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  • Title: Design of LFA-1 antagonists based on a 2,3-dihydro-1H-pyrrolizin-5(7aH)-one scaffold.
    Author: Dodd DS, Sheriff S, Chang CJ, Stetsko DK, Phillips LM, Zhang Y, Launay M, Potin D, Vaccaro W, Poss MA, McKinnon M, Barrish JC, Suchard SJ, Murali Dhar TG.
    Journal: Bioorg Med Chem Lett; 2007 Apr 01; 17(7):1908-11. PubMed ID: 17291752.
    Abstract:
    A new class of lymphocyte function-associated antigen-1 (LFA-1) antagonists is described. Elaboration of the 2,3-dihydro-1H-pyrrolizin-5(7aH)-one scaffold resulted in the synthesis of potent inhibitors of the LFA-1/ICAM-1 interaction. Along with the in vitro activity, we present the X-ray crystal structure of the complex of compound 9b, in a novel binding mode to the I-domain of LFA-1.
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