2-methyl-4,5-dihydro-3H-1,2a,5-triaza-benzo[cd]azulen-6-one | 66596-64-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 2-methyl-4,5-dihydro-3H-1,2a,5-triaza-benzo[cd]azulen-6-one
• 英文别名: 2-Methyl-7-oxo-4,5,6,7-tetrahydroimidazo(4,5,1-jk)[1,4]benzodiazepine；2-methyl-1,3,10-triazatricyclo[6.4.1.04,13]trideca-2,4,6,8(13)-tetraen-9-one
• CAS: 66596-64-3
• 化学式: C₁₁H₁₁N₃O
• 分子量: 201.228
• InChiKey: FCMKDOLGAHPHGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-4,5-dihydro-3H-1,2a,5-triaza-benzo[cd]azulen-6-one 、 氢化铝锂 以68%的产率得到
  参考文献：
  名称：

  GENESTE P.; KAMENKA J.-M.; VIDAL Y.; FAUQNET J.-P.; MOREL E. M.; MULLER P+, EUR. J. MED. CHEM., 1978, 13, NO 1, 53-59

  摘要：

  DOI：
• 作为产物：
  描述：

  2-溴-3-硝基苯甲酸甲酯 在 palladium on activated charcoal 氢气 、 sodium hydrogensulfite 、 溶剂黄146 作用下， 以 N,N-二甲基乙酰胺 、 乙酸乙酯 为溶剂， 100.0 ℃ 、344.75 kPa 条件下， 反应 6.5h， 生成 2-methyl-4,5-dihydro-3H-1,2a,5-triaza-benzo[cd]azulen-6-one
  参考文献：
  名称：

  Tricyclic Benzimidazoles as Potent Poly(ADP-ribose) Polymerase-1 Inhibitors

  摘要：

  Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD(+) depletion and ADPribose polymer formation caused by chemically induced DNA damage.

  DOI：

  10.1021/jm0255769

文献信息

• Design and synthesis of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. part 4: Biological evaluation of imidazobenzodiazepines as potent PARP-1 inhibitors for treatment of ischemic injuries
  作者：Dana Ferraris、Rica Pargas Ficco、David Dain、Mark Ginski、Susan Lautar、Kathy Lee-Wisdom、Shi Liang、Qian Lin、May X.-C Lu、Lisa Morgan、Bert Thomas、Lawrence R Williams、Jie Zhang、Yinong Zhou、Vincent J Kalish

  DOI：10.1016/s0968-0896(03)00333-x

  日期：2003.8

  A class of poly(ADP-ribose) polymerase (PARP-1) inhibitors, the imidazobenzodiazepines, are presented in this text. Several derivatives were designed and synthesized with ionizable groups (i.e., tertiary amines) in order to promote the desired pharmaceutical characteristics for administration in ischemic injury. Within this series, several compounds have excellent in vitro potency and our computational models accurately justify the structure-activity relationships (SARs) and highlight essential hydrogen bonding residues and hydrophobic pockets within the catalytic domain of PARP-1. Administration of these compounds (5q, 17a and 17e) in the mouse model of streptozotocin-induced diabetes results in maintainance of glucose levels. Furthermore, one such inhibitor (5g, IC50 = 26 nM) demonstrated significant reduction of infarct volume in the rat model of permanent focal cerebral ischemia. (C) 2003 Elsevier Ltd. All rights reserved.
• US7235557B2
  申请人：——

  公开号：US7235557B2

  公开（公告）日：2007-06-26
• US7915280B2
  申请人：——

  公开号：US7915280B2

  公开（公告）日：2011-03-29
• USRE41150E1
  申请人：——

  公开号：USRE41150E1

  公开（公告）日：2010-02-23
• Tricyclic Benzimidazoles as Potent Poly(ADP-ribose) Polymerase-1 Inhibitors
  作者：Donald J. Skalitzky、Joseph T. Marakovits、Karen A. Maegley、Anne Ekker、Xiao-Hong Yu、Zdenek Hostomsky、Stephen E. Webber、Brian W. Eastman、Robert Almassy、Jianke Li、Nicola J. Curtin、David R. Newell、A. Hilary Calvert、Roger J. Griffin、Bernard T. Golding

  DOI：10.1021/jm0255769

  日期：2003.1.1

  Novel tricyclic benzimidazole carboxamide poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been synthesized. Several compounds were found to be powerful chemopotentiators of temozolomide and topotecan in both A549 and LoVo cell lines. In vitro inhibition of PARP-1 was confirmed by direct measurement of NAD(+) depletion and ADPribose polymer formation caused by chemically induced DNA damage.