ethyl 12-cyanododecanoate | 133310-02-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 12-cyanododecanoate
• CAS: 133310-02-8
• 化学式: C₁₅H₂₇NO₂
• 分子量: 253.385
• InChiKey: IFMXKKMHMPBTBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  18
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 12-cyanododecanoate 在 sodium phosphinate 、 水 、 sodium hexamethyldisilazane 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 顺式-13-十八碳烯酸
  参考文献：
  名称：

  Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2

  摘要：

  It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50, of 9 mu M and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GIyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 mu M. This novel class of compounds show considerable promise as a first generation of GIyT2 transport inhibitors.

  DOI：

  10.1021/acschemneuro.7b00105
• 作为产物：
  描述：

  12-溴十二烷酸 在 乙酰氯 作用下， 反应 22.0h， 生成 ethyl 12-cyanododecanoate
  参考文献：
  名称：

  Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2

  摘要：

  It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50, of 9 mu M and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GIyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 mu M. This novel class of compounds show considerable promise as a first generation of GIyT2 transport inhibitors.

  DOI：

  10.1021/acschemneuro.7b00105

文献信息

• Palladium-Catalyzed Negishi Cross-Coupling Reactions of Unactivated Alkyl Iodides, Bromides, Chlorides, and Tosylates
  作者：Jianrong Zhou、Gregory C. Fu

  DOI：10.1021/ja0363258

  日期：2003.10.1

  A single method (2% Pd(2)(dba)(3)/8% PCyp(3)/NMI in THF/NMP at 80 degrees C; Cyp = cyclopentyl) achieves the cross-coupling of a range of beta-hydrogen-containing primary alkyl iodides, bromides, chlorides, and tosylates with an array of alkyl-, alkenyl-, and arylzinc halides. The process is compatible with a variety of functional groups, including esters, amides, imides, nitriles, and heterocycles

  单一方法（2% Pd(2)(dba)(3)/8% PCyp(3)/NMI in THF/NMP 在 80 摄氏度；Cyp = 环戊基）实现了一系列 β-氢的交叉偶联- 包含伯烷基碘化物、溴化物、氯化物和甲苯磺酸盐以及一系列烷基-、烯基-和芳基卤化锌。该工艺与多种官能团兼容，包括酯、酰胺、酰亚胺、腈和杂环。
• [EN] NOVEL GLYCINE TRANSPORT INHIBITORS FOR THE TREATMENT OF PAIN<br/>[FR] NOUVEAUX INHIBITEURS DE TRANSPORT DE GLYCINE POUR LE TRAITEMENT DE LA DOULEUR
  申请人：UNIV SYDNEY

  公开号：WO2018132876A1

  公开（公告）日：2018-07-26

  The present invention relates to novel glycine transport inhibitor compounds and their use for treating pain.

  本发明涉及新型甘氨酸转运抑制剂化合物及其用于治疗疼痛的用途。
• Carbon Chain Length Modulates MDA‐MB‐231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids
  作者：Michael Murray、Ariane Roseblade、Yongjuan Chen、Kirsi Bourget、Tristan Rawling

  DOI：10.1002/cmdc.201900577

  日期：2020.1.17

  anticancer agents. We designed an aryl-urea fatty acid (1 g; 16([4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl-ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10-17 carbons. Using the dye JC-1, the C12-C17 analogues

  靶向肿瘤细胞线粒体可以产生新型抗癌药。我们设计了一种芳基脲脂肪酸（1 g； 16（[4-氯-3-（三氟甲基）苯基]氨基甲酰基}氨基）十六烷酸）破坏线粒体并降低MDA-MB-231乳腺癌细胞的活力。为了优化芳基脲，本研究评估了1 g含10-17个碳原子之间烷基链的类似物的线粒体靶向性。使用染料JC-1，C12-C17类似物可有效破坏线粒体膜电位（IC50为3.5±1.2至7.6±1.1μM）并破坏ATP的产生；较短的类似物活性较低。7-氨基放线菌素D / annexin V染色和流式细胞仪显示这些试剂在不同程度上激活了坏死和细胞凋亡的杀伤机制（7-氨基放线菌素D / annexin V染色比为4.3-6.0）。的确，1 g及其C17类似物分别优先激活坏死和凋亡（比率2.1和16）。综上所述，烷基链长是芳基脲对线粒体靶向的决定因素，可以改变以开发出以调节方式激活细胞凋亡或坏死的类似物。
• Alpha-(omega-cyanoalkanoyl)-gamma-butyrolactone and method for producing the same
  申请人：UBE INDUSTRIES, LTD.

  公开号：EP0402063A2

  公开（公告）日：1990-12-12

  Disclosed are α-(ω-Cyanoalkanoyl)-γ-butyrolactone represented by the formula: wherein n represents an integer of 7 to 11, and a method for producing the same, which comprises reacting ω-cyano fatty acid ester represented by the formula: NC-(CH₂)n-COOR      (II) wherein R represents an alkyl group having 1 to 4 carbon atoms and n has the same meaning as in the above, with γ-butyrolactone in the presence of alkali metal alcoholate represented by the formula: R′OM      (III) wherein R′ represents an alkyl group having 1 to 4 carbon atoms and M represents an alkali metal.

  所公开的α-(ω-氰基烷酰基)-γ-丁内酯由式表示： 其中 n 代表 7 至 11 的整数、 以及一种生产该物质的方法，其中包括使由式.NC-(CH₂)代表的ω-氰基脂肪酸酯反应： NC-(CH₂)n-COOR (II) 其中 R 代表具有 1 至 4 个碳原子的烷基，n 的含义与上文相同、 与γ-丁内酯在碱金属醇酸酯存在下进行反应，碱金属醇酸酯的代表式为 R′OM (III) 其中 R′代表具有 1 至 4 个碳原子的烷基，M 代表碱金属。
• Antiproliferative and Antimigratory Actions of Synthetic Long Chain n-3 Monounsaturated Fatty Acids in Breast Cancer Cells That Overexpress Cyclooxygenase-2
  作者：Pei H. Cui、Tristan Rawling、Kirsi Bourget、Terry Kim、Colin C. Duke、Munikumar R. Doddareddy、David E. Hibbs、Fanfan Zhou、Bruce N. Tattam、Nenad Petrovic、Michael Murray

  DOI：10.1021/jm300673z

  日期：2012.8.23

  Cyclooxygenase-2 (COX-2) is overexpressed in many human cancers and converts the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid to prostaglandin E-2 (PGE(2)), which drives tumorigenesis; in contrast, n-3 PUFA inhibit tumorigenesis. We tested the hypothesis that these antitumor actions of n-3 PUFA may involve the n-3 olefinic bond. n-3 Monounsaturated fatty acids (MUFAs) of chain length C16-C22 were synthesized and evaluated in MDA-MB-468 breast cancer cells that stably overexpressed COX-2 (MDA-COX-2 cells). Longer chain (C19-C22) n-3 MUFAs inhibited proliferation, activated apoptosis, decreased PGE2 formation, and decreased cell invasion; C16-C18 analogues were less active. Molecular modeling showed that interactions of Arg120, Tyr355, and several hydrophobic amino acid residues in the COX-2 active site with C19-C22 MUFA analogues were favored. Thus, longer-chain n-3 MUFAs may be prototypes of novel anticancer agents that decrease the formation of PGE2 in tumor cells that contain high levels of COX-2.