Synthesis and bioactivities of novel bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridines as inhibitors of tumor necrosis factor-alpha (TNF-alpha) production.
We synthesized bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives, and evaluated for their ability to inhibit LPS-stimulated production of TNF-alpha. Several compounds revealed excellent in vivo activity. Furthermore, an effective compound was found in adjuvant-induced arthritic model (AIA) of rat.
Pharmaceutical Research Laboratories, Nikken Chemicals Co., Ltd., 1-346, Kitabukuro-cho, Saitama-shi, Saitama 330-0835, Japan. mfujita-nikken@nifty.com
Masakazu
M
Fujita
Taketsugu
T
Seki
Naoko
N
Ikeda
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004195:Disease Models, Animal; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D001643:Bridged Bicyclo Compounds; D008070:Lipopolysaccharides; D011725:Pyridines; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha