3-furylmethyl 4-phenylbutanoate | 191471-32-6

• 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: 3-furylmethyl 4-phenylbutanoate
• 英文别名: (Furan-3-yl)methyl 4-phenylbutanoate；furan-3-ylmethyl 4-phenylbutanoate
• CAS: 191471-32-6
• 化学式: C₁₅H₁₆O₃
• 分子量: 244.29
• InChiKey: WBZDXJHCGRJKBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-furylmethyl 4-phenylbutanoate 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 27.0h， 生成 2-hydroxymethyl-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
• 作为产物：
  描述：

  3-呋喃甲醇 、 4-苯基丁酸 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 27.0h， 以69%的产率得到3-furylmethyl 4-phenylbutanoate
  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 novel calcineurin (PP2B) inhibitors
  作者：John H. Tatlock、M. Angelica Linton、Xinjun J. Hou、Charles R. Kissinger、Laura A. Pelletier、Richard E. Showalter、Anna Tempczyk、J. Ernest Villafranca

  DOI：10.1016/s0960-894x(97)00141-8

  日期：1997.4

  The design, synthesis, and evaluation of small molecule, in vitro, inhibitors of human calcineurin is described. These ligands were derived from the known nonspecific phosphatase inhibitor endothall, and were modified to enhance binding and selectivity toward calcineurin using protein crystal structure information. (C) 1997 Elsevier Science Ltd.
• 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.