5-chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamine | 1454653-85-0

• 物质功能分类: 医药中间体 - 杂环化合物 - 吡嗪类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡嗪类
• 英文名称: 5-chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamine
• 英文别名: 5-chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-amine；5-chloro-[1,2,4]triazolo[1,5-a]pyrazine-2-amine；5-Chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-amine
• CAS: 1454653-85-0
• 化学式: C₅H₄ClN₅
• 分子量: 169.573
• InChiKey: XWZGFYCINZXWMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium diacetate 、 sodium hexamethyldisilazane 、 potassium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 叔丁醇 为溶剂， 反应 12.0h， 生成 3-[5-(1-methyl-1 H-indazol-5-yl)-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamino]-benzenesulfonamide
  参考文献：
  名称：

  [EN] TRIAZOLOPYRAZINE DERIVATIVES
  [FR] DÉRIVÉS DE TRIAZOLOPYRAZINE

  摘要：

  式(I)中R1、R2和R4具有权利要求1中所指示的含义的化合物是GCN2的抑制剂，可用于治疗癌症。

  公开号：

  WO2013131609A1
• 作为产物：
  描述：

  (6-chloropyrazin-2-yl)-3-carboethoxythiourea 在 盐酸羟胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.0h， 以64%的产率得到5-chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-ylamine
  参考文献：
  名称：

  Triazolopyridines as Selective JAK1 Inhibitors: From Hit Identification to GLPG0634

  摘要：

  Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohns disease (CD).

  DOI：

  10.1021/jm501262q

文献信息

• TRIAZOLOPYRAZINE DERIVATIVES
  申请人：Merck Patent GmbH

  公开号：US20150051202A1

  公开（公告）日：2015-02-19

  Compounds of the formula I in which R 1 , R 2 and R 4 have the meanings indicated in Claim 1, are inhibitors of GCN2, and can be employed, inter alia, for the treatment of cancer.

  公式I中，R1、R2和R4的含义如权利要求1所示的化合物是GCN2的抑制剂，可以用于治疗癌症等疾病。
• Design, Synthesis, and Antitumor Efficacy of Substituted 2-Amino[1,2,4]triazolopyrimidines and Related Heterocycles as Dual Inhibitors for Microtubule Polymerization and Janus Kinase 2
  作者：Li Chen、Yunfei Hu、Zhonghui Lu、Zeyin Lin、Lanqing Li、Jia-Qiang Wu、Zhi-Ling Yu、Chunye Wang、Wen-Hua Chen、Jinhui Hu

  DOI：10.1021/acs.jmedchem.3c01690

  日期：2023.11.9

  heterocycles as dual inhibitors for tubulin polymerization and JAK2. Most of these compounds exhibited potent antiproliferative activity against the selected cancer cells, with compound 7g being the most active. This compound effectively inhibits both tubulin assembly and JAK2 activity. Furthermore, phosphorylated compound 7g (i.e., compound 7g–P) could efficiently convert to compound 7g in vivo. Compound

  临床前和临床研究已经证明微管靶向药物与 Janus 激酶 2 (JAK2) 抑制剂联合使用具有协同作用，从而促进了通过双重抑制微管蛋白聚合和 JAK2 来增强治疗效果的单一药物的开发。在此，我们设计并合成了一系列取代的2-氨基[1,2,4]三唑并嘧啶和相关杂环化合物作为微管蛋白聚合和JAK2的双重抑制剂。大多数这些化合物对选定的癌细胞表现出有效的抗增殖活性，其中化合物7g 的活性最强。该化合物可有效抑制微管蛋白组装和 JAK2 活性。此外，磷酸化的化合物7g（即化合物7g - P）可以在体内有效地转化为化合物7g 。化合物7g ，无论是直接给药还是以磷酸化前药（即化合物7g - P ）的形式给药，均显着抑制裸鼠体内A549异种移植物的生长。目前的研究结果强烈表明化合物7g代表了一种有前途的具有高抗肿瘤功效的化疗剂。
• [EN] FUSED AZOLE AND FURAN BASED NUCLEOSIDE ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE NUCLÉOSIDES À BASE D'AZOLE ET DE FURANE FUSIONNÉS ET LEURS UTILISATIONS
  申请人：[en]MOYA BIO LTD.

  公开号：WO2023021498A1

  公开（公告）日：2023-02-23

  The present invention is directed to compounds and compositions comprising thereof. Further, methods of use such as for the treatment and prevention of cancer and other diseases responsive to the inhibition of UAE and/or UBA6 in a subject in need thereof are also provided.
• Triazolopyridines as Selective JAK1 Inhibitors: From Hit Identification to GLPG0634
  作者：Christel J. Menet、Stephen R Fletcher、Guy Van Lommen、Raphael Geney、Javier Blanc、Koen Smits、Nolwenn Jouannigot、Pierre Deprez、Ellen M. van der Aar、Philippe Clement-Lacroix、Liên Lepescheux、René Galien、Béatrice Vayssiere、Luc Nelles、Thierry Christophe、Reginald Brys、Muriel Uhring、Fabrice Ciesielski、Luc Van Rompaey

  DOI：10.1021/jm501262q

  日期：2014.11.26

  Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the compound library was screened against JAK1, resulting in the identification of a triazolopyridine-based series of inhibitors represented by 3. Optimization within this chemical series led to identification of GLPG0634 (65, filgotinib), a selective JAK1 inhibitor currently in phase 2B development for RA and phase 2A development for Crohns disease (CD).
• [EN] TRIAZOLOPYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZOLOPYRAZINE
  申请人：MERCK PATENT GMBH

  公开号：WO2013131609A1

  公开（公告）日：2013-09-12

  Compounds of the formula (I) in which R1, R2 and R4 have the meanings indicated in Claim 1, are inhibitors of GCN2, and can be employed, inter alia, for the treatment of cancer.

  式(I)中R1、R2和R4具有权利要求1中所指示的含义的化合物是GCN2的抑制剂，可用于治疗癌症。