methyl 1-(4-methanesulfonylphenyl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylate | 960214-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 1-(4-methanesulfonylphenyl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylate
• 英文别名: Methyl 5-(4-methylphenyl)-1-(4-methylsulfonylphenyl)pyrazole-3-carboxylate
• CAS: 960214-96-4
• 化学式: C₁₉H₁₈N₂O₄S
• 分子量: 370.429
• InChiKey: DVWIGJIICCGUFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  86.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 1-(4-methanesulfonylphenyl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 15.0h， 以82%的产率得到1-(4-(methylsulfonyl)phenyl)-5-(p-tolyl)-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids: Synthesis, nitric oxide release studies and anti-inflammatory activities

  摘要：

  A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs) wherein an O(2)-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (11a-c) NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids were synthesized. The diazen-1-ium-1,2-diolate compounds 11a-c all released a low amount of NO upon incubation with phosphate buffer (PBS) at pH 7.4 (7.7-9.3% range). In comparison, the percentage of NO released was significantly higher (67.5-73.6% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies suggest that both NO and the anti-inflammatory 1-(4-methanesulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3- carboxylic acid (9a-c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The 1-(4-methanesulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3- carboxylic acids (9a-c) exhibited AI activities (ID(50) = 85.2-104.4 mg/kg po range) between that exhibited by the reference drugs aspirin (ID(50) = 128.7 mg/kg po) and celecoxib (ID(50) = 10.8 mg/kg po). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO-coxibs) offers a potential drug design concept targeted toward the development of anti-inflammatory drugs that are devoid of adverse ulcerogenic and/or cardiovascular effects. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.028
• 作为产物：
  描述：

  对甲基苯乙酮 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 methyl 1-(4-methanesulfonylphenyl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells

  摘要：

  COX-2可以被视为临床相关的分子靶点，特别是用于辅助治疗，尤其是放射增敏治疗。在这方面，使用选择性COX-2抑制剂，例如与放疗或内放射治疗结合使用，代表了一种有趣的治疗选择。基于我们自己的发现，一氧化氮（NO）释放和Celecoxib衍生的COX-2抑制剂（COXIBs）在体外显示出有前途的放射增敏效果，我们在此介绍了一系列八种新型NO-COXIBs的开发，这些化合物在其周围取代模式和化学和体外特性上有所不同。发现COX-1和COX-2的抑制能力与领先的NO-COXIBs相当，而NO释放特性主要受到吡唑酮4位取代基（Cl vs. H）的影响。在磺酰胺残基处引入N-丙酰胺作为潜在的前药策略，可显著降低脂溶性并消除COX抑制，而NO释放特性则没有明显影响。在体外测试NO-COXIBs与单剂外部X射线照射以及[177Lu]LuCl3治疗在HIF2α阳性小鼠嗜铬细胞瘤（MPC-HIF2a）肿瘤球体中的联合应用。当直接应用于X射线照射或177Lu治疗之前时，NO-COXIBs表现出放射保护效果，Celecoxib作为对照也是如此。当在X射线照射后短时间内应用时，观察到放射增敏效果。总的来说，与Celecoxib相比，NO-COXIBs被发现具有更强的放射保护作用，这不需要进一步的嗜铬细胞瘤前临床研究。然而，可以考虑将这里开发的NO-COXIBs作为放射保护剂评估用于健康组织，特别是在照射之前直接使用。

  DOI：

  10.3390/molecules27196587

文献信息

• Methods and compositions for diagnostic and therapeutic targeting of COX-2
  申请人：Marnett J. Lawrence

  公开号：US20070292352A1

  公开（公告）日：2007-12-20

  The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

  目前公开的主题提供了选择性结合环氧合酶-2并包含治疗和/或诊断基团的组合物。还提供了使用公开的组合物进行诊断（即通过成像）目标细胞和/或治疗与环氧合酶-2生物活性相关的疾病的方法。
• Deuteration <i>versus</i> ethylation – strategies to improve the metabolic fate of an ¹⁸F-labeled celecoxib derivative
  作者：Markus Laube、Cemena Gassner、Christin Neuber、Robert Wodtke、Martin Ullrich、Cathleen Haase-Kohn、Reik Löser、Martin Köckerling、Klaus Kopka、Torsten Kniess、Evamarie Hey-Hawkins、Jens Pietzsch

  DOI：10.1039/d0ra04494f

  日期：——

  The aim of this study is to investigate the influence of deuteration and elongation on an ¹⁸F-labeled COX-2 inhibitor with focus on metabolic stability to develop suitable COX-2 targeting radiotracers.

  这项研究的目的是调查氘代和延长对一种¹⁸F标记的COX-2抑制剂的影响，重点关注代谢稳定性，以开发适用于COX-2靶向放射示踪剂。
• METHODS AND COMPOSITIONS FOR DIAGNOSTIC AND THERAPEUTIC TARGETING OF COX-2
  申请人：Marnett Lawrence J.

  公开号：US20130052138A1

  公开（公告）日：2013-02-28

  The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

  目前披露的主题提供了选择性结合环氧合酶-2并包含治疗和/或诊断部分的组合物。还提供了使用所披露的组合物进行诊断（即通过成像）靶细胞和/或治疗与环氧合酶-2生物活性相关的疾病的方法。
• US7736624B2
  申请人：——

  公开号：US7736624B2

  公开（公告）日：2010-06-15
• US8865130B2
  申请人：——

  公开号：US8865130B2

  公开（公告）日：2014-10-21