Title of article :
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 Original Research Article
Author/Authors :
Fumihito Muro، نويسنده , , Shin Iimura، نويسنده , , Yoshiyuki Yoneda، نويسنده , , Jun Chiba، نويسنده , , Toshiyuki Watanabe، نويسنده , , Masaki Setoguchi، نويسنده , , Yutaka Iigou، نويسنده , , Gensuke Takayama، نويسنده , , Mika Yokoyama، نويسنده , , Tohru Takashi، نويسنده , , Atsushi Nakayama، نويسنده , , Nobuo Machinaga، نويسنده ,
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 α4 antibody (R1-2). Furthermore, this compound significantly blocked bronchial hyper-responsiveness in the model.
