Design, synthesis, and biological evaluation of 1,2,3,7-tetrahydro-6h-purin-6-one and 3,7-dihydro-1h-purine-2,6-dione derivatives as corticotropin-releasing factor(1) receptor antagonists

Journal of Medicinal Chemistry
Richard A HartzGeorge L Trainor

Abstract

A growing body of evidence suggests that CRF(1) receptor antagonism offers considerable therapeutic potential in the treatment of diseases resulting from elevated levels of CRF, such as anxiety and depression. A series of novel 1,2,3,7-tetrahydro-6H-purin-6-one and 3,7-dihydro-1H-purine-2,6-dione derivatives was synthesized and evaluated as corticotropin releasing factor-1 (CRF(1)) receptor antagonists. Compounds within this series, represented by compound 12d (IC(50) = 5.4 nM), were found to be highly potent CRF(1) receptor antagonists. In addition, compounds 12d and 12j were determined to be selective CRF(1) antagonists. The synthesis, structure-activity relationships and pharmacokinetic properties of compounds within this series is presented.

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Citations

Jul 1, 2006·Expert Opinion on Therapeutic Patents·Paul J Gilligan
Jul 25, 2015·Molecular BioSystems·Eleonora CorradiniArjen Scholten
Jan 23, 2013·Magnetic Resonance in Chemistry : MRC·Charles PathiranaVenkatapuram Palaniswamy
Apr 25, 2006·Molecular Pharmacology·Martin Beinborn
Dec 10, 2016·Organic Letters·Megumi NoshitaTakashi Ohshima

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