4-氨基-3-氟-N-(1-甲基哌啶-4-基)苯甲酰胺 | 1001345-97-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氨基-3-氟-N-(1-甲基哌啶-4-基)苯甲酰胺
• 英文名称: 4-amino-3-fluoro-N-(1-methylpiperidin-4-yl)benzamide
• 英文别名: 4-amino-3-fluoro-N-(1-methyl-4-piperidyl)benzamide
• CAS: 1001345-97-6
• 化学式: C₁₃H₁₈FN₃O
• mdl: MFCD17112066
• 分子量: 251.304
• InChiKey: VCVDMAIRMJCLMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (7R)-2-氯-8-环戊基-7-乙基-7,8-二氢-5-甲基-6(5H)-蝶啶酮 、 4-氨基-3-氟-N-(1-甲基哌啶-4-基)苯甲酰胺 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 以34%的产率得到(R)-4-((8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-fluoro-N-(1-methylpiperidin-4-yl)benzamide
  参考文献：
  名称：

  BRD4 Structure–Activity Relationships of Dual PLK1 Kinase/BRD4 Bromodomain Inhibitor BI-2536

  摘要：

  A focused library of analogues of the dual PLK1 kinase/BRD4 bromodomain inhibitor BI-2536 was prepared and then analyzed for BRD4 and PLK1 inhibitory activities. Particularly, replacement of the cyclopentyl group with a 3-bromobenzyl moiety afforded the most potent BRD4 inhibitor of the series (39j) with a K-i = 8.7 nM, which was equipotent against PLK1. The superior affinity of 39j over the parental compound to BRD4 possibly derives from improved interactions with the WPF shelf. Meanwhile, substitution of the pyrimidine NH with an oxygen atom reversed the PLK1/BRD4 selectivity to convert BI-2536 into a BRD4-selective inhibitor, likely owing to the loss of a critical hydrogen bond in PLK1. We believe further fine-tuning will furnish a BRD4 "magic bullet" or an even more potent PLK1/BRD4 dual inhibitor toward the expansion and improved efficacy of the chemotherapy arsenal.

  DOI：

  10.1021/acsmedchemlett.5b00084
• 作为产物：
  描述：

  4-氨基-1-甲基哌啶 在 tin(II) chloride dihdyrate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 4-氨基-3-氟-N-(1-甲基哌啶-4-基)苯甲酰胺
  参考文献：
  名称：

  BRD4 Structure–Activity Relationships of Dual PLK1 Kinase/BRD4 Bromodomain Inhibitor BI-2536

  摘要：

  A focused library of analogues of the dual PLK1 kinase/BRD4 bromodomain inhibitor BI-2536 was prepared and then analyzed for BRD4 and PLK1 inhibitory activities. Particularly, replacement of the cyclopentyl group with a 3-bromobenzyl moiety afforded the most potent BRD4 inhibitor of the series (39j) with a K-i = 8.7 nM, which was equipotent against PLK1. The superior affinity of 39j over the parental compound to BRD4 possibly derives from improved interactions with the WPF shelf. Meanwhile, substitution of the pyrimidine NH with an oxygen atom reversed the PLK1/BRD4 selectivity to convert BI-2536 into a BRD4-selective inhibitor, likely owing to the loss of a critical hydrogen bond in PLK1. We believe further fine-tuning will furnish a BRD4 "magic bullet" or an even more potent PLK1/BRD4 dual inhibitor toward the expansion and improved efficacy of the chemotherapy arsenal.

  DOI：

  10.1021/acsmedchemlett.5b00084

文献信息

• NOVEL COMPOUNDS
  申请人：HALSALL Christopher Thomas

  公开号：US20080009482A1

  公开（公告）日：2008-01-10

  There is provided a compound of formula (I): processes for the manufacture thereof, pharmaceutical compositions thereof and uses in therapy.

  提供了一个化合物的化学式(I)： 其制备方法，药物组合物以及在治疗中的用途。
• [EN] (5,6-DIHYDRO)PYRIMIDO[4,5-E]INDOLIZINES<br/>[FR] (5,6-DIHYDRO)PYRIMIDO[4,5-E]INDOZILINES
  申请人：NETHERLANDS TRANSLATIONAL RES CT B V

  公开号：WO2015155042A1

  公开（公告）日：2015-10-15

  The invention relates to a compound of Formula (I) wherein, R1 and R2 independently are selected from the group consisting of optionally substituted (6-10C)aryl and (1-5C)heteroaryl groups. The compounds can be used in pharmaceutical compositions, in particular in the treatment of cancer.

  本发明涉及一种公式(I)的化合物，其中R1和R2独立地选自包括可选择性取代的（6-10C）芳基和（1-5C）杂芳基基团在内的组。这些化合物可用于药物组合物中，特别是在癌症治疗中。
• Compounds
  申请人：AstraZeneca AB

  公开号：US07709471B2

  公开（公告）日：2010-05-04

  There is provided a compound of formula (I): processes for the manufacture thereof, pharmaceutical compositions thereof and uses in therapy.

  提供了一个公式（I）的化合物：其制造过程，制药组合物及其在治疗中的用途。
• Polo-like kinase inhibitors
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2564850A1

  公开（公告）日：2013-03-06

  Compounds of the formula: wherein the variables are as defined herein, are provided. Also provided are pharmaceutical compositions, methods and intermediates useful for making the compounds; and medical uses of the compounds.

  式中的化合物： 其中变量如本文所定义。此外，还提供了药物组合物、用于制造这些化合物的方法和中间体，以及这些化合物的医疗用途。
• WO2008/40951
  申请人：——

  公开号：——

  公开（公告）日：——