2-(cyclopropylamino)pyrimidine-5-carboxylic acid | 1242458-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(cyclopropylamino)pyrimidine-5-carboxylic acid
• 英文别名: 2-(Cyclopropylamino)-5-pyrimidinecarboxylic acid
• CAS: 1242458-50-9
• 化学式: C₈H₉N₃O₂
• 分子量: 179.178
• InChiKey: GTCVZQGSDGEQLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  75.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(cyclopropylamino)pyrimidine-5-carboxylic acid 、 3-amino-4-methyl-N-(4-((4-methylpiperazin-1-yl) methyl)-3-(trifluoromethyl)phenyl)benzamide 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 12.0h， 以48%的产率得到2-(cyclopropylamino)-N-(2-methyl-5-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)pyrimidine-5-carboxamide
  参考文献：
  名称：

  Identification and Optimization of New Dual Inhibitors of B-Raf and Epidermal Growth Factor Receptor Kinases for Overcoming Resistance against Vemurafenib

  摘要：

  Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-Raf(V600E) inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-Raf(V600E) mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively. The compound also strongly suppressed the proliferation of a panel of intrinsic and acquired resistant melanoma and/or colorectal cancer cells harboring overexpressed EGFR with submicromolar IC50 values. Further mechanism investigation revealed that 6a could sustainably inhibit the activation of the MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR amplification. Our results support the hypothesis that the EGFR/B-Raf(V600E) dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-Raf(V600E) inhibitor therapy.

  DOI：

  10.1021/jm500007h
• 作为产物：
  描述：

  Methyl 2-(cyclopropylamino)pyrimidine-5-carboxylate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 2-(cyclopropylamino)pyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Identification and Optimization of New Dual Inhibitors of B-Raf and Epidermal Growth Factor Receptor Kinases for Overcoming Resistance against Vemurafenib

  摘要：

  Epidermal growth factor receptor (EGFR) amplification has been demonstrated to be critical for the inherent and/or acquired resistance against current B-Raf(V600E) inhibitor therapy for melanoma and colorectal cancer patients. We describe the discovery and structure-activity relationship study of a series of 1H-pyrazolo[3,4-b]pyridine-5-carboxamide analogues as novel dual inhibitors of EGFR and B-Raf(V600E) mutant. One of the most promising compounds, 6a, potently inhibited both of the kinases with IC50 values of 8.0 and 51 nM, respectively. The compound also strongly suppressed the proliferation of a panel of intrinsic and acquired resistant melanoma and/or colorectal cancer cells harboring overexpressed EGFR with submicromolar IC50 values. Further mechanism investigation revealed that 6a could sustainably inhibit the activation of the MAPK path way in the resistant SK-MEL-28 PR30 melanoma cancer cells and WiDr colorectal cancer cells with EGFR amplification. Our results support the hypothesis that the EGFR/B-Raf(V600E) dual inhibition might be a tractable strategy to overcome the intrinsic and acquired resistance of melanoma and/or colorectal cancers against the current B-Raf(V600E) inhibitor therapy.

  DOI：

  10.1021/jm500007h

文献信息

• NEW COMPOUNDS
  申请人：HAUEL Norbert

  公开号：US20100240669A1

  公开（公告）日：2010-09-23

  The present invention relates to the compounds of general formula I wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X are defined as described hereinafter, the enantiomers, the diastereomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with organic or inorganic acids or bases, which have valuable properties, the preparation thereof, the medicaments containing the pharmacologically effective compounds, the preparation thereof and the use thereof.

  本发明涉及一般式I的化合物，其中n、R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和X的定义如下所述，其对映体、非对映体、混合物及其盐，特别是其与有机或无机酸或碱形成的生理上可接受的盐，具有有价值的性质，其制备方法，含有药理学有效化合物的药物，其制备方法和用途。
• Imidazo[4,5-C]pyridine and pyrrolo[2,3-C]pyridine derivatives as SSAO inhibitors
  申请人：PROXIMAGEN, LLC

  公开号：US10428066B2

  公开（公告）日：2019-10-01

  The compounds of formula (I) are inhibitors of SSAO activity wherein V, W, X, Y, Z, R1 and R2 are as defined in the claims.

  式（I）化合物是 SSAO 活性抑制剂 其中 V、W、X、Y、Z、R1 和 R2 如权利要求中所定义。
• Imidazo[4,5-c]pyridine and pyrrolo[2,3-c]pyridine derivatives as SSAO inhibitors
  申请人：PROXIMAGEN, LLC

  公开号：US10766897B2

  公开（公告）日：2020-09-08

  The compounds of formula (I) are inhibitors of SSAO activity wherein V, W, X, Y, Z, R1 and R2 are as defined in the claims.

  式（I）化合物是 SSAO 活性抑制剂 其中 V、W、X、Y、Z、R1 和 R2 如权利要求中所定义。
• VERBINDUNGEN ALS BRADYKININ-B1-ANTAGONISTEN
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2401256A1

  公开（公告）日：2012-01-04
• Verbindungen als Bradykinin-B1-Antagonisten
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2401256B1

  公开（公告）日：2013-04-17