Benzothiophene and naphthalene derived constrained SERMs.
For selective estrogen receptor modulators (SERMs), the orientation of the basic side chain relative to the SERM core has a significant impact on function. The synthesis and biological evaluation of two series of SERMs are disclosed, where the ligand side chain is constrained to adopt a defined orientation. Compounds where the side chain is forced into the plane of the SERM core have a different profile compared to those compounds where the side chain is pseudo-orthogonal, particularly with regard to antagonism of estradiol action on an Ishikawa uterine cell line.
Wallace
Owen B
OB
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. owen.wallace@lilly.com
Bryant
Henry U
HU
Shetler
Pamela K
PK
Adrian
Mary D
MD
Geiser
Andrew G
AG
D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008024:Ligands; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000502:physiology
D008024:Ligands; D009281:Naphthalenes; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; C088015:benzothiophene