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.
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D011817:Rabbits; D051381:Rats; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005466:Fluorocarbons
D000804:Angiotensin II; D014633:Valine; C032415:hexafluorovaline; D005466:Fluorocarbons