(2-{2-[2-(2-Chlorocarbonylmethoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-acetyl chloride | 608513-15-1

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 酰卤
• 英文名称: (2-{2-[2-(2-Chlorocarbonylmethoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-acetyl chloride
• 英文别名: 3,6,9,12,15-Pentaoxaheptadecane-1,17-dioyl dichloride；2-[2-[2-[2-[2-(2-chloro-2-oxoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]acetyl chloride
• CAS: 608513-15-1
• 化学式: C₁₂H₂₀Cl₂O₇
• 分子量: 347.193
• InChiKey: FYLNLRVLJGYVAL-UHFFFAOYSA-N

物化性质

• 沸点：
  412.2±40.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2-{2-[2-(2-Chlorocarbonylmethoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-acetyl chloride 、 (2S,5S)-O-acetylobenzolactam 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  New Bivalent PKC Ligands Linked by a Carbon Spacer:  Enhancement in Binding Affinity

  摘要：

  Protein kinase C (PKC) is known to play an important role in many signal transduction pathways involved in hormone release, mitogenesis, and tumor promotion. In continuation of our efforts to find highly potent activators of PKC for possible use as Alzheimer's disease therapeutics, we designed and synthesized molecules containing two binding moieties (amides of benzolactams or esters of naphthylpyrrolidones) connected by a flexible spacer chain, which could theoretically bind to both the C1a and C1b activator binding domains of the catalytic region or to the C1 domains of two adjacent PKC molecules. The dimers 2a- g of benzolactam showed a 200-fold increase in affinity to PKCalpha and -delta as the spacer length increased from 4 to 20 carbon atoms. Replacement of the oligomethylene chain with an oligoethylene glycol unit (compounds 2h, 2i) showed a 4000- to 7000-fold decrease in affinity to PKCalpha. The dimers of naphthylpyrrolidones 4a-g did not show any marked improvement in binding affinities to PKC in comparison to the monomers synthesized earlier. The dimer of benzolactam. 2e did not show much selectivity for PKCalpha, -betaI, -delta, -epsilon, and -gamma. The high binding affinity of compounds 2d-g to PKCs gives us the impetus to design additional molecules that would retain this enhanced activity and would also show selectivity for the PKC isoforms.

  DOI：

  10.1021/jm0302041
• 作为产物：
  描述：

  di-tert-butyl 3,6,9,12,15-pentaoxaheptadecanedioate 在 草酰氯 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2-{2-[2-(2-Chlorocarbonylmethoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-acetyl chloride
  参考文献：
  名称：

  Ligand Recognition by E- and P-Selectin:  Chemoenzymatic Synthesis and Inhibitory Activity of Bivalent Sialyl Lewis x Derivatives and Sialyl Lewis x Carboxylic Acids

  摘要：

  Described is the preparation of five sLe(x) dimers and five sLe(x) carboxylic acids by coupling chemoenzymatically synthesized amino-substituted sialyl Lewis x (sLe(x)) derivative 4 to homobifunctional cross-linkers 20-24 of varying chain length. 20-24 were obtained by alkylating low-molecular-weight oligoethylene glycols with tert-butyl bromoacetate and subsequent transformation of the di-tert-butyl esters into disuccinimide esters. The products were assayed for inhibition against binding of a sLe(a)-polymer to immobilized E- and P-selectin. In the E-selectin assay all dimers had lower IC50 values than the sLex monomer. The results show that comparable binding enhancements can be obtained with linkers of completely different length and rigidity. In the P-selectin assay four of the five sLe(x) carboxylic acids displayed significantly improved inhibitory potency. The lowest IC50 value was observed for the compound with the shortest spacer between the sLex moiety and the additional carboxylate, being ca. 20-40 times more potent than unmodified sLex. These findings should be of importance for the design of new multivalent forms of sLe(x) as well as sLe(x) mimetics as high-affinity selectin ligands.

