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ID: ALA1149493
Journal: Bioorg Med Chem Lett
Title: Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: optimization of the 4-substituted piperidine.
Authors: Burgey CS, Stump CA, Nguyen DN, Deng JZ, Quigley AG, Norton BR, Bell IM, Mosser SD, Salvatore CA, Rutledge RZ, Kane SA, Koblan KS, Vacca JP, Graham SL, Williams TM.
Abstract: In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented.
CiteXplore: 16889959