4-(3-bromo-10-methoxy-8-methyl-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidine | 218290-71-2

• 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-(3-bromo-10-methoxy-8-methyl-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidine
• 英文别名: 3-Bromo-6,11-dihydro-10-methoxy-8-methyl-11-(4-piperidinylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine；6-bromo-15-methoxy-13-methyl-2-piperidin-4-ylidene-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene
• CAS: 218290-71-2
• 化学式: C₂₁H₂₃BrN₂O
• 分子量: 399.33
• InChiKey: UURDNXNNQDGFGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  34.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-bromo-10-methoxy-8-methyl-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidine 在 正丁基锂 作用下， 以 二氯甲烷 为溶剂， 生成 4-[3-(1-Hydroxy-1-methyl-ethyl)-10-methoxy-8-methyl-5,6-dihydro-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene]-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Analogs of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N-oxide as inhibitors of farnesyl protein transferase

  摘要：

  A series of 3-substituted analogs 3 of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N-oxide 2 was prepared and evaluated as FPT inhibitors. The objective of this study was to identify other substituents at C-3 in this series of FPT inhibitors that would have the FPT potency enhancement similar to that found for a C-3 bromo substituent. The 3-methyl analog 17b was found to be tenfold less active than 2, and other C-3 substituents having more steric bulk were found to cause a further reduction in activity, (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00287-5
• 作为产物：
  描述：

  3-甲基-5-硝基-2-吡啶甲腈 在 盐酸 、 三氟甲磺酸 、 硫酸 、 氢溴酸 、 铁粉 、 三乙胺 、 N,N-二甲基甲酰胺 、 calcium chloride 、 lithium diisopropyl amide 、 sodium nitrite 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 水 、 甲苯 为溶剂， 反应 36.5h， 生成 4-(3-bromo-10-methoxy-8-methyl-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-piperidine
  参考文献：
  名称：

  Analogues of 1-(3,10-Dibromo-8-chloro-6,11-dihydro-5 H -benzo[5,6]-cyclohepta[1,2- b ]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase

  摘要：

  The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]-pyridin-11-yl)pi perazine/piperidine 3 is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds 7a-7g led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues 7i, 13i, and 13j. The 11R(-) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity.

  DOI：

  10.1016/s0968-0896(99)00103-0

文献信息

• Analogues of 1-(3,10-Dibromo-8-chloro-6,11-dihydro-5 H -benzo[5,6]-cyclohepta[1,2- b ]pyridin-11-yl)piperidine as inhibitors of farnesyl protein transferase
  作者：Adriano Afonso、Jay Weinstein、Joseph Kelly、Ronald Wolin、Stuart B. Rosenblum、Michael Connolly、Timothy Guzi、Linda James、Donna Carr、Robert Patton、W.Robert Bishop、Paul Kirshmeier、M. Liu、L. Heimark、K.J. Chen、A.A. Nomeir

  DOI：10.1016/s0968-0896(99)00103-0

  日期：1999.9

  The synthesis of several 4-pyridylacetyl N-oxide derivatives of 4-(3-bromo-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]-pyridin-11-yl)pi perazine/piperidine 3 is described. This study was aimed at identifying fomesyl protein transferase (FPT) inhibitors in these two series of tricycles containing different phenyl ring substituents. The in vitro activity profile of the initial group of compounds 7a-7g led to the synthesis of the 8-methyl-10-methoxy and 8-methyl-10-bromo analogues 7i, 13i, and 13j. The 11R(-) enantiomers of these compounds were found to exhibit potent in vitro FPT inhibition activity.
• Analogs of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2-b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N-oxide as inhibitors of farnesyl protein transferase
  作者：Adriano Afonso、Joseph Kelly、Jay Weinstein、Linda James、W.Robert Bishop

  DOI：10.1016/s0960-894x(99)00287-5

  日期：1999.7

  A series of 3-substituted analogs 3 of 4-(3-bromo-8-methyl-10-methoxy-6,11-dihydro-5H-benzo[5,6]-cyclohepta[1,2b]pyridin-11-yl)-1-(4-pyridinylacetyl)piperidine N-oxide 2 was prepared and evaluated as FPT inhibitors. The objective of this study was to identify other substituents at C-3 in this series of FPT inhibitors that would have the FPT potency enhancement similar to that found for a C-3 bromo substituent. The 3-methyl analog 17b was found to be tenfold less active than 2, and other C-3 substituents having more steric bulk were found to cause a further reduction in activity, (C) 1999 Elsevier Science Ltd. All rights reserved.