3-bromo-8-chloro-5,6-dihydro-7-nitro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one | 193276-51-6

• 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: 3-bromo-8-chloro-5,6-dihydro-7-nitro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one
• 英文别名: 3-bromo-8-chloro-7-nitro-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-one；6-Bromo-13-chloro-12-nitro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-one
• CAS: 193276-51-6
• 化学式: C₁₄H₈BrClN₂O₃
• 分子量: 367.586
• InChiKey: MECWVZTZKVNHMI-UHFFFAOYSA-N

物化性质

• 熔点：
  201-203 °C
• 沸点：
  551.7±50.0 °C(Predicted)
• 密度：
  1.721±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  75.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-bromo-8-chloro-5,6-dihydro-7-nitro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one 在 盐酸 、 硫酸 、 水 、 铁粉 、 溶剂黄146 、 copper(l) chloride 、 calcium chloride 、 sodium nitrite 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 3-bromo-7,8-dichloro-5,6-dihydro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one
  参考文献：
  名称：

  (+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide (SCH-66336):  A Very Potent Farnesyl Protein Transferase Inhibitor as a Novel Antitumor Agent

  摘要：

  We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.

  DOI：

  10.1021/jm980462b
• 作为产物：
  描述：

  4-(3-溴-8-氯-5,6-二氢-11H-苯并[5,6]环庚[1,2-B]吡啶-11-亚基)哌啶-1-羧酸乙酯 在 ruthenium trichloride 、 sodium nitrate 、 sodium periodate 、 硫酸 作用下， 以 水 、 乙腈 为溶剂， 反应 3.5h， 生成 3-bromo-8-chloro-5,6-dihydro-7-nitro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one
  参考文献：
  名称：

  (+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide (SCH-66336):  A Very Potent Farnesyl Protein Transferase Inhibitor as a Novel Antitumor Agent

  摘要：

  We have previously shown that appropriate modification of the benzocycloheptapyridine tricyclic ring system can provide potent farnesyl protein transferase (FPT) inhibitors with good cellular activity. Our laboratories have also established that incorporation of either pyridinylacetyl N-oxide or 4-N-carboxamidopiperidinylacetyl moieties results in pharmacokinetically stable inhibitors that are orally efficacious in nude mice. We now demonstrate that further elaboration of the tricyclic ring system by introducing a bromine atom at the 7- or the 10-position of the 3-bromo-8-chlorotricyclic ring system provides compounds that have superior potency and selectivity in FPT inhibition. These compounds have good serum levels and half-lives when given orally to rodents and primates. In vitro and in vivo evaluation of a panel of these inhibitors has led to identification of 15 (SCH 66336) as a highly potent (IC50 = 1.9 nM) antitumor agent that is currently undergoing human clinical trials.

  DOI：

  10.1021/jm980462b

文献信息

• A Novel Iodide-Catalyzed Reduction of Nitroarenes and Aryl Ketones with H₃PO₂ or H₃PO₃: Its Application to the Synthesis of a Potential Anticancer Agent
  作者：George G. Wu、Frank X. Chen、Danny LaFrance、Zhijian Liu、Scott G. Greene、Yee-Shing Wong、Ji Xie

  DOI：10.1021/ol102174w

  日期：2011.10.7

  A novel iodide-catalyzed reduction method using hypophosphorous and/or phosphorus acids was developed to reduce both diaryl ketones and nitroarenes chemoselectively in the presence of chloro and bromo substituents in high yield. This efficient and practical method has been successfully applied to a large scale production of a potential anticancer agent.

  开发了一种使用次磷酸和/或磷酸的碘化物催化还原新方法，可以在氯和溴取代基存在下，以高收率化学还原二芳基酮和硝基芳烃。这种有效和实用的方法已成功地应用于大规模生产潜在的抗癌剂。
• NOVEL TRICYCLIC PIPERIDINYL COMPOUNDS USEFUL AS INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0931078B1

  公开（公告）日：2006-11-15
• TRICYCLIC ANTITUMOR COMPOUNDS BEING FARNESYL PROTEIN TRANSFERASE INHIBITORS
  申请人：SCHERING CORPORATION

  公开号：EP0929544B1

  公开（公告）日：2004-11-10
• TRICYCLIC INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0929545B1

  公开（公告）日：2004-12-29
• [EN] ENANTIOSELECTIVE ALKYLATION OF TRICYCLIC COMPOUNDS<br/>[FR] PROCEDE ENANTIOSELECTIF
  申请人：SCHERING CORP

  公开号：WO2004031153A3

  公开（公告）日：2004-07-15