2-[1-(benzenesulfonyl)piperidin-4-yl]-1-[4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl]ethanone

• 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: 2-[1-(benzenesulfonyl)piperidin-4-yl]-1-[4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl]ethanone
• 化学式: C₃₂H₃₄Br₂ClN₃O₃S
• 分子量: 735.967
• InChiKey: ZTMYMHHVUSBOAB-WJOKGBTCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯磺酰氯 、 (+)-4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11(R)-yl)-1-<(4-piperidinyl)acetyl>piperidine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以89%的产率得到2-[1-(benzenesulfonyl)piperidin-4-yl]-1-[4-[(2R)-6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl]piperidin-1-yl]ethanone
  参考文献：
  名称：

  Identification of Pharmacokinetically Stable 3,10-Dibromo-8-chlorobenzocycloheptapyridine Farnesyl Protein Transferase Inhibitors with Potent Enzyme and Cellular Activities

  摘要：

  Farnesyl protein transferase (FPT) is a promising target for the development of cancer chemotherapeutics because it is responsible for the farnesylation of oncogenic p21 Ras proteins which are found in nearly 30% of all human cancers and necessary for cellular development and growth. The recent discovery and progression to phase II clinical trials of trihalobenzocycloheptapyridine Sch-66336 as a potent inhibitor of FPT with oral, in vivo efficacy in mice have spawned extensive structure-activity relationship studies (SAR) of this class of compounds. Of the many trihalobenzocycloheptapyridine analogues prepared, we have identified several which inhibit FPT and cellular proliferation at single-digit nanomolar concentrations and which have good pharmacokinetic properties in mice.

  DOI：

  10.1021/jm990059k