5-Aryl-1,2,3,4-tetrahydrochromeno[3,4-f]quinolin-3-ones as a novel class of nonsteroidal progesterone receptor agonists: effect of A-ring modification.

Article Details

Citation
Copy to clipboard

Zhi L, Tegley CM, Marschke KB, Mais DE, Jones TK

5-Aryl-1,2,3,4-tetrahydrochromeno[3,4-f]quinolin-3-ones as a novel class of nonsteroidal progesterone receptor agonists: effect of A-ring modification.

J Med Chem. 1999 Apr 22;42(8):1466-72.

PubMed ID
10212133 [ View in PubMed
]
Abstract

Optimization of the 1,2-dihydroquinoline A-ring of a nonsteroidal human progesterone receptor (hPR) agonist pharmacophore (1) was performed by using the cotransfection and receptor binding assays as guides. The 3-keto group was discovered to regain the potent agonist activity which was lost upon removal of the 3,4-olefin, and it led to a novel hPR agonist series, 5-aryl-1,2,3,4-tetrahydrochromeno[3, 4-f]quinolin-3-ones. The new progestins demonstrated potent hPR agonist activity in the cotransfection assay and high binding affinity similar to progesterone. T47D human breast cancer cell line was employed for further characterization of the new progestins and a number of reference analogues. It was found that the new 3-keto analogues showed full agonist activity in the T47D assay, while the reference compounds from other related nonsteroidal hPR agonist series exhibited only partial agonist activity.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Medroxyprogesterone acetateProgesterone receptorKi (nM)0.34N/AN/ADetails
Medroxyprogesterone acetateProgesterone receptorEC 50 (nM)0.15N/AN/ADetails
Medroxyprogesterone acetateProgesterone receptorEC 50 (nM)0.33N/AN/ADetails
ProgesteroneAndrogen receptorKi (nM)8.5N/AN/ADetails
ProgesteroneGlucocorticoid receptorKi (nM)31N/AN/ADetails
ProgesteroneProgesterone receptorKi (nM)3.5N/AN/ADetails
ProgesteroneProgesterone receptorEC 50 (nM)2.9N/AN/ADetails
ProgesteroneProgesterone receptorEC 50 (nM)1.8N/AN/ADetails