4,6-二氯-2-吡啶甲腈 | 40314-71-4

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4,6-二氯-2-吡啶甲腈
• 中文别名: 4,6-二氯吡啶-2-甲腈
• 英文名称: 4,6-dichloropicolinonitrile
• 英文别名: 4,6-dichloropyridine-2-carbonitrile
• CAS: 40314-71-4
• 化学式: C₆H₂Cl₂N₂
• 分子量: 173.001
• InChiKey: IYSMNJAHSIHMEK-UHFFFAOYSA-N

物化性质

• 沸点：
  251.1±35.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  2至8℃，惰性气体

反应信息

• 作为反应物：
  描述：

  4,6-二氯-2-吡啶甲腈 在 potassium tert-butylate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 N-(4-((2-chloro-6-cyanopyridin-4-yl)oxy)-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
  参考文献：
  名称：

  Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity

  摘要：

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.

  DOI：

  10.1021/ml500066m
• 作为产物：
  描述：

  2,4-二氯吡啶 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 24.5h， 生成 4,6-二氯-2-吡啶甲腈
  参考文献：
  名称：

  [EN] IMIDAZO[1,2-A]PYRIDINE DERIVATIVES AS HISTONE DEMETHYLASE INHIBITORS
  [FR] DÉRIVÉS D'IMIDAZO[1,2-A]PYRIDINE UTILISÉS EN TANT QU'INHIBITEURS D'HISTONE DÉMÉTHYLASE

  摘要：

  这份披露涉及抑制组蛋白去甲基化酶活性的化合物等内容。具体而言，该披露涉及抑制组蛋白赖氨酸去甲基化酶KDM5B的化合物，药物组合物和使用方法，例如使用本文披露的化合物和药物组合物治疗癌症的方法。

  公开号：

  WO2017214413A1

文献信息

• PYRIDINES AND PYRIMIDINES AND USE THEREOF
  申请人：Purdue Pharma L.P.

  公开号：US20170008882A1

  公开（公告）日：2017-01-12

  The present disclosure provides pyridines and pyrimidines of Formula I and pharmaceutically acceptable salts and solvates thereof: wherein A, G, W 1 , W 2 , W 3 , and R 5 are defined as set forth in the specification. The present disclosure also provides uses of the compounds of Formula I and pharmaceutically acceptable salts and solvates thereof. In certain embodiments, Compounds of the present disclosure are useful for treating pain. In another embodiment, Compounds of the present disclosure are useful for treating a disorder responsive to blockade of sodium channels, or alleviating symptoms of the disorder.

  本公开提供了Formula I的吡啶和嘧啶以及其药用可接受的盐和溶剂化合物：其中A、G、W1、W2、W3和R5如规范中所述。本公开还提供了Formula I化合物及其药用可接受的盐和溶剂的用途。在某些实施例中，本公开的化合物对治疗疼痛有用。在另一实施例中，本公开的化合物对治疗对钠通道阻滞有反应的疾病，或缓解该疾病的症状有用。
• [EN] PYRIDINES AND PYRIMIDINES AND USE THEREOF<br/>[FR] PYRIDINES ET PYRIMIDINES, ET LEUR UTILISATION
  申请人：PURDUE PHARMA LP

  公开号：WO2015112801A1

  公开（公告）日：2015-07-30

  The present disclosure provides pyridines and pyrimidines of Formula I and pharmaceutically acceptable salts and solvates thereof: wherein A, G, W1, W2, W3, and R5 are defined as set forth in the specification. The present disclosure also provides uses of the compounds of Formula I and pharmaceutically acceptable salts and solvates thereof. In certain embodiments, Compounds of the present disclosure are useful for treating pain. In another embodiment, Compounds of the present disclosure are useful for treating a disorder responsive to blockade of sodium channels, or alleviating symptoms of the disorder.

  本公开提供了式I的吡啶和嘧啶以及其药用可接受的盐和溶剂化合物：其中A、G、W1、W2、W3和R5的定义如规范中所述。本公开还提供了式I化合物及其药用可接受的盐和溶剂的用途。在某些实施例中，本公开的化合物对治疗疼痛有用。在另一实施例中，本公开的化合物对治疗对钠通道阻滞有反应的疾病，或者缓解该疾病的症状有用。
• Oxadiazolopyridine Derivates for Use as Ghrelin O-Acyl Transferase (GOAT) Inhibitors
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20180037594A1

  公开（公告）日：2018-02-08

  The present invention relates to compounds of general formula I, wherein the groups R 1 , R 2 and n are defined as in claim 1 , which have valuable pharmacological properties, in particular bind to ghrelin O-acyl transferase (GOAT) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular obesity.

  本发明涉及通式I的化合物，其中基团R1、R2和n的定义如权利要求书中所述，该化合物具有有价值的药理学特性，特别是结合到生长激素释放激素酰基转移酶（GOAT）并调节其活性。这些化合物适用于治疗和预防可能受该受体影响的疾病，如代谢性疾病，特别是肥胖症。
• Palladium-Catalyzed Site-Selective Amidation of Dichloroazines
  作者：Ian S. Young、Anna-Lena Glass、Theresa Cravillion、Chong Han、Haiming Zhang、Francis Gosselin

  DOI：10.1021/acs.orglett.8b01483

  日期：2018.7.6

  A highly site-selective amidation reaction of substituted 2,4-dichloroazines is reported. Palladium acetate/1,1′-bis(diphenylphosphino)ferrocene (dppf) was identified as the optimal catalyst system, producing >99:1 C-2/C-4 selectivity for most examples. The generality of this transformation was demonstrated through a survey of a diverse amide/substituted 2,4-dichloroazine scope, leading to the preparation

  报道了取代的2，4-二氯嗪的高度位点选择性酰胺化反应。乙酸钯/ 1,1'-双（二苯基膦基）二茂铁（dppf）被确定为最佳催化剂体系，在大多数实例中，其生成的C> 2 / C-4选择性> 99：1。通过各种酰胺/取代的2,4-二氯嗪范围的调查证明了这种转化的一般性，从而以良好至极好的收率制备了所需的C-2酰胺化产品。
• SUBSTITUTED PYRIDINE AND PYRIMIDINES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20190308950A1

  公开（公告）日：2019-10-10

  Substituted pyrimidine and pyridines as NR2B receptor ligands. Such compounds may be used in NR2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by NR2B receptor activity.

  用嘧啶和吡啶替代作为NR2B受体配体。这些化合物可用于NR2B受体调节以及用于治疗由NR2B受体活性介导的疾病状态、紊乱和病况的药物组合物和方法。