| 1428979-97-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 1428979-97-8
• 化学式: C₁₆H₁₉N₃OS
• 分子量: 301.412
• InChiKey: WKQQKVHXRMYSHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  38.13
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  (5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)(piperidin-1-yl)methanone 在 sodiumsulfide nonahydrate 、 sulfur 、 sodium tetrahydroborate 作用下， 以 N,N-二甲基甲酰胺 、 乙醇 为溶剂， 反应 1.0h， 生成 、 [3-Methyl-5-[[5-methyl-2-phenyl-4-(piperidine-1-carbonyl)pyrazol-3-yl]disulfanyl]-1-phenylpyrazol-4-yl]-piperidin-1-ylmethanone
  参考文献：
  名称：

  Disulfide linked pyrazole derivatives inhibit phagocytosis of opsonized blood cells

  摘要：

  Immune thrombocytopenia (ITP) is caused by production of an autoantibody to autologous platelets. ITP can be treated either by reducing platelet destruction or by increasing platelet production. Fc gamma receptor mediated phagocytosis of the opsonized blood cells is a well-accepted mechanism for the underlying pathogenesis of ITP and inhibition of this phagocytosis process with small molecules is a potential strategy for the development of drugs against ITP. A broad screen indicated that 4-methyl-1-phenyl-pyrazole derivative (1) could inhibit the phagocytosis of opsonized blood cells with weak potency. We reveal here the discovery of the polysulfide products, synthesis of various 1-phenyl-pyrazole derivatives, and the biological evaluation of pyrazole derivatives as inhibitors of phagocytosis for potential use as therapeutics for ITP. Substitution at C4 of the pyrazole moiety in the disulfide-bridged dimers influenced the potency in the increasing order of 10 congruent to 11 congruent to 16 < 19 < 20. A novel scaffold, 20 with an IC50 of 100 nM inhibiting opsonized blood cell phagocytosis was identified as a potential candidate for further studies. Confirmation of the disulfide bridge additionally provides clues for the non-thiol or non-disulfide bridge carrying ligands targeting ITP and other similar disorders. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.064