Bioorganic & Medicinal Chemistry Letters 2011-01-01

Structure-activity relationship (SAR) of the α-amino acid residue of potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonists.

Min Zhong, Emily J Hanan, Wang Shen, Minna Bui, Michelle R Arkin, Kenneth J Barr, Marc J Evanchik, Ute Hoch, Jennifer Hyde, Jose R Martell, Johan D Oslob, Kumar Paulvannan, Saileta Prabhu, Jeffrey A Silverman, Jasmin Wright, Chul H Yu, Jiang Zhu, W Mike Flanagan

Index: Bioorg. Med. Chem. Lett. 21(1) , 307-10, (2011)

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Abstract

This letter describes the structure-activity relationship (SAR) of the 'right-wing' α-amino acid residue of potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonists. Novel (S)-substituted heteroaryl-bearing α-amino acids have been identified as replacements of the 'right-wing' (S)-2,3-diaminopropanoic acid (DAP) moiety. Improvement of potency in the Hut-78 assay in the presence of 10% human serum has also been achieved.Copyright © 2010 Elsevier Ltd. All rights reserved.