8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5,a]-pyridine-2-ylamine | 1257704-13-4

• 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: 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5,a]-pyridine-2-ylamine
• 英文别名: 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine；8-(4-methanesulfonylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine；8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine
• CAS: 1257704-13-4
• 化学式: C₁₃H₁₂N₄O₂S
• 分子量: 288.33
• InChiKey: WDNUVLHOFJIDRO-UHFFFAOYSA-N

物化性质

• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  98.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5,a]-pyridine-2-ylamine 在 盐酸 、 2,2-双(二环己膦基)-1,1-联苯 、 palladium diacetate 、 caesium carbonate 、 copper dichloride 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-[3-(4-甲基-1-哌嗪基)苯基]-8-[4-(甲磺酰基)苯基]-[1,2,4]三唑并[1,5-a]吡啶-2-胺
  参考文献：
  名称：

  An Improved Synthesis of the Free Base and Diglycolate Salt of CEP-33779; A Janus Kinase 2 Inhibitor

  摘要：

  CEP-33779 is a triazole that has been reported to show highly selective inhibition of Janus kinase 2 (JAIC2). An efficient process to form CEP-33779 will be presented that uses multiple palladium couplings to provide the drug substance in a convergent manner. The existing medicinal chemistry route was modified to avoid chromatographic purification, improve safety, and utilize palladium ligands which are available in quantities amenable to scale-up. Challenges faced during the development of the new process included optimization of conditions for Buchwald-Hartwig and Suzuki couplings, control of homocoupled impurities and removal of residual palladium. In addition, a screen of conditions to form a diglycolate salt of the parent compound are also presented.

  DOI：

  10.1021/acs.oprd.6b00311
• 作为产物：
  描述：

  1-(3-bromopyridine-2-yl)-3-carboethoxythiourea 在 盐酸羟胺 、 palladium diacetate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 8-(4-methanesulfonyl-phenyl)-[1,2,4]triazolo[1,5,a]-pyridine-2-ylamine
  参考文献：
  名称：

  An Improved Synthesis of the Free Base and Diglycolate Salt of CEP-33779; A Janus Kinase 2 Inhibitor

  摘要：

  CEP-33779 is a triazole that has been reported to show highly selective inhibition of Janus kinase 2 (JAIC2). An efficient process to form CEP-33779 will be presented that uses multiple palladium couplings to provide the drug substance in a convergent manner. The existing medicinal chemistry route was modified to avoid chromatographic purification, improve safety, and utilize palladium ligands which are available in quantities amenable to scale-up. Challenges faced during the development of the new process included optimization of conditions for Buchwald-Hartwig and Suzuki couplings, control of homocoupled impurities and removal of residual palladium. In addition, a screen of conditions to form a diglycolate salt of the parent compound are also presented.

  DOI：

  10.1021/acs.oprd.6b00311

文献信息

• Preparation and Uses of 1,2,4-Triazolo [1,5a] Pyridine Derivatives
  申请人：Cephalon, Inc.

  公开号：US20130296312A1

  公开（公告）日：2013-11-07

  This application relates, in part, to compounds of the general Formula I and/or salts thereof, wherein X, R 1A , R 1B , R 2 , R 3 , R 4 , and R 5 are as defined herein. The application also relates to compositions and methods of inhibiting at least JAK2 in subjects in recognized need thereof for the treatment of diseases or disorders for which inhibition of at least JAK2 is indicated.

  该应用程序部分涉及一般式I化合物和/或其盐，其中X、R1A、R1B、R2、R3、R4和R5的定义如本文所述。该应用程序还涉及组合物和方法，用于抑制至少在有需要的患者中的JAK2，以治疗需要抑制至少JAK2的疾病或疾病。
• Preparation and uses of 1,2,4-triazolo [1,5a] pyridine derivatives
  申请人：Curry Matthew A.

  公开号：US08501936B2

  公开（公告）日：2013-08-06

  This application relates to compounds of the general Formula I and salts thereof, wherein X, R1A, R1B, R2, R3, R4, and R5 are as defined herein. The application also relates to compositions and methods of treatment of hyperproliferative diseases or disorders.

  本申请涉及一般式I的化合物及其盐，其中X、R1A、R1B、R2、R3、R4和R5的定义如本文所述。本申请还涉及治疗过度增殖性疾病或障碍的组合物和方法。
• JANUS KINASE 2 (JAK2) INHIBITOR FOR THE TREATMENT OF LUPUS
  申请人：Cephalon, Inc.

  公开号：EP2648728B1

  公开（公告）日：2016-04-27
• A Selective, Orally Bioavailable 1,2,4-Triazolo[1,5-<i>a</i>]pyridine-Based Inhibitor of Janus Kinase 2 for Use in Anticancer Therapy: Discovery of CEP-33779
  作者：Benjamin J. Dugan、Diane E. Gingrich、Eugen F. Mesaros、Karen L. Milkiewicz、Matthew A. Curry、Allison L. Zulli、Pawel Dobrzanski、Cynthia Serdikoff、Mahfuza Jan、Thelma S. Angeles、Mark S. Albom、Jennifer L. Mason、Lisa D. Aimone、Sheryl L. Meyer、Zeqi Huang、Kevin J. Wells-Knecht、Mark A. Ator、Bruce A. Ruggeri、Bruce D. Dorsey

  DOI：10.1021/jm300248q

  日期：2012.6.14

  Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 inhibitor. A program to optimize selective JAK2 inhibitors to combat cancer while reducing the risk of immune suppression associated with JAK3 inhibition was undertaken. The structure-activity relationships and biological evaluation of a novel series of compounds based on a 1,2,4-triazolo[1,5-a]pyridine scaffold are reported. Para substitution on the aryl at the C8 position of the core was optimum for JAK2 potency (17). Substitution at the C2 nitrogen position was required for cell potency (21). Interestingly, meta substitution of C2-NH-aryl moiety provided exceptional selectivity for JAK2 over JAK3 (23). These efforts led to the discovery of CEP-33779 (29), a novel, selective, and orally bioavailable inhibitor of JAK2.
• PREPARATION AND USES OF 1,2,4-TRIAZOLO [1,5a]PYRIDINE DERIVATIVES
  申请人：Cephalon, Inc.

  公开号：EP2438066A2

  公开（公告）日：2012-04-11