ethyl 3-acetyl-tetrahydro-4,5-dioxo-2-(2-oxopropyl)furan-2-carboxylate | 100118-65-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl 3-acetyl-tetrahydro-4,5-dioxo-2-(2-oxopropyl)furan-2-carboxylate
• 英文别名: 2-acetonyl-3-acetyl-4,5-dioxo-tetrahydro-furan-2-carboxylic acid ethyl ester；2-Acetonyl-3-acetyl-4,5-dioxo-tetrahydro-furan-2-carbonsaeure-aethylester；Ethyl 3-acetyl-4,5-dioxo-2-(2-oxopropyl)oxolane-2-carboxylate
• CAS: 100118-65-8
• 化学式: C₁₂H₁₄O₇
• 分子量: 270.239
• InChiKey: WDBOLWVNIWQCIL-UHFFFAOYSA-N

物化性质

• 熔点：
  87-88 °C(Solv: water (7732-18-5))
• 沸点：
  466.4±45.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-acetyl-tetrahydro-4,5-dioxo-2-(2-oxopropyl)furan-2-carboxylate 在 magnesium oxide 作用下， 以 水 为溶剂， 反应 0.75h， 以42%的产率得到3-羟基-5-甲基苯甲酸
  参考文献：
  名称：

  New Phenylaminopyrimidine (PAP) Anticancer Lead Compound with High Efficacy: Design, Synthesis, and in vitro Screening

  摘要：

  苯氨基嘧啶是一大类新的选择性抗癌剂，其中大多数通过抑制特定激酶发挥作用。本研究设计并合成了一系列新的 N-取代-2-氨基嘧啶。在单剂量浓度为 10 ${\mu}M$ 的条件下，对 60 种癌症细胞系进行了筛选。化合物 12e 对几乎所有 60 种细胞系都表现出了极大的抑制作用和强烈的致死效应，因此进一步进行了 5 剂量测试，以确定其 $IC_{50}$ 值。此外，还对 52 种激酶进行了测试，以了解其对激酶的抑制作用，结果发现该化合物对 FLT3 激酶有选择性抑制作用，但作用温和。

  DOI：

  10.5012/bkcs.2010.31.7.1848
• 作为产物：
  描述：

  乙酰丙酮酸乙酯 在 sodium acetate 作用下， 生成 ethyl 3-acetyl-tetrahydro-4,5-dioxo-2-(2-oxopropyl)furan-2-carboxylate
  参考文献：
  名称：

  Berner; Laland, Acta Chemica Scandinavica (1947), 1949, vol. 3, p. 335,347

  摘要：

  DOI：

文献信息

• PYRAZOLE COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST ROS KINASE
  申请人：LEE So Ha

  公开号：US20110015395A1

  公开（公告）日：2011-01-20

  Disclosed herein are novel pyrazole compounds, pharmaceutically acceptable salts thereof, a method for preparing the same, and uses thereof as anticancer agents.

  本文披露了新型吡唑化合物，其药用盐，其制备方法，以及作为抗癌剂的用途。
• New Phenylaminopyrimidine (PAP) Anticancer Lead Compound with High Efficacy: Design, Synthesis, and in vitro Screening
  作者：Ibrahim Mustafa El-Deeb、Dong-Keun Han、In-Tae Kim、So-Ha Lee

  DOI：10.5012/bkcs.2010.31.7.1848

  日期：2010.7.20

  Phenylaminopyrimidines represent a large group of new selective anticancer agents, the majority of which exert their action through the inhibition of specific kinases. In this study, a new series of N-substituted-2-aminopyrimidines has been designed and synthesized. A selected group of the synthesized derivatives was screened at a single dose concentration of 10 $\mu}M$ over a panel of 60 cancer cell-lines. Compound 12e has showed great inhibitory and strong lethal effect over almost all of the 60 cell-lines and accordingly was further tested in a 5-dose testing mode to determine its $IC_50}$ values, where it showed great efficacies with intermediate potencies over the tested cell-lines. The compound was also tested over a panel of 52 kinases to explore its kinase inhibitory profile, and was found to be a selective but moderate inhibitor over FLT3 kinase.

  苯氨基嘧啶是一大类新的选择性抗癌剂，其中大多数通过抑制特定激酶发挥作用。本研究设计并合成了一系列新的 N-取代-2-氨基嘧啶。在单剂量浓度为 10 $\mu}M$ 的条件下，对 60 种癌症细胞系进行了筛选。化合物 12e 对几乎所有 60 种细胞系都表现出了极大的抑制作用和强烈的致死效应，因此进一步进行了 5 剂量测试，以确定其 $IC_50}$ 值。此外，还对 52 种激酶进行了测试，以了解其对激酶的抑制作用，结果发现该化合物对 FLT3 激酶有选择性抑制作用，但作用温和。
• Design, synthesis and biological evaluation of new potent and highly selective ROS1-tyrosine kinase inhibitor
  作者：Byung Sun Park、Ibrahim M. El-Deeb、Kyung Ho Yoo、Chang-Hyun Oh、Seung Joo Cho、Dong Keun Han、Hye-Seung Lee、Jae Yeol Lee、So Ha Lee

  DOI：10.1016/j.bmcl.2009.06.066

  日期：2009.8

  ROS1 protein is a receptor tyrosine kinase that has been reported mainly in meningiomas and astrocytomas, and until now, there is no selective inhibitor for this kinase. In this study, we illustrate for the synthesis of a highly potent and selective inhibitor for ROS1 kinase. The synthesized compound 1 was tested initially at a single dose concentration of 10 mu M over 45 different kinases. At this concentration, a 94% inhibition of the enzymatic activity of ROS1 kinase was observed, while the inhibition in activity was below 30% in all of the other kinases. The pyrazole compound 1 was further tested in a 10-dose IC50 mode and showed an IC50 value of 199 nM for ROS1 kinase. The compound 1 can be used as a promising lead for the development of new selective inhibitors for ROS1 kinase, and it may open the way for new selective therapeutics for astrocytomas. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of Reserpine Analogs^1,2
  作者：FRED A. TURNER、JAMES E. GEARIEN

  DOI：10.1021/jo01094a031

  日期：1959.12
• Design, synthesis, screening, and molecular modeling study of a new series of ROS1 receptor tyrosine kinase inhibitors
  作者：Ibrahim M. El-Deeb、Byung Sun Park、Su Jin Jung、Kyung Ho Yoo、Chang-Hyun Oh、Seung Joo Cho、Dong Keun Han、Jae Yeol Lee、So Ha Lee

  DOI：10.1016/j.bmcl.2009.08.029

  日期：2009.10

  A series of rationally designed ROS1 tyrosine kinase inhibitors was synthesized and screened. Compound 12b has showed good potency with IC50 value of 209 nM, which is comparable with that of the reference lead compound 1. Molecular modeling studies have been performed, that is, a homology model for ROS1 was built, and the screened inhibitors were docked into its major identified binding site. The docked poses along with the activity data have revealed a group of the essential features for activity. Overall, simplification of the lead compound 1 into compound 12b has maintained the activity, while facilitated the synthetic advantages. A molecular interaction model for ROS1 kinase and inhibitors has been proposed. (C) 2009 Elsevier Ltd. All rights reserved.