6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4] triazolo [4,3-a] pyridine | 668981-02-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4] triazolo [4,3-a] pyridine
• 英文别名: 6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-r[1,2,4]triazolo[4,3-a]pyridine；3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo[4,3-a]pyridine；6-[4-(2,5-Difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridine；6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4]triazolo(4,3-a)pyridine；6-[4-(2,5-difluorophenyl)oxazol-5-yl]-3-isopropyl[1,2,4]triazolo[4,3-a]pyridine；1,2,4-Triazolo(4,3-a)pyridine, 6-(4-(2,5-difluorophenyl)-5-oxazolyl)-3-(1-methylethyl)-；4-(2,5-difluorophenyl)-5-(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1,3-oxazole
• CAS: 668981-02-0
• 化学式: C₁₈H₁₄F₂N₄O
• 分子量: 340.332
• InChiKey: UACOXBQBNWQWOK-UHFFFAOYSA-N

物化性质

• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO: 10mg/mL, clear

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  56.2
• 氢给体数：
  0
• 氢受体数：
  6

制备方法与用途

CP-281384是一种有效的p38α选择性抑制剂。

反应信息

• 作为反应物：
  描述：

  6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4] triazolo [4,3-a] pyridine 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 0.5h， 以50%的产率得到6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4]triazolo(4,3-a)pyridine hydrogen chloride
  参考文献：
  名称：

  Novel crystalline forms of 3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-A]pyridine

  摘要：

  本发明涉及3-异丙基-6-[4-(2,5-二氟苯基)-噁唑-5-基]-[1,2,4]三唑-[4,3-a]吡啶的新结晶形式，以及含有这种晶体形式的制药组合物和治疗方法。3-异丙基-6-[4-(2,5-二氟苯基)-噁唑-5-基]-[1,2,4]三唑-[4,3-a]吡啶是MAP激酶的有效抑制剂，优选为p38激酶（MAPK14/CSBP/RK激酶）。3-异丙基-6-[4-(2,5-二氟苯基)-噁唑-5-基]-[1,2,4]三唑-[4,3-a]吡啶在治疗炎症、骨关节炎、类风湿性关节炎、癌症、中风或心脏病的再灌注或缺血、自身免疫性疾病和其他疾病方面有用。

  公开号：

  US20040143119A1
• 作为产物：
  描述：

  3-异丙基[1,2,4]三唑并[4,3-a]吡啶-6-甲醛 、 α-甲苯磺酰-(2,5-二氟苄基)异丁酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 22.0h， 以61%的产率得到6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4] triazolo [4,3-a] pyridine
  参考文献：
  名称：

  [EN] DI AND TRIFLUORO-TRIAZOLO-PYRIDINES ANTI-INFLAMMATORY COMPOUNDS
  [FR] COMPOSES ANTI-INFLAMMATOIRES A BASE DE DI- ET TRIFLUORO-TRIAZOLO-PYRIDINES

  摘要：

  本发明涉及式(I)的新型三唑吡啶，其中R1为氟；s为2至3的整数；R2为（C3-C6）环烷基，可选地取代为从卤素，（Cl-C4）烷基，羟基，（Cl-C6）烷氧基和（C1-C6）烷基-（C=O）-0-中独立选择的一种或两种基团；或R2为（Cl-C6）烷基，可选地取代为从卤素，（C1-C6）烷基，羟基，（C1-C6）烷氧基和（C1-C6）烷基-（C=O）-0-中独立选择的一种或两种基团；但是，具有式(I)的化合物不能为6-[4-(2,4-二氟苯基)-噁唑-5-基]-3-异丙基-[1,2,4]三唑并[4,3-a]吡啶；或6-[4-(3,4-二氟苯基)-噁唑-5-基]-3-异丙基-[1,2,4]三唑并[4,3-a]吡啶；本发明还涉及其制备中间体、含有它们的制药组合物以及它们的医药用途。本发明的化合物是MAP激酶，特别是p38激酶的有效抑制剂。它们在炎症，骨关节炎，类风湿性关节炎，癌症，中风或心脏病的再灌注或缺血，自身免疫性疾病和其他疾病的治疗中有用。

  公开号：

  WO2004020440A1

文献信息

• Alkyl-[4-(difluorophenyl)-oxazol-5-yl]-triazolo-pyridines
  申请人：Pfizer Inc

  公开号：US20040092547A1

  公开（公告）日：2004-05-13

  The present invention relates to novel alkyl-[4-(difluorophenyl)-oxazol-5-yl]-triazolo-pyridines, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the present invention are potent inhibitors of MAP kinases, preferably p38 kinase. They are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及一种新型烷基-［4-(二氟苯基)-噁唑-5-基］-三唑-吡啶类化合物，其中包括用于制备它们的中间体、含有它们的制药组合物以及它们在医学上的应用。本发明的化合物是MAP激酶的有效抑制剂，特别是p38激酶。它们在治疗炎症、骨关节炎、类风湿性关节炎、癌症、脑卒中或心肌梗塞的再灌注或缺血、自身免疫性疾病和其他疾病中有用。
• Combination therapies utilizing benzamide inhibitors of the P2X7 receptor
  申请人：Chung B. James

