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 1) and 61.2 ± 1.0 mmHg (compound 4) 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 1 were consistent with its anti-hypertension effects in vivo. The safety of new compounds was confirmed by the influence on the rats’ heart rates and other symptoms which couldn’t been observed during whole process. Thence, compounds 1 and 4 may be considered as potential antihypertension drug candidates.