Tibur Schmidlin

Valsartan, a potent, orally active angiotensin II antagonist developed from the structurally new amino acid series

Abstract Starting from the structure of DuP-753 and a 3-dimensional model of the pentapeptide Tyr-Ile-His-Pro-Ile, a series of new and highly potent antagonists has been designed where the imidazole moiety of the Du Pont compound has been replaced by an N-acylated aminoacid residue. VALSARTAN (Ex. 4e CGP48933, (S)-N-Valeryl-N-[2′-(1H-tetrazol-5-yl-)biphenyl-4-yl]methyl-valine), has been selected for clinical investigation.

Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists.

The design of a novel series of NPY-Y5 receptor antagonists is described. Key elements for the design were the identification of weak Y5 hits from a Y1 program, results from a combinatorial approach and database mining. This led to the discovery of the quinazoline 4 and the aryl-sulphonamide moiety as major components of the pharmacophore for Y5 affinity. The synthesis and SAR towards CGP71683A is described.