N-cyclopropyl-3-fluoro-4-methyl-5-(1'-(methylsulfonyl)-2-oxospiro[indoline-3,4'-piperidine]-6-yl)benzamide | 1190860-13-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-cyclopropyl-3-fluoro-4-methyl-5-(1'-(methylsulfonyl)-2-oxospiro[indoline-3,4'-piperidine]-6-yl)benzamide
• 英文别名: N-cyclopropyl-3-fluoro-4-methyl-5-(1'-methylsulfonyl-2-oxospiro[1H-indole-3,4'-piperidine]-6-yl)benzamide
• CAS: 1190860-13-9
• 化学式: C₂₄H₂₆FN₃O₄S
• 分子量: 471.553
• InChiKey: YGCLZBSXHNGAIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-cyclopropyl-5-fluoro-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzamide 、 6-bromo-1'-(methylsulfonyl)spiro[indoline-3,4'-piperidin]-2-one 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-cyclopropyl-3-fluoro-4-methyl-5-(1'-(methylsulfonyl)-2-oxospiro[indoline-3,4'-piperidine]-6-yl)benzamide
  参考文献：
  名称：

  Indolin-2-one p38α inhibitors II: Lead optimisation

  摘要：

  Optimisation of a series of indolin-2-one p38 alpha inhibitors was achieved via both blocking of a potential metabolic 'hot spot' and by increasing overall polarity of the lead series leading to non-cytotoxic compounds which showed improved oral bioavailabilities in the rat. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.033

文献信息

• New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors
  申请人：Laboratorios Almirall, S.A.

  公开号：EP2108641A1

  公开（公告）日：2009-10-14

  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 SPIRO[CYCLOALKYL-1,3'-INDOL]-2'(1'H)-ONE DERIVATIVES AND THEIR USE AS P38 MITOGEN-ACTIVATED KINASE INHIBITORS
  申请人：Eastwood Paul Robert

  公开号：US20110053936A1

  公开（公告）日：2011-03-03

  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.

  本公开涉及新的p38丝裂原活化蛋白激酶抑制剂，其具有一般式(I)，其制备方法，其药物组合物以及其使用方法。
• NEW SUBSTITUTED SPIRO[CYCLOALKYL-1,3'-INDO]-2'(1'H)-ONE DERIVATIVES AND THEIR USE AS P38 MITOGEN-ACTIVATED KINASE INHIBITORS
  申请人：Almirall, S.A.

  公开号：EP2280943B1

  公开（公告）日：2013-11-06
• US8772288B2
  申请人：——

  公开号：US8772288B2

  公开（公告）日：2014-07-08
• Indolin-2-one p38α inhibitors II: Lead optimisation
  作者：Paul Eastwood、Jacob González、Elena Gómez、Francisco Caturla、Cristina Balagué、Adelina Orellana、María Domínguez

  DOI：10.1016/j.bmcl.2011.07.033

  日期：2011.9

  Optimisation of a series of indolin-2-one p38 alpha inhibitors was achieved via both blocking of a potential metabolic 'hot spot' and by increasing overall polarity of the lead series leading to non-cytotoxic compounds which showed improved oral bioavailabilities in the rat. (C) 2011 Elsevier Ltd. All rights reserved.