2-(异丙基氨基)-5-嘧啶羧酸 | 148741-64-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-(异丙基氨基)-5-嘧啶羧酸
• 英文名称: 2-Isopropylamino-5-carboxypyrimidine
• 英文别名: 2-(Isopropylamino)pyrimidine-5-carboxylic acid；2-(propan-2-ylamino)pyrimidine-5-carboxylic acid
• CAS: 148741-64-4
• 化学式: C₈H₁₁N₃O₂
• 分子量: 181.194
• InChiKey: KHKCJJIQFAWEGW-UHFFFAOYSA-N

物化性质

• 沸点：
  371.1±34.0 °C(Predicted)
• 密度：
  1.282±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• 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-(异丙基氨基)-5-嘧啶羧酸 、 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30%的产率得到2-(isopropylamino)-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：

  甲基2-(异丙基氨基)-5-嘧啶羧酸酯 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以850 mg (92%)的产率得到2-(异丙基氨基)-5-嘧啶羧酸
  参考文献：
  名称：

  Compounds having a guanidine structure

  摘要：

  化合物I具有以下结构式，对于促进神经轴突的生长、修复和再生以及治疗神经病和肌病非常有用：##STR1## 其中R.sub.2，R.sub.3和R.sub.4与它们附着的氮原子一起形成一个杂环。

  公开号：

  US05480884A1

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。
• Modulators of S1P and Methods of Making And Using
  申请人：Bannen Lynne Canne

  公开号：US20100249071A1

  公开（公告）日：2010-09-30

  The invention is directed to Compounds of Formula I: as well as methods of making and using the compounds.

  本发明涉及式I的化合物，以及制备和使用该化合物的方法。
• Compounds having a guanidine structure
  申请人：Centre National De La Recherche Scientifique

  公开号：US05480884A1

  公开（公告）日：1996-01-02

  Compounds are provided useful for promoting growth, repair and regeneration of a neuronal axon and for treating neuropathies and myopathies having formula I ##STR1## wherein R.sub.2, R.sub.3 and R.sub.4 together with the nitrogen atoms to which they are attached forms a heterocyclic ring.

  化合物I具有以下结构式，对于促进神经轴突的生长、修复和再生以及治疗神经病和肌病非常有用：##STR1## 其中R.sub.2，R.sub.3和R.sub.4与它们附着的氮原子一起形成一个杂环。
• Compounds having a guanidine structure and pharmaceutical composition
  申请人：Centre National De La Recherche Scientifique(CNRS)

  公开号：US05719187A1

  公开（公告）日：1998-02-17

  Guanidine derivatives are provided useful for promoting growth, repair and regeneration of a neuronal axon and for treating neuropathies and myopathies. The compounds have the formula: ##STR1## wherein R.sub.1 is an isopropyl radical, a benzyl radical which is optionally substituted by one or more (C.sub.1 -C.sub.6)alkoxy radicals or a radical: ##STR2## R.sub.2, R.sub.3 and R.sub.4 together with the nitrogen atoms to which they are attached and the carbon atom to which the said nitrogen atoms are attached form a pyrimidine ring of formula II or a pyrimidinium ring of formula IIa: ##STR3##

  提供了一种鸟嘌呤衍生物，用于促进神经轴突的生长、修复和再生，以及治疗神经病和肌病。该化合物的化学式为：##STR1## 其中R.sub.1是异丙基基团、苄基基团（可选地被一个或多个（C.sub.1-C.sub.6）烷氧基基团取代）或基团：##STR2## R.sub.2、R.sub.3和R.sub.4与它们连接的氮原子以及连接这些氮原子的碳原子共同形成公式II的嘧啶环或公式IIa的嘧啶阳离子环：##STR3##
• COMPOSES A STRUCTURE GUANIDIQUE ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：Etablissement Public dit: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：EP0572635B1

  公开（公告）日：1996-12-27