(2S)-1-(6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)-N-(pyridin-3-ylmethyl)piperidine-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并环庚烷吡啶
• 英文名称: (2S)-1-(6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)-N-(pyridin-3-ylmethyl)piperidine-2-carboxamide
• 化学式: C₂₆H₂₅Br₂ClN₄O
• 分子量: 604.772
• InChiKey: DCMMFESPZVINMW-XADRRFQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one 在 N-甲基吗啉 、 lithium hydroxide 、 sodium tetrahydroborate 、 氯化亚砜 、 乙胺嗪 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 98.0h， 生成 (2S)-1-(6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)-N-(pyridin-3-ylmethyl)piperidine-2-carboxamide
  参考文献：
  名称：

  Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced binding

  摘要：

  Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring, FT inhibitors with activities in the picomolar range have been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b bound to FT shows the enhanced activity is a result of interacting with the active-site zinc. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.09.026

文献信息

• Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced binding
  作者：F. George Njoroge、Bancha Vibulbhan、Patrick Pinto、Corey Strickland、Paul Kirschmeier、W. Robert Bishop、V. Girijavallabhan

  DOI：10.1016/j.bmcl.2004.09.026

  日期：2004.12

  Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring, FT inhibitors with activities in the picomolar range have been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b bound to FT shows the enhanced activity is a result of interacting with the active-site zinc. (C) 2004 Elsevier Ltd. All rights reserved.