| Literature DB >> 17402721 |
Carolyn D Dzierba1, Andrew J Tebben, Richard G Wilde, Amy G Takvorian, Maria Rafalski, Padmaja Kasireddy-Polam, John D Klaczkiewicz, Anthony D Pechulis, Amy L Davis, Mark P Sweet, Alex M Woo, Zhicai Yang, Sarah M Ebeltoft, Thaddeus F Molski, Ge Zhang, Robert C Zaczek, George L Trainor, Andrew P Combs, Paul J Gilligan.
Abstract
The CRF antagonist pharmacophore is a heterocyclic ring bearing a critical hydrogen-bond acceptor nitrogen and an orthogonal aromatic ring. CRFR1 antagonists have shown a 40-fold and 200-fold loss in potency against the CRFR1 H199V and M276I mutant receptors, suggesting key interactions with these residues. We have derived a two component computational model that correlates CRFR1 binding affinity within the reported series to antagoinst/H199 complexation energy and M276 hydrophobic contacts.Entities:
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Year: 2007 PMID： 17402721 DOI： 10.1021/jm0611410
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446