Document Report Card

ID: ALA1123786

Journal: J Med Chem

Title: Design of nonpeptidal ligands for a peptide receptor: cholecystokinin antagonists.

Authors: Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, Gould NP, Lundell GF, Homnick CF, Veber DF.

Abstract: A series of 3-substituted 5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), have been synthesized. Designed on the basis of facts regarding CCK, its natural-product antagonist asperlicin (3), and the antianxiety agent diazepam (4), these compounds represent a significant departure from existing CCK antagonists. They also constitute perhaps the first examples of simple, nonpeptidal ligands for a peptide receptor to arise by design rather than by screening. These compounds serve to illuminate the distinction between central and peripheral CCK receptors, as well as to provide orally effective CCK antagonists of potential pharmacological or therapeutic utility. One rationale for their receptor affinity has possible applications in the design of nonpeptidal ligands for other receptors, peptidal as well as nonpeptidal.

CiteXplore: 2885419

DOI: 10.1021/jm00390a019