title: 5-benzylidene-1,2-dihydrochromeno[3,4-f]quinolines as selective progesterone receptor modulators.
abstract: A series of 5-benylidene-1,2-dihydrochromeno[3,4-f]quinolines (4) were synthesized and tested in bioassays to evaluate their progestational activities, receptor- and tissue-selectivity profiles as selective progesterone receptor modulators (SPRMs). Most of the new analogues exhibited as highly potent progestins with more than 100-fold receptor selectivity over other steroid hormone receptors and LG120920 (7b) demonstrated tissue selectivity toward uterus and vagina versus breasts in a rodent model after oral administration.
authors.affiliation: Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, California 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: Mehrnouch
authors.initials: M
authors.lastname: Motamedi
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: D059002:Androgen Receptor Antagonists; D000818:Animals; D001597:Benzylidene Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004970:Estrone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects; D017258:Medroxyprogesterone Acetate / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D045167:Progesterone Congeners / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014599:Uterus / Q000166:cytology / Q000187:drug effects; D014621:Vagina / Q000166:cytology / Q000187:drug effects
chemical_list: D059002:Androgen Receptor Antagonists; D001597:Benzylidene Compounds; D045167:Progesterone Congeners; D011804:Quinolines; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D004970:Estrone; D011374:Progesterone; D017258:Medroxyprogesterone Acetate