8-{[5-chloro-2-(4-methylpiperazin-1-yl)isonicotinoyl]amino}-1-(3,4-difluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide | 1273318-83-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 8-{[5-chloro-2-(4-methylpiperazin-1-yl)isonicotinoyl]amino}-1-(3,4-difluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
• 英文别名: 8-(5-chloro-2-(4-methylpiperazin-1-yl)isonicotinamido)-1-(3,4-difluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide；8-[[5-chloro-2-(4-methylpiperazin-1-yl)pyridine-4-carbonyl]amino]-1-(3,4-difluorophenyl)-4,5-dihydrobenzo[g]indazole-3-carboxamide
• CAS: 1273318-83-4
• 化学式: C₂₉H₂₆ClF₂N₇O₂
• 分子量: 578.021
• InChiKey: FURWSAGJNCIHCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  lithium 2-ethoxy-1-(7-nitro-1-oxo-3,4-dihydronaphthalen-2(1H)-ylidene)-2-oxoethan-1-olate 在 氨 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 锌 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 8-{[5-chloro-2-(4-methylpiperazin-1-yl)isonicotinoyl]amino}-1-(3,4-difluorophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide
  参考文献：
  名称：

  Aminopyridinecarboxamide-based inhaled IKK-2 inhibitors for asthma and COPD: Structure–activity relationship

  摘要：

  Installation of sites for metabolism in the lead compound PHA-767408 was the key focus of the IKK-2 inhaled program. This paper reports our efforts to identify a novel series of aminopyridinecarboxamide-based IKK-2 inhibitors, which display low nanomolar potency against IKK-2 with long duration of action (DOA), and metabolically labile to phase I and/or phase II metabolizing enzymes with potential capability for multiple routes of clearance. Several compounds have demonstrated their potential usefulness in the treatment of asthma and chronic obstructive pulmonary disease (COPD). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.027

文献信息

• Aminopyridinecarboxamide-based inhaled IKK-2 inhibitors for asthma and COPD: Structure–activity relationship
  作者：Jin Xie、Gennadiy I. Poda、Yiding Hu、Natalie X. Chen、Richard F. Heier、Serge G. Wolfson、Matthew T. Reding、Patrick J. Lennon、Ravi G. Kurumbail、Shaun R. Selness、Xiong Li、Nandini N. Kishore、Cynthia D. Sommers、Lori Christine、Sheri L. Bonar、Neetu Venkatraman、Sumathy Mathialagan、Sarah J. Brustkern、Horng-Chih Huang

  DOI：10.1016/j.bmc.2010.12.027

  日期：2011.2

  Installation of sites for metabolism in the lead compound PHA-767408 was the key focus of the IKK-2 inhaled program. This paper reports our efforts to identify a novel series of aminopyridinecarboxamide-based IKK-2 inhibitors, which display low nanomolar potency against IKK-2 with long duration of action (DOA), and metabolically labile to phase I and/or phase II metabolizing enzymes with potential capability for multiple routes of clearance. Several compounds have demonstrated their potential usefulness in the treatment of asthma and chronic obstructive pulmonary disease (COPD). (C) 2010 Elsevier Ltd. All rights reserved.