5-iodo-6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile | 1160848-93-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-iodo-6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile
• 英文别名: 5-iodo-6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]pyridine-3-carbonitrile
• CAS: 1160848-93-0
• 化学式: C₁₆H₁₃IN₄
• 分子量: 388.211
• InChiKey: YEBSZPPMTBMVAY-UHFFFAOYSA-N

物化性质

• 沸点：
  508.1±50.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  64.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-乙烯基吡啶 、 5-iodo-6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile 在 palladium diacetate 、 三(邻甲基苯基)磷 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以89%的产率得到6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]-5-[(E)-2-pyridin-2-ylvinyl]nicotinonitrile
  参考文献：
  名称：

  [EN] 5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS
  [FR] 5-ALKYL/ALCÉNYL-3-CYANOPYRIDINES EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开号：

  WO2009076602A8
• 作为产物：
  描述：

  4-甲基-5-氨基吲哚 、 4-氯-5-碘-6-甲基吡啶-3-腈 以 乙醇 为溶剂， 反应 96.0h， 生成 5-iodo-6-methyl-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile
  参考文献：
  名称：

  [EN] 5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS
  [FR] 5-ALKYL/ALCÉNYL-3-CYANOPYRIDINES EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开号：

  WO2009076602A8

文献信息

• [EN] INDOLE-SUBSTITUTED 3-CYANOPYRIDINES AS KINASE INHIBITORS<br/>[FR] 3-CYANOPYRIDINES INDOLE-SUBSTITUÉES EN TANT QU'INHIBITEURS DE KINASE
  申请人：WYETH CORP

  公开号：WO2009076571A1

  公开（公告）日：2009-06-18

  Disclosed are compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X is -O-, -N(R3)-, -S-, -S(O)- or -S(O)2-; R2 is a C1-4 alkyl group or -CF3; and R1, R3, R4 and p are as defined herein; wherein the compounds are useful as kinase inhibitors. Also disclosed are pharmaceutical compositions containing, and intermediate compounds and methods for making the compounds of formula (I) and their pharmaceutically acceptable salts; and methods of using the foregoing to treat inflammatory and autoimmune diseases such as asthma, colitis, multiple sclerosis, psoriasis, arthritis, rheumatoid arthritis, inflammatory bowel disease, and joint inflammation.

  揭示了具有以下结构的化合物（I）及其药学上可接受的盐，其中X为-O-、-N(R3)-、-S-、-S(O)-或-S(O)2-；R2为C1-4烷基或-CF3；而R1、R3、R4和p如本文所定义；这些化合物可用作激酶抑制剂。还揭示了含有这些化合物的药物组合物，以及制备这些化合物及其药学上可接受的盐的中间体化合物和方法；以及利用上述化合物来治疗炎症和自身免疫性疾病，如哮喘、结肠炎、多发性硬化症、牛皮癣、关节炎、类风湿关节炎、炎症性肠病和关节炎的方法。
• Indole-substituted 3-cyanopyridines As Kinase Inhibitors
  申请人：Boschelli Diane Harris

  公开号：US20110028455A1

  公开（公告）日：2011-02-03

  Disclosed are compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X is —O—, —N(R 3 )—, —S—, —S(O)— or —S(O) 2 —; R 2 is a C 1-4 alkyl group or —CF 3 ; and R 1 , R 3 , R 4 and p are as defined herein; wherein the compounds are useful as kinase inhibitors. Also disclosed are pharmaceutical compositions containing, and intermediate compounds and methods for making the compounds of formula (I) and their pharmaceutically acceptable salts; and methods of using the foregoing to treat inflammatory and autoimmune diseases such as asthma, colitis, multiple sclerosis, psoriasis, arthritis, rheumatoid arthritis, inflammatory bowel disease, and joint inflammation.

  本发明公开了式（I）化合物及其药学上可接受的盐，其中X为—O—、—N（R3）—、—S—、—S（O）—或—S（O）2—；R2为C1-4烷基或—CF3；R1、R3、R4和p如本文所定义；所述化合物可用作激酶抑制剂。还公开了含有上述化合物的制药组合物，以及制备式（I）化合物及其药学上可接受的盐的中间体化合物和方法；以及使用上述化合物治疗炎症和自身免疫性疾病，如哮喘、结肠炎、多发性硬化症、牛皮癣、关节炎、类风湿性关节炎、炎症性肠病和关节炎的方法。
• 5-Vinyl-3-pyridinecarbonitrile inhibitors of PKCθ: Optimization of enzymatic and functional activity
  作者：L. Nathan Tumey、Niala Bhagirath、Agnes Brennan、Natasja Brooijmans、Julie Lee、Xiaoke Yang、Diane H. Boschelli

  DOI：10.1016/j.bmc.2009.10.020

  日期：2009.12

  PKC theta is a serine/threonine kinase involved in the regulation of IL2 production in T cells. It has recently become an attractive therapeutic target for a variety of immunological disorders. We describe the optimization of the enzymatic and cellular potency of a series of 5-vinyl-3-pyridinecarbonitrile inhibitors of PKC theta. A binding model was developed that explains much of the SAR observed for this series, including the enzymatic potency observed for 19. An analysis of functional potency against various physiochemical parameters suggests that cellular potency is correlated with Log D(7.4), but not with c Log P, PAMPA permeability, or TPSA. (c) 2009 Elsevier Ltd. All rights reserved.
• INDOLE-SUBSTITUTED 3-CYANOPYRIDINES AS KINASE INHIBITORS
  申请人：Wyeth LLC

  公开号：EP2229376A1

  公开（公告）日：2010-09-22
• 5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS
  申请人：Wyeth LLC

  公开号：EP2229377A1

  公开（公告）日：2010-09-22