[2,3'-bipyridine]-5-carbonitrile | 35989-11-8

• 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: [2,3'-bipyridine]-5-carbonitrile
• 英文别名: 6-pyridin-3-ylpyridine-3-carbonitrile
• CAS: 35989-11-8
• 化学式: C₁₁H₇N₃
• 分子量: 181.197
• InChiKey: FNWSCQGLFYBYGY-UHFFFAOYSA-N

物化性质

• 熔点：
  107-109 °C(Solv: methanol (67-56-1))
• 沸点：
  362.2±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：

  [2,3'-bipyridine]-5-carbonitrile 在 盐酸 作用下， 生成 [2,3-联吡啶]-5-羧酸
  参考文献：
  名称：

  Otroschtschenko; Sadykow, Zhurnal Obshchei Khimii, 1954, vol. 24, p. 1685,1686; engl. Ausg. S. 1661, 1662

  摘要：

  DOI：
• 作为产物：
  描述：

  2-溴-5-氰基吡啶 在 lithium chloro-isopropyl-magnesium chloride 、 copper(II) bis(trifluoromethanesulfonate) 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.75h， 生成 [2,3'-bipyridine]-5-carbonitrile
  参考文献：
  名称：

  使用格氏试剂和吡啶基锍盐合成双杂芳基化合物

  摘要：

  本文报道了格氏试剂与吡啶基锍盐的配体偶联反应。该方法具有广泛的官能团耐受性，能够形成双杂环键，包括 2,4'-、2,3'-和 2,2'-联吡啶，以及与嘧啶、吡嗪、异恶唑连接的吡啶，和苯并噻吩。该方法成功地应用于天然产物 caerulomycin A 和 E 的合成。

  DOI：

  10.1021/acs.orglett.1c03379

文献信息

• 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。
• 3-[5-(4,5-Dihydro-1<i>H</i>-imidazol-2-yl)-furan-2-yl]phenylamine (Amifuraline), a Promising Reversible and Selective Peripheral MAO-A Inhibitor
  作者：Francesco Gentili、Nathalie Pizzinat、Catherine Ordener、Sophie Marchal-Victorion、Agnès Maurel、Robert Hofmann、Pierre Renard、Philippe Delagrange、Maria Pigini、Angelo Parini、Mario Giannella

  DOI：10.1021/jm060605r

  日期：2006.9.1

  On the basis of the observation that the central side effects of MAO inhibitors may represent a major limit for their use in pathological processes involving peripheral MAOs, we investigated the possibility of generating novel inhibitors able to target specifically peripheral MAOs. To address this issue, we designed compounds 7-28. From biological results, the 2-( 5-phenyl-furan-2-yl)-4,5-dihydro-1H-imidazole ( Furaline, 17) proved to be a suitable lead. In fact, in enzyme assays on homogenate preparation from rat liver and HEK cells expressing MAO-A or MAO-B, compounds possessing the frame of 17 behaved as selective and reversible MAO-A inhibitors. Interestingly, in in vivo studies the amino derivative 21 ( Amifuraline), endowed with good hydrophilic character, was able to significantly inhibit liver but not brain MAO-A.
• Otroschtschenko; Sadykow, Zhurnal Obshchei Khimii, 1954, vol. 24, p. 1885; engl. Ausg. S. 1847
  作者：Otroschtschenko、Sadykow

  DOI：——

  日期：——
• NOVEL MICROBIOCIDES
  申请人：Syngenta Participations AG

  公开号：EP2951167B1

  公开（公告）日：2017-01-25
• US9655363B2
  申请人：——

  公开号：US9655363B2

  公开（公告）日：2017-05-23