(+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N[2-[N-(2-hydroxycarbonyl-ethylcarbonyl)aminoethyl]]-3-isoquinolinecarboxyamide | 250698-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N[2-[N-(2-hydroxycarbonyl-ethylcarbonyl)aminoethyl]]-3-isoquinolinecarboxyamide
• 英文别名: 4-[2-[Butan-2-yl-[1-(2-chlorophenyl)isoquinoline-3-carbonyl]amino]ethylamino]-4-oxobutanoic acid
• CAS: 250698-58-9
• 化学式: C₂₆H₂₈ClN₃O₄
• 分子量: 481.979
• InChiKey: KRBQZMCHWJVXPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  99.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N[2-[N-(2-hydroxycarbonyl-ethylcarbonyl)aminoethyl]]-3-isoquinolinecarboxyamide 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 5'-O-[2-[2-[N-(1-methylpropyl),N-[1-(2-chlorophenyl)isoquinoline-3-carbonyl]amino]ethylaminocarbonyl]ethylcarbonyl]gemcitabine
  参考文献：
  名称：

  Selective Protection of 2‘,2‘-Difluorodeoxycytidine (Gemcitabine)

  摘要：

  Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH2, 5'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH2, 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PER ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.

  DOI：

  10.1021/jo9911140
• 作为产物：
  描述：

  丁二酸酐 、 (+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N-(2-aminoethyl)-3-isoquinolinecarboxamide dihydrochloride 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以83%的产率得到(+/-)-1-(2-chlorophenyl)-N-(1-methylpropyl)-N[2-[N-(2-hydroxycarbonyl-ethylcarbonyl)aminoethyl]]-3-isoquinolinecarboxyamide
  参考文献：
  名称：

  Selective Protection of 2‘,2‘-Difluorodeoxycytidine (Gemcitabine)

  摘要：

  Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH2, 5'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH2, 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PER ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.

  DOI：

  10.1021/jo9911140