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Identification of novel SAR properties of the Jak2 small molecule inhibitor G6: Significance of the para-hydroxyl orientation

  作者 Baskin, R; Gali, M; Park, SO; Zhao, ZJ; Keseru, GM; Bisht, KS; Sayeski, PP  
  选自 期刊  Bioorganic & Medicinal Chemistry Letters;  卷期  2012年22-3;  页码  1402-1407  
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[摘要]In this study, we analyzed the structure-activity relationship properties of the small molecule Jak2 inhibitor G6. We synthesized a set of derivatives containing the native para-hydroxyl structure or an alternative meta-hydroxyl structure and examined their Jak2 inhibitory properties. We found that the para-hydroxyl derivative known as NB15 had excellent Jak2 inhibitory properties in silico, in vitro, and ex vivo when compared with meta-hydroxyl derivatives. These results indicate that NB15 is a potent derivative of the Jak2 inhibitor G6, and that maintaining the para-hydroxyl orientation of G6 is critical for its Jak2 inhibitory potential. (C) 2011 Elsevier Ltd. All rights reserved.

 
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