Design, synthesis and bioactivities of novel diarylthiophenes: inhibitors of tumor necrosis factor-alpha (TNF-alpha) production.
The design, synthesis and SAR of novel diarylthiophene derivatives were performed. These compounds were designed by structural hybridization of TNF-alpha production inhibitors bearing 4-fluorophenyl and 4-pyridyl groups such as FR133605, FR167653 and SB210313, and 6-acetyl-3-ethoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine (1) found previously by us. As a result, several compounds were more potent in vitro than FR133605 against TNF-alpha production stimulated with lipopolysaccharide (LPS).
Fujita
Masakazu
M
Pharmaceutical Research Laboratories, Nikken Chemicals Co., Ltd., 1-346, Kitabukuro-cho, Saitama-shi, Saitama, Japan. mfujita-nikken@nifty.com
Hirayama
Tetsuya
T
Ikeda
Naoko
N
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D001798:Blood Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015195:Drug Design; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; C105818:FR 133605; C104334:FR 167653; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011720:Pyrazoles; D011725:Pyridines; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha