Synthesis and pharmacological activity of the metabolites of Pratosartan

  • Chem Pharm Bull (Tokyo). 2006 Jun;54(6):782-7. doi: 10.1248/cpb.54.782.
Motoharu Sonegawa  1 ,  Hiroaki Suzaka ,  Akira Tomiyama ,  Tsuyoshi Tomiyama
Affiliations
  • 1. Kotobuki Research Laboratories, Kotobuki Seiyaku Company, Ltd, Sakaki-Machi, Nagano 389-0697, Japan. [email protected]
PMID: 16755044 DOI: 10.1248/cpb.54.782
Abstract

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 II 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 (1)H-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-ylmethyl]-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one ((S)-(-)-1). 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.

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