2-{3-[1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazol-3-yl]-propyl}-isoindole-1,3-dione | 1287761-11-8

• 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-{3-[1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazol-3-yl]-propyl}-isoindole-1,3-dione
• 英文别名: 2-{3-[1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazol-3-yl]propyl}isoindole-1,3-dione；2-[3-[1-(4-Methylsulfonylphenyl)-5-phenylpyrazol-3-yl]propyl]isoindole-1,3-dione
• CAS: 1287761-11-8
• 化学式: C₂₇H₂₃N₃O₄S
• 分子量: 485.563
• InChiKey: JHSKBVGBCLQAJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  97.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-{3-[1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazol-3-yl]-propyl}-isoindole-1,3-dione 在 一水合肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 1-{3-[1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazol-3-yl]propyl}-3-(3-trifluoromethylphenyl)urea
  参考文献：
  名称：

  PYRAZOLE INHIBITORS OF COX-2 AND SEH

  摘要：

  本发明提供了化合物和组合物，例如一系列化合物，其中1,5-联苯吡唑基通过不可断裂的共价链与尿素基结合，这些化合物可用作双COX-2/sEH抑制剂。本文披露的化合物具有与花生四烯酸级联相关的活性。这些化合物的活性是使用大鼠脂多糖（LPS）诱导的疼痛模型进行证明的。与同等剂量的Celecoxib（即COX-2抑制剂）以及同等剂量的t-AUCB（即sEH抑制剂）相比，本发明的化合物表现出优越的抗痛觉过敏活性，也与同时给予的Celecoxib和t-AUCB的同等剂量相比。本发明的双重抑制剂在伤害性行为测定中显示出增强的体内抗痛觉过敏活性。此外，本发明的化合物还表现出对内皮细胞（HUVEC）具有强效的抗血管生成作用，并且在体外、体内和体内抑制血管生成。本发明的双重抑制剂还表现出抗血管生成效应，可以减缓体内乳腺肿瘤生长。

  公开号：

  US20140038923A1
• 作为产物：
  描述：

  4-(甲基磺酰基)苯肼盐酸盐 在 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 三苯基膦 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 mineral oil 为溶剂， 反应 35.0h， 生成 2-{3-[1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazol-3-yl]-propyl}-isoindole-1,3-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies of Urea-Containing Pyrazoles as Dual Inhibitors of Cyclooxygenase-2 and Soluble Epoxide Hydrolase

  摘要：

  A series of dual inhibitors containing a 1,5-diarylpyrazole and a urea were designed, synthesized, and evaluated as novel COX-2/sEH dual:inhibitors in vitro using recombinant enzyme assays and in vivo using a lipopolysaccharide (LPS) induced model of pain in rats. The best inhibition potencies and selectivity for sEH and COX-2 over COX-1 were obtained with compounds (21b, 211, and 21j) in which both the 1,5-diaryl-pyrazole group aid the urea group are linked with a three-methylene group. Compound 21i showed the best pharmacokinetic profiles in both mice and rats (higher AUC and longer half life). Following subcutaneous administration at 10 mg/kg, compound 21i exhibited antiallodynic activity that is more effective than the same dose of either a COX-2 inhibitor (celecoxib) or a sEH inhibitor (t-AUCB) alone, as well as coadministration of:both inhibitors. Thus, these novel dual inhibitors exhibited enhanced in vivo antiallodynic activity in a nociceptive behavioral assay.

  DOI：

  10.1021/jm2001376

文献信息

• US9096532B2
  申请人：——

  公开号：US9096532B2

  公开（公告）日：2015-08-04
• [EN] PYRAZOLE INHIBITORS OF COX-2 AND sEH<br/>[FR] PYRAZOLES INHIBITEURS DE COX-2 ET DE SEH
  申请人：UNIV CALIFORNIA

  公开号：WO2012082647A2

  公开（公告）日：2012-06-21

  The present invention provides compounds and compositions, e.g., a series of compounds wherein a 1,5-biarylpyrazole group is conjugated to a urea group by a non-cleavable covalent chain, that are useful as dual COX-2/sEH inhibitors. The compounds disclosed herein have activity associated with the arachidonate cascade. The activity of these compounds was demonstrated using a lipopolysaccharide (LPS) induced model of pain in the rat. The compounds of the present invention demonstrated superior anti-allodynic activity as compared to the same dose of celecoxib, i.e., a COX-2 inhibitor, also as compared to the same dose of t-AUCB, i.e., a sEH inhibitor, and also as compared to the co-administered same dose of both celecoxib and t-AUCB. The dual inhibitors of the present invention demonstrate enhanced in vivo anti-allodynic activity in a nociceptive behavioral assay. In addition, the compounds of the present invention also demonstrated to have potent anti-angiogenic effects toward endothelial cells (HUVEC) and inhibit angiogenesis in vitro, ex vivo and in vivo. The dual inhibitors of the present invention also demonstrate anti-angiogenic effect to slow breast tumor growth in vivo.