5-(2-diethylaminoethyl)-3-methyl-6,7,8,9-tetrahydro-1H,5H-1,5-diazacyclopentacycloocten-4-one | 1256377-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 5-(2-diethylaminoethyl)-3-methyl-6,7,8,9-tetrahydro-1H,5H-1,5-diazacyclopentacycloocten-4-one
• 英文别名: 5-[2-(diethylamino)ethyl]-3-methyl-6,7,8,9-tetrahydro-1H-pyrrolo[3,2-c]azocin-4-one
• CAS: 1256377-66-8
• 化学式: C₁₆H₂₇N₃O
• 分子量: 277.41
• InChiKey: JBAXOLNNWRFUQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(2-diethylaminoethyl)-3-methyl-6,7,8,9-tetrahydro-1H,5H-1,5-diazacyclopentacycloocten-4-one 在 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.25h， 生成 (Z)-5-(2-diethylaminoethyl)-2-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-3-methyl-6,7,8,9-tetrahydro-1H,5H-1,5-diazacyclopentacycloocten-4-one
  参考文献：
  名称：

  Novel Potent Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitors: Synthesis, Structure−Activity Relationships, and Antitumor Activities of 2-Indolinone Derivatives

  摘要：

  The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR). and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically ( < 50 nM) and cellularly, ( < 50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.

  DOI：

  10.1021/jm101036c
• 作为产物：
  描述：

  3,5-二甲基-1-氢-吡咯-2-羧酸叔丁酯-4-羧酸乙酯 在 ammonium cerium (IV) nitrate 、 5% Pd(II)/C(eggshell) 、 水 、 氢溴酸 、 氢气 、 三甲基铝 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 6.75h， 生成 5-(2-diethylaminoethyl)-3-methyl-6,7,8,9-tetrahydro-1H,5H-1,5-diazacyclopentacycloocten-4-one
  参考文献：
  名称：

  Novel Potent Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitors: Synthesis, Structure−Activity Relationships, and Antitumor Activities of 2-Indolinone Derivatives

  摘要：

  The inhibition of receptor tyrosine kinases (RTKs) has become a successful approach in the development of anticancer agents. Many potent small-molecule kinase inhibitors have been discovered. We report herein a series of pyrrolo-fused-heterocycle-2-indolinone analogues as inhibitors of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR). and c-Kit. Among them, some pyrrolo-fused six- and seven-membered-heterocycle derivatives such as 9, 15, 23, and 25 are potent inhibitors of VEGFR, PDGFR, and c-Kit both enzymatically ( < 50 nM) and cellularly, ( < 50 nM). Furthermore, compounds 9 and 25 possess favorable pharmacokinetic profiles and demonstrate good efficacies against human HT-29 cell colon tumor xenografts in nude mice. Further evaluations are in progress.

  DOI：

  10.1021/jm101036c