  DOI：

  10.1021/jo980350s

文献信息

• Molecular Recognition of Pyrophosphate with Extended Bis(Zn(II)-DPA) Derivatives
  作者：Jinrok Oh、Jong-In Hong

  DOI：10.1021/acs.joc.9b01726

  日期：2019.12.20

  their binding affinities toward both PPi and adenosine triphosphate were evaluated in N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid-buffered solution. The presence of two hydrogen bond donors slightly retarded the reaction rate of anionic guest exchange, while four had a significant retardation effect. A macrocyclic receptor, 17, exhibited superior selectivity toward PPi compared with acyclic

  合成了一系列焦磷酸盐（PPi）受体，并在N-（2-羟乙基）哌嗪-N'-乙烷磺酸缓冲溶液中评估了它们对PPi和三磷酸腺苷的结合亲和力。两个氢键供体的存在略微阻碍了阴离子客体交换的反应速率，而四个具有显着的阻滞作用。与无环受体相比，大环受体17对PPi具有更好的选择性，这可能是由于有效的空间相互作用所致。等温滴定热法实验和电位滴定实验揭示了取代基结构对阴离子客体稳定度和与锌离子结合的水分子去质子化的影响，以及客体结合热力学。
• Ligand Recognition by E- and P-Selectin:  Chemoenzymatic Synthesis and Inhibitory Activity of Bivalent Sialyl Lewis x Derivatives and Sialyl Lewis x Carboxylic Acids
  作者：Valentin Wittmann、Shuichi Takayama、Ke Wei Gong、Gabriele Weitz-Schmidt、Chi-Huey Wong

  DOI：10.1021/jo980350s

  日期：1998.7.1

  Described is the preparation of five sLe(x) dimers and five sLe(x) carboxylic acids by coupling chemoenzymatically synthesized amino-substituted sialyl Lewis x (sLe(x)) derivative 4 to homobifunctional cross-linkers 20-24 of varying chain length. 20-24 were obtained by alkylating low-molecular-weight oligoethylene glycols with tert-butyl bromoacetate and subsequent transformation of the di-tert-butyl esters into disuccinimide esters. The products were assayed for inhibition against binding of a sLe(a)-polymer to immobilized E- and P-selectin. In the E-selectin assay all dimers had lower IC50 values than the sLex monomer. The results show that comparable binding enhancements can be obtained with linkers of completely different length and rigidity. In the P-selectin assay four of the five sLe(x) carboxylic acids displayed significantly improved inhibitory potency. The lowest IC50 value was observed for the compound with the shortest spacer between the sLex moiety and the additional carboxylate, being ca. 20-40 times more potent than unmodified sLex. These findings should be of importance for the design of new multivalent forms of sLe(x) as well as sLe(x) mimetics as high-affinity selectin ligands.
• New Bivalent PKC Ligands Linked by a Carbon Spacer:  Enhancement in Binding Affinity
  作者：Jayalakshmi Sridhar、Zhi-Liang Wei、Ireneusz Nowak、Nancy E. Lewin、Jolene A. Ayres、Larry V. Pearce、Peter M. Blumberg、Alan P. Kozikowski

  DOI：10.1021/jm0302041

  日期：2003.9.1

  Protein kinase C (PKC) is known to play an important role in many signal transduction pathways involved in hormone release, mitogenesis, and tumor promotion. In continuation of our efforts to find highly potent activators of PKC for possible use as Alzheimer's disease therapeutics, we designed and synthesized molecules containing two binding moieties (amides of benzolactams or esters of naphthylpyrrolidones) connected by a flexible spacer chain, which could theoretically bind to both the C1a and C1b activator binding domains of the catalytic region or to the C1 domains of two adjacent PKC molecules. The dimers 2a- g of benzolactam showed a 200-fold increase in affinity to PKCalpha and -delta as the spacer length increased from 4 to 20 carbon atoms. Replacement of the oligomethylene chain with an oligoethylene glycol unit (compounds 2h, 2i) showed a 4000- to 7000-fold decrease in affinity to PKCalpha. The dimers of naphthylpyrrolidones 4a-g did not show any marked improvement in binding affinities to PKC in comparison to the monomers synthesized earlier. The dimer of benzolactam. 2e did not show much selectivity for PKCalpha, -betaI, -delta, -epsilon, and -gamma. The high binding affinity of compounds 2d-g to PKCs gives us the impetus to design additional molecules that would retain this enhanced activity and would also show selectivity for the PKC isoforms.