ethyl α-(hydroxyimino)-β-(5-chloroindol-3-yl)-propanoate | 121994-46-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl α-(hydroxyimino)-β-(5-chloroindol-3-yl)-propanoate
• 英文别名: (E)-ethyl 3-(5-chloro-1H-indol-3-yl)-2-(hydroxyimino)propanoate；ethyl (2E)-3-(5-chloro-1H-indol-3-yl)-2-hydroxyiminopropanoate
• CAS: 121994-46-5
• 化学式: C₁₃H₁₃ClN₂O₃
• 分子量: 280.711
• InChiKey: ASCIFWCQMCRWDK-FOWTUZBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  74.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl α-(hydroxyimino)-β-(5-chloroindol-3-yl)-propanoate 在 lithium hydroxide monohydrate 、 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 (E)-3-(5-chloro-1H-indol-3-yl)-2-(trityloxyimino)propanoic acid
  参考文献：
  名称：

  Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities

  摘要：

  A SAR study has been carried out around a modified scaffold of the natural product psammaplin A obtained by replacing the o-bromophenol unit by an indole ring. A series of indole psammaplin A constructs were generated in a short synthetic sequence that starts with the functionalization of the C3 indole position with in situ generated nitrosoacrylate, and this is followed by protection of the beta-indole-alpha-oximinoesters, saponification, condensation with symmetrical diamines, and deprotection. Biochemical and cellular characterization using U937 and MCF-7 cells confirmed that many of these analogues displayed more potent actitivies than the parent natural product. Moreover, in addition to the reported HDAC and DNMT dual epigenetic inhibitory profile of the parent compound, some analogues, notably 4a (UVI5008), also inhibited the NAD(+)-dependent SIRT deacetylase enzymes. The SAR study provides structural insights into the mechanism of action of these multiple epigenetic ligands and paves the way for additional structural exploration to optimize their pharmacological profiles. Because of their multi(epi)target features and their action in ex vivo samples, the indole-based psammaplin A derivatives are attractive molecules for the modulation of epigenetic disorders.

  DOI：

  10.1021/jm300618u
• 作为产物：
  描述：

  3-溴丙酮酸乙酯 在 盐酸羟胺 、 sodium carbonate 、 ethyl 2-nitrosopropenoate 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 42.0h， 生成 ethyl α-(hydroxyimino)-β-(5-chloroindol-3-yl)-propanoate
  参考文献：
  名称：

  Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities

  摘要：

  A SAR study has been carried out around a modified scaffold of the natural product psammaplin A obtained by replacing the o-bromophenol unit by an indole ring. A series of indole psammaplin A constructs were generated in a short synthetic sequence that starts with the functionalization of the C3 indole position with in situ generated nitrosoacrylate, and this is followed by protection of the beta-indole-alpha-oximinoesters, saponification, condensation with symmetrical diamines, and deprotection. Biochemical and cellular characterization using U937 and MCF-7 cells confirmed that many of these analogues displayed more potent actitivies than the parent natural product. Moreover, in addition to the reported HDAC and DNMT dual epigenetic inhibitory profile of the parent compound, some analogues, notably 4a (UVI5008), also inhibited the NAD(+)-dependent SIRT deacetylase enzymes. The SAR study provides structural insights into the mechanism of action of these multiple epigenetic ligands and paves the way for additional structural exploration to optimize their pharmacological profiles. Because of their multi(epi)target features and their action in ex vivo samples, the indole-based psammaplin A derivatives are attractive molecules for the modulation of epigenetic disorders.

  DOI：

  10.1021/jm300618u

文献信息

• 1,3-Dipolar cycloaddition of nitrones with nitriles.
  作者：Pedro H.H. Hermkens、Jan H.v. Maarseveen、Chris G. Kruse、Hans W. Scheeren

  DOI：10.1016/s0040-4020(01)89838-0

  日期：——

  nitriles 14–16, proceeded under thermal as well as under high pressure conditions with complete regioselectivity to give Δ4-1,2,4-oxadiazolines 17–19. In general, the cycloaddition seemed to be controlled by a HOMO(nitrone)- LUMO(nitrile) interaction. However, a crossover in the orbital control is probable observed with nitrile 16c. Nitrone-nitrile cycloadditions are normal type II cycloadditions so that

  硝酮的1,3-偶极环加成1-6与腈14-16，下热以及与完整区域选择性高的压力条件下进行，得到Δ 4 -1,2,4-恶二唑啉17-19。通常，环加成似乎受HOMO（硝酮）-LUMO（腈）相互作用控制。但是，用腈16c可能会在轨道控制中发生交叉现象。腈-腈环加成是正常的II型环加成，因此腈具有U形反应性曲线。溶剂极性和Hammett方程的动力学研究表明，从机理上讲，腈-腈环加成与硝基-烯烃环加成是一致的。