α-(3,4-methylenedioxybenzylidene)-γ-butyrolactone | 102271-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: α-(3,4-methylenedioxybenzylidene)-γ-butyrolactone
• 英文别名: (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene)dihydrofuran-2(3H)-one；3-(3,4-Methylendioxy-benzyliden)-tetrahydrofuran-2-on；3-Piperonyliden-2-oxo-tetrahydrofuran；3-benzo[1,3]dioxol-5-ylmethylene-dihydro-furan-2-one；3-piperonylidene-dihydro-furan-2-one；3-Piperonyliden-dihydro-furan-2-on；3-(1,3-Benzodioxol-5-ylmethylene)dihydro-2(3H)-furanone；(3E)-3-(1,3-benzodioxol-5-ylmethylidene)oxolan-2-one
• CAS: 102271-83-0
• 化学式: C₁₂H₁₀O₄
• 分子量: 218.209
• InChiKey: UZLHPXPKYRQXJV-WEVVVXLNSA-N

物化性质

• 熔点：
  178-178.5 °C(Solv: 1,4-dioxane (123-91-1))
• 沸点：
  430.5±34.0 °C(Predicted)
• 密度：
  1.405±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  α-(3,4-methylenedioxybenzylidene)-γ-butyrolactone 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 0.75h， 以74%的产率得到2-[(3,4-methylenedioxyphenyl)methylene]-1,4-butanediol
  参考文献：
  名称：

  A New Class of Potential Chloroquine-Resistance Reversal Agents for Plasmodia:  Syntheses and Biological Evaluation of 1-(3‘-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines

  摘要：

  1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

  DOI：

  10.1021/jm000083u
• 作为产物：
  描述：

  γ-丁内酯 、 胡椒醛 在 sodium hydride 作用下， 以 甲苯 为溶剂， 以26%的产率得到α-(3,4-methylenedioxybenzylidene)-γ-butyrolactone
  参考文献：
  名称：

  亚苄基杂环的系统多样化产生对Dyrk1A，Clk1和CK2有选择性的新型抑制剂支架

  摘要：

  双特异性酪氨酸调节激酶​​1A（Dyrk1A）作为阿尔茨海默氏病（AD）的药理靶标引起了广泛兴趣，但它在恶性脑肿瘤中也起着重要作用。由于两种疾病都是多因素的，因此提出了进一步的蛋白激酶，例如Clk1和CK2，来促进发病机理。我们设计了一类新型的α-亚苄基-γ-丁内酯抑制剂，该抑制剂对Dyrk1A和/或Clk1的微摩尔浓度低，并且在最常报道的脱靶激酶中具有良好的选择性。杂环部分的系统取代使人们能够以有趣的选择性分布获得更多抑制剂类别，这表明亚苄基杂环为开发CMGC激酶家族成员Dyr1A / 1B，Clk1 / 4和CK2的抑制剂提供了多功能的工具箱。在基于细胞的测定中证明了抑制Dyrk1A介导的tau磷酸化的功效。还获得了多靶点但非非特异性激酶抑制剂，其共抑制了脂质激酶PI3Kα/γ。这些化合物显示出在低微摩尔范围内抑制U87MG细胞的增殖。基于分子特性，此处描述的抑制剂有望实现CNS活性。

  DOI：

  10.1016/j.ejmech.2016.02.017

文献信息

• Studies on styrene derivatives. I. Synthesis and antiinflammatory activities of .ALPHA.-benzylidene-.GAMMA.-butyrolactone derivatives.
  作者：IKUO KATSUMI、HIDEO KONDO、KATSUJI YAMASHITA、TAKAYOSHI HIDAKA、KAZUNORI HOSOE、TOSHIAKI YAMASHITA、KIYOSHI WATANABE

  DOI：10.1248/cpb.34.121

  日期：——

  Two α-benzylidene-γ-butyrolactones, α-(3, 5-dimethyl-4-hydroxybenzylidene)-γ-butyrolactone and α-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), were found to have platelet aggregation inhibitory activity; the latter also had potent antiinflammatory activity and inhibited not only prostaglandin synthetase (PGS) but also 5-lipoxygenase. Further α-benzylidene-γ-butyrolactones were synthesized, and tested for antiinflammatory activity in carrageenin-induced rat paw edema assay (CPE) and for PGS inhibitory activity. It was found that the structural combination of a tert-butyl group at the 3 position, an alkyl group at the 5 position and an oxygen atom at the Δ position in α-benzylidene-γ-butyrolactone is necessary for antiinflammatory activity, and that rather broad structural variation is possible for inhibitors of PGS. The structural requirements for antiinflammatory activity in the CPE assay also seem to be partial requirements for inhibitory activity against PGS.

