4-amino-3-methoxy-N-((1-methylpiperidin-4-yl)methyl)benzamide | 1187094-61-6

• 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: 4-amino-3-methoxy-N-((1-methylpiperidin-4-yl)methyl)benzamide
• 英文别名: 4-amino-3-methoxy-N-[(1-methylpiperidin-4-yl)methyl]benzamide
• CAS: 1187094-61-6
• 化学式: C₁₅H₂₃N₃O₂
• 分子量: 277.367
• InChiKey: JFQVZKLVKXNMHP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-3-methoxy-N-((1-methylpiperidin-4-yl)methyl)benzamide 、 (R)-6-chloro-4-cyclopentyl-1,3-dimethyl-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 叔丁醇 为溶剂， 以85%的产率得到(R)-4-((4-cyclopentyl-1,3-dimethyl-2-oxo-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-6-yl)amino)-3-methoxy-N-((1-methylpiperidin-4-yl)methyl)benzamide
  参考文献：
  名称：

  Dual Inhibition of TAF1 and BET Bromodomains from the BI-2536 Kinase Inhibitor Scaffold

  摘要：

  Recent reports have highlighted the dual bromodomains of TAF1 (TAF1(1,2)) as synergistic with BET inhibition in cellular cancer models, engendering interest in TAF/BET polypharmacology. Here, we examine structure activity relationships within the BI-2536 PLK1 kinase inhibitor scaffold, previously reported to bind BRD4. We examine binding by this ligand to TAF1(2) and apply structure guided design strategies to discriminate binding to both the PLK1 kinase and BRD4(1) bromodomain while retaining activity on TAF1(2). Through this effort we discover potent dual inhibitors of TAF1(2)/BRD4(1), as well as biased derivatives showing marked TAF1 selectivity. We resolve X-ray crystallographic data sets to examine the mechanisms of the observed TAF1 selectivity and to provide a resource for further development of this scaffold.

  DOI：

  10.1021/acsmedchemlett.9b00243
• 作为产物：
  描述：

  (1-甲基-4-哌啶-)甲胺 、 4-氨基-3-甲氧基苯甲酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以84%的产率得到4-amino-3-methoxy-N-((1-methylpiperidin-4-yl)methyl)benzamide
  参考文献：
  名称：

  Dual Inhibition of TAF1 and BET Bromodomains from the BI-2536 Kinase Inhibitor Scaffold

  摘要：

  Recent reports have highlighted the dual bromodomains of TAF1 (TAF1(1,2)) as synergistic with BET inhibition in cellular cancer models, engendering interest in TAF/BET polypharmacology. Here, we examine structure activity relationships within the BI-2536 PLK1 kinase inhibitor scaffold, previously reported to bind BRD4. We examine binding by this ligand to TAF1(2) and apply structure guided design strategies to discriminate binding to both the PLK1 kinase and BRD4(1) bromodomain while retaining activity on TAF1(2). Through this effort we discover potent dual inhibitors of TAF1(2)/BRD4(1), as well as biased derivatives showing marked TAF1 selectivity. We resolve X-ray crystallographic data sets to examine the mechanisms of the observed TAF1 selectivity and to provide a resource for further development of this scaffold.

  DOI：

  10.1021/acsmedchemlett.9b00243

文献信息

• [EN] POLO-LIKE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE DE TYPE POLO
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2009067547A1

  公开（公告）日：2009-05-28

  Compounds of the following formula are provided for use with kinases, wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.

  提供以下公式的化合物供激酶使用，其中变量如本文所定义。还提供包含这些化合物的药物组合物、试剂盒和制造物品；用于制备这些化合物的方法和中间体；以及使用这些化合物的方法。
• Pyridopyrimidines used as Plk1 (polo-like kinase) inhibitors
  申请人：4SC AG

  公开号：EP2100894A1

  公开（公告）日：2009-09-16

  The invention relates to pyridopyrimidinone compounds according to formula (I), wherein the substituents and symbols are as defined in the description. The compounds are inhibitors of Plk1.

  本发明涉及根据式(I)的吡啶并嘧啶酮化合物，其中所述取代基和符号如说明书中所定义。这些化合物是Plk1的抑制剂。
• PYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
  申请人：Hollick Jonathan James

  公开号：US20110046093A1

  公开（公告）日：2011-02-24

  The present invention relates to a compound of formula (VII)I, or a pharmaceutically acceptable salt or ester thereof, wherein: X is NR 7 ; Y is O or N—(CH 2 ) n R 19 ; n is 1, 2 or 3; m is 1 or 2; R 1 and R 2 are each independently H, alkyl or cycloalkyl; R 4 and R 4′ each independently H alkyl; or R 4 and R 4′ together form a spiro cycloalkyl group; R 19 is H, alkyl, aryl or a cycloalkyl group; R 6 is OR 8 or halogen; and R 7 and R 8 are each independently H or alkyl. Further aspects relate to pharmaceutical compositions comprising said compounds and use therefore in the treatment of proliferative disorders and the like.

  本发明涉及一种化合物，其化学式为(VII)I，或其药学上可接受的盐或酯，其中：X为NR7；Y为O或N-(CH2)nR19；n为1、2或3；m为1或2；R1和R2各自独立地为H、烷基或环烷基；R4和R4′各自独立地为H烷基；或R4和R4′共同形成一个螺环烷基；R19为H、烷基、芳基或环烷基；R6为OR8或卤素；R7和R8各自独立地为H或烷基。此外，该发明还涉及包含上述化合物的制药组合物以及其在治疗增生性疾病等方面的用途。
• [EN] PYRIDOPYRIMIDINES AS PLK1 ( POLO-LIKE KINASE) INHIBITORS<br/>[FR] PYRIDOPYRIMIDINONES COMME INHIBITEURS DE PLK1 (KINASE DE TYPE POLO)
  申请人：4SC AG

  公开号：WO2009112524A1

  公开（公告）日：2009-09-17

  The invention relates to pyridopyrimidinone compounds according to formula (I), wherein the substituents and symbols are as defined in the description. The compounds are inhibitors of Plk1.