Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines.

Article Details

Citation
Copy to clipboard

Arhancet GB, Woodard SS, Dietz JD, Garland DJ, Wagner GM, Iyanar K, Collins JT, Blinn JR, Numann RE, Hu X, Huang HC

Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines.

J Med Chem. 2010 May 27;53(10):4300-4. doi: 10.1021/jm1002827.

PubMed ID
20408553 [ View in PubMed
]
Abstract

A number of known 1,4-dihydropyridine CCBs were identified as having comparable potency to the steroidal MR antagonist eplerenone. Chiral resolution of mebudipine revealed that MR and CCB activity reside in opposite enantiomers. Small molecule X-ray crystal structures showed that the C4 stereochemistry of optimized selective MR analogues, e.g. 5, is consistent with MR-active mebudipine. Molecular modeling supports a binding pose consistent with that previously proposed for DHP diesters.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
EplerenoneMineralocorticoid receptorIC 50 (nM)135N/AN/ADetails