title: A new series of estrogen receptor modulators: effect of alkyl substituents on receptor-binding affinity.
abstract: New types of selective estrogen receptor modulators (SERMs) were synthesized and evaluated for their binding affinity and biological effect on reproductive cells. A proposed lead structure (B) was derivatized to provide compounds 30 and 44, which showed good estrogen-receptor binding affinity (K(i) values: 6.3 and 10 nM, respectively), as well as minimal impact on mammary and uterine carcinoma cells. Introduction of an alkyl group in the core structure considerably enhanced receptor-binding affinity of the compounds tested. Synthesis and structure-activity relationships of these compounds are described.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co., Ltd.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kitazawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okabe
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Nara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hamaoka
authors.forename: Shin
authors.initials: S
authors.lastname: Araki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hagiwara
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000478:Alkylation; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol; D000469:Alkaline Phosphatase