Novel nonsteroidal selective estrogen receptor modulators. Carbon and heteroatom replacement of oxygen in the ethoxypiperidine region of raloxifene

C R Schmid; J P Sluka; K M Duke; A W Glasebrook

doi:10.1016/s0960-894x(99)00050-5

Novel nonsteroidal selective estrogen receptor modulators. Carbon and heteroatom replacement of oxygen in the ethoxypiperidine region of raloxifene

Bioorg Med Chem Lett. 1999 Feb 22;9(4):523-8. doi: 10.1016/s0960-894x(99)00050-5.

Authors

C R Schmid¹, J P Sluka, K M Duke, A W Glasebrook

Affiliation

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

PMID: 10098655
DOI: 10.1016/s0960-894x(99)00050-5

Abstract

Compounds were synthesized where oxygen in the ethoxypiperidine region of raloxifene is replaced with carbon, sulfur, or nitrogen linkages. Thia- and aza-substituted compounds were prepared by novel methodology. The compounds were evaluated in vitro as selective estrogen receptor modulators (SERMs). Calculations suggested the compounds exhibit an ER-alpha binding affinity/conformational energy relationship.

MeSH terms

Binding, Competitive
Carbon / chemistry*
Cell Division / drug effects
Cell Line
Crystallography, X-Ray
Humans
Oxygen / chemistry*
Piperidines / chemistry*
Piperidines / metabolism
Piperidines / pharmacology*
Raloxifene Hydrochloride
Receptors, Estrogen / drug effects*
Receptors, Estrogen / metabolism
Structure-Activity Relationship

Substances

Piperidines
Receptors, Estrogen
Raloxifene Hydrochloride
Carbon
Oxygen