IMIDAZOLE BASED NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONISTS - INVESTIGATION OF THE EFFECT OF THE ORIENTATION OF THE IMIDAZOLE RING ON BIOLOGICAL-ACTIVITY

Non-peptide angiotensin II receptor antagonists related to losartan (D uP 753, CAS 114798-26-4) were prepared and evaluated for antagonist ac tivity in the rat isolated uterus assay. The synthetic strategy concen trated on changes in the orientation of the imidazole ring relative to the substituents, which were maintained in a similar pattern to that found in losartan. The results indicate that biological activity of su ch antagonists shows little dependence on the orientation of the imida zole ring, but that the spacing of the substituents is of primary impo rtance.