N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)propionamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)propionamide
• 英文别名: N-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-sulfonyl]propanamide；4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-N-propionylbenzenesulfonamide；N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]sulfonylpropanamide
• 化学式: C₂₀H₁₈F₃N₃O₃S
• 分子量: 437.442
• InChiKey: XBRFSAUQBGTLPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)propionamide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以98.8%的产率得到N-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]sulfonyl]propanamide sodium salt
  参考文献：
  名称：

  Celecoxib prodrug

  摘要：

  N-[[4-[[5-(4-甲基苯基)-3-(三氟甲基)-1H-吡唑-1-基]苯基]-磺酰]丙酰胺及其药用盐是选择性COX-2抑制药物美洛昔布的有效前药，可通过任何合适的途径给予受试者。

  公开号：

  US20040092566A1
• 作为产物：
  描述：

  丙酸酐 、 塞来西布 在 4-二甲氨基吡啶 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以90.4%的产率得到N-((4-(5′-(p-tolyl)-3′-(trifluoromethyl)-1H-pyrazol-1′-yl)phenyl)sulfonyl)propionamide
  参考文献：
  名称：

  Celecoxib prodrug

  摘要：

  N-[[4-[[5-(4-甲基苯基)-3-(三氟甲基)-1H-吡唑-1-基]苯基]-磺酰]丙酰胺及其药用盐是选择性COX-2抑制药物美洛昔布的有效前药，可通过任何合适的途径给予受试者。

  公开号：

  US20040092566A1

文献信息

• Celebrex derivatives: Synthesis, α-glucosidase inhibition, crystal structures and molecular docking studies
  作者：Nabeela Kausar、Saeed Ullah、Maria Aqeel Khan、Humaira Zafar、Atia-tul-Wahab、M. Iqbal Choudhary、Sammer Yousuf

  DOI：10.1016/j.bioorg.2020.104499

  日期：2021.1

  synthesized derivatives were evaluated for anti-inflammatory activity but none was found to be active. Subsequently a random biological screening was carried out. Interestingly many of them were found to be potent α-glucosidase inhibitors in vitro. All the structures of synthesized derivatives were deduced through 1H-NMR, FAB-MS, HR-MS, FT-IR analysis. The single-crystal X-ray structures of compounds

  通常用作抗炎药的Celebrex ( 1 ) 被功能化（化合物2-9）以鉴定新的 α-葡萄糖苷酶抑制剂。最初，评估了所有合成衍生物的抗炎活性，但没有发现具有活性。随后进行随机生物筛选。有趣的是，在体外发现它们中的许多是有效的 α-葡萄糖苷酶抑制剂。所有合成衍生物的结构均通过1 H-NMR、FAB-MS、HR-MS、FT-IR分析推导出来。化合物1和5的单晶X射线结构进一步证实了指定的结构。化合物表现出有效的 α-葡萄糖苷酶抑制活性 (IC 50= 92.32 ± 1.530 - 445.20 ± 1.04 µM) 与测试的标准阿卡波糖 (IC 50 = 875.75 ± 2.08 µM) 相比，除了化合物2和4显示为无活性。其中，化合物9 (IC 50 = 92.32 ± 1.530 µM) 是最有效的 α-葡萄糖苷酶抑制剂。分子对接研究表明，化合物6和9通过 H 键和 π-π 堆积相互作用与
• [EN] CELECOXIB PRODRUG<br/>[FR] PROMEDICAMENT DE CELECOXIB
  申请人：PHARMACIA CORP

  公开号：WO2004043934A1

  公开（公告）日：2004-05-27

  N-[[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-sulfonyl]propanamide and pharmaceutically acceptable salts thereof are useful prodrugs of the selective COX-2 inhibitory drug celecoxib, which can be administrated to a subject by any suitable route.

