Discovery of potent and selective orally bioavailable β-substituted phenylalanine derived dipeptidyl peptidase IV inhibitors

anti-Substituted biaryl beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors that suffer from suboptimal selectivity and pharmacokinetics. This letter describes the substitution of the beta-methyl substituent with beta-polar substituents, culminating in the discovery of a beta-dimethylamide substituted phenylalanine derivative with an excellent potency, selectivity, and pharmacokinetic profile. (c) 2005 Elsevier Ltd. All rights reserved.