C-[5-tert-butyl-1-(4-methanesulfonylphenyl)-1H-pyrazol-3-yl]methylamine | 1287761-19-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: C-[5-tert-butyl-1-(4-methanesulfonylphenyl)-1H-pyrazol-3-yl]methylamine
• 英文别名: [5-tert-butyl-1-(4-methanesulfonylphenyl)-1H-pyrazol-3-yl]methylamine；C-[5-tert-Butyl-1-(4-methanesulfonyl-phenyl)-1H-pyrazol-3-yl]-methylamine；[5-tert-butyl-1-(4-methylsulfonylphenyl)pyrazol-3-yl]methanamine
• CAS: 1287761-19-6
• 化学式: C₁₅H₂₁N₃O₂S
• 分子量: 307.417
• InChiKey: XEBZYRSUJQXRAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  C-[5-tert-butyl-1-(4-methanesulfonylphenyl)-1H-pyrazol-3-yl]methylamine 、 3-(三氟甲基)异氰酸苯酯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到1-[5-tert-butyl-1-(4-methanesulfonylphenyl)-1H-pyrazol-3-ylmethyl]-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：

  5-叔丁基-1-(4-甲磺酰基苯基)-1H-吡唑-3-羧酸乙酯 在 lithium aluminium tetrahydride 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 13.0h， 生成 C-[5-tert-butyl-1-(4-methanesulfonylphenyl)-1H-pyrazol-3-yl]methylamine
  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

文献信息

• Pyrazole inhibitors of COX-2 and sEH
  申请人：Hammock Bruce D.

  公开号：US09096532B2

  公开（公告）日：2015-08-04

  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.

  本发明提供了一系列化合物和组合物，例如一系列化合物，其中1,5-双芳基吡唑基团通过不可切断的共价链与尿素基团共轭，这些化合物对于作为双重COX-2 / sEH抑制剂是有用的。本文所述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。与同剂量的COX-2抑制剂Celecoxib，即与同剂量的sEH抑制剂t-AUCB以及同时共同给予的Celecoxib和t-AUCB相比，本发明的化合物表现出优越的抗痛觉过敏活性。本发明的双重抑制剂在伤害感知行为测定中表现出增强的体内抗痛觉过敏活性。此外，本发明的化合物还展示了对内皮细胞（HUVEC）具有强效的抗血管生成作用，并在体外、体内和体外抑制血管生成。本发明的双重抑制剂还表现出抗血管生成作用，以减缓体内乳腺肿瘤生长。
• Synthesis and Structure−Activity Relationship Studies of Urea-Containing Pyrazoles as Dual Inhibitors of Cyclooxygenase-2 and Soluble Epoxide Hydrolase
  作者：Sung Hee Hwang、Karen M. Wagner、Christophe Morisseau、Jun-Yan Liu、Hua Dong、Aaron T. Wecksler、Bruce D. Hammock

  DOI：10.1021/jm2001376

  日期：2011.4.28

  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.
• 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.