5-benzylidene-1,2-dihydrochromeno[3,4-f]quinolines as selective progesterone receptor modulators.
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.
Zhi
Lin
L
Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, California 92121, USA. lzhi@ligand.com
Tegley
Christopher M
CM
Pio
Barbara
B
Edwards
James P
JP
Motamedi
Mehrnouch
M
Jones
Todd K
TK
Marschke
Keith B
KB
Mais
Dale E
DE
Risek
Boris
B
Schrader
William T
WT
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
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