Novel nonsteroidal selective estrogen receptor modulators. Carbon and heteroatom replacement of oxygen in the ethoxypiperidine region of raloxifene.
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.
Schmid
C R
CR
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Sluka
J P
JP
Duke
K M
KM
Glasebrook
A W
AW
D001667:Binding, Competitive; D002244:Carbon / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D010100:Oxygen / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020849:Raloxifene Hydrochloride; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D010880:Piperidines; D011960:Receptors, Estrogen; D020849:Raloxifene Hydrochloride; D002244:Carbon; D010100:Oxygen