1-(4-sulfamoylphenyl)-5-p-tolyl-1H-pyrazol-3-carbonic acid | 850829-08-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-sulfamoylphenyl)-5-p-tolyl-1H-pyrazol-3-carbonic acid
• 英文别名: 1-(4-sulfamoylphenyl)-5-(p-tolyl)-1H-pyrazole-3-carboxylic acid；1-(4-(methylsulfonyl)phenyl)-5-(p-tolyl)-1H-pyrazole-3-carboxylic acid；(4-sulfamoylphenyl)-5-(p-tolyl)-1H-pyrazole-3-carboxylic acid；1-[4-(aminosulfon-yl)phenyl]-5-(4-methylphenyl)-1H-pyrazol-3-carboxylic acid；celecoxib；1-(4-sulfamoyl-phenyl)-5-p-tolyl-1H-pyrazole-3-carboxylic acid；5-(4-methylphenyl)-1-(4-sulfamoylphenyl)pyrazole-3-carboxylic acid
• CAS: 850829-08-2
• 化学式: C₁₇H₁₅N₃O₄S
• 分子量: 357.39
• InChiKey: WVVMXACTNGMBBT-UHFFFAOYSA-N

物化性质

• 沸点：
  637.3±65.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-sulfamoylphenyl)-5-p-tolyl-1H-pyrazol-3-carbonic acid 在 三异丙基硅烷醇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 1.5h， 生成 N-(8-(hydroxyamino)-8-oxooctyl)-1-(4-sulfamoylphenyl)-5-(p-tolyl)-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase

  摘要：

  We herein disclose a series of compounds with potent inhibitory activities towards histone deacetylases (HDAC) and cyclooxygenases (COX). These compounds potently inhibited the growth of cancer cell lines consistent with their anti-COX and anti-HDAC activities. While compound 2b showed comparable level of COX-2 selectivity as celecoxib, compound lib outperformed indomethacin in terms of selectivity towards COX-2 relative to COX-1. An important observation with our lead compounds (2b, 8, 11b, and 17b) is their enhanced cytotoxicity towards androgen dependent prostate cancer cell line (LNCaP) relative to androgen independent prostate cancer cell line (DU-145). Interestingly, compounds 2b and 17b arrested the cell cycle progression of LNCaP in the S-phase, while compound 8 showed a G0/G1 arrest, similar to SAHA. Relative to SAHA, these compounds displayed tumor-selective cytotoxicity as they have low anti-proliferative activity towards healthy cells (VERO); an attribute that makes them attractive candidates for drug development. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.12.032
• 作为产物：
  描述：

  4-(4-甲基苯基)-2,4-二氧代丁酸甲酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 23.5h， 生成 1-(4-sulfamoylphenyl)-5-p-tolyl-1H-pyrazol-3-carbonic acid
  参考文献：
  名称：

  Synthesis of novel dansyl-labeled Celecoxib derivatives

  摘要：

  Four novel dansyl-labeled derivatives of Celecoxib, a cyclooxygenase-2 (COX-2) selective inhibitor, were designed and synthesized. To realize the fluorophore-linker-approach divergent and convergent synthetic strategies were applied. Therefore Celecoxib p-benzoic acid, 8, was synthesized in a new and convenient way. The yield and the synthetic route to Celecoxib, 1, its pyrazolylic acid, 7, and its pyrazolylic methyl ester, 6, were improved. Through a convenient synthesis 1,11-diamino-3,6,9-trioxundecane, 19, was obtained in high yield and purity and used as a linker for the dansyl moiety. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.09.025

文献信息

• Synthesis of novel hybrids of pyrazole and coumarin as dual inhibitors of COX-2 and 5-LOX
  作者：Fa-Qian Shen、Zhong-Chang Wang、Song-Yu Wu、Shen-Zhen Ren、Ruo-Jun Man、Bao-Zhong Wang、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2017.07.020

