Structure-based design of six novel classes of nonpeptide antagonists of the bradykinin B-2 receptor

Six classes of nonpeptide bradykinin antagonists were designed using a temp late derived from structural studies of peptide antagonists. Several compou nds from each class were synthesized and assayed for binding to the human b radykinin B-2 receptor. Each family showed compounds active at the level of the smallest template peptide; three classes contained compounds with K-d < 8 <mu>M. These results provide diverse leads for a medicinal chemistry-ba sed optimization program. (C) 2000 Elsevier Science Ltd. All rights reserve d.