Benzofuran based angiotensin II antagonists related to GR117289: enhancement of potency in vitro and oral activity

• Published in: Bioorganic & medicinal chemistry letters 1993, Vol.3 (4), p.589-594
• Main Authors: Middlemiss, D., Watson, S.P., Ross, B.C., Dowle, M.D., Scopes, D.I.C., Montana, J.G., Shah, P., Hirst, G.C., Panchal, T.A., Paton, J.M.S., Pass, M., Hubbard, T., Hamblett, J., Cardwell, K.S., Jack, T.I., Stuart, G., Coote, S., Bradshaw, J., Drew, G.M., Hilditch, A., Clark, K.L., Robertson, M.J., Bayliss, M.K., Donnelly, M., Palmer, E., Manchee, G.R.M.
• Format: Article
• Language: English
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)81235-X

A study of structure activity relationships based on the bromobenzofuran angiotensin II antagonist GR117289 is reported. This study led to the identification of compounds with potency in vitro enhanced by ca. 10 fold. Also reported is the enhancement of the oral activity of the acid analogue (1) conferred by formation of the double ester pro-drug (2). Prodrug (2) causes marked and long-lasting falls in blood pressure after oral administration at 0.3 mg/kg in renal artery ligated hypertensive rats. A study of structure activity relationships based on the bromobenzofuran angiotensin II antagonist GR117289 is reported. Also reported is the enhancement of the oral activity of a close analogue of GR117289 conferred by formation of the double ester pro-drug (2) Graphic