Synthesis and evaluation of new sartan derivatives

As prodrugs series of new sartan-derived molecules were designed, synthesized, and evaluated. Most of the synthesized compounds could decrease blood pressure efficiently in spontaneously hypertensive rats. It could be ratiocinated that the original drugs could be released from the prodrugs exactly at the connecting position catalyzed by the hydrolyzation enzymes. The maximal response of mean blood pressure (MBP) lowered 70.2 ± 5.0 mmHg (compound I1) and 61.2 ± 1.0 mmHg (compound II1) at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan and were similar with Telmisartan. Pharmacokinetics test results of I1 were consistent with its antihypertension effects in vivo. The safety was confirmed by the influence on the rats’ heart rates and other symptoms which could not be observed during the whole process. Therefore, compounds I1 and II1 could be considered potential antihypertension drug candidates.