2-(hydroxymethyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzenesulfonamide | 678987-46-7

• 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-(hydroxymethyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzenesulfonamide
• 英文别名: 2-Hydroxymethyl-4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonamide；2-(hydroxymethyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
• CAS: 678987-46-7
• 化学式: C₁₈H₁₆F₃N₃O₃S
• 分子量: 411.405
• InChiKey: HPGHKJXZFPDDRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  丙酸酐 、 2-(hydroxymethyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzenesulfonamide 在 吡啶 、 丙酸 作用下， 反应 14.0h， 生成 Propionic acid 2-sulfamoyl-5-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzyl ester
  参考文献：
  名称：

  Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors

  摘要：

  Several chemical modifications in the N-1-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.027
• 作为产物：
  描述：

  5-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide 在 lithium aluminium tetrahydride 、 盐酸 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 4.0h， 以47%的产率得到2-(hydroxymethyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzenesulfonamide
  参考文献：
  名称：

  [EN] LARGE CONDUCTANCE CALCIUM-ACTIVATED K CHANNEL OPENER
  [FR] AGENT D'OUVERTURE DE CANAUX K ACTIVES PAR LE CALCIUM A CONDUCTANCE ELEVEE

  摘要：

  公开号：

  WO2005037271A3

文献信息

• 2-Hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide (DRF-4367): an orally active COX-2 inhibitor identified through pharmacophoric modulation
  作者：Sunil Kumar Singh、Saibaba Vobbalareddy、Srinivasa Rao Kalleda、Shaikh Abdul Rajjak、Seshagiri Rao Casturi、Srinivasa Raju Datla、Rao N. V. S. Mamidi、Ramesh Mullangi、Ravikanth Bhamidipati、Rajagopalan Ramanujam、Venkateswarlu Akella、Koteswar Rao Yeleswarapu

  DOI：10.1039/b402787f

  日期：——

  Analogs of 1,5-diarylpyrazoles with a novel pharmacophore at N1 were designed, synthesized and evaluated for the in-vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The variations at/around position-4 of the C-5 phenyl ring in conjunction with a CF3 and CHF2 groups at C-3 exhibited a high degree of potency and selectivity index (SI) for COX-2 inhibition. The in-vivo evaluation of these potent compounds with a few earlier ones indicated the 4-OMe-phenyl analog 6 and the 4-NHMe-phenyl analog 9 with a CF3, and the 4-OEt-phenyl analog 19 with a CHF2 group at C-3 to possess superior potency than celecoxib. In addition to its impressive anti-inflammatory, antipyretic, analgesic and anti-arthritic properties, compound 6 (DRF-4367) was found to possess an excellent pharmacokinetic profile, gastrointestinal (GI) safety in the long-term arthritis study and COX-2 potency in human whole blood assay. Thus, compound 6 was selected as an orally active anti-inflammatory candidate for pre-clinical evaluation.

  在N1位含有新颖药效团的1,5-二芳基吡唑类类似物被设计、合成并对体外环氧合酶（COX-1/COX-2）抑制活性进行了评估。在C-5苯环的4位及其周围的变异与C-3位的CF3和CHF2基团结合，展现出高度的效力和选择性指数（SI），用于COX-2抑制。这些强效化合物的体内评估与先前的一些化合物相比，显示4-OMe-苯基类似物6和4-NHMe-苯基类似物9（C-3位含CF3），以及4-OEt-苯基类似物19（C-3位含CHF2）对COX-2的抑制效力超过了塞来昔布。除了出色的抗炎、解热、镇痛和抗关节炎特性外，化合物6（DRF-4367）被发现具有优秀的药代动力学特性，长期关节炎研究中的胃肠道安全性，以及在人体全血检测中的COX-2效力。因此，化合物6被选为口服活性的抗炎候选物进行临床前评估。
• Large conductance calcium-activated k channel opener
  申请人：Imanishi Yasuhiro

  公开号：US20070060629A1

  公开（公告）日：2007-03-15

  The present invention provides a large conductance calcium-activated K channel opener comprising a compound of the formula (I): wherein R 1 and R 3 are each sulfonamide, carbamoyl, acyl, amino, and the like, m and n are each 0 to 2, R 2 and R 4 are each cyano, nitro, hydroxyl, an alkoxy, a halogen, or an alkyl, Ring A is benzene or a heterocyclic ring, Ring B is benzene, a heterocyclic ring, a cycloalkane etc, and Ring Q is pyrazole or isoxazole, or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明提供了一种大导电性钙激活K通道开放剂，其包括以下式子（I）的化合物：其中R1和R3各自为磺酰胺基，氨基甲酰基，酰基，氨基等，m和n各自为0到2，R2和R4各自为氰基，硝基，羟基，烷氧基，卤素或烷基，环A为苯环或杂环，环B为苯环，杂环，环己烷等，环Q为吡唑环或异噁唑环，或其药学上可接受的盐作为活性成分。
• LARGE CONDUCTANCE CALCIUM-ACTIVATED K CHANNEL OPENER
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP1675585A2

  公开（公告）日：2006-07-05
• Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors
  作者：Sunil K. Singh、P.Ganapati Reddy、K.Srinivasa Rao、Braj B. Lohray、P. Misra、Shaikh A. Rajjak、Yeleswarapu K. Rao、A. Venkateswarlu

  DOI：10.1016/j.bmcl.2003.10.027

  日期：2004.1

  Several chemical modifications in the N-1-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. (C) 2003 Elsevier Ltd. All rights reserved.
• [EN] LARGE CONDUCTANCE CALCIUM-ACTIVATED K CHANNEL OPENER<br/>[FR] AGENT D'OUVERTURE DE CANAUX K ACTIVES PAR LE CALCIUM A CONDUCTANCE ELEVEE
  申请人：TANABE SEIYAKU CO

  公开号：WO2005037271A3

  公开（公告）日：2005-09-01