  公开号：US20060018904A1

  公开（公告）日：2006-01-26

  This invention provides methods of treatment of IL-1 mediated diseases comprising administering a pharmaceutically effective amount of a pharmaceutical agent selected from the group of sulfasalazine, a statin, a glucocorticoid agent, an inhibitor of p38 kinase, an anti-IL-6-receptor antibody, anakinra, an IL-1 monoclonal antibody, an inhibitor of JAK3 protein tyrosine kinase, a M-CSF monoclonal antibody or a humanized anti-CD20 monoclonal antibody and a benzamide inhibitor of the P2X 7 receptor of the formula: wherein R 1 -R 3 are as defined herein. The methods of the invention are useful in the treatment of IL-1 mediated disorders, including, without limitation, inflammatory diseases such as osteoarthritis and rheumatoid arthritis; allergies, asthma, COPD, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明提供了治疗IL-1介导疾病的方法，包括给予从磺胺嘧啶、他汀、糖皮质激素、p38激酶抑制剂、抗IL-6受体抗体、阿那西单抗、IL-1单克隆抗体、JAK3蛋白酪氨酸激酶抑制剂、M-CSF单克隆抗体或人源化的抗CD20单克隆抗体和P2X7受体苯甲酰胺抑制剂中选择的药物剂量。本发明的方法对于治疗IL-1介导的疾病非常有用，包括但不限于炎症性疾病如骨关节炎和类风湿性关节炎；过敏、哮喘、COPD、癌症、中风或心脏病的再灌注或缺血、自身免疫性疾病和其他疾病。
• Novel processes and intermediates for preparing triazolo-pyridines
  申请人：Pfizer Inc.

  公开号：US20040053959A1

  公开（公告）日：2004-03-18

  The present invention relates and intermediates to a novel process for preparing triazolo-pyridines of the formula I 1 wherein R 1 is selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl or other suitable substituents; R 3 is selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl or other suitable substituents; s is an integer from 0-5; R 4 is hydrogen or a suitable substituent and to intermediates for their preparation. The compounds prepared by the methods of the present invention are potent inhibitors of MAP kinases, preferably p38 kinase. They are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及一种制备式I1中的三唑吡啶的新工艺，其中R1选自氢、(C1-C6)烷基或其他适当取代基组成的群体；R3选自氢、(C1-C6)烷基或其他适当取代基组成的群体；s是0-5的整数；R4是氢或适当的取代基，以及其制备的中间体。通过本发明的方法制备的化合物是MAP激酶，特别是p38激酶的有效抑制剂。它们在治疗炎症、骨关节炎、类风湿性关节炎、癌症、脑卒中或心脏病发作的再灌注或缺血、自身免疫性疾病和其他疾病方面有用。
• Di and trifluoro-triazolo-pyridines anti-inflammatory compounds
  申请人：Pfizer Inc.

  公开号：US20040053958A1

  公开（公告）日：2004-03-18

  The present invention relates to novel triazolo-pyridines of the formula I 1 wherein R 1 is fluoro; s is an integer from two to three; R 2 is (C 3 -C 6 )cycloalkyl optionally substituted by one or two moieties independently selected from the group consisting of halo, (C 1 -C 4 )alkyl, hydroxy, (C 1 -C 6 )alkoxy and (C 1 -C 6 )alkyl-(C═O)—O—; or R 2 is (C 1 -C 6 )alkyl optionally substituted by one or two moieties independently selected from the group consisting of halo, (C 1 -C 6 )alkyl, hydroxy, (C 1 -C 6 )alkoxy and (C 1 -C 6 )alkyl-(C═O)—O—; with the proviso that said compound of formula I cannot be 6-[4-(2,4-Difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridine; or 6-[4-(3,4-Difluoro-phenyl)-oxazol-5-yl]-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridine; to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the present invention are potent inhibitors of MAP kinases, preferably p38 kinase. They are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, repurfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及式I1的新型三唑啉-吡啶化合物，其中R1为氟；s为2至3的整数；R2为（C3-C6）环烷基，可选地被一或两个基团独立地选自卤素、（C1-C4）烷基、羟基、（C1-C6）烷氧基和（C1-C6）烷基-(C═O)-O-；或者R2为（C1-C6）烷基，可选地被一或两个基团独立地选自卤素、（C1-C6）烷基、羟基、（C1-C6）烷氧基和（C1-C6）烷基-(C═O)-O-；但式I化合物不能是6-[4-(2,4-二氟苯基)-噁唑-5-基]-3-异丙基-[1,2,4]三唑啉[4,3-a]吡啶；或6-[4-(3,4-二氟苯基)-噁唑-5-基]-3-异丙基-[1,2,4]三唑啉[4,3-a]吡啶；本发明化合物是MAP激酶的有效抑制剂，优选为p38激酶。它们可用于治疗炎症、骨关节炎、类风湿性关节炎、癌症、脑卒中或心脏病的再灌注或缺血、自身免疫性疾病和其他疾病。本发明还涉及其制备的中间体、含有它们的制药组合物和它们的药用用途。
• Crystalline forms of 3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-A]pyridine
  申请人：Kang Ming

  公开号：US06949652B2

  公开（公告）日：2005-09-27

  The present invention relates to novel crystalline forms of 3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-a]pyridine to pharmaceutical compositions containing such crystal forms and to methods of treatment. 3-Isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-a]pyridine is a potent inhibitor of MAP kinases, preferably p38 kinase (MAPK14/CSBP/RK kinase). 3-Isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-a]pyridine is useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, reperfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

  本发明涉及3-异丙基-6-[4-(2,5-二氟苯基)-噁唑-5-基]-[1,2,4]三唑-[4,3-a]吡啶的新晶体形态，以及含有这种晶体形态的制药组合物和治疗方法。3-异丙基-6-[4-(2,5-二氟苯基)-噁唑-5-基]-[1,2,4]三唑-[4,3-a]吡啶是MAP激酶的有效抑制剂，优选是p38激酶（MAPK14/CSBP/RK激酶）。3-异丙基-6-[4-(2,5-二氟苯基)-噁唑-5-基]-[1,2,4]三唑-[4,3-a]吡啶在治疗炎症、骨关节炎、类风湿性关节炎、癌症、中风或心脏病的再灌注或缺血、自身免疫性疾病和其他疾病方面具有用途。