Synthesis and evaluation of isoxazole derivatives as lysophosphatidic acid (LPA) antagonists

Takashi Yamamoto; Koichi Fujita; Sayaka Asari; Akira Chiba; Yuka Kataba; Koji Ohsumi; Naoko Ohmuta; Yuko Iida; Chiori Ijichi; Satoshi Iwayama; Naoyuki Fukuchi; Masataka Shoji

doi:10.1016/j.bmcl.2007.04.024

Synthesis and evaluation of isoxazole derivatives as lysophosphatidic acid (LPA) antagonists

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3736-40. doi: 10.1016/j.bmcl.2007.04.024. Epub 2007 Apr 10.

Authors

Takashi Yamamoto¹, Koichi Fujita, Sayaka Asari, Akira Chiba, Yuka Kataba, Koji Ohsumi, Naoko Ohmuta, Yuko Iida, Chiori Ijichi, Satoshi Iwayama, Naoyuki Fukuchi, Masataka Shoji

Affiliation

¹ Pharmaceutical Research Laboratories, Ajinomoto Company Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki-shi 210-8681, Japan.

PMID: 17467986
DOI: 10.1016/j.bmcl.2007.04.024

Abstract

A series of isoxazole derivatives were synthesized and their antagonistic activities against LPA stimulation on both LPA(1)/CHO cells and rHSC cells were evaluated. Among them, 3-(4-[4-[1-(2-chloro-cyclopent-1-enyl)-ethoxycarbonylamino]-isoxazol-3- y]]-benzylsulfanyl)-propionic acid (34) showed the most potent activities.

MeSH terms

Animals
CHO Cells
Cell Proliferation
Chemistry, Pharmaceutical / methods*
Cricetinae
Cricetulus
Drug Design
Fibrosis / pathology
Humans
Inhibitory Concentration 50
Isoxazoles / chemical synthesis*
Isoxazoles / chemistry
Liver / cytology
Lysophospholipids / antagonists & inhibitors*
Lysophospholipids / chemistry
Propionates / chemistry
Rats

Substances

Isoxazoles
Lysophospholipids
Propionates
propionic acid
lysophosphatidic acid