(+)-1-<<1-(chloroacetyl)-4-piperidinyl>acetyl>-4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-yl)piperidine | 210646-40-5

• 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: (+)-1-<<1-(chloroacetyl)-4-piperidinyl>acetyl>-4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-yl)piperidine
• 英文别名: 2-[1-(2-chloroacetyl)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
• CAS: 210646-40-5
• 化学式: C₂₈H₃₁Br₂Cl₂N₃O₂
• 分子量: 672.287
• InChiKey: JFDSNQJNOKGCJE-HHHXNRCGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  53.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲基咪唑 、 (+)-1-<<1-(chloroacetyl)-4-piperidinyl>acetyl>-4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-yl)piperidine 在 sodium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 18.0h， 生成 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]-2-[1-[2-(4-methylimidazol-1-yl)acetyl]piperidin-4-yl]ethanone
  参考文献：
  名称：

  COMPOUNDS USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE

  摘要：

  公开号：

  EP0942906B1
• 作为产物：
  描述：

  氯乙酰氯 、 (+)-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 1.5h， 以100%的产率得到(+)-1-<<1-(chloroacetyl)-4-piperidinyl>acetyl>-4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-yl)piperidine
  参考文献：
  名称：

  COMPOUNDS USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE

  摘要：

  公开号：

  EP0942906B1

文献信息

• Identification of Pharmacokinetically Stable 3,10-Dibromo-8-chlorobenzocycloheptapyridine Farnesyl Protein Transferase Inhibitors with Potent Enzyme and Cellular Activities
  作者：Arthur G. Taveras、Jeff Deskus、Jianping Chao、Cynthia J. Vaccaro、F. George Njoroge、Bancha Vibulbhan、Pat Pinto、Stacy Remiszewski、Jocelyn del Rosario、Ronald J. Doll、Carmen Alvarez、Tarik Lalwani、Alan K. Mallams、Randall R. Rossman、Adriano Afonso、Viyyoor M. Girijavallabhan、Ashit K. Ganguly、Birendra Pramanik、Larry Heimark、W. Robert Bishop、Lynn Wang、Paul Kirschmeier、Linda James、Donna Carr、Robert Patton、Mathew S. Bryant、Amin A. Nomeir、Ming Liu

  DOI：10.1021/jm990059k

  日期：1999.7.1

  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.
• COMPOUNDS USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0942906B1

  公开（公告）日：2004-11-03