Identification of N-acyl 4-(3-pyridonyl)phenylalanine derivatives and their orally active prodrug esters as dual acting α4β1 and α4β7 receptor antagonists.

From a series of N-acyl 4-(3-pyridonyl)phenylalanine derivatives, the trifluoromethyl derivative 28 was identified as a potent, dual acting alpha4 integrin antagonist with activity in primate models of allergic asthma. The prodrug ester 48 gave high blood levels of 28 when dosed orally in cynomolgus monkeys, but was only slowly converted in dogs.