Author/Authors :
Cory R. Theberge، نويسنده , , Rodney A. Bednar، نويسنده , , Ian M. Bell، نويسنده , , Halea A. Corcoran، نويسنده , , John F. Fay، نويسنده , , James C. Hershey، نويسنده , , Victor K. Johnston، نويسنده , , Stefanie A. Kane، نويسنده , , Scott Mosser، نويسنده , , Christopher A. Salvatore، نويسنده , , Theresa M. Williams، نويسنده , , C. Blair Zartman، نويسنده , , Xufang Zhang، نويسنده , , Samuel L. Graham، نويسنده , , Joseph P. Vacca، نويسنده ,
Abstract :
The previously disclosed spirohydantoin-based CGRP receptor antagonists were optimized for potency through modification of the benzimidazolone substituents. Compounds were identified which had minimal shift in the cAMP functional assay containing 50% human serum. Blockade of CGRP-mediated vasodilation was observed with these compounds in a rhesus pharmacodynamic assay and the in vivo potency correlated with the in vitro activity in the serum-shifted functional assay.
Keywords :
Migraine , CGRP , Benzimidazole , Spirohydantoin
