octanedioic acid bis[4-[(6R,7R,7aS)-5,6,7,7a-tetrahydro-(6-isopropyl-3,3-dimethyl-5-oxo-1H-pyrrolo[1,2-c]oxazol-7-yl)]-1-naphthyl] ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: octanedioic acid bis[4-[(6R,7R,7aS)-5,6,7,7a-tetrahydro-(6-isopropyl-3,3-dimethyl-5-oxo-1H-pyrrolo[1,2-c]oxazol-7-yl)]-1-naphthyl] ester
• 英文别名: bis[4-[(6R,7R,7aS)-3,3-dimethyl-5-oxo-6-propan-2-yl-1,6,7,7a-tetrahydropyrrolo[1,2-c][1,3]oxazol-7-yl]naphthalen-1-yl] octanedioate
• 化学式: C₅₀H₆₀N₂O₈
• 分子量: 817.035
• InChiKey: GFXZJNFXCGXEHO-BPLZTPAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  60
• 可旋转键数：
  15
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  octanedioic acid bis[4-[(6R,7R,7aS)-5,6,7,7a-tetrahydro-(6-isopropyl-3,3-dimethyl-5-oxo-1H-pyrrolo[1,2-c]oxazol-7-yl)]-1-naphthyl] ester 在 三氟化硼乙醚 、 1,2-乙二硫醇 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以95%的产率得到bis[4-[(2S,3R,4R)-2-(hydroxymethyl)-5-oxo-4-propan-2-ylpyrrolidin-3-yl]naphthalen-1-yl] octanedioate
  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：

  1,8-二辛酰氯 、 (6R,7R,7aS)-7-(4-Hydroxy-naphthalen-1-yl)-6-isopropyl-3,3-dimethyl-tetrahydro-pyrrolo[1,2-c]oxazol-5-one 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 36.0h， 以48%的产率得到octanedioic acid bis[4-[(6R,7R,7aS)-5,6,7,7a-tetrahydro-(6-isopropyl-3,3-dimethyl-5-oxo-1H-pyrrolo[1,2-c]oxazol-7-yl)]-1-naphthyl] ester
  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

文献信息

• 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.