ChemInform Abstract: Discovery of 1,5‐Benzodiazepines with Peripheral Cholecystokinin (CCK‐ A) Receptor Agonist Activity (II): Optimization of the C3 Amino Substituent.

Abstract

Discovery of 1,5-Benzodiazepines with Peripheral Cholecystokinin (CCK-A) Receptor Agonist Activity (II): Optimization of the C3 Amino Substituent.-The synthesis and biological profile of analogues of (VIIa) are reported which explore both substitution and/or replacement of the C-3-position phenyl urea moiety. The goal is to identify compounds which are orally active agents in a rat feeding model. The derivatives (VIIb) and (VIId) are potent, fully efficacious and orally active in the mouse gallbladder emptying assay. (VIIb) is a potent mixed CCK-A agonist/CCK-B antagonist which is orally active in two in vivo models of CCK-A mediated agonist activity. -(HIRST, G. C.; AQUINO, C.; BIRKEMO, L.; CROOM, D. K.; DEZUBE, M.; DOUGHERTY, R. W. JUN.; ERVIN, G. N.; GRIZZLE, M. K.; HENKE, B.; JAMES, M. K.; JOHNSON, M. F.; MOMTAHEN, T.; QUEEN, K. L.; SHERRILL, R. G.; SZEWCZYK, J.; WILLSON, T. M.; SUGG, E. E.; J. Med.