5-Alkyl 1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal progesterone receptor modulators.
A series of nonsteroidal human progesterone receptor (hPR) agonists, 5-alkyl 1,2-dihydrochromeno[3,4-f]quinolines, was synthesized and evaluated in cotransfection and competitive receptor binding assays. The 5-alkyl substitution was shown to be responsible for the agonist activity and substitution at C9 dramatically enhanced the potency. A number of analogues in this series showed activities similar to or better than progesterone in the cotransfection and binding assays and analogue 15 exhibited similar in vivo activity as medroxyprogesterone acetate (MPA) in murine uterine wet weight/mammary gland morphology assays.
Zhi
L
L
Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Tegley
C M
CM
Edwards
J P
JP
West
S J
SJ
Marschke
K B
KB
Gottardis
M M
MM
Mais
D E
DE
Jones
T K
TK
D000818:Animals; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011980:Receptors, Progesterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013329:Structure-Activity Relationship
D011804:Quinolines; D011980:Receptors, Progesterone