1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)urea

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)urea
• 英文别名: 1-[3-fluoro-4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl]-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]urea
• 化学式: C₁₇H₁₂F₄N₈O₂
• 分子量: 436.328
• InChiKey: COWSMIMAJBATIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-氨基-2-氟苯酚 在 sodium hydroxide 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 反应 18.5h， 生成 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)urea
  参考文献：
  名称：

  Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model

  摘要：

  Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential molecular target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (1), which showed a moderate inhibitory activity againt FLT3. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structureactivity relationship analysis led to the discovery of a number of potent FLT3 inhibitors. One of the most active compounds, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (18b), was then chosen for in-depth antipsoriasis studies because this compound displayed the highest potency in a preliminary antipsoriasis test. Compound 18b exhibited significant antipsoriatic effects in the K14-VEGF transgenic mouse model of psoriasis, and no recurrence was found 15 days later after the last administration. Detailed mechanisms of action of compound 18b were also investigated. Collectively, compound 18b could be a potential drug candidate for psoriasis treatment.

  DOI：

  10.1021/acs.jmedchem.6b00604

文献信息

• 4-Position Substituted Pyrazolopyrimidine Derivative, And Use Thereof In Drug Preparation
  申请人：Guangxi Wuzhou Pharmaceuticals (Group) Co., Ltd.

  公开号：US20150315191A1

  公开（公告）日：2015-11-05

  The invention belongs to the technical field of organic synthetic drugs, and particularly relates to a pyrazolopyrimidine derivative and a preparation method and medical uses thereof. The invention provides a new pyrazolopyrimidine derivative mainly having position 4 substituted, i.e., position substituted by Y in formula I. The pyrazolopyrimidine derivative of the invention has a structural formula I as follows: The invention provides a new pyrazolopyrimidine derivative and a simple, efficient and low-cost preparation method thereof. The pyrazolopyrimidine derivative of the invention has good inhibitory activity for multiple kinases, has inhibitory action on multiple solid tumors, leukemia and autoimmune diseases, provides a new effective choice for preparation of kinase inhibitors, medicines for autoimmune diseases, angiogenesis inhibitors and antitumor drugs, and has good application prospect.
• US9828375B2
  申请人：——

  公开号：US9828375B2

  公开（公告）日：2017-11-28