2-(1,1-dimethylethyl)-5-(4-fluorophenyl)-3-N-hydroxy-4-(pyrid-3-onyl)-imidazole | 457081-01-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(1,1-dimethylethyl)-5-(4-fluorophenyl)-3-N-hydroxy-4-(pyrid-3-onyl)-imidazole
• 英文别名: 4-[2-tert-butyl-4-(4-fluorophenyl)-1-hydroxy-1H-imidazol-5-yl]pyridin-2(1H)-one；4-[2-tert-butyl-5-(4-fluorophenyl)-3-hydroxyimidazol-4-yl]-1H-pyridin-2-one
• CAS: 457081-01-5
• 化学式: C₁₈H₁₈FN₃O₂
• 分子量: 327.358
• InChiKey: CZIBAYYBRMCRHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1,1-dimethylethyl)-5-(4-fluorophenyl)-3-N-hydroxy-4-(pyrid-3-onyl)-imidazole 在 盐酸 、 titanium(III) chloride 作用下， 以 甲醇 为溶剂， 以97%的产率得到2-(1,1-dimethylethyl)-9-fluoro-1H-benz[h]isoquinolin-3-one-[5,6-d]imidazole
  参考文献：
  名称：

  Photochemical preparation of a pyridone containing tetracycle: A jak protein kinase inhibitor

  摘要：

  Jak3 is a protein tyrosine kinase that is associated with the shared 7 chain of receptors for cytokines IL2, IL4, IL7, IL9, and IL13. We have discovered that a pyridone-containing tetracycle (6) may be prepared front trisubstituted imidazole (5) in high yield by irradiation with >350 nm light. Compound 6 inhibits Jak3 with K-I = 5 nM: it also inhibits Jak family members Tyk2 and Jak2 with IC50 = 1 nM and murine Jak 1 with IC50 = 15 nM. Compound 6 vas tested as an inhibitor of 21 other protein kinases: it inhibited these kinases with IC(50)s ranging from 130 nM to > 10 muM. Compound 6 also blocks IL2 and IL4 dependent proliferation of CTLL cells and inhibits the phosphorylation of STAT5 (an in vivo substrate of the Jak family) as measured by Western blotting. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00106-3
• 作为产物：
  描述：

  对氟苯甲酸乙酯 在 盐酸 、 亚硝酸特丁酯 、 ammonium acetate 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 反应 5.25h， 生成 2-(1,1-dimethylethyl)-5-(4-fluorophenyl)-3-N-hydroxy-4-(pyrid-3-onyl)-imidazole
  参考文献：
  名称：

  Photochemical preparation of a pyridone containing tetracycle: A jak protein kinase inhibitor

  摘要：

  Jak3 is a protein tyrosine kinase that is associated with the shared 7 chain of receptors for cytokines IL2, IL4, IL7, IL9, and IL13. We have discovered that a pyridone-containing tetracycle (6) may be prepared front trisubstituted imidazole (5) in high yield by irradiation with >350 nm light. Compound 6 inhibits Jak3 with K-I = 5 nM: it also inhibits Jak family members Tyk2 and Jak2 with IC50 = 1 nM and murine Jak 1 with IC50 = 15 nM. Compound 6 vas tested as an inhibitor of 21 other protein kinases: it inhibited these kinases with IC(50)s ranging from 130 nM to > 10 muM. Compound 6 also blocks IL2 and IL4 dependent proliferation of CTLL cells and inhibits the phosphorylation of STAT5 (an in vivo substrate of the Jak family) as measured by Western blotting. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00106-3

文献信息

• [EN] BENZIMIDAZO[4,5-f]ISOQUINOLINONE DERIVATIVES<br/>[FR] DERIVES DE LA BENZIMIDAZO[4,5-F]ISOQUINOLINONE
  申请人：MERCK & CO INC

  公开号：WO2003011285A1

  公开（公告）日：2003-02-13

  Benzimidazo[4,5-f]isoquinolinone derivatives are inhibitors of Janus protein tyrosine kinases (Jak), and as such are useful as immunosuppressants, and in the treatment of diseases including asthma, allergies, autoimmune diseases .

  苯并咪唑[4,5-f]异喹啉酮衍生物是Janus蛋白酪氨酸激酶（Jak）的抑制剂，因此可用作免疫抑制剂，并用于治疗哮喘、过敏、自身免疫性疾病等疾病。
• Benzimisazo[4,5-f]isoquinolinone derivatives
  申请人：——

  公开号：US20040176601A1

  公开（公告）日：2004-09-09

  Benzimidazo[4,5-f]isoquinolinone derivatives are inhibitors of Janus protein tyrosine kinases (Jak), and as such are useful as immunosuppressants, and in the treatment of diseases including asthma, allergies, autoimmune diseases.

  苯并咪唑[4,5-f]异喹啉酮衍生物是Janus蛋白酪氨酸激酶（Jak）的抑制剂，因此可用作免疫抑制剂，并用于治疗哮喘、过敏和自身免疫性疾病等疾病。
• EP1414443A4
  申请人：——

  公开号：EP1414443A4

  公开（公告）日：2005-05-11
• BENZIMIDAZO 4,5-f|ISOQUINOLINONE DERIVATIVES
  申请人：Merck & Co., Inc.

  公开号：EP1414443B1

  公开（公告）日：2006-11-15
• BENZIMIDAZO 4,5-f]ISOQUINOLINONE DERIVATIVES
  申请人：Merck & Co., Inc.

  公开号：EP1414443A1

  公开（公告）日：2004-05-06