The conformation and activity relationship of benzofuran type of angiotensin II receptor antagonists

As a continuing effort to establish the structure and activity relationship in a benzofuran type of angiotensin II antagonist, we synthesized various regioisomers and performed a series of QSAR analyses. The conformational an alyses of target isomers were carried out using molecular mechanics and fin e-tuned using the information from the NMR NOE experiment. The conformation s of compounds with a good binding activity are quite similar to that of Du P753, a prototype of AII antagonist, suggesting that these compounds also b ind to the same site of Ail receptor. We then studied the compounds with a varied length of the hydroxyl group bearing side chain to find out the opti mum distance between the hydroxyl group and the imidazole ring. The CoMFA w ith these compounds gave acceptable statistical measures (cross-validated r (2) and conventional r(2) to be 0.881 and 0.974, respectively) and the map was well consistent with the previously proposed pharmacophore. (C) 2000 El sevier Science Ltd. All rights reserved.