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

文献信息

• Novel Potent Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitors: Synthesis, Structure−Activity Relationships, and Antitumor Activities of 2-Indolinone Derivatives
  作者：Peng Cho Tang、Yi Dong Su、Jun Feng、Jian Hong Fu、Jiang Liang Yang、Lu Xiao、Jiang Hua Peng、Ya Li Li、Lei Zhang、Bing Hu、Ying Zhou、Fang Qiong Li、Bei Bei Fu、Li Guang Lou、Ai Shen Gong、Gao Hong She、Wei Hong Sun、Xian Tai Mong

  DOI：10.1021/jm101036c

  日期：2010.11.25

  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.