4-chloro-5-(3,4-dimethoxyphenyl)-3-pyridinecarbonitrile | 959972-23-7

• 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: 4-chloro-5-(3,4-dimethoxyphenyl)-3-pyridinecarbonitrile
• 英文别名: 4-chloro-5-(3,4-dimethoxyphenyl)nicotinonitrile；4-chloro-5-(3,4-dimethoxyphenyl)pyridine-3-carbonitrile
• CAS: 959972-23-7
• 化学式: C₁₄H₁₁ClN₂O₂
• 分子量: 274.707
• InChiKey: DJJVYXBJTMVSHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-5-(3,4-dimethoxyphenyl)-3-pyridinecarbonitrile 、 3-氨基苯酚 以 乙醇 为溶剂， 反应 0.11h， 生成 5-(3,4-dimethoxyphenyl)-4-[(3-hydroxyphenyl)amino]nicotinonitrile
  参考文献：
  名称：

  Substituted Cyanopyridines as protein kinase inhibitors

  摘要：

  本教学提供了公式I的化合物及其药学上可接受的盐、水合物和酯，其中R1、R2和X的定义如本文所述。本教学还提供制备公式I化合物的方法，以及通过向哺乳动物，包括人类，投与公式I化合物或化合物的治疗有效量来治疗自身免疫和炎症性疾病的方法。

  公开号：

  US20070287738A1
• 作为产物：
  描述：

  5-(3,4-dimethoxyphenyl)-4-hydroxy-3-pyridinecarbonitrile 在 三氯氧磷 、 sodium hydroxide 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 1.5h， 以91%的产率得到4-chloro-5-(3,4-dimethoxyphenyl)-3-pyridinecarbonitrile
  参考文献：
  名称：

  Substituted Cyanopyridines as protein kinase inhibitors

  摘要：

  本发明的教导提供了公式I的化合物及其药用可接受的盐、水合物和酯，其中R1、R2和X如本文所述定义。本发明的教导还提供了制造公式I化合物的方法，以及通过向哺乳动物包括人类施用治疗有效量的公式I化合物或化合物来治疗自身免疫性和炎症性疾病的方法。

  公开号：

  US20070287738A1

文献信息

• Substituted 3-cyanopyridines as protein kinase inhibitors
  申请人：Cole Cecil Derek

  公开号：US20070287708A1

  公开（公告）日：2007-12-13

  The present teachings provide compounds of formula I and their pharmaceutically acceptable salts, hydrates, and esters, wherein R 1 , R 2 , and X are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating autoimmune and inflammatory diseases by administering a therapeutically effective amount of a compound or compounds of formula I to a mammal including a human.

  本发明的教导提供了公式I的化合物及其药用可接受的盐、水合物和酯，其中R1、R2和X如本文所述定义。本发明的教导还提供了制造公式I化合物的方法，以及通过向哺乳动物包括人类施用治疗有效量的公式I化合物或化合物来治疗自身免疫性和炎症性疾病的方法。
• Identification, Characterization and Initial Hit-to-Lead Optimization of a Series of 4-Arylamino-3-Pyridinecarbonitrile as Protein Kinase C theta (PKCθ) Inhibitors
  作者：Derek C. Cole、Magda Asselin、Agnes Brennan、Robert Czerwinski、John W. Ellingboe、Lori Fitz、Rita Greco、Xinyi Huang、Diane Joseph-McCarthy、Michael F. Kelly、Matthew Kirisits、Julie Lee、Yuanhong Li、Paul Morgan、Joseph R. Stock、Désirée H. H. Tsao、Allan Wissner、Xiaoke Yang、Divya Chaudhary

  DOI：10.1021/jm800214a

  日期：2008.10.9

  The protein kinase C (PKC) family of serine/threonine kinases is implicated in a wide variety of cellular processes. The PKC theta (PKCO) isoform is involved in TCR signal transduction and T cell activation and regulates T cell mediated diseases, including lung inflammation and airway hyperresponsiveness. Thus inhibition of PKCO enzyme activity by a small molecule represents an attractive strategy for the treatment of asthma. A PKCO high-throughput screening (HTS) campaign led to the identification of 4-(3-bromophenylamino)-5-(3,4-dimethoxyphenyl)-3-pyridinecarbonitrile 4a, a low mu M ATP competitive PKC theta inhibitor. Structure based hit-to-lead optimization led to the identification of 5-(3,4-dimethoxyphenyl)-4(1H-indol-5-ylamino)-3-pyridinecarbonitrile 4p, a 70 nM PKC theta inhibitor. Compound 4p was selective for inhibition of novel PKC isoforms over a panel of 21 serine/threonine, tyrosine, and phosphoinositol kinases, in addition to the conventional and atypical PKCs, PKC beta, and PKC zeta, respectively. Compound 4p also inhibited IL-2 production in antiCD3/anti-CD28 activated T cells enriched from splenocytes.
• Optimization of 5-phenyl-3-pyridinecarbonitriles as PKCθ inhibitors
  作者：Diane H. Boschelli、Daniel Wang、Amar S. Prashad、Joan Subrath、Biqi Wu、Chuan Niu、Julie Lee、Xiaoke Yang、Agnes Brennan、Divya Chaudhary

  DOI：10.1016/j.bmcl.2009.04.126

  日期：2009.7

  The key intermediate, 4-chloro-5-iodo-3-pyridinecarbonitrile, allowed for ready optimization of the PKC theta inhibitory activity of a series of 3-pyridinecarbonitriles. Analog 13b with a 4-methylindol-5-ylamino group at C-4 and a 4-(2-(4-methylpiperazin-1-yl)ethoxy) phenyl group at C-5 had an IC(50) value of 7.4 nM for the inhibition of PKC theta. (C) 2009 Elsevier Ltd. All rights reserved.
• SUBSTITUTED CYANOPYRIDINES AS PROTEIN KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP2027093A2

  公开（公告）日：2009-02-25
• SUBSTITUTED 3-CYANOPYRIDINES AS PROTEIN KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP2029543A2

  公开（公告）日：2009-03-04