methyl 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylate

• 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 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylate
• 英文别名: methyl-1-[4-(aminosulfonyl)phenyl]-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxylate；Methyl 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)pyrazole-3-carboxylate
• 化学式: C₁₈H₁₇N₃O₅S
• 分子量: 387.416
• InChiKey: GUCORJUOFXDDKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylate 在 甲醇 、 sodium hydroxide 作用下， 反应 6.0h， 生成 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Discovery of novel sulfonamide-containing aminophosphonate derivatives as selective COX-2 inhibitors and anti-tumor candidates

  摘要：

  As an essential enzyme with a variety of physiological functions, Cyclooxygenase-2 (COX-2) is also closely related to carcinoma due to the observed overexpression. In this work, a novel series of sulfonamide-containing aminophosphonate derivatives (A1-A25) were developed as selective COX-2 inhibitors and anti-cancer candidates. The top hit compound A23 presented applicative COX-2 inhibitory activity (IC₅₀ = 0.28 µM) and anti-proliferative capability against several cancer cell lines (IC₅₀ = 2.34-16.43 µM for HeLa, MCF-7, HCT116 and HepG2 cells). Among them, A23 has the most significant inhibitory effect on HCT116 cells, which were comparable with that of the positive controls respectively (eg: IC₅₀ = 8.73 µM for HCT116). The binding pattern of A23 was inferred by the molecular docking simulation. Moreover, A23 could induce the apoptosis via a mitochondrion-dependent mode and cause the arrest of the cell-cycle in G1 stage. A further investigation in the checkpoints of apoptosis indicated that the node Bcl-2 might connect the selective COX-2 inhibition and the anti-tumor activity. Therefore, this work brought new information for developing COX-2 inhibitors in anti-tumor therapies in future.

  DOI：

  10.1016/j.bioorg.2020.104390
• 作为产物：
  描述：

  对甲氧基苯乙酮 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 12.08h， 生成 methyl 5-(4-methoxyphenyl)-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  从基于蛋白激酶抑制剂的抗癌药开发抗真菌农药

  摘要：

  重新使用新型的p21活化的蛋白激酶抑制剂化合物15，可以确定其对五种所选植物致病真菌的抗真菌活性。基于其结构的前导优化产生了一个集中的20种衍生物的库，其中化合物3c的活性比化合物15高，甚至与多菌灵，戊唑醇和吡唑醚菌酯等市场上的某些商业化杀菌剂相当。这项研究表明，p21激活的蛋白激酶抑制剂化合物15 能够作为开发针对真菌植物病原体的有效杀真菌剂的分子平台，并表明筛选现有的蛋白激酶抑制剂可能是鉴定用于开发抗真菌农药的主要化合物的有效方法。

  DOI：

  10.1016/j.ejmech.2018.02.040

文献信息

• Design, synthesis and evaluation of benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives as COX-1/COX-2 agents against solid tumors
  作者：Xiao-Yuan Lu、Zhong-Chang Wang、Ting Wei、Xiao-Qiang Yan、Peng-Fei Wang、Hai-Liang Zhu

  DOI：10.1039/c6ra02168a

  日期：——

  phenylacetohydrazide derivatives have been designed, synthesized and evaluated for their biological activities as selective COX-2 inhibitors with anticancer potential. In vitro the bioassay results revealed that some of them displayed potent inhibitory activity in the enzymatic and cellular assays. Among them, compound 48 showed the most powerful and potent selective inhibitory activity (IC50 = 82.21 μM

  已经设计，合成并评估了新型的含苯乙酰肼衍生物的苯磺酰胺取代的1,5-二芳基吡唑类化合物作为具有抗癌潜力的选择性COX-2抑制剂的生物活性。在体外，生物测定结果表明，其中一些在酶和细胞测定中显示出有效的抑制活性。其中，化合物48显示出最有力和有效的选择性的抑制活性（IC 50 = 82.21μM为COX-1和IC 50 = 0.37μM为COX-2），相媲美的控制正化合物塞来考昔（40.29μM，0.15μM） 。抗增殖试验结果表明该化合物48在体外对A549细胞具有强大的抗增殖活性，IC 50值为0.78μM。然后，我们对化合物48进行了PI染色测定和细胞凋亡分析，发现其有效引起A549细胞凋亡。进一步进行对接模拟以将化合物48定位在COX-2活性位点中以确定可能的结合模型。建立3D-QSAR模型是为了将来合理设计选择性COX-2抑制剂。
• Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis
  作者：Xiao-Yuan Lu、Zhong-Chang Wang、Shen-Zhen Ren、Fa-Qian Shen、Ruo-Jun Man、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2016.06.037

