A New Class Of Balanced At(1)/At(2) Angiotensin-Ii Antagonists - Quinazolinone Aii Antagonists With Acylsulfonamide And Sulfonylcarbamate Acidic Functionalities

The structure activity relationships of a series of 2-alkyl-6-(acylamino)-3-[((2'-acylaminosulfonyl)biphenyl-4- yl)methyl]quinazolin-4-(3H)-ones were studied in order to identify balanced angiotensin II antagonists capable of potent binding to both AT(1) and AT(2) angiotensin receptor subtypes. The optimization of the substitution pattern led to the discovery of a potent, balanced quinazolinone antagonist L-162,393, which displayed long lasting blockade of angiotensin presser response in rats, dogs and rhesus monkeys.