A tissue-selective nonsteroidal progesterone receptor modulator: 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4- f]quinoline.

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Pedram B, van Oeveren A, Mais DE, Marschke KB, Verbost PM, Groen MB, Zhi L

A tissue-selective nonsteroidal progesterone receptor modulator: 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4- f]quinoline.

J Med Chem. 2008 Jul 10;51(13):3696-9. doi: 10.1021/jm8004256. Epub 2008 Jun 14.

PubMed ID
18553958 [ View in PubMed
]
Abstract

The progesterone receptor plays an important role in the female reproductive system. Here we describe the discovery of a new selective progesterone receptor modulator (SPRM). In rats, the lead compound, 7,9-difluoro-5-(3-methylcyclohex-2-enyl)-2,2,4-trimethyl-1,2-dihydrochromeno[3,4- f]quinoline ( 5c), inhibited ovulation and showed full efficacy in uterine and vaginal tissue but was a mixed partial agonist/antagonist in breast tissue. The compound also suppressed ovulation in monkeys, but in contrast to currently approved steroidal PR agonists, it did not suppress estradiol levels.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Medroxyprogesterone acetateProgesterone receptorEC 50 (nM)0.5N/AN/ADetails
Medroxyprogesterone acetateProgesterone receptorEC 50 (nM)0.4N/AN/ADetails
Medroxyprogesterone acetateProgesterone receptorKi (nM)1.4N/AN/ADetails
ProgesteroneProgesterone receptorEC 50 (nM)0.5N/AN/ADetails
ProgesteroneProgesterone receptorEC 50 (nM)2.2N/AN/ADetails
ProgesteroneProgesterone receptorKi (nM)3.4N/AN/ADetails