A comparative molecular field analysis and molecular modelling studies on pyridylimidazole type of angiotensin II antagonists

A large number of compounds known as "AII (Angiotensin II) antagonists" hav e been developed for the treatment of various heart diseases such as hypert ension, congestive heart failure, and chronic renal failure. Most of the cu rrently known AII receptor antagonists share a similar chemical structure, consisting of nitrogen atoms, a lipophilic alkyl side chain and an acidic g roup. As a new series, we have designed and synthesized various pyridylimid azole derivatives. In this report we would like to discuss the structure-ac tivity relationship of these series of compounds using the comparative mole cular field analysis (CoMFA) methods. We could come up with a good CoMFA mo del (cross-validated and conventional r(2) Values equal to 0.702 and 0.991, respectively) and the validity of the model was confirmed by synthesizing and measuring their biological activity of additional 6 compounds suggested by the model. This result provides additional information on the structura l requirement for structurally diverse group of AII receptor antagonists. ( C) 1999 Elsevier Science Ltd. All rights reserved.