Serendipitous oxidation product of BIBN4096BS: a potent CGRP receptor antagonist.

Abstract An oxidation product ( 5 ) formed during the synthesis of BIBN-4096BS ( 1 ) was found to be a potent CGRP antagonist (IC 50 = 0.11 nM). While 5 was found to be ten-fold less potent than 1 , another analog 8 with lower molecular weight containing the oxidized fragment demonstrated twenty-fold higher activity than its parent 7 . Alternative conditions which preclude the formation of the oxidation product are described. The activities of 1 , 5 , 7 and 8 in functional cAMP assay are also discussed.