4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>-pyridin-11-yl)-1-<(4-piperidinyl)-acetyl>-piperidine | 193276-75-4

• 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: 4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>-pyridin-11-yl)-1-<(4-piperidinyl)-acetyl>-piperidine
• 英文别名: 1-[4-(6,15-Dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidin-1-yl]-2-piperidin-4-ylethanone
• CAS: 193276-75-4
• 化学式: C₂₆H₂₈Br₂ClN₃O
• 分子量: 593.789
• InChiKey: RBIMGTDMUHZPOB-UHFFFAOYSA-N

物化性质

• 沸点：
  684.1±55.0 °C(predicted)
• 密度：
  1.516±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>-pyridin-11-yl)-1-<(4-piperidinyl)-acetyl>-piperidine 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 (+)-4-<2-<4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>-pyridin-11-yl)-1-4-piperidinyl>-2-oxoethyl>-1-piperidinecarboxamide
  参考文献：
  名称：

  Atropisomeric trihalobenzocycloheptapyridine analogues provide stereoselective FPT inhibitors with antitumor activity

  摘要：

  Introduction of bromine at the 10-position of 3-bromo-8-chloro-benzocycloheptapyridine analogues of type 3 results in formation of atropisomeric compounds of type (+/-)-1 and (+/-)-2 that are easily separable at room temperature on a ChiralPak(R) AD column providing pure atropisomers, (+)-1, (-)-1, and (+)-2 (-)-2, respectively. Evaluation of the FPT activity of these atropisomers revealed that compounds (+)-1 and (+) -2 were more potent in the FPT enzyme and cellular assay than their (-)-isomer counterparts. Compounds(+)-l and (+)-2 were found to inhibit FPT processing in COS cells at low micro molar range. They were also found to have excellent cellular antitumor activity. Evaluation of compound (+)-1 and (+)-2 in DLD-tumor model in nude mice revealed that they were efficacious, inhibiting tumor growth by 55 and 63% at 50 mpk, respectively. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00052-8
• 作为产物：
  描述：

  1-叔丁氧羰基-4-哌啶乙酸 在 N-甲基吗啉 、 乙胺嗪 、 1-羟基苯并三唑 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 4-(8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>-pyridin-11-yl)-1-<(4-piperidinyl)-acetyl>-piperidine
  参考文献：
  名称：

  Atropisomeric trihalobenzocycloheptapyridine analogues provide stereoselective FPT inhibitors with antitumor activity

  摘要：

  Introduction of bromine at the 10-position of 3-bromo-8-chloro-benzocycloheptapyridine analogues of type 3 results in formation of atropisomeric compounds of type (+/-)-1 and (+/-)-2 that are easily separable at room temperature on a ChiralPak(R) AD column providing pure atropisomers, (+)-1, (-)-1, and (+)-2 (-)-2, respectively. Evaluation of the FPT activity of these atropisomers revealed that compounds (+)-1 and (+) -2 were more potent in the FPT enzyme and cellular assay than their (-)-isomer counterparts. Compounds(+)-l and (+)-2 were found to inhibit FPT processing in COS cells at low micro molar range. They were also found to have excellent cellular antitumor activity. Evaluation of compound (+)-1 and (+)-2 in DLD-tumor model in nude mice revealed that they were efficacious, inhibiting tumor growth by 55 and 63% at 50 mpk, respectively. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00052-8

文献信息

• 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
• TRICYCLIC INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0929545B1

  公开（公告）日：2004-12-29
• Atropisomeric trihalobenzocycloheptapyridine analogues provide stereoselective FPT inhibitors with antitumor activity
  作者：F.George Njoroge、Bancha Vibulbhan、W.Robert Bishop、Paul Kirschmeier、Mathew S. Bryant、Amin A. Nomeir、Ming Liu、Ronald J. Doll、Viyyoor M. Girijavallabhan、Ashit K. Ganguly

  DOI：10.1016/s0968-0896(99)00052-8

  日期：1999.5

  Introduction of bromine at the 10-position of 3-bromo-8-chloro-benzocycloheptapyridine analogues of type 3 results in formation of atropisomeric compounds of type (+/-)-1 and (+/-)-2 that are easily separable at room temperature on a ChiralPak(R) AD column providing pure atropisomers, (+)-1, (-)-1, and (+)-2 (-)-2, respectively. Evaluation of the FPT activity of these atropisomers revealed that compounds (+)-1 and (+) -2 were more potent in the FPT enzyme and cellular assay than their (-)-isomer counterparts. Compounds(+)-l and (+)-2 were found to inhibit FPT processing in COS cells at low micro molar range. They were also found to have excellent cellular antitumor activity. Evaluation of compound (+)-1 and (+)-2 in DLD-tumor model in nude mice revealed that they were efficacious, inhibiting tumor growth by 55 and 63% at 50 mpk, respectively. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.