  日期：2017.8

  In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin who was reported to exhibit 5-LOX inhibition to select potent compounds using adequate biological trials sequentially including selective inhibition

  在我们先前的研究中，我们设计了一系列吡唑衍生物作为新型COX-2抑制剂。为了获得新型的COX-2和5-LOX双重抑制剂，我们在此设计并合成了20种化合物，方法是将吡唑与取代的香豆素杂交，据报道，该香豆素具有5-LOX抑制作用，并使用包括选择性抑制在内的充分生物学试验依次选择有效的化合物。 COX-2和5-LOX的表达，体外抗增殖，细胞凋亡和细胞周期。其中，最有效的化合物11g（ COX-2的IC 50 = 0.23±  0.16μM，5-LOX的IC 50 = 0.87±0.07μM， 针对A549的IC 50 = 4.48±0.57μM）与阳性对照相比具有初步优势。控制塞来昔布（ 对于COX-2，IC 50 = 0.41± 0.28μM， 对于A549 ，IC 50 = 7.68± 0.55μM）和Zileuton（ 对于5-LOX，IC 50 = 1.35± 0.24μM）。进一步的研
• CONJUGATES DERIVED FROM NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND METHODS OF USE THEREOF IN IMAGING
  申请人：Reiley Pharmaceuticals, Inc.

  公开号：US20150374858A1

  公开（公告）日：2015-12-31

  Conjugates derived from non-steroidal anti-inflammatory drugs (NSAIDs) and methods of use thereof are disclosed, useful for, inter alia, identifying and localizing the site of pathology and/or inflammation responsible for the sensation of pain in a patient; for identifying the sites of primary, secondary, benign, or malignant tumors; and for diagnosing infection or confirming or ruling out suspected infection. The NSAID-based conjugates contain an imaging moiety. The conjugates concentrate at sites of increased cyclooxygenase expression, thus revealing the sites of increased prostaglandin production, which is correlated with pain and inflammation, and correlated with tumor presence and/or location. Identifying areas of increased COX expressing can also aid in screening for infections.

  披露了来自非甾体抗炎药（NSAIDs）的衍生物及其使用方法，这对于识别和定位患者疼痛感觉的病理和/或炎症部位；识别原发、继发、良性或恶性肿瘤的部位；以及诊断感染或确认或排除疑似感染非常有用。基于NSAID的偶联物含有成像基团。这些偶联物在环氧化酶表达增加的部位富集，从而揭示了前列腺素产生增加的部位，这与疼痛和炎症有关，并与肿瘤存在和/或位置有关。识别COX表达增加的区域也有助于筛查感染。
• 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。
• NOVEL TARGET PROTEIN OF ANTICANCER AGENT AND NOVEL ANTICANCER AGENT (SPNAL) CORRESPONDING THERETO
  申请人：Reverse Proteomics Research Institute Co., Ltd

  公开号：EP1690852A1

  公开（公告）日：2006-08-16

  The present invention provides a pharmaceutical composition containing, as an active ingredient, a compound that specifically binds to KSRP or a functional fragment thereof, and a screening method for the compound. KSRP is a novel target protein for anticancer agents; a compound capable of regulating the expression and activity of such a protein and a pharmaceutical composition containing it are highly useful for proliferative diseases, particularly as anticancer agents. By providing the novel target protein, the mechanism behind the anticancer effect that has conventionally been unexplainable can be elucidated.

  本发明提供了一种药物组合物，其包含一种特异性结合于KSRP或其功能性片段的化合物作为活性成分，并提供了一种筛选该化合物的方法。KSRP是一种新型的抗癌药物靶蛋白；能够调节该蛋白的表达和活性的化合物以及含有它的药物组合物在增生性疾病中特别是作为抗癌药物非常有用。通过提供这种新型的靶蛋白，可以阐明传统上难以解释的抗癌效应的机制。
• 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。