2-cinnamyl-4-pentynoic acid | 716316-68-6

• 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: 2-cinnamyl-4-pentynoic acid
• 英文别名: (E)-5-phenyl-2-prop-2-ynylpent-4-enoic acid
• CAS: 716316-68-6
• 化学式: C₁₄H₁₄O₂
• 分子量: 214.264
• InChiKey: VRPKJZFOCWVEGX-UXBLZVDNSA-N

物化性质

• 沸点：
  402.7±45.0 °C(Predicted)
• 密度：
  1.117±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-cinnamyl-4-pentynoic acid 在 N-溴代丁二酰亚胺(NBS) 、 四丁基氢氧化铵 、 potassium hydrogencarbonate 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以61.4%的产率得到3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Haloenol Lactones:  Site-Directed and Isozyme-Selective Glutathione S-Transferase Inhibitors

  摘要：

  Overexpression of glutathione S-transferase (GST), particularly the GST-pi isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-pi inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-pi, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-pi inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-pi was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-pi with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.

  DOI：

  10.1021/jm0499615
• 作为产物：
  描述：

  diethyl (E)-cinnamyl malonate 在 sodium hydroxide 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 2-cinnamyl-4-pentynoic acid
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Haloenol Lactones:  Site-Directed and Isozyme-Selective Glutathione S-Transferase Inhibitors

  摘要：

  Overexpression of glutathione S-transferase (GST), particularly the GST-pi isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-pi inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-pi, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-pi inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-pi was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-pi with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.

  DOI：

  10.1021/jm0499615

文献信息

• US5767147A
  申请人：——

  公开号：US5767147A

  公开（公告）日：1998-06-16
• US6103665A
  申请人：——

  公开号：US6103665A

  公开（公告）日：2000-08-15
• US6495370B1
  申请人：——

  公开号：US6495370B1

  公开（公告）日：2002-12-17
• [EN] INHIBITION OF GLUTATHIONE TRANSFERASE BY HALOENOL LACTONES<br/>[FR] INHIBITION DE GLUTATHION-TRANSFERASE PAR DES LACTONES HALOENOL
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：WO1996032936A1

  公开（公告）日：1996-10-24

  (EN) This invention relates to novel haloenol lactone compounds. These compounds have general structure (I), in which Ar is an aryl group and Y is a haloenol lactone moiety. The compounds of the invention are useful for the specific measurement of particular isoenzymes of glutathione S-transferase. Measurements of glutathione S-transferase isoenzymes has importance in diagnostic medicine. The compounds of the invention are also useful for treatment of drug resistance in cancer and for preventing herbicide resistance in plants.(FR) L'invention concerne de nouveaux composés à base de lactone haloénol, qui ont la structure générale (I). Dans cette structure, Ar est un groupe aryle et Y est une fraction de lactone haloénol. Les composés décrits sont utiles pour les mesures spécifiques relatives à des isoenzymes particulières de la glutathion S-transférase. Les mesures de ces isoenzymes sont importantes pour l'établissement du diagnostic en médecine. Par ailleurs, les composés en question sont efficaces pour traiter la résistance aux médicaments dans les cas du cancer et pour empêcher les plantes de développer une résistance aux herbicides.