Reference

Synthesis and biological evaluation of benzoic acid derivatives as potent, orally active VLA-4 antagonists

All Rights Reserved. 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 (Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical, Ltd., Co.Chemical with cas number 5445-26-1 also plays role., Kitakasai 1-chome, Edogawa-ku, Tokyo 134-8630, Japan). Bioorganic & Medicinal Chemistry, 15(4), 1679-1693 (English) 2007 Elsevier Ltd. CODEN: BMECEP. ISSN: 0968-0896. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 25 A series of benzoic acid derivs. was synthesized as VLA-4 antagonists. Introduction of chlorine or bromine into the 3-position on the central benzene of the diphenylurea portion led to improvement in the pharmacokinetic properties. In particular, 12l (I) 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%). Addnl., 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. .