7-ethyl-10-(prop-2-ynyloxy)camptothecin | 1436411-00-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: 7-ethyl-10-(prop-2-ynyloxy)camptothecin
• 英文别名: (S)-4,11-diethyl-4-hydroxy-9-(prop-2-yn-1-yloxy)-1,12-dihydro-14H-pyrano[3,4’:6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione；(19S)-10,19-diethyl-19-hydroxy-7-prop-2-ynoxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
• CAS: 1436411-00-5
• 化学式: C₂₅H₂₂N₂O₅
• 分子量: 430.46
• InChiKey: VAFHRLNZTJHJLI-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  89
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-ethyl-10-(prop-2-ynyloxy)camptothecin 在 copper(l) iodide 、 茴香硫醚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 26.0h， 生成 8-[4-[[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]oxymethyl]triazol-1-yl]-N-hydroxyoctanamide
  参考文献：
  名称：

  Dual-acting histone deacetylase-topoisomerase I inhibitors

  摘要：

  Current chemotherapy regimens are comprised mostly of single-target drugs which are often plagued by toxic side effects and resistance development. A pharmacological strategy for circumventing these drawbacks could involve designing multivalent ligands that can modulate multiple targets while avoiding the toxicity of a single-targeted agent. Two attractive targets, histone deacetylase (HDAC) and topoisomerase I (Topo I), are cellular modulators that can broadly arrest cancer proliferation through a range of downstream effects. Both are clinically validated targets with multiple inhibitors in therapeutic use. We describe herein the design and synthesis of dual-acting histone deacetylase-topoisomerase I inhibitors. We also show that these dual-acting agents retain activity against HDAC and Topo I, and potently arrest cancer proliferation. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.03.108
• 作为产物：
  描述：

  (S)-9-((2,6-bis(prop-2-yn-1-yloxy)benzyl)oxy)-4,11-diethyl-4-hydroxy-1,12-dihydro-14H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione 在 palladium 、 potassium carbonate 作用下， 以 aq. phosphate buffer 、 N,N-二甲基甲酰胺 为溶剂， 生成 7-ethyl-10-(prop-2-ynyloxy)camptothecin
  参考文献：
  名称：

  通过钯功能化微器件对伊立替康活性代谢物进行生物正交解笼

  摘要：

  SN-38 是伊立替康的活性代谢物，在肝脏水解后释放，介导有效的抗肿瘤活性。然而，全身暴露于 SN-38 也会导致严重的副作用。为了通过控制 SN-38 生成的地点和时间来降低全身毒性，专门设计了一种新的前药，使其代谢稳定并能快速进行钯介导的激活。用 2,6-双（炔丙氧基）苄基阻断 SN-38 的酚羟基导致细胞毒性活性显着降低（高达 44 倍）。在异质钯 (Pd) 催化剂存在下，抗癌特性迅速恢复，可杀死结直肠癌和神经胶质瘤细胞，证明了这种新型芳香羟基掩蔽策略的有效性。与 Pd 激活的 5FU 前药组合增强了治疗的抗增殖效力，而在没有 Pd 源的情况下则没有活性，这说明了通过相同的生物正交催化剂顺序或同时实现多种已批准治疗药物的控制释放的好处以增加抗癌活性。

  DOI：

  10.1002/chem.201803725

文献信息

• Protein Modification at Tyrosine with Iminoxyl Radicals
  作者：Katsuya Maruyama、Takashi Ishiyama、Yohei Seki、Kentaro Sakai、Takaya Togo、Kounosuke Oisaki、Motomu Kanai

  DOI：10.1021/jacs.1c09066

  日期：2021.12.1

  acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes;

