Synthesis and biological activity of trans-2,3-dihydroraloxifene

C R Schmid; A L Glasebrook; J W Misner; G A Stephenson

doi:10.1016/s0960-894x(99)00145-6

Synthesis and biological activity of trans-2,3-dihydroraloxifene

Bioorg Med Chem Lett. 1999 Apr 19;9(8):1137-40. doi: 10.1016/s0960-894x(99)00145-6.

Authors

C R Schmid¹, A L Glasebrook, J W Misner, G A Stephenson

Affiliation

¹ Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285-4813, USA.

PMID: 10328300
DOI: 10.1016/s0960-894x(99)00145-6

Abstract

The synthesis and biological evaluation of trans-2,3-dihydroraloxifene, 2, is described. The synthesis proceeds in 8 steps in 20% overall yield. Relative trans 2,3-stereochemistry is definitively established in ester 6, which is converted to the title compound via derivatization, Grignard addition, and deprotection. Evaluation in vitro shows the compound to be a potent selective estrogen receptor modulator (SERM).

MeSH terms

Binding, Competitive
Cell Division / drug effects
Dose-Response Relationship, Drug
Estrogen Antagonists / pharmacology*
Models, Molecular
Piperidines / chemical synthesis*
Piperidines / chemistry
Raloxifene Hydrochloride
Tumor Cells, Cultured

Substances

2,3-dihydroraloxifene
Estrogen Antagonists
Piperidines
Raloxifene Hydrochloride