5-(3,4-dimethoxyphenyl)-4-[(4-phenoxyphenyl)amino]nicotinonitrile | 960040-64-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(3,4-dimethoxyphenyl)-4-[(4-phenoxyphenyl)amino]nicotinonitrile
• 英文别名: 5-(3,4-Dimethoxyphenyl)-4-[(4-phenoxyphenyl)amino]pyridine-3-carbonitrile；5-(3,4-dimethoxyphenyl)-4-(4-phenoxyanilino)pyridine-3-carbonitrile
• CAS: 960040-64-6
• 化学式: C₂₆H₂₁N₃O₃
• 分子量: 423.471
• InChiKey: ALJLIYUQIVIGHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-chloro-5-(3,4-dimethoxyphenyl)-3-pyridinecarbonitrile 、 4-氨基二苯醚 在 吡啶盐酸盐 作用下， 以 乙二醇乙醚 为溶剂， 反应 8.0h， 生成 5-(3,4-dimethoxyphenyl)-4-[(4-phenoxyphenyl)amino]nicotinonitrile
  参考文献：
  名称：

  Identification, Characterization and Initial Hit-to-Lead Optimization of a Series of 4-Arylamino-3-Pyridinecarbonitrile as Protein Kinase C theta (PKCθ) Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm800214a

文献信息

• Substituted Cyanopyridines as protein kinase inhibitors
  申请人：Cole Derek Cecil

  公开号：US20070287738A1

  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。
• SUBSTITUTED CYANOPYRIDINES AS PROTEIN KINASE INHIBITORS
  申请人：Wyeth

  公开号：EP2027093A2

  公开（公告）日：2009-02-25
• [EN] SUBSTITUTED CYANOPYRIDINES AS PROTEIN KINASE INHIBITORS<br/>[FR] CYANOPYRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE PROTÉINE KINASES
  申请人：WYETH CORP

  公开号：WO2007146323A2

  公开（公告）日：2007-12-21

  [EN] The present teachings provide compounds of formula I XR R2 XN and their pharmaceutically acceptable salts, hydrates, and esters, wherein R1, R2, 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.
  [FR] La présente invention a pour objet des composés de formule I XR R2 XN et leurs sels, hydrates et esters de qualité pharmaceutique, R1, R2 et X étant tels que définis dans la présente invention. La présente invention a également pour objet des méthodes de fabrication des composés de formule I, ainsi que des méthodes de traitement de maladies auto-immunes et inflammatoires par administration d'une quantité thérapeutiquement active d'un ou de plusieurs composés de formule I à un mammifère, y compris à un humain.
• 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.