4-(3-{3-[3-(2,6-diisopropyl-phenyl)-ureido]-propyl}-5-phenyl-pyrazol-1-yl)-benzenesulfonamide | 1287760-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(3-{3-[3-(2,6-diisopropyl-phenyl)-ureido]-propyl}-5-phenyl-pyrazol-1-yl)-benzenesulfonamide
• 英文别名: 4-(3-{3-[3-(2,6-diisopropylphenyl)ureido]propyl}-5-phenylpyrazol-1-yl)benzenesulfonamide；1-[2,6-di(propan-2-yl)phenyl]-3-[3-[5-phenyl-1-(4-sulfamoylphenyl)pyrazol-3-yl]propyl]urea
• CAS: 1287760-96-6
• 化学式: C₃₁H₃₇N₅O₃S
• 分子量: 559.732
• InChiKey: TWFZIOFRMSSAER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-磺酰胺基苯肼盐酸盐 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 4-(3-{3-[3-(2,6-diisopropyl-phenyl)-ureido]-propyl}-5-phenyl-pyrazol-1-yl)-benzenesulfonamide
  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

• METHODS OF IMPROVING CANCER CHEMOTHERAPY
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20200197368A1

  公开（公告）日：2020-06-25

  Provided are methods and compositions for prolonging survival and/or reducing or inhibiting tumor growth in a cancer subject receiving a regimen of one or more chemotherapeutic agents, an inhibitor of soluble epoxide hydrolase (sEHi) and a non-steroidal anti-inflammatory drug (NSAID) that inhibits one or more enzymes selected from the group consisting of cyclo-oxygenase (“COX”)-1, COX-2, and 5-lipoxygenase (“5-LOX”). The methods and compositions decrease toxicity and/or adverse side effects in subjects receiving a regimen of one or more chemotherapeutic agents.
• METHODS OF IMPROVING CELL-BASED THERAPY
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20210145891A1

  公开（公告）日：2021-05-20

  Provided are methods for improving the efficacy and success of cell-based therapies by administration of stem cells which have been preconditioned with an inhibitor of soluble epoxide hydrolase (sEHI), as well as kits, stents and patches for administering sEHI-preconditioned stem cells, as sole active agent or in combination with an agent that increases the production and or levels of EETs.
• METHODS OF INHIBITING FORMATION OF ALPHA SYNUCLEIN AGGREGATES
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20210161881A1

  公开（公告）日：2021-06-03

  Provided are methods of preventing, delaying, mitigating, reducing and/or inhibiting alpha-synuclein aggregates in the brains of a subject at risk of developing or suffering a cognitive disease associated with, caused and/or mediated at least in part by alpha-synuclein aggregates, for example, Parkinson's Disease or Dementia with Lewy Bodies (DLB).
• [EN] METHODS OF IMPROVING CELL-BASED THERAPY<br/>[FR] PROCÉDÉS D'AMÉLIORATION D'UNE THÉRAPIE CELLULAIRE
  申请人：UNIV CALIFORNIA

  公开号：WO2018231702A1

  公开（公告）日：2018-12-20

  Provided are methods for improving the efficacy and success of cell-based therapies by administration of stem cells which have been preconditioned with an inhibitor of soluble epoxide hydrolase (sEHI), as well as kits, stents and patches for administering sEHI-preconditioned stem cells, as sole active agent or in combination with an agent that increases the production and or levels of EETs.
• [EN] METHODS OF IMPROVING CANCER CHEMOTHERAPY<br/>[FR] PROCÉDÉS D'AMÉLIORATION D'UNE CHIMIOTHÉRAPIE ANTICANCÉREUSE
  申请人：UNIV CALIFORNIA

  公开号：WO2019040319A1

  公开（公告）日：2019-02-28

  Provided are methods and compositions for prolonging survival and/or reducing or inhibiting tumor growth in a cancer subject receiving a regimen of one or more chemotherapeutic agents, an inhibitor of soluble epoxide hydrolase (sEHi) and a non-steroidal anti-inflammatory drug (NSAID) that inhibits one or more enzymes selected from the group consisting of cyclo-oxygenase ("COX") -1, COX-2, and 5-lipoxygenase ("5-LOX"). The methods and compositions decrease toxicity and/or adverse side effects in subjects receiving a regimen of one or more chemotherapeutic agents.