Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369627 | Bioorganic & Medicinal Chemistry Letters | 2012 | 4 Pages |
Abstract
We report the synthesis of rigid spirocyclic systems as conformationally constrained variants of the Ala-Phe-NH2 dipeptide amide C-terminus of the calcitonin gene-related peptide (CGRP). CGRP receptor antagonists containing these moieties displayed potent affinity, functional antagonism and excellent oxidative stability. Structure–activity relationship studies demonstrated the relative importance of hydrogen bond donor/acceptor functionalities and the preferred orientation of an aromatic ring. Antagonists showed potent and full reversal of CGRP-induced dilation of ex vivo human intracranial arteries.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Prasad V. Chaturvedula, Sokhom Pin, George Tholady, Charlie M. Conway, John E. Macor, Gene M. Dubowchik,