  蛋白质的翻译后修饰 (PTM) 是一种可逆地控制蛋白质功能的生物学机制。特定规范氨基酸的合成蛋白修饰 (SPM) 可以模拟 PTM。然而，蛋白质中疏水氨基酸残基上的可逆 SPM 尤其有限。在这里，我们报告了一种酪氨酸 (Tyr) 选择性 SPM，它利用持久的亚氨基氧基自由基，这些自由基很容易通过单电子氧化从空间位阻肟生成。亚氨氧基自由基与 Tyr 的反应性取决于肟的空间和电子需求；异丙基甲基哌啶肟1f形成稳定的加合物，而叔丁基甲基哌啶肟1o的反应是可逆的。1f和1o之间的可逆性差异（仅由一个甲基区分）是由于亚氨基氧基自由基的稳定性，这部分取决于肟 O-H 基团的键解离能。用1f和1o进行的 Tyr 选择性修饰是在生理相关的温和条件下进行的。具体来说，用1f进行的稳定 Tyr 修饰将功能性小分子（包括偶氮苯光开关）引入蛋白质。此外，通过 SPM 用1o掩盖关键的 Tyr 残基，以及随后由硫醇
• INDOLE STRUCTURE-SELECTIVE CROSSLINKING AGENT AND COMPOSITE IN WHICH SAME IS USED
  申请人：The University of Tokyo

  公开号：US20190100518A1

  公开（公告）日：2019-04-04

  The present invention relates to a cross-linking agent for cross-linking an indole-structure-containing molecule to a desired molecule, the cross-linking agent containing, as an effective component, a radical compound having an N-oxy radical group and a group capable of bonding to the desired molecule.

  本发明涉及一种交联剂，用于将含有吲哚结构的分子与所需的分子交联，该交联剂含有作为有效成分的具有N-氧自由基基团和能够与所需分子结合的基团的自由基化合物。
• Dual-acting histone deacetylase-topoisomerase I inhibitors
  作者：William Guerrant、Vishal Patil、Joshua C. Canzoneri、Li-Pan Yao、Rebecca Hood、Adegboyega K. Oyelere

  DOI：10.1016/j.bmcl.2013.03.108

  日期：2013.6

  Current chemotherapy regimens are comprised mostly of single-target drugs which are often plagued by toxic side effects and resistance development. A pharmacological strategy for circumventing these drawbacks could involve designing multivalent ligands that can modulate multiple targets while avoiding the toxicity of a single-targeted agent. Two attractive targets, histone deacetylase (HDAC) and topoisomerase I (Topo I), are cellular modulators that can broadly arrest cancer proliferation through a range of downstream effects. Both are clinically validated targets with multiple inhibitors in therapeutic use. We describe herein the design and synthesis of dual-acting histone deacetylase-topoisomerase I inhibitors. We also show that these dual-acting agents retain activity against HDAC and Topo I, and potently arrest cancer proliferation. Published by Elsevier Ltd.
• Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium‐Functionalized Microdevices
  作者：Catherine Adam、Ana M. Pérez‐López、Lloyd Hamilton、Belén Rubio‐Ruiz、Thomas L. Bray、Dirk Sieger、Paul M. Brennan、Asier Unciti‐Broceta

  DOI：10.1002/chem.201803725

  日期：2018.11.13

  presence of heterogeneous palladium (Pd) catalysts to kill colorectal cancer and glioma cells, proving the efficacy of this novel masking strategy for aromatic hydroxyls. Combination with a Pd‐activated 5FU prodrug augmented the antiproliferative potency of the treatment, while displaying no activity in the absence of the Pd source, which illustrates the benefit of achieving controlled release of multiple

  SN-38 是伊立替康的活性代谢物，在肝脏水解后释放，介导有效的抗肿瘤活性。然而，全身暴露于 SN-38 也会导致严重的副作用。为了通过控制 SN-38 生成的地点和时间来降低全身毒性，专门设计了一种新的前药，使其代谢稳定并能快速进行钯介导的激活。用 2,6-双（炔丙氧基）苄基阻断 SN-38 的酚羟基导致细胞毒性活性显着降低（高达 44 倍）。在异质钯 (Pd) 催化剂存在下，抗癌特性迅速恢复，可杀死结直肠癌和神经胶质瘤细胞，证明了这种新型芳香羟基掩蔽策略的有效性。与 Pd 激活的 5FU 前药组合增强了治疗的抗增殖效力，而在没有 Pd 源的情况下则没有活性，这说明了通过相同的生物正交催化剂顺序或同时实现多种已批准治疗药物的控制释放的好处以增加抗癌活性。