methyl 1-hydroxy-8-methoxy-6,6-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate | 65012-24-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 1-hydroxy-8-methoxy-6,6-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate
• CAS: 65012-24-0
• 化学式: C₁₇H₂₂O₄
• 分子量: 290.359
• InChiKey: AVFYGCKSPBDQFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  55.76
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 1-hydroxy-8-methoxy-6,6-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate 在 sodium periodate 、 四氧化锇 、 对甲苯磺酸 作用下， 以 苯 为溶剂， 生成
  参考文献：
  名称：

  Total synthesis of illudinine, illudalic acid, and illudacetalic acid

  摘要：

  DOI：

  10.1021/ja00466a038
• 作为产物：
  描述：

  methyl 8-methoxy-2,2-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate 在 chromium(VI) oxide 、 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 methyl 1-hydroxy-8-methoxy-6,6-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate
  参考文献：
  名称：

  Total synthesis of illudinine, illudalic acid, and illudacetalic acid

  摘要：

  DOI：

  10.1021/ja00466a038

文献信息

• Synthesis and PTP Inhibitory Activity of Illudalic Acid and Its Methyl Ether, with Insights into Selectivity for LAR PTP over Other Tyrosine Phosphatases under Physiologically Relevant Conditions
  作者：Brandon S. McCullough、Paratchata Batsomboon、Kacey B. Hutchinson、Gregory B. Dudley、Amy M. Barrios

  DOI：10.1021/acs.jnatprod.9b00663

  日期：2019.12.27

  includes many attractive therapeutic targets, such as those in the leukocyte common antigen-related (LAR) subfamily of receptor PTPs. Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether are described, with a focus on selective inhibition of LAR PTP relative to a small collection of other representative PTPs. The synthesis comprises 16 steps and provides illudalic acid in up to

  蛋白质酪氨酸磷酸酶（PTP）酶家族包括许多有吸引力的治疗靶标，例如受体PTP的白细胞常见抗原相关（LAR）亚家族中的靶标。描述了乙二酸及其甲基醚的合成和PTP抑制活性，重点是相对于少量其他代表性PTP选择性抑制LAR PTP。合成过程包括16个步骤，并从新戊烯基稠合的苯甲酸酯1（购自商业原料的20个步骤）中提供了高达12％的总产率的杜鹃酸。与以前的共价结合报道相一致，异丁酸的剂量依赖性（测得的IC50 = 2.1±0.2μM）和时间依赖性抑制LAR。杜鹃酸对LAR的抑制动力学与两步机制一致，其中抑制剂和酶首先非共价相互作用（KI = 130±50μM），然后以kinact = 1.3±0.4 min-1的速率共价连接。如本文所讨论的，运动/ KI之比104对应于0.5分钟的∞1/2。在我们的剂量反应分析中，发现伊达酸的酚甲基醚效力较低（测得的IC50 = 55±6μM），但对LAR的选择性
• Illudalic acid as a potential LAR inhibitor: Synthesis, SAR, and preliminary studies on the mechanism of action
  作者：Qing Ling、Yue Huang、Yueyang Zhou、Zhengliang Cai、Bing Xiong、Yahui Zhang、Lanping Ma、Xin Wang、Xin Li、Jia Li、Jingkang Shen

  DOI：10.1016/j.bmc.2008.06.014

  日期：2008.8

  A novel synthesis of the human leukocyte common antigen-related (LAR) phosphatase inhibitor, illudalic acid, has been achieved by a route more amenable to structure modi. cations. A series of simpler analogues of illudalic acid was synthesized and evaluated for potency in inhibiting LAR. The structure -activity relationship (SAR) study has shown that the 5-formyl group and the hemi-acetal lactone are crucial for effective inhibition of LAR activity, and are the key pharmacophores of illudalic acid. The fused dimethylcyclopentene ring moiety evidently helps to enhance the potency of illudalic acid against LAR. A preliminary study of the mechanism of action of illudalic acid against LAR was conducted using electrospray ionization mass spectrometry (ESI-MS) and molecular docking techniques. The results are in full agreement with the described mechanism. (C) 2008 Elsevier Ltd. All rights reserved.