952210-98-9Relevant academic research and scientific papers
Synthesis and biological evaluation of benzoic acid derivatives as potent, orally active VLA-4 antagonists
Chiba, Jun,Iimura, Shin,Yoneda, Yoshiyuki,Watanabe, Toshiyuki,Muro, Fumito,Tsubokawa, Masao,Iigou, Yutaka,Satoh, Atsushi,Takayama, Gensuke,Yokoyama, Mika,Takashi, Tohru,Nakayama, Atsushi,Machinaga, Nobuo
, p. 1679 - 1693 (2008/02/03)
A series of benzoic acid derivatives was synthesized as VLA-4 antagonists. Introduction of chlorine or bromine into the 3-position on the central benzene of the diphenylurea portion as in lead compound 2 led to improvement in the pharmacokinetic properties. In particular, 12l demonstrated an acceptable plasma clearance and bioavailability in mice and rats as well as dogs (mice, CL = 18.5 ml/min/kg, F = 28 %; rats, CL = 5.2 ml/min/kg, F = 36 %; dogs, CL = 3.6 ml/min/kg, F = 55 %). Additionally, 12l exhibited potent activity with an IC50 value of 0.51 nM and efficacy by oral administration at a dosage of 10 mg/kg in a rat pleurisy model.