  N-[[4-[5-(4-甲基苯基)-3-(三氟甲基)-1H-吡唑-1-基]苯基]-磺酰]丙酰胺及其药学上可接受的盐是选择性COX-2抑制药物Celecoxib的有用前药，可以通过任何适当途径给受试者使用。
• NO-RELEASING NONOATE(NITROGEN-BOUND)SULFONAMIDE-LINKED-COXIB ANTI-CANCER AGENTS
  申请人：Euclises Pharmaceuticals, Inc.

  公开号：US20140018544A1

  公开（公告）日：2014-01-16

  The present invention provides NO-releasing NONOate(nitrogen bound)sulfonamide-linked-coxib anti-cancer agents, having the structure of Formula (I): wherein R 1 , X, L, R 2 , R 3 , R 4 , and Z are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis or acne, using a compound of Formula (I).

  本发明提供了一种NO释放的NONOate（氮结合）磺酰胺-联苯并咪唑类抗癌药物，具有以下结构式（I）：其中R1、X、L、R2、R3、R4和Z如详细说明中所定义；包括至少一种式（I）化合物的制药组合物；以及使用式（I）化合物有益于治疗伤口、预防和治疗癌症、或治疗光化性角化症、囊性纤维化或痤疮的方法。
• Oral dosage form of a sulfonamide prodrug
  申请人：——

  公开号：US20030100595A1

  公开（公告）日：2003-05-29

  A pharmaceutical composition that is substantially free of water comprises at least one orally deliverable dosage unit comprising a therapeutically effective amount of a sulfonamide prodrug and, where the prodrug is readily degradable ex vivo, has means to inhibit such degradation prior to oral administration. Illustratively the prodrug is parecoxib or a water-soluble salt thereof, and the composition has means to inhibit conversion of the parecoxib to valdecoxib. A method of treating or preventing a COX-2 mediated disorder in a subject comprises (a) dissolving at least one dosage unit of such a composition in a pharmaceutically acceptable aqueous vehicle to form a solution, and (b) orally administering the solution to the subject before substantial precipitation of insoluble matter occurs in the solution.

  一种基本上不含水的药物组合物包含至少一个口服给药剂量单位，其中含有治疗有效量的磺胺原药，如果原药在体内外容易降解，则在口服给药前具有抑制这种降解的方法。举例来说，原药是帕瑞昔布或其水溶性盐，组合物具有抑制帕瑞昔布转化为缬癸昔布的方法。一种治疗或预防受试者 COX-2 介导的疾病的方法包括：(a)将至少一个剂量单位的这种组合物溶解在药学上可接受的水性载体中以形成溶液，和(b)在溶液中出现大量不溶物沉淀之前将溶液口服给受试者。
• Synthesis and Cyclooxygenase-2 Inhibiting Property of 1,5-Diarylpyrazoles with Substituted Benzenesulfonamide Moiety as Pharmacophore:  Preparation of Sodium Salt for Injectable Formulation^†
  作者：Manojit Pal、Manjula Madan、Srinivas Padakanti、Vijaya R. Pattabiraman、Srinivas Kalleda、Akhila Vanguri、Ramesh Mullangi、N. V. S. Rao Mamidi、Seshagiri R. Casturi、Alpeshkumar Malde、B. Gopalakrishnan、Koteswar R. Yeleswarapu

  DOI：10.1021/jm020563g

  日期：2003.9.1

  A series of 1,5-diarylpyrazoles having a substituted benzenesulfonamide moiety as pharmacophore was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Through SAR and molecular modeling, it was found that fluorine substitution on the benzenesulfonamide moiety along with an electron-donating group at the 4-position of the 5-aryl ring yielded selectivity as well as potency for COX-2 inhibition in vitro. Among such compounds 3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide 3 displayed interesting pharmacokinetic properties along with antiinflammatory activity in vivo. Among the sodium salts tested in vivo, 10, the propionyl analogue of 3, showed excellent antiinflammatory activity and therefore represents a new lead structure for the development of injectable COX-2 specific inhibitors.