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  • Title: Identification of 4-[1-[3-chloro-4-[N'-(5-fluoro-2-methylphenyl)ureido]phenylacetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]benzoic acid as a potent, orally active VLA-4 antagonist.
    Author: Muro F, Iimura S, Yoneda Y, Chiba J, Watanabe T, Setoguchi M, Iigou Y, Takayama G, Yokoyama M, Takashi T, Nakayama A, Machinaga N.
    Journal: Bioorg Med Chem; 2008 Dec 01; 16(23):9991-10000. PubMed ID: 18952443.
    Abstract:
    Optimization of benzoic acid derivatives by introducing substituents into the diphenyl urea moiety led to the identification of compound 20l as a potent VLA-4 antagonist. Compound 20l inhibited eosinophil infiltration into bronchial alveolar lavage fluid in a murine asthma model by oral dosing and its efficacy was comparable to anti-mouse alpha4 antibody (R1-2). Furthermore, this compound significantly blocked bronchial hyper-responsiveness in the model.
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