The design, binding affinity prediction and synthesis of macrocyclic angiotensin II AT1 and AT2 receptor antagonists

Analysis of the SAR of AT1 selective and AT1/AT2 balanced affinity angiotensin II antagonists led to the design of macrocyclic quinazolinone ligands. CoMFA analysis was used to predict the binding affinities of these novel ligands. The synthesis, X-ray crystal structure, binding affinity and the relevance of these studies to the determination of the biologically relevant binding conformation is discussed.