Synthesis and antiestrogenic activity of [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]phenyl]methanone, methanesulfonic acid salt

Publisher Website
Google Scholar
Abstract
Acylation of the sodio anion of .beta.-tetralone with phenyl anisoate, followed by a Grignard reaction of the resultant 4 [3,4-dihydro-1-(4-methoxybenzoyl)-2(1H)-naphthalenone] with 4-methoxyphenylmagnesium bromide, gave rise to 2 novel dihydronaphthalene isomers 5 [[1,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl](4-methoxyphenyl)methanone] and 6 [[3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl](4-methoxyphenyl)methanone]. Regioselective demethylation of 5 or 6 by NaSEt produced [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl](4-hydroxyphenyl)methanone (7). Etherification of the phenolic group of 7 by N-(2-chloroethyl)pyrrolidine and subsequent methanesulfonate salt formation provided [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]phenyl]methanone, methane sulfonic acid salt (3). Potent antiestrogenic activity of 3 was demonstrated by both oral and s.c. administration to rats and mice. In vitro binding studies with rat uterine cytosol estrogen receptors indicate compound 3 has a very high binding affinity which exceeds that of estradiol.

This publication has 0 references indexed in Scilit: