Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazolineneuropeptide YY5 receptor antagonists

The design of a novel series of NPY-Y-5 receptor antagonists is described. Key elements for the design were the identification of weak Y-5 hits from a Y-1 program, results from a combinatorial approach and database mining. Th is led to the discovery of the quinazoline 4 and the aryl-sulphonamide moie ty as major components of the pharmacophore for Y-5 affinity. The synthesis and SAR towards CGP71683A is described. (C) 2000 Elsevier Science Ltd. All rights reserved.