3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol | 193276-56-1

• 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: 3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol
• 英文别名: 6,15-dibromo-13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ol
• CAS: 193276-56-1
• 化学式: C₁₄H₁₀Br₂ClNO
• 分子量: 403.5
• InChiKey: YJBINVJTNZDOSD-UHFFFAOYSA-N

物化性质

• 沸点：
  465.4±45.0 °C(Predicted)
• 密度：
  1.848±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 3,10-dibromo-8,11-dichloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine
  参考文献：
  名称：

  NOVEL TRICYCLIC PIPERIDINYL COMPOUNDS USEFUL AS INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE

  摘要：

  公开号：

  EP0931078B1
• 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 盐酸 、 ruthenium trichloride 、 sodium nitrate 、 sodium tetrahydroborate 、 sodium periodate 、 硫酸 、 水 、 溴 、 亚膦酸 、 铁粉 、 溶剂黄146 、 calcium chloride 、 sodium nitrite 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 37.5h， 生成 3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol
  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
• 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
• BENZPYRIDO CYCLOHEPTANE COMPOUNDS USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0989983B1

  公开（公告）日：2004-08-11
• TRICYCLIC INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
  申请人：SCHERING CORPORATION

  公开号：EP0929545B1

  公开（公告）日：2004-12-29
• Farnesyl protein transferase inhibitors targeting the catalytic zinc for enhanced binding
  作者：F. George Njoroge、Bancha Vibulbhan、Patrick Pinto、Corey Strickland、Paul Kirschmeier、W. Robert Bishop、V. Girijavallabhan

  DOI：10.1016/j.bmcl.2004.09.026

  日期：2004.12

  Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring, FT inhibitors with activities in the picomolar range have been achieved as exemplified by compounds 12a and 12b. An X-ray structure of 11b bound to FT shows the enhanced activity is a result of interacting with the active-site zinc. (C) 2004 Elsevier Ltd. All rights reserved.