Design, Synthesis, and Structure−Affinity Relationships of Novel Series of Sialosides as CD22-Specific Inhibitors

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• 作者：Hajjaj H. M. Abdu-Allah ; Taichi Tamanaka ; Jie Yu ; Lu Zhuoyuan ; Magesh Sadagopan ; Takahiro Adachi ; Takeshi Tsubata ; Soerge Kelm ; Hideharu Ishida ; Makoto Kiso
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：November 13, 2008
• 年：2008
• 卷：51
• 期：21
• 页码：6665-6681
• 全文大小：411K
• 年卷期：v.51,no.21(November 13, 2008)
• ISSN：1520-4804

文摘

Sialosides incorporating substituted amides or amines at 9-position of sialic acid moiety have been synthesized and evaluated as CD22 inhibitors. Several derivatives exhibited inhibitory potency in sub- to low micromolar range (e. g., 8o, 9d, 9g, and 9k showed IC₅₀ values 0.40, 0.47, 0.24, and 0.23 μM, respectively, for hCD22, while 8p, 8q, and 9f, showed IC₅₀ values 1.70, 2.90, and 4.10 μM, respectively, for mCD22). The most significant result was the strongly enhanced affinity of 9g and 9k containing 9-(2′ or 4′-hydroxy-4-biphenyl) methylamino substituents (600-fold more potent for hCD22 than the corresponding 9-hydroxy derivative; 7a). Molecular modeling study was carried out to get some insights into the molecular basis of CD22 inhibition. To the best of our knowledge, this is the first systematic structure−affinity relationship study on inhibition of CD22.