title: Synthesis and biological activity of 5-methylidene 1,2-dihydrochromeno[3,4-f]quinoline derivatives as progesterone receptor modulators.
abstract: A series of 5-methylidene 1,2-dihydrochromeno[3,4-f]quinoline derivatives were synthesized and tested in biological assays to evaluate scope and limitations of the nonsteroidal SPRM pharmacophore (3). A number of orally available highly potent nonsteroidal modulators were identified by modification of the substituents at 5-methylidene position.
authors.affiliation: Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA. lzhi@ligand.com
authors.forename: Lin
authors.initials: L
authors.lastname: Zhi
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tegley
authors.forename: Barbara
authors.initials: B
authors.lastname: Pio
authors.forename: James P
authors.initials: JP
authors.lastname: Edwards
authors.forename: Todd K
authors.initials: TK
authors.lastname: Jones
authors.forename: Keith B
authors.initials: KB
authors.lastname: Marschke
authors.forename: Dale E
authors.initials: DE
authors.lastname: Mais
authors.forename: Boris
authors.initials: B
authors.lastname: Risek
authors.forename: William T
authors.initials: WT
authors.lastname: Schrader
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D011374:Progesterone / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014599:Uterus / Q000166:cytology / Q000187:drug effects
chemical_list: D011804:Quinolines; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D011374:Progesterone; D004958:Estradiol