2-formyl-4-(4-phenylbutanoyloxymethyl)furan | 304642-44-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-formyl-4-(4-phenylbutanoyloxymethyl)furan
• 英文别名: (5-Formylfuran-3-yl)methyl 4-phenylbutanoate；(5-formylfuran-3-yl)methyl 4-phenylbutanoate
• CAS: 304642-44-2
• 化学式: C₁₆H₁₆O₄
• 分子量: 272.301
• InChiKey: POWNXBSCIIBJGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-formyl-4-(4-phenylbutanoyloxymethyl)furan 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.0h， 以83%的产率得到2-hydroxymethyl-3-(4-phenylbutanoyloxymethyl)furan
  参考文献：
  名称：

  Structure-Based Design of a Highly Selective Catalytic Site-Directed Inhibitor of Ser/Thr Protein Phosphatase 2B (Calcineurin)

  摘要：

  Protein serine/threonine phosphatases (PP1, PP2A and PP2B) play important roles in intracellular signal transcluctions. The immunosuppressant drugs FK506 and cyclosporin A (CsA) bind to immunophilins, and these complexes selectively inhibit PP2B (calcineurin), leading to the suppression of T-cell proliferation. Both FK506 and CsA must, however, form complexes with immunophilins to exert their inhibitory action on PP2B. Thus, it is of interest to find a direct and selective inhibitor of PP2B that does not involve the immunophilins as a biological tool for studies of PP2B and also as a candidate therapeutic agent. We selected the simple natural product cantharidin, a known PP2A-selective inhibitor, as a lead compound for this project. Primary SAR indicated that norcantharidin (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride) inhibits not only PP1 and PP2A but also PP2B, and a binding model of norcantharidin carboxylate to the PP2B catalytic site was computationally constructed. Based on this binding model, we designed and synthesized several cantharidin derivatives. Among these compounds, 1, 5-dibenzoyloxymethyl-substituted norcantharidin was found to inhibit PP2B without inhibiting PP1 or PP2A. To our knowledge, this is the first highly selective catalytic site-directed inhibitor of PP2B.

  DOI：

  10.1021/ja034694y
• 作为产物：
  描述：

  3-呋喃甲醇 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 31.0h， 生成 2-formyl-4-(4-phenylbutanoyloxymethyl)furan
  参考文献：
  名称：

  Structure-Based Design of a Highly Selective Catalytic Site-Directed Inhibitor of Ser/Thr Protein Phosphatase 2B (Calcineurin)

  摘要：

  Protein serine/threonine phosphatases (PP1, PP2A and PP2B) play important roles in intracellular signal transcluctions. The immunosuppressant drugs FK506 and cyclosporin A (CsA) bind to immunophilins, and these complexes selectively inhibit PP2B (calcineurin), leading to the suppression of T-cell proliferation. Both FK506 and CsA must, however, form complexes with immunophilins to exert their inhibitory action on PP2B. Thus, it is of interest to find a direct and selective inhibitor of PP2B that does not involve the immunophilins as a biological tool for studies of PP2B and also as a candidate therapeutic agent. We selected the simple natural product cantharidin, a known PP2A-selective inhibitor, as a lead compound for this project. Primary SAR indicated that norcantharidin (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride) inhibits not only PP1 and PP2A but also PP2B, and a binding model of norcantharidin carboxylate to the PP2B catalytic site was computationally constructed. Based on this binding model, we designed and synthesized several cantharidin derivatives. Among these compounds, 1, 5-dibenzoyloxymethyl-substituted norcantharidin was found to inhibit PP2B without inhibiting PP1 or PP2A. To our knowledge, this is the first highly selective catalytic site-directed inhibitor of PP2B.

  DOI：

  10.1021/ja034694y

文献信息

• Structure-Based Design of a Highly Selective Catalytic Site-Directed Inhibitor of Ser/Thr Protein Phosphatase 2B (Calcineurin)
  作者：Yoshiyasu Baba、Nozomu Hirukawa、Naoto Tanohira、Mikiko Sodeoka

  DOI：10.1021/ja034694y

  日期：2003.8.1

  Protein serine/threonine phosphatases (PP1, PP2A and PP2B) play important roles in intracellular signal transcluctions. The immunosuppressant drugs FK506 and cyclosporin A (CsA) bind to immunophilins, and these complexes selectively inhibit PP2B (calcineurin), leading to the suppression of T-cell proliferation. Both FK506 and CsA must, however, form complexes with immunophilins to exert their inhibitory action on PP2B. Thus, it is of interest to find a direct and selective inhibitor of PP2B that does not involve the immunophilins as a biological tool for studies of PP2B and also as a candidate therapeutic agent. We selected the simple natural product cantharidin, a known PP2A-selective inhibitor, as a lead compound for this project. Primary SAR indicated that norcantharidin (7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride) inhibits not only PP1 and PP2A but also PP2B, and a binding model of norcantharidin carboxylate to the PP2B catalytic site was computationally constructed. Based on this binding model, we designed and synthesized several cantharidin derivatives. Among these compounds, 1, 5-dibenzoyloxymethyl-substituted norcantharidin was found to inhibit PP2B without inhibiting PP1 or PP2A. To our knowledge, this is the first highly selective catalytic site-directed inhibitor of PP2B.