  两种α-苄叉基-γ-丁内酯，即α-(3, 5-二甲基-4-羟基苄叉基)-γ-丁内酯和α-(3, 5-二叔丁基-4-羟基苄叉基)-γ-丁内酯（KME-4），被发现具有血小板聚集抑制活性；后者还具有强效的抗炎活性，不仅抑制前列腺素合成酶（PGS），还抑制5-脂氧合酶。进一步合成了α-苄叉基-γ-丁内酯，并测试了它们在卡拉胶诱导的大鼠足跖水肿试验（CPE）中的抗炎活性和PGS抑制活性。研究发现，在α-苄叉基-γ-丁内酯中，3位叔丁基、5位烷基和Δ位氧原子的结构组合对发挥抗炎活性是必要的，而且对PGS抑制剂来说，其结构变化非常广泛。在CPE试验中对发挥抗炎活性的结构要求似乎也是对PGS抑制活性的部分要求。
• 3-(Arylmethyl)-1-(3'-diethylaminopropyl) pyrrolidines and process of preparation thereof
  申请人：Council of Scientific and Industrial Research

  公开号：EP0562185A1

  公开（公告）日：1993-09-29

  The novel compounds 3-(arylmethyl)-1-(3'-diethylaminopropyl) pyrrolidines are disclosed which have the general formula: wherein R represents an alkoxy group having 1 to 6 carbon atoms, like methoxy, ethoxy, propoxy or butoxy and a process for preparing the same. Particularly, the invention provides the compound having the above said formula wherein the alkoxy substituent is in the 4 position of the benzene ring or the substituent methylenedioxy at 3 and 4 position. The compounds have the property of reversing the resistance of chloroquine resistant strains of the malarial parasite P. berghi in vivo and P. falciparum in vitro and can be used for reversing the resistance of human malarial parasites, particularly P. falciparum. The invention also includes compositions containing the new compounds and an anti-malarial drug, preferably chloroquine.

  本发明揭示了一种新型化合物3-(芳基甲基)-1-(3'-二乙基氨基丙基)吡咯烷，其具有以下通式： 其中R代表1至6个碳原子的烷氧基，例如甲氧基、乙氧基、丙氧基或丁氧基，并提供一种制备该化合物的方法。特别地，本发明提供了上述通式中烷氧基取代基位于苯环的4位或取代基为3和4位的亚甲二氧基。该化合物具有在体内逆转氯喹耐药性疟原虫P. berghi和体外逆转P. falciparum的特性，并可用于逆转人类疟原虫，特别是P. falciparum的耐药性。本发明还包括含有新化合物和抗疟药物（优选为氯喹）的组合物。
• Substituted γ-Lactones. I. Preparation of α-Substituted γ-Butyrolactones by Condensation of γ-Butyrolactone with Aldehydes. Hydrogenation of the Condensation Products
  作者：HANS ZIMMER、JOHANNES ROTHE

  DOI：10.1021/jo01083a009

  日期：1959.1
• Batra, Sanjay; De, Dibyendu; Seth, Manju, Journal of Chemical Research, Miniprint, 1993, # 6, p. 1228 - 1238
  作者：Batra, Sanjay、De, Dibyendu、Seth, Manju、Bhaduri, Amiya Prasad

  DOI：——

  日期：——
• Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2
  作者：Marica Mariano、Rolf W. Hartmann、Matthias Engel

  DOI：10.1016/j.ejmech.2016.02.017

  日期：2016.4

  The dual-specificity tyrosine-regulated kinase 1A (Dyrk1A) has gathered much interest as a pharmacological target in Alzheimer's disease (AD), but it plays a role in malignant brain tumors as well. As both diseases are multi-factorial, further protein kinases, such as Clk1 and CK2, were proposed to contribute to the pathogenesis. We designed a new class of α-benzylidene–γ-butyrolactone inhibitors that

  双特异性酪氨酸调节激酶​​1A（Dyrk1A）作为阿尔茨海默氏病（AD）的药理靶标引起了广泛兴趣，但它在恶性脑肿瘤中也起着重要作用。由于两种疾病都是多因素的，因此提出了进一步的蛋白激酶，例如Clk1和CK2，来促进发病机理。我们设计了一类新型的α-亚苄基-γ-丁内酯抑制剂，该抑制剂对Dyrk1A和/或Clk1的微摩尔浓度低，并且在最常报道的脱靶激酶中具有良好的选择性。杂环部分的系统取代使人们能够以有趣的选择性分布获得更多抑制剂类别，这表明亚苄基杂环为开发CMGC激酶家族成员Dyr1A / 1B，Clk1 / 4和CK2的抑制剂提供了多功能的工具箱。在基于细胞的测定中证明了抑制Dyrk1A介导的tau磷酸化的功效。还获得了多靶点但非非特异性激酶抑制剂，其共抑制了脂质激酶PI3Kα/γ。这些化合物显示出在低微摩尔范围内抑制U87MG细胞的增殖。基于分子特性，此处描述的抑制剂有望实现CNS活性。