5-cyano-2,4'-bipyridine | 834881-86-6

• 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
• 英文名称: 5-cyano-2,4'-bipyridine
• 英文别名: [2,4'-Bipyridine]-5-carbonitrile；6-pyridin-4-ylpyridine-3-carbonitrile
• CAS: 834881-86-6
• 化学式: C₁₁H₇N₃
• 分子量: 181.197
• InChiKey: YRHQQFYBLAUBDL-UHFFFAOYSA-N

物化性质

• 沸点：
  347.5±32.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-cyano-2,4'-bipyridine 在 正丁基锂 、 sodium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 以83%的产率得到5-formyl-2,4'-bipyridine
  参考文献：
  名称：

  Novel bipyridine derivatives

  摘要：

  该发明提供了一种对制药产品、农药化学品、电子感光材料、染料等具有中间体作用的双吡啶衍生物，其为一种由通式（I）表示的双吡啶衍生物及其盐：其中R1代表具有取代基的2至20个碳原子的烷基基团，取代或未取代氨甲基基团，三氟甲基基团，取代或未取代硫甲基基团，取代或未取代烯基基团，取代或未取代烷氧基团，取代或未取代芳氧基团，取代羰基团，取代磺酰基团，未取代或单取代的氨甲酰基团，未取代或单取代的磺酰胺基团，取代或未取代硫醇基团，未取代或单取代的氨基团，取代羰基氨基团，取代或未取代脲基团，硝基基团，氰基团，甲酰基团或其等效物，碘原子或氟原子。

  公开号：

  US20050085642A1
• 作为产物：
  描述：

  氰化亚铜 、 5-溴-2,4'-联吡啶 在 sodium hydroxide 作用下， 以 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 3.0h， 以83%的产率得到5-cyano-2,4'-bipyridine
  参考文献：
  名称：

  Novel bipyridine derivatives

  摘要：

  该发明提供了一种对制药产品、农药化学品、电子感光材料、染料等具有中间体作用的双吡啶衍生物，其为一种由通式（I）表示的双吡啶衍生物及其盐：其中R1代表具有取代基的2至20个碳原子的烷基基团，取代或未取代氨甲基基团，三氟甲基基团，取代或未取代硫甲基基团，取代或未取代烯基基团，取代或未取代烷氧基团，取代或未取代芳氧基团，取代羰基团，取代磺酰基团，未取代或单取代的氨甲酰基团，未取代或单取代的磺酰胺基团，取代或未取代硫醇基团，未取代或单取代的氨基团，取代羰基氨基团，取代或未取代脲基团，硝基基团，氰基团，甲酰基团或其等效物，碘原子或氟原子。

  公开号：

  US20050085642A1

文献信息

• Bipyridine Derivatives
  申请人：Fujifilm Finechemicals Co., Ltd.

  公开号：US07301029B2

  公开（公告）日：2007-11-27

  The invention provides a bipyridine derivative useful as an intermediate for pharmaceutical products, agricultural chemicals, electrophotographic photosensitive materials, dyes and the like, which is a bipyridine derivative represented by the general formula (I) and a salt thereof: wherein R1 represents an alkyl group with 2 to 20 carbon atoms having a substituent, substituted or unsubstituted aminomethyl group, trifluoromethyl group, substituted or unsubstituted thiomethyl group, substituted or unsubstituted alkenyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted aryloxy group, substituted carbonyl group, substituted sulfonyl group, unsubstituted or monosubstituted carbamoyl group, unsubstituted or monosubstituted sulfamoyl group, substituted or unsubstituted thiol group, unsubstituted or monosubstituted amino group, substituted carbonylamino group, substituted or unsubstituted ureido group, nitro group, cyano group, formyl group or an equivalent thereof, iodine atom or fluorine atom.

  本发明提供了一种双吡啶衍生物，可用作制药产品、农药、电子感光材料、染料等的中间体，其为一种由通式（I）表示的双吡啶衍生物及其盐：其中R1代表具有取代基的2至20个碳原子的烷基，取代或未取代的氨甲基基团、三氟甲基基团、取代或未取代的硫甲基基团、取代或未取代的烯基基团、取代或未取代的烷氧基团、取代或未取代的芳氧基团、取代的羰基团、取代的磺酰基团、未取代或单取代的氨基甲酰基团、未取代或单取代的磺酰胺基团、取代或未取代的硫醇基团、未取代或单取代的氨基团、取代的羰基氨基团、取代或未取代的脲基团、硝基团、氰基团、甲酰基团或其等效物、碘原子或氟原子。
• Novel 2,6,9-Trisubstituted Purines as Potent CDK Inhibitors Alleviating Trastuzumab-Resistance of HER2-Positive Breast Cancers
  作者：Ratnakar Reddy Kuchukulla、Injeoung Hwang、Sang Won Park、Sojeong Moon、Suhn Hyung Kim、Sumin Kim、Hwan Won Chung、Mi-Jung Ji、Hyun-Mee Park、Gu Kong、Wooyoung Hur

