6-(3-Amino-6-methyl-1H-indazol-7-yl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-2-one | 1192744-45-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 6-(3-Amino-6-methyl-1H-indazol-7-yl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-2-one
• 英文别名: 6-(3-amino-6-methyl-1H-indazol-7-yl)spiro[1H-indole-3,4'-oxane]-2-one
• CAS: 1192744-45-8
• 化学式: C₂₀H₂₀N₄O₂
• 分子量: 348.404
• InChiKey: IZJYQNPWFYDXJT-UHFFFAOYSA-N

物化性质

• 沸点：
  667.5±55.0 °C(predicted)
• 密度：
  1.41±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  93
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氟-4-甲基苯腈 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 碘 、 caesium carbonate 、 一水合肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 为溶剂， 生成 6-(3-Amino-6-methyl-1H-indazol-7-yl)-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-2-one
  参考文献：
  名称：

  Indolin-2-one p38α inhibitors III: Bioisosteric amide replacement

  摘要：

  Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38 alpha inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.006

文献信息

• New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors
  申请人：Laboratorios Almirall, S.A.

  公开号：EP2113503A1

  公开（公告）日：2009-11-04

  This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.

  这项发明涉及具有一般式(I)的新p38丝裂原活化蛋白激酶抑制剂；其制备方法；包含它们的药物组合物；以及它们在治疗中的应用。
• SUBSTITUTED INDOLIN-2-ONE DERIVATIVES AND THEIR USE AS P38 MITOGEN-ACTIVATED KINASE INHIBITORS
  申请人：Eastwood Paul Robert

  公开号：US20110046097A1

  公开（公告）日：2011-02-24

  The present disclosure is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I), processes for preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

  本公开涉及具有一般式（I）的p38有丝分裂原活化蛋白激酶的新抑制剂，其制备过程，其制药组合物以及其使用方法。
• NEW SUBSTITUTED INDOLIN-2-ONE DERIVATIVES AND THEIR USE AS P38 MITOGEN-ACTIVATED KINASE INHIBITORS
  申请人：Almirall, S.A.

  公开号：EP2280953B1

  公开（公告）日：2012-05-09
• US8450341B2
  申请人：——

  公开号：US8450341B2

  公开（公告）日：2013-05-28
• Indolin-2-one p38α inhibitors III: Bioisosteric amide replacement
  作者：Paul Eastwood、Jacob González、Elena Gómez、Francisco Caturla、Nuria Aguilar、Marta Mir、Josep Aiguadé、Victor Matassa、Cristina Balagué、Adelina Orellana、María Domínguez

  DOI：10.1016/j.bmcl.2011.09.006

  日期：2011.11

  Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38 alpha inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation. (C) 2011 Elsevier Ltd. All rights reserved.