3-bromo-8-chloro-9-amino-5,6-dihydro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one | 193276-53-8

• 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-9-amino-5,6-dihydro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one
• 英文别名: 14-Amino-6-bromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaen-2-one
• CAS: 193276-53-8
• 化学式: C₁₄H₁₀BrClN₂O
• 分子量: 337.603
• InChiKey: HYDFGLDKOVUNNS-UHFFFAOYSA-N

物化性质

• 沸点：
  533.9±50.0 °C(Predicted)
• 密度：
  1.655±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 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：
  56
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-bromo-8-chloro-9-amino-5,6-dihydro-11H-benzo<5,6>cyclohepta<1,2-b>pyridin-11-one 在 盐酸 、 溴 、 亚膦酸 、 溶剂黄146 、 sodium nitrite 作用下， 反应 18.0h， 生成 3,10-dibromo-8-chloro-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 、 水 、 铁粉 、 calcium chloride 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 19.5h， 生成 3-bromo-8-chloro-9-amino-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

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
• 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
• 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