Biphenyl compounds and use thereof as oestrogenic agents

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

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514732, 514734, 514735, 514736, 564337, 568718, 568719, 568730, A61K 31135, C07C21103

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061471194

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BRIEF SUMMARY
This application is a 371 of PCT/FR97/00184 filed Jan. 30, 1997.
A subject of the invention is new biphenyl compounds, their preparation process and the intermediates of this process, their use as medicaments and the pharmaceutical compositions containing them.
A subject of the invention is the compounds of general formula (I): ##STR2## in which [X] represent the following aromatic carbocycles: ##STR3## in which R.sub.1 represents an alkyl radical containing from 1 to 4 carbon atoms or a hydrogen atom, R.sub.2 represents an alkyl radical containing from 1 to 4 carbon atoms or a hydrogen atom, R.sub.3 represents a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 4 carbon atoms or an alkoxy radical containing from 1 to 4 carbon atoms, R.sub.4 in para or meta position represents a hydrogen atom, a halogen atom, a hydroxyl radical, an alkyl, alkenyl or alkynyl radical containing at most 4 carbon atoms, an alkoxy, alkylthio radical in which alkyl contains from 1 to 4 carbon atoms, an --NR.sub.A R.sub.B group in which R.sub.A and R.sub.B identical or different represent a hydrogen atom, an alkyl radical containing from 1 to 4 carbon atoms or form together with the nitrogen to which they are linked a saturated heterocycle with 5 or 6 members optionally containing a second heteroatom chosen from nitrogen, oxygen and sulphur, their --NR.sub.A R.sub.B group being optionally in oxidized form, a group of general formula --O--(CH.sub.2).sub.n --NR.sub.A R.sub.B in which n is an integer which varies from 2 to 7 and in which --NR.sub.A R.sub.B is as defined previously, R.sub.5 represents a hydrogen atom or a halogen atom, R.sub.6 and R.sub.7 identical or different represent a hydrogen atom, a halogen atom, an alkyl radical containing from 1 to 4 carbon atoms, or a phenyl radical optionally substituted in meta or para position by an R.sub.4 radical as defined previously as well as the addition salts with acids or bases, with the exception of the compounds of formula (I) in which [X] represents the group (A) in which R.sub.1, R.sub.2, R.sub.3 are hydrogen atoms and R.sub.4 represents a hydroxyl radical and those in which [X] represents the group (B) in which R.sub.5, R.sub.6 and R.sub.7 are hydrogen atoms or R.sub.5 and R.sub.6 are hydrogen atoms and R.sub.7 represents an alkyl radical containing from 1 to 4 carbon atoms.
When R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.6, R.sub.7, R.sub.A and R.sub.B represent an alkyl radical containing from 1 to 4 carbon atoms, it is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radical. When R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are halogen atoms, it is fluorine, chlorine, bromine or iodine. Preferably, it is chlorine. When R.sub.4 is an alkenyl radical containing at most 4 carbon atoms, preferably it is a vinyl or propenyl radical. When R.sub.4 is an alkynyl radical containing at most 4 carbon atoms, preferably it is an ethynyl or propynyl radical. When R.sub.3 or R.sub.4 represent an alkyloxy radical containing from 1 to 4 carbon atoms, preferably it is a methoxy, ethoxy, propyloxy, isopropyloxy or butyloxy radical. When R.sub.4 is an alkylthio radical containing from 1 to 4 carbon atoms, preferably it is a methylthio, ethylthio, propylthio, isopropylthio or butylthio radical. When R.sub.4 is an NR.sub.A R.sub.B radical in which R.sub.A and R.sub.B identical or different represent a hydrogen atom or an alkyl radical containing from 1 to 4 carbon atoms, preferably it is an amino, methylamino, ethylamino, dimethylamino, diethylamino or methylethylamino radical. When R.sub.4 is an --NR.sub.A R.sub.B group in which R.sub.A and R.sub.B form with the nitrogen a saturated heterocycle, preferably it is pyrrolidino, piperidino, piperazino, morpholino or thiomorpholino groups, each of these amino groups being optionally in oxidized form.
Naturally the invention extends to the salts of the compounds de formula (I), in particular when the compounds of formula (I) contain an amino function. These are the salts formed for example with the following ac

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