2-iodo-5-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine | 1202490-65-0

• 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: 2-iodo-5-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine
• CAS: 1202490-65-0
• 化学式: C₁₃H₁₀IN₃O
• 分子量: 351.146
• InChiKey: AFIWFKWVUXNMNS-UHFFFAOYSA-N

物化性质

• 密度：
  1.75±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 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：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-甲基哌嗪)苯胺 、 2-iodo-5-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以30%的产率得到5-(4-methoxyphenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine
  参考文献：
  名称：

  2-氨基-[1,2,4]三唑并[1,5- a ]吡啶作为JAK2抑制剂

  摘要：

  最初从高通量筛选中鉴定出的一系列配体有效的2-氨基-[1,2,4]三唑并[1,5- a ]吡啶已发展为在小鼠异种移植模型中具有药效学活性的JAK2抑制剂。披露。 下载：下载全图

  DOI：

  10.1016/j.bmcl.2013.06.008
• 作为产物：
  描述：

  5-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine 在 对甲苯磺酸 、 potassium iodide 、 sodium nitrite 作用下， 以 乙腈 为溶剂， 以71%的产率得到2-iodo-5-(4-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine
  参考文献：
  名称：

  2-氨基-[1,2,4]三唑并[1,5- a ]吡啶作为JAK2抑制剂

  摘要：

  最初从高通量筛选中鉴定出的一系列配体有效的2-氨基-[1,2,4]三唑并[1,5- a ]吡啶已发展为在小鼠异种移植模型中具有药效学活性的JAK2抑制剂。披露。 下载：下载全图

  DOI：

  10.1016/j.bmcl.2013.06.008

文献信息

• [EN] TRIAZOLOPYRIDINE JAK INHIBITOR COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS TRIAZOLOPYRIDINE INHIBITEURS DE JAK KINASE ET PROCÉDÉS
  申请人：GENENTECH INC

  公开号：WO2009155565A1

  公开（公告）日：2009-12-23

  A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed.

  公式I的化合物、对映体、二对映异构体、互变异构体或其药用可接受的盐，其中R1、R2、R3、R4和R5在此处定义，可用作JAK激酶抑制剂。公开了包含公式I的化合物和药用可接受的载体、辅料或载体的药物组合物，以及治疗或减轻患者对JAK激酶活性抑制响应的疾病或病情的方法。
• [EN] NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES.<br/>[FR] NOUVEAUX COMPOSÉS UTILES POUR LE TRAITEMENT DE MALADIES DÉGÉNÉRATIVES ET INFLAMMATOIRES
  申请人：GALAPAGOS NV

  公开号：WO2010010188A1

  公开（公告）日：2010-01-28

  Novel [l,2,4]triazolo[l,5-a]pyridine compounds are disclosed that have a formula represented by the Formula I. The compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non- limiting example, diseases involving cartilage degradation, bone and/or joint degradation, for example osteoarthritis; and/or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g. diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6 and transplantation rejection (e.g. organ transplant rejection) and proliferative diseases.

  揭示了具有由公式I表示的化学式的新型[l,2,4]三唑[1,5-a]吡啶化合物。这些化合物可以制备为药物组合物，并可用于预防和治疗包括人类在内的哺乳动物的各种疾病，例如涉及软骨降解、骨骼和/或关节降解的疾病，例如骨关节炎；以及涉及炎症或免疫反应的疾病，如克罗恩病、类风湿性关节炎、牛皮癣、过敏性气道疾病（如哮喘、鼻炎）、儿童特发性关节炎、结肠炎、炎性肠病、内毒素驱动的疾病状态（如旁路手术后的并发症或慢性内毒素状态导致的慢性心力衰竭等）、涉及软骨周转障碍的疾病（例如涉及软骨细胞合成促进的疾病）、先天软骨畸形、与IL6过度分泌和移植排斥有关的疾病（例如器官移植排斥）和增生性疾病。
• TRIAZOLOPYRIDINE JAK INHIBITOR COMPOUNDS AND METHODS
  申请人：ZHU Bing-Yan

  公开号：US20100035875A1

  公开（公告）日：2010-02-11

  A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed.

  公式I的化合物、对映异构体、二对映异构体、互变异构体或其药学上可接受的盐，其中R1、R2、R3、R4和R5在此定义，可用作JAK激酶抑制剂。还公开了一种包括公式I的化合物和药学上可接受的载体、佐剂或载体的制药组合物，以及治疗或减轻患者对JAK激酶活性抑制有反应的疾病或病情的方法。
• Triazolopyridine JAK inhibitor compounds and methods
  申请人：Zhu Bing-Yan

  公开号：US08889673B2

  公开（公告）日：2014-11-18

  A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4 and R5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed.

  公式I的化合物、对映异构体、顺反异构体、互变异构体或其药学上可接受的盐，其中R1、R2、R3、R4和R5的定义如本文所述，可用作JAK激酶抑制剂。本发明还涉及一种包括公式I化合物和药学上可接受的载体、辅料或载体的制药组合物，以及治疗或减轻患有对JAK激酶活性抑制敏感的疾病或病情的方法。
• 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).