abstract |
The present invention provides novel benzothiophene compounds of formula In n wherein n R is -H, -OH, -O(C₁-C₄ alkyl), -O-CO-(C₁-C₆ alkyl), -O-CO-Ar in which Ar is optionally substituted phenyl, or -O-SO₂-(C₄-C₆ alkyl); n R¹ is -H, -OH, -O(C₁-C₄ alkyl), -O-CO-(C₁-C₆ alkyl), -O-CO-Ar in which Ar is optionally substituted phenyl, -O-SO₂-(C₄-C₆ alkyl) chloro or bromo; n R is -H or -OH; n n is 2 or 3; and n R³ and R⁴ each are independently C₁-C₄ alkyl, or combine to form 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-l-pyrrolidinyl, 4-morpholino, or 1-hexamethyleneimino; nor a pharmaceutically acceptable salt thereof. n Further provided are methods for alleviating the symptoms of post-menopausal syndrome, and inhibiting endometriosis, uterine fibrosis, and aortal smooth muscle cell proliferation. Also provided are pharmaceutical formulations with formula I compounds, optionally including estrogen or progestin. n The present invention further provides a process for preparing a compound of formula Icn n wherein n R a and R 1a each are -OH or -OR⁵; n R³ and R⁴ each are independently C₁-C₄ alkyl, or combine to form 1-piperidinyl, 1-pyrrolidinyl, methoxy-1-pyrrolidinyl, dimethyl-l-pyrrolidinyl, 4-morpholino, or 1-hexamethyleneimino; and n R⁵ is a hydroxy protecting group capable of resisting reduction by a strong reducing agent; or a pharmaceutically acceptable salt thereof, which comprisesn a) optionally removing the R⁵ hydroxy protecting groups of a compound of formula IIn wherein n n, R³, R⁴, and R⁵ are as defined above, or a salt thereof; b) reacting said formula II compound with a reducing agent in the presence of a solvent having a boiling point in the range from about 150° C to about 200° C, and heating the mixture to reflux; and c) optionally salifying the reaction product from step b). |