represents an alkenyl or alkynyl group containing from 2 to 4 carbon atoms, is submitted to the action of a reducing agent of the double bond or of the triple bond, in order to obtain the compounds of formula (I) in which X is a hydroxyl group and Y is an alkyl group containing from 2 to 4 carbon atoms, this compound of formula (I) being submitted if necessary to a reaction of esterification of the 17-OH group and/or to a reaction of salification. 7. Use of the compounds of general formula (I) as defined in Claim 1 as medicines. 8. Use of the compounds of general formula (I) as defined in Claims 2, 3 or 4 as medicines. 9. Use of the compounds of general formula (I) as defined in Claim 1 as medicines for hormone replacement therapy of the menopause or of the perimenopause, in particular for prevention or treatment of osteoporosis, exhibiting little or no oestrogen activity with respect to the uterus, and for protection of cardiovascular system. 10. Use of the compounds of general formula (I) as defined in Claim 1 as medicines for hormone replacement therapy of the menopause or of the perimenopause, in particular for prevention or treatment of osteoporosis in women at risk from mammary tumours. 11. Pharmaceutical compositions containing the compound as defined in Claim 1.