6-Bromo-13-chloro-2-piperidin-4-yl-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene | 183482-79-3

• 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: 6-Bromo-13-chloro-2-piperidin-4-yl-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
• CAS: 183482-79-3
• 化学式: C₁₉H₂₀BrClN₂
• 分子量: 391.738
• InChiKey: QVQVBDKFMADYBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-叔丁氧羰基-4-哌啶乙酸 、 6-Bromo-13-chloro-2-piperidin-4-yl-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene 在 N-甲基吗啉 、 2-二乙氨基氯乙烷盐酸盐 、 1-羟基苯并三唑 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 生成 Tert-butyl 4-[2-[4-(6-bromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)piperidin-1-yl]-2-oxoethyl]piperidine-1-carboxylate
  参考文献：
  名称：

  TRICYCLIC INHIBITORS OF FARNESYL PROTEIN TRANSFERASE

  摘要：

  公开号：

  EP0929545B1
• 作为产物：
  描述：

  Ethyl 4-(13-chloro-6-nitro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl)piperidine-1-carboxylate 在 盐酸 、 氢溴酸 、 溴 、 铁粉 、 calcium chloride 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 33.0h， 生成 6-Bromo-13-chloro-2-piperidin-4-yl-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
  参考文献：
  名称：

  Potent, Selective, and Orally Bioavailable Tricyclic Pyridyl Acetamide N-Oxide Inhibitors of Farnesyl Protein Transferase with Enhanced in Vivo Antitumor Activity

  摘要：

  We previously reported compound 1 as a potent farnesyl protein transferase (FPT) inhibitor that exhibited reasonable pharmacokinetic stability and showed moderate in vivo activity against a variety of tumor cell lines. The analogous C-11 single compound, pyridylacetamide 2, was found to be more potent than 1 in FPT inhibition. Further studies showed that modification of the ethano bridge of the tricyclic ring system by conversion into a double bond with concomitant introduction of a single bond at C-11 piperidine resulted in compound 3 that had superior FPT activity and pharmacokinetic stability. Compound 4, a 5-bromo-substituted analogue of 3, showed improved FPT activity, had good cellular activity, and demonstrated a remarkably improved pharmacokinetic profile with AUC of 84.9 and t(1/2) of 82 min. Compound 4 inhibited the growth of solid tumor in DLD-1 model by 70% at 50 mpk and 52% at 10 mpk.

  DOI：

  10.1021/jm980013b

文献信息

• BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDINE DERIVATIVES USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP1019398B1

  公开（公告）日：2004-09-15
• BENZO(5,6)CYCLOHEPTA(1,2B)PYRIDINE DERIVATIVES USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0993460B1

  公开（公告）日：2004-09-15