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-alky l 1,2-dihydrochromeno[3,4-f]quinolines, was synthesized and evaluated in co transfection and competitive receptor binding assays. The 5-alkyl substitut ion was shown to be responsible for the agonist activity and substitution a t C9 dramatically enhanced the potency. A number of analogues in this serie s showed activities similar to or better than progesterone in the cotransfe ction and binding assays and analogue 15 exhibited similar in vivo activity as medroxyprogesterone acetate (MPA) in murine uterine wet weight/mammary gland morphology assays. (C) 1998 Elsevier Science Ltd. All rights reserved .