Naphthyl and dihydronaphthyl intermediates, compounds,...

C - Chemistry – Metallurgy – 07 – D

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C07D 295/088 (2006.01) A61K 31/135 (2006.01) A61K 31/21 (2006.01) A61K 31/40 (2006.01) A61K 31/445 (2006.01) A61K 31/535 (2006.01) A61K 31/55 (2006.01) C07C 49/82 (2006.01) C07C 49/84 (2006.01) C07C 205/45 (2006.01) C07C 217/20 (2006.01) C07C 225/20 (2006.01) C07D 207/06 (2006.01) C07D 295/092 (2006.01)

Patent

CA 2228178

The present invention provides compounds of formula (I), wherein R1 is -H, -OH, -O(C1-C4 alkyl), - OCO6H5, -OCO(C1-C6 alkyl), or -OSO2(C4-C6 alkyl); R2 is C1-C6 alkyl or C5-C7 cycloalkyl which is optionally substituted with 1 to 3 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, hydroxy, amino, nitro, and halo; X is -CH(OH)- or -CH2- ; M is -CH2CH2- or -CH=CH-; n is 2 or 3; and R3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof. Also provided are methods of using the compounds of the present invention for the treatment of various medical indications associated with post-menopausal syndrome, uterine fibroid disease, endometriosis, and aortal smooth muscle cell profiferation. The present invention further provides pharmaceutical compositions of compounds of formula (I), as well as intermediate compounds for the preparation thereof.

La présente invention porte sur des composés de formule (I), où R1 est -H, -OH, -O(alkyle en C1-C4), -OCO6H5, -OCO(alkyle en C1-C6) ou -OSO2(alkyle en C4-C6 ); R2 est un alkyle en C1-C6 ou un cycloalkyle en C5-C7 qui est facultativement substitué par 1 à 3 substituants choisis parmi les groupes alkyle en C1-C4, alcoxy en C1-C4, hydroxy, amino, nitro, et halo; X est -CH(OH)- ou -CH2-; M est -CH2CH2- ou -CH=CH-; n est 2 ou 3; et R3 est un groupe 1-pipéridinyle, 1-pyrrolidinyle, méthyl-1-pyrrolidinyle, diméthyl-1-pyrrolidinyle, 4-morpholino, diméthylamino, diéthylamino ou 1-hexaméthylèneimino; ou un sel pharmaceutiquement acceptable de ces derniers. On fournit également des méthodes d'utilisation des composés de la présente invention pour le traitement de divers états médicaux liés au syndrome post-ménopausique, à la fibrose utérine, à l'endométriose et à la prolifération des cellules des muscles lisses de l'aorte. La présente invention porte également sur des formulations pharmaceutiques des composés de formule (I) ainsi que sur des composés intermédiaires pour la préparation de ces dernières.

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