4-bromo-1-(difluoromethoxy)-2-iodobenzene | 1261679-49-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-bromo-1-(difluoromethoxy)-2-iodobenzene
• CAS: 1261679-49-5
• 化学式: C₇H₄BrF₂IO
• 分子量: 348.913
• InChiKey: QJBYPLBWCKHTNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-bromo-1-(difluoromethoxy)-2-iodobenzene 在 盐酸 、 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲苯 为溶剂， 反应 2.0h， 生成 3-[2-(difluoromethoxy)-5-(methylsulfanyl)phenyl]-4-nitro-1H-pyrazole
  参考文献：
  名称：

  [EN] JANUS KINASES INHIBITORS, COMPOSITIONS THEREOF AND USE THEREOF
  [FR] INHIBITEURS DES JANUS KINASES, LEURS COMPOSITIONS ET LEUR UTILISATION

  摘要：

  公开号：

  WO2017089390A8
• 作为产物：
  描述：

  4-溴-2-碘苯酚 、 sodium chlorodifluoroacetate 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到4-bromo-1-(difluoromethoxy)-2-iodobenzene
  参考文献：
  名称：

  [EN] TETRAZOLE-SUBSTITUTED PYRAZOLOPYRIMIDINE INHIBITORS OF JAK KINASES AND USES THEREOF
  [FR] INHIBITEURS DE PYRAZOLOPYRIMIDINE À SUBSTITUTION TÉTRAZOLE DE KINASES JAK ET LEURS UTILISATIONS

  摘要：

  本文描述了化学式（I）中R1、R2、R3、R4、R5和R6的化合物及其盐，这些化合物可作为JAK激酶抑制剂。还提供了包括这种JAK抑制剂和药用载体、辅料或载体的药物组合物，并提供了治疗或减轻患者对Janus激酶活性抑制响应的疾病或病况的方法。

  公开号：

  WO2020257142A1

文献信息

• THERAPEUTIC COMPOUNDS AND COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：Genentech, Inc.

  公开号：US20180333416A1

  公开（公告）日：2018-11-22

  Compounds and salts thereof that are useful as JAK kinse inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor 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 a Janus kinase activity in a patient.

  本文描述了作为JAK激酶抑制剂有用的化合物及其盐。还提供了包括这种JAK抑制剂和药用可接受载体、辅料或载体的药物组合物，以及治疗或减轻患者对Janus激酶活性抑制响应的疾病或病况的方法。
• PYRAZOLOPYRIMIDINE SULFONE INHIBITORS OF JAK KINASES AND USES THEREOF
  申请人：Genentech, Inc.

  公开号：US20200399275A1

  公开（公告）日：2020-12-24

  Compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined herein, and salts thereof that are useful as JAK kinse inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor 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 a Janus kinase activity in a patient.

  本文描述了化学式（I）中的化合物，其中R1、R2、R3、R4、R5和R6如本文所定义，并且其盐是作为JAK激酶抑制剂有用的。还提供了包括这种JAK抑制剂和药用可接受的载体、辅料或载体的药物组合物，并且提供了用于治疗或减轻对Janus激酶活性抑制有响应的疾病或病况的方法。
• [EN] PYRAZOLOPYRIMIDINE ARYL ETHER INHIBITORS OF JAK KINASES AND USES THEREOF<br/>[FR] INHIBITEURS ÉTHER-ARYL-PYRAZOLOPYRIMIDINE DE KINASES JAK ET LEURS UTILISATIONS
  申请人：GENENTECH INC

  公开号：WO2020257143A1

  公开（公告）日：2020-12-24

  Compounds and salts thereof that are useful as JAK kinase inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor 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 a Janus kinase activity in a patient.

  本文描述了作为JAK激酶抑制剂有用的化合物及其盐。还提供了包括这种JAK抑制剂和药用可接受载体、辅料或载体的药物组合物，以及治疗或减轻患者对Janus激酶活性抑制响应的疾病或病况的方法。
• Therapeutic compounds and compositions, and methods of use thereof
  申请人：Genentech, Inc.

  公开号：US10307426B2

  公开（公告）日：2019-06-04

  Compounds and salts thereof that are useful as JAK kinse inhibitors are described herein. Also provided are pharmaceutical compositions that include such a JAK inhibitor 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 a Janus kinase activity in a patient.

  本文描述了可用作 JAK 激酶抑制剂的化合物及其盐类。还提供了包括这种 JAK 抑制剂和药学上可接受的载体、辅助剂或载体的药物组合物，以及治疗或减轻对抑制患者体内 Janus 激酶活性有反应的疾病或病症的严重程度的方法。
• Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling
  作者：Mark Zak、Emily J. Hanan、Patrick Lupardus、David G. Brown、Colin Robinson、Michael Siu、Joseph P. Lyssikatos、F. Anthony Romero、Guiling Zhao、Terry Kellar、Rohan Mendonca、Nicholas C. Ray、Simon C. Goodacre、Peter H. Crackett、Neville McLean、Christopher A. Hurley、Po-wai Yuen、Yun-Xing Cheng、Xiongcai Liu、Marya Liimatta、Pawan Bir Kohli、Jim Nonomiya、Gary Salmon、Gerry Buckley、Julia Lloyd、Paul Gibbons、Nico Ghilardi、Jane R. Kenny、Adam Johnson

  DOI：10.1016/j.bmcl.2019.04.008

  日期：2019.6

  Disruption of interleukin-13 (IL-13) signaling with large molecule antibody therapies has shown promise in diseases of allergic inflammation. Given that IL-13 recruits several members of the Janus Kinase family (JAK1, JAK2, and TYK2) to its receptor complex, JAK inhibition may offer an alternate small molecule approach to disrupting IL-13 signaling. Herein we demonstrate that JAK1 is likely the isoform most important to IL-13 signaling. Structure-based design was then used to improve the JAK1 potency of a series of previously reported JAK2 inhibitors. The ability to impede IL-13 signaling was thereby significantly improved, with the best compounds exhibiting single digit nM IC50's in cell-based assays dependent upon IL-13 signaling. Appropriate substitution was further found to influence inhibition of a key off-target, LRRK2. Finally, the most potent compounds were found to be metabolically labile, which makes them ideal scaffolds for further development as topical agents for IL-13 mediated diseases of the lungs and skin (for example asthma and atopic dermatitis, respectively).