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Preparation of imidazoles as potent calcitonin gene-related peptide (CGRP) antagonists |
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| Authors: | George Tora Andrew P. Degnan Charles M. Conway Walter A. Kostich Carl D. Davis Sokhom S. Pin Richard Schartman Cen Xu Kimberly A. Widmann John E. Macor Gene M. Dubowchik |
| Affiliation: | 1. Medicinal Chemistry, Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb, 311 Pennington-Rocky Hill Road, Pennington, NJ 08534, USA;2. Medicinal Chemistry, Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT 06492-7660, USA |
| Abstract: | Several new potent CGRP receptor antagonists have been prepared in which the amide bond of lead compound 1 has been replaced by bioisosteric imidazole moieties. Substitution at N-1 of the imidazole was optimized to afford compounds with comparable potency to that of lead 1. Conformational restraint of the imidazole to form tetrahydroimidazo[1,5-a]pyrazine 43 gave substantially improved permeability. |
| Keywords: | CGRP receptor antagonists CGRP Migraine Migraineurs Imidazoles |
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