<atl>Substituted N-(3,5-Dichlorobenzenesulfonyl)-l-prolyl-phenylalanine analogues as potent VLA-4 antagonists

A series of substituted N-(3,5-dichlorobenzenesulfonyl)-l-prolyl- and α-methyl-l-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50∼1 nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series. [Copyright &y& Elsevier]