SYNTHESIS AND ANTI-ESTROGENIC ACTIVITY OF [3,4-DIHYDRO-2-(4-METHOXYPHENYL)-1-NAPHTHALENYL][4-[2-(1-PYRROLIDINYL)ETHOXY]PHENYL]METHANONE, METHANESULFONIC-ACID SALT

Acylation of the sodio anion of β-tetralone with phenyl anisoate, followed by a Grignard reaction of the resultant 4 with 4-methoxyphenylmagnesium bromide, gave rise to two novel dihydronaphthalene isomers 5 and 6. Regioselective demethylation of either 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 subcutaneous 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. © 1979, American Chemical Society. All rights reserved.