5-Aryl-1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal human progesterone receptor agonists.
Article Details
- CitationCopy to clipboard
Zhi L, Tegley CM, Kallel EA, Marschke KB, Mais DE, Gottardis MM, Jones TK
5-Aryl-1,2-dihydrochromeno[3,4-f]quinolines: a novel class of nonsteroidal human progesterone receptor agonists.
J Med Chem. 1998 Jan 29;41(3):291-302.
- PubMed ID
- 9464360 [ View in PubMed]
- Abstract
The development of a novel class of nonsteroidal human progesterone receptor (hPR) agonists, 5-aryl-1,2-dihydro-5H-chromeno[3,4-f]quinolines 2, is described. The introduction of a 5-aryl group into the 1,2-dihydrocoumarino[3,4-f]quinoline core 1 is the key for progestational activities. The structure-activity relationship (SAR) studies of the 5-aryl substituents generated a series of potent hPR agonists, which exhibited similar biological activity (EC50 = 8-30 nM) to the natural hormone progesterone (EC50 = 2.9 nM) in cell-based assays with efficacies ranging from 28% to 96%. Most of the analogues displayed similar or greater binding affinity (Ki = 0.41-3.6 nM) than progesterone (Ki = 3.5 nM). Three representative analogues (13, 15, and 24) demonstrated in vivo activities in mammary gland morphology/uterine wet weight assay in ovariectomized rats.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Medroxyprogesterone acetate Progesterone receptor Ki (nM) 0.34 N/A N/A Details Medroxyprogesterone acetate Progesterone receptor EC 50 (nM) 0.15 N/A N/A Details Progesterone Androgen receptor IC 50 (nM) 37 N/A N/A Details Progesterone Androgen receptor Ki (nM) 8.5 N/A N/A Details Progesterone Glucocorticoid receptor IC 50 (nM) >1000 N/A N/A Details Progesterone Glucocorticoid receptor Ki (nM) 30.5 N/A N/A Details Progesterone Mineralocorticoid receptor IC 50 (nM) 14 N/A N/A Details Progesterone Progesterone receptor Ki (nM) 3.5 N/A N/A Details Progesterone Progesterone receptor EC 50 (nM) 2.9 N/A N/A Details