Zhi L, Tegley C M, Edwards J P, West S J, Marschke K B, Gottardis M M, Mais D E, Jones T K
Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 1998 Dec 1;8(23):3365-70. doi: 10.1016/s0960-894x(98)00608-8.
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.
合成了一系列非甾体类人孕酮受体（hPR）激动剂，即5-烷基-1,2-二氢色烯并[3,4-f]喹啉，并在共转染和竞争性受体结合试验中进行了评估。结果表明，5-烷基取代是激动剂活性的原因，而C9位的取代显著增强了效力。该系列中的许多类似物在共转染和结合试验中表现出与孕酮相似或优于孕酮的活性，类似物15在小鼠子宫湿重/乳腺形态学试验中表现出与醋酸甲羟孕酮（MPA）相似的体内活性。
