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Specific and dual antagonists of alpha(4)beta(1) and alpha(4)beta(7) integrins
Linus S Lin1, Thomas Lanza, Ermenegilda McCauley
1Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. linus_lin@merck.com
Bioorganic & Medicinal Chemistry Letters
|January 5, 2002
Abstract:
N-(3,5-Dichlorophenylsulfonyl)-(R)-thioprolyl biarylalanine 10a has been identified as a potent and specific antagonist of the alpha(4)beta(1) integrin. Altering the configuration of thioproline from R to S led to a series of dual antagonists of alpha(4)beta(1) and alpha(4)beta(7), and the N-acetyl analogue 8b was found to be the most potent dual antagonist. A binding site model for alpha(4)beta(1) and alpha(4)beta(7) is proposed to explain the structure-activity relationship.