924309-79-5Relevant academic research and scientific papers
BENZOISOINDOLE DERIVATIVES AND THEIR USE AS EP4 RECEPTOR AGONISTS
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Page/Page column 34, (2008/12/05)
The present invention relates to benzoisoindole phenylacetic acid derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine as EP4 receptor organists.
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.
