Synthesis and pharmacological activity of the metabolites of Pratosartan.

Three hydroxylated metabolites of 2-propyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (Pratosartan), which is a selective angiotensin 11 receptor antagonist, were synthesized in confirmation of their structures and in studies of their pharmacological properties. An MTPA ester of the human main metabolite was identified with the synthesized compound by comparing H-1-NMR spectra, MS spectra, and HPLC retention time. The structure of the human main metabolite was confirmed to be (S)-(-)-2(1 -hydroxypropyl)-3- [2'-(1H-tetrazol-5-yl)biphenyl-4-ylm ethyl]-5,6,7,8-tetrahydro-3H-cyclo heptimidazol-4-one Also, the rat main metabolites were confirmed to be 8-hydroxylated compound (2) and 5-hydroxylated compound (3). These metabolites showed lower antagonistic activity than that of the parent compound.