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ID: ALA1135072

Journal: Bioorg Med Chem Lett

Title: Substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl-phenylalanine analogues as potent VLA-4 antagonists.

Authors: Kopka IE, Young DN, Lin LS, Mumford RA, Magriotis PA, MacCoss M, Mills SG, Van Riper G, McCauley E, Egger LE, Kidambi U, Schmidt JA, Lyons K, Stearns R, Vincent S, Colletti A, Wang Z, Tong S, Wang J, Zheng S, Owens K, Levorse D, Hagmann WK.

Abstract: A series of substituted N-(3,5-dichlorobenzenesulfonyl)-L-prolyl- and alpha-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 approximately 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.

CiteXplore: 11844689

DOI: 10.1016/s0960-894x(01)00821-6