Synthesis and Biological Evaluation of Novel Antihypertensive Compounds

Hypertension has been associated as a pathogenesis involved in the renin angiotensin system. The most commonly used drug to block the AT 1 R, is Losartan which has specific pharmacophore groups such as imidazole and biphenyl. However the development of new selective antagonists would be advantagous to improving the treatment of hypertension. We investigated innovative antihypertensive candidates 1-3 using in vitro and in vivo assays. Although only Compound 2 showed low affinity to the AT 1 R, it had no effect on blood pressure. Compound 1 produced a reduction in blood pressure and this effect seems to be mediated through ACE inhibition and not the blockage of the AT 1 R. Compound 1 was able to inhibit the ACE activity in a similar way to captopril, while Compounds 2 and 3 showed no effect on the enzyme activity. Further studies need to be conducted to understand the mechanisms involved as well as signaling pathways.