Przejdź do zawartości
Merck
  • 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.

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.

Bioorganic & medicinal chemistry (2008-10-28)
Fumihito Muro, Shin Iimura, Yoshiyuki Yoneda, Jun Chiba, Toshiyuki Watanabe, Masaki Setoguchi, Yutaka Iigou, Gensuke Takayama, Mika Yokoyama, Tohru Takashi, Atsushi Nakayama, Nobuo Machinaga
ABSTRAKT

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.