Author/Authors :
Christopher S. Burgey، نويسنده , , Craig A. Stump، نويسنده , , Diem N. Nguyen، نويسنده , , James Z. Deng، نويسنده , , Amy G. Quigley، نويسنده , , Beth R. Norton، نويسنده , , Ian M. Bell، نويسنده , , Scott D. Mosser، نويسنده , , Christopher A. Salvatore، نويسنده , , Ruth Z. Rutledge، نويسنده , , Stefanie A. Kane، نويسنده , , Kenneth S. Koblan، نويسنده , , Joseph P. Vacca، نويسنده , , Samuel L. Graham، نويسنده , , Theresa M. Williams، نويسنده ,
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.
