C-linked pyrazole biaryl tetrazoles as antagonists of angiotensin II Part II: pharmacokinetics and an efficient regioselective synthesis

• Published in: Bioorganic & medicinal chemistry letters Vol. 4; no. 1; pp. 151 - 156
• Main Authors: Watson, S.P., Middlemiss, D., Pass, M., Hubbard, T., Panchai, T.A., Heron, N.M., Paton, J.M.S., Butt, A., Dean, A.W., Donnelly, M., Bayliss, M.K.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1994
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)81138-0

C-linked N-alkyl pyrazole biaryl tetrazoles (1) are highly potent antagonists of angiostensin II. Pharmacokinetic parameters in the rat are reported for two of these compounds. The N-cyclopropylmethyl pyrazole (1a) has an oral bioavailability of 58%. In addition an efficient regioselective synthesis of pyrazoles (1) is described. C-linked N-alkyl biaryl tetraoles (1) are highly potent antagonists of angiotensin II. Pharmacokinetic parameters in the rat are reported for two of these compounds. The N-cyclopropylmethyl pyrazole (1a) has an oral bioavailability of 58%. In additiion an efficient regioselective synthesis of pyrazoles (1) is described.