  日期：2016.8

  Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2 promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhibition and anticancer. Among them, compound 7t showed most powerful selective inhibitory and antiproliferative activity (IC50 = 0.09 μM for COX-2, IC50 = 48

  环氧合酶2在恶性肿瘤中经常过度表达，产物PGE 2促进癌细胞的发展和转移。我们设计了一系列香豆素磺酰胺衍生物，以改善COX-2抑制和抗癌的生物活性。其中，化合物7吨表明最强大的选择性的抑制和抗增殖活性（IC 50  = 0.09μM为COX-2，IC 50  = 48.20μM为COX-1，IC 50  = 0.36μM对HeLa细胞），具有可比性到控制正化合物塞来昔布（0.31μM，43.37μM，7.79μM）。进行癌细胞凋亡测定，结果表明化合物7t以剂量和时间依赖性有效地促进HeLa细胞凋亡。此外，7t可以显着抑制癌细胞的粘附，迁移和侵袭，这是癌症转移的重要过程。对接模拟结果进一步表明，化合物7t可以很好地与COX-2活性位点结合，并在将来指导合理设计具有抗癌活性的选择性COX-2抑制剂。
• [EN] SUBSTITUTED PYRAZOLYL BENZENESULFONAMIDES FOR USE IN VETERINARY THERAPIES AS ANTIINFLAMMATORY AGENTS<br/>[FR] PYRAZOLYL BENZENESULFONAMIDES SUBSTITUES DESTINES A ETRE UTILISES DANS DES THERAPIES VETERINAIRES COMME AGENTS ANTI-INFLAMMATOIRES
  申请人：G.D. SEARLE & CO.

  公开号：WO1997011704A1

  公开（公告）日：1997-04-03

  (EN) A method of using pyrazolyl benzenesulfonamide compounds in treating inflammation and inflammation-related disorders in animals.(FR) L'invention porte sur un procédé d'utilisation de composés de pyrazolyl benzènesulfonamides dans le traitement d'inflammations et de troubles liés à des inflammations chez les animaux.

  一种使用吡唑基苯磺酰胺类化合物治疗动物炎症和与炎症相关的疾病的方法。
• [EN] SUBSTITUTED PYRAZOLYL BENZENESULFONAMIDES FOR THE TREATMENT OF INFLAMMATION<br/>[FR] BENZENESULFONAMIDES DE PYRAZOLYLE SUBSTITUES DESTINES AU TRAITEMENT DES INFLAMMATIONS
  申请人：G. D. SEARLE & CO.

  公开号：WO1995015316A1

  公开（公告）日：1995-06-08

  (EN) A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by formula (II), whrein R2 is selected from hydrido, alkyl, haloalkyl, alkoxycarbonyl, cyano, cyanoalkyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, cycloalkylaminocarbonyl, arylaminocarbonyl, carboxyalkylaminocarbonyl, carboxyalkyl, aralkoxycarbonylalkylaminocarbonyl, aminocarbonylalkyl, alkoxycarbonylcyanoalkenyl and hydroxyalkyl; wherein R3 is selected from hydrido, alkyl, cyano, hydroxyalkyl, cycloalkyl, alkylsulfonyl and halo; and wherein R4 is selected from aralkenyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic; wherein R4 is optionally substituted at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsulfonyl, cyano, nitro, haloalkyl, alkyl, hydroxyl, alkenyl, hydroxyalkyl, carboxyl, cycloalkyl, alkylamino, dialkylamino, alkoxycarbonyl, aminocarbonyl, alkoxy, haloalkoxy, sulfamyl, heterocyclic and amino; provided R2 and R3 are not both hydrido; further provided that R2 is not carboxyl or methyl when R3 is hydrido and when R4 is phenyl; further provided that R4 is not triazolyl when R2 is methyl; further provided that R4 is not aralkenyl when R2 is carboxyl, aminocarbonyl or ethoxycarbonyl; further provided that R4 is not phenyl when R2 is methyl and R3 is carboxyl; and further provided