1H-Imidazo[4,5-c]quinoline derivatives as novel potent TNF-α suppressors: synthesis and structure–activity relationship of 1-, 2-and 4-substituted 1H-imidazo[4,5-c]quinolines or 1H-imidazo[4,5-c]pyridines

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• 作者：Izumi ; Tomoyuki ; Sakaguchi ; Jun ; Takeshita ; Makoto ; Tawara ; Harumi ; Kato ; Ken-ichi ; Dose ; Hitomi ; et. al.
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2003
• 出版时间：June 12, 2003
• 年：2003
• 卷：11
• 期：12
• 页码：2541-2550
• 全文大小：301 K

文摘

Structural modification of imiquimod (1), which is known as an interferon-α (IFN-α) inducer, for the aim of finding a novel and small-molecule tumor necrosis factor-α (TNF-α) suppressor and structure–activity relationship (SAR) are described. Structural modification of a imiquimod analogue, 4-amino-1-[2-(1-benzyl-4-piperidyl)ethyl-1H-imidazo[4,5-c]quinoline (2), which had moderate TNF-α suppressing activity without IFN-α inducing activity, led to a finding of 4-chloro-2-phenyl-1-[2-(4-piperidyl)ethyl]-1H-imidazo[4,5-c]quinoline (10) with potent TNF-α suppressing activity. The relation between conformational direction of 2-(4-piperidyl)ethyl group at position 1 and TNF-α suppressing activity is also demonstrated by NMR.