No abstract

A selective estrogen receptor modulator (SERM) for the potential treatment of hot flushes is described. (R)-(+)-7,9-difluoro-5-[4-(2-piperidin-1-ylethoxy)phenyl]-5H-6-oxachrysen-2-ol, LSN2120310, potently binds ERalpha and ERbeta and is an antagonist in MCF-7 breast adenocarcinoma and Ishikawa uterine cancer cell lines. The compound is a potent estrogen antagonist in the rat uterus. In ovariectomized rats, the compound lowers cholesterol, maintains bone mineral density, and is efficacious in a morphine dependent rat model of hot flush efficacy.

Quinoline derivatives Quinoline derivatives R 0410Tetrahydroquinoline-Based Selective Estrogen Receptor Modulators (SERMs).-The design and synthesis of a series of substituted tetrahydroquinolines such as (VI) and (X) starting from commercially available N-oxide (I), their binding affinities to estrogen receptors and antagonism of estradiol in MCF-7 breast adenocarcinoma cells are reported. Compound (X) is the most potent inhibitor of MCF-7 proliferation identified in this series. -(WALLACE*, O. B.; LAUWERS, K. S.; JONES, S. A.; DODGE, J. A.; Bioorg. Med.