Discovery of novel phosphonic acid derivatives as new chemical leads for inhibitors of TNF-alpha production

Toshiaki Matsui; Shinya Takahashi; Naoki Matsunaga; Kazunori Nakamura; Nagashige Omawari; Masaru Sakai; Wataru Kamoshima; Kouichiro Terai; Hiroyuki Ohno; Takaaki Obata; Hisao Nakai; Masaaki Toda

doi:10.1016/s0968-0896(02)00343-7

Discovery of novel phosphonic acid derivatives as new chemical leads for inhibitors of TNF-alpha production

Bioorg Med Chem. 2002 Dec;10(12):3807-15. doi: 10.1016/s0968-0896(02)00343-7.

Authors

Toshiaki Matsui¹, Shinya Takahashi, Naoki Matsunaga, Kazunori Nakamura, Nagashige Omawari, Masaru Sakai, Wataru Kamoshima, Kouichiro Terai, Hiroyuki Ohno, Takaaki Obata, Hisao Nakai, Masaaki Toda

Affiliation

¹ Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Yamagishi, Mikuni, Sakai, Fukui, Japan. [email protected]

PMID: 12413834
DOI: 10.1016/s0968-0896(02)00343-7

Abstract

2-(Acylamino)benzylphosphonic acid 6 derived from an artificial substrate of sphingomyelinase was found to show inhibitory activity of TNF-alpha production. Structural optimization was started with the chemical modification of 6. The discovery of another chemical leads 7, 8, 10 and 16 for the development of structurally new inhibitors of TNF-alpha production is reported.

MeSH terms

Animals
Dose-Response Relationship, Drug
Indans / chemical synthesis*
Indans / pharmacology
Inhibitory Concentration 50
Injections, Intraperitoneal
Lipopolysaccharides / pharmacology
Male
Mice
Mice, Inbred BALB C
Phosphinic Acids / chemical synthesis*
Phosphinic Acids / pharmacology
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / analysis
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Tumor Necrosis Factor-alpha / biosynthesis

Substances

Indans
Lipopolysaccharides
Phosphinic Acids
Tumor Necrosis Factor-alpha