Long-acting angiotensin II inhibitors containing hexafluorovaline in position 8.

An improved synthesis of hexafluorovaline (Hfv) derivatives, i.e., DL-Hfv-OBzl and Boc-DL-Hfv, is described. Incorporation of hexafluorovaline into angiotensin resulted in [Sar1,Hfv8]AII and [Sar1,D-Hfv8]AII. At the nanogram/milliliter dose range, the L congener was 20-100 times more active as either angiotensin agonist or angiotensin antagonist than its D diastereomer on isolated tissue preparations. At the microgram dose range, both [Sar1,Hfv8]AII and [Sar1,D-Hfv8]AII were significantly more effective than [Sar1,Leu8]AII as angiotensin II inhibitors, producing prolonged blockade of the pressor response toward angiotensin II for over 1 h.