  DOI：10.3390/ph15091041

  日期：——

  HER2-positive (HER2+) breast cancer is defined by HER2 oncogene amplification on chromosome 17q12 and accounts for 15–20% population of breast-cancer patients. Therapeutic anti-HER2 antibody such as trastuzumab is used as the first-line therapy for HER2-positive breast cancers. However, more than 50% of the patients respond poorly to trastuzumab, illustrating that novel therapy is warranted to overcome the resistance. We previously reported that in the majority of HER2+ breast-cancer patients, CDK12 is co-amplified on 17q12 and involved in developing tumors and trastuzumab resistance, proposing CDK12 as a potential drug target for HER2+ breast cancers. Here, we designed and synthesized novel 2,6,9-trisubstituted purines as potent CDK12 inhibitors showing strong, equipotent antiproliferative activity against trastuzumab-sensitive HER2+ SK-Br3 cells and trastuzumab-resistant HER2+ HCC1954 cells (GI50 values < 50 nM) both of which express a high level of CDK12. Two potent analogue 30d and 30e at 40, 200 nM greatly downregulated the levels of cyclinK and Pol II p-CTD (Ser2), as well as the expression of CDK12 downstream genes (IRS1 and WNT1) in a dose-dependent manner. We also observed structure-property relationship for a subset of potent analogues, and found that 30e is highly stable in liver microsomes with lack of CYP inhibition. In addition, 30d exhibited a synergy with trastuzumab in the both cells, suggesting that our inhibitors could be applied to alleviate trastuzumab-resistance of HER2+ breast cancers and escalate the efficacy of trastuzumab as well. Our study may provide insight into developing a novel therapy for HER2+ breast cancers.

  HER2阳性（HER2+）乳腺癌是由17q12染色体上HER2癌基因扩增定义的，占乳腺癌患者人群的15-20％。治疗HER2阳性乳腺癌的一线疗法是使用抗HER2抗体如曲妥珠单抗。然而，超过50％的患者对曲妥珠单抗反应不佳，说明需要新的治疗方法来克服耐药性。我们先前报道，在大多数HER2+乳腺癌患者中，CDK12在17q12上共扩增，并参与肿瘤和曲妥珠单抗耐药性的发展，因此建议CDK12作为HER2+乳腺癌的潜在药物靶点。在这里，我们设计和合成了新型2,6,9-三取代嘌呤作为强效CDK12抑制剂，对曲妥珠单抗敏感的HER2+ SK-Br3细胞和曲妥珠单抗耐药的HER2+ HCC1954细胞（GI50值<50 nM），都表现出强大、等效的抗增殖活性，这两种细胞都表达高水平的CDK12。两种强效类似物30d和30e在40、200 nM时，明显降低了cyclinK和Pol II p-CTD（Ser2）的水平，以及CDK12下游基因（IRS1和WNT1）的表达，呈剂量依赖性。我们还观察到一些强效类似物的结构-性质关系，并发现30e在肝微粒体中非常稳定，没有CYP抑制作用。此外，30d在两种细胞中与曲妥珠单抗表现出协同作用，表明我们的抑制剂可用于减轻HER2+乳腺癌对曲妥珠单抗的耐药性，并提高曲妥珠单抗的疗效。我们的研究可能为HER2+乳腺癌的新型治疗提供洞见。
• US7301029B2
  申请人：——

  公开号：US7301029B2

  公开（公告）日：2007-11-27
• [EN] METABOTROPIC GLUTAMATE RECEPTORS 5 MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS 5 MÉTABOTROPIQUES DU GLUTAMATE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：SUNOVION PHARMACEUTICALS INC

  公开号：WO2012162635A1

  公开（公告）日：2012-11-29

  Compounds that modulate GluR5 activity and methods of using the same are disclosed.
• Novel bipyridine derivatives
  申请人：Kuwabara Hirokazu

  公开号：US20050085642A1

  公开（公告）日：2005-04-21

  The invention provides a bipyridine derivative useful as an intermediate for pharmaceutical products, agricultural chemicals, electrophotographic photosensitive materials, dyes and the like, which is a bipyridine derivative represented by the general formula (I) and a salt thereof: wherein R1 represents an alkyl group with 2 to 20 carbon atoms having a substituent, substituted or unsubstituted aminomethyl group, trifluoromethyl group, substituted or unsubstituted thiomethyl group, substituted or unsubstituted alkenyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted aryloxy group, substituted carbonyl group, substituted sulfonyl group, unsubstituted or monosubstituted carbamoyl group, unsubstituted or monosubstituted sulfamoyl group, substituted or unsubstituted thiol group, unsubstituted or monosubstituted amino group, substituted carbonylamino group, substituted or unsubstituted ureido group, nitro group, cyano group, formyl group or an equivalent thereof, iodine atom or fluorine atom.

  该发明提供了一种对制药产品、农药化学品、电子感光材料、染料等具有中间体作用的双吡啶衍生物，其为一种由通式（I）表示的双吡啶衍生物及其盐：其中R1代表具有取代基的2至20个碳原子的烷基基团，取代或未取代氨甲基基团，三氟甲基基团，取代或未取代硫甲基基团，取代或未取代烯基基团，取代或未取代烷氧基团，取代或未取代芳氧基团，取代羰基团，取代磺酰基团，未取代或单取代的氨甲酰基团，未取代或单取代的磺酰胺基团，取代或未取代硫醇基团，未取代或单取代的氨基团，取代羰基氨基团，取代或未取代脲基团，硝基基团，氰基团，甲酰基团或其等效物，碘原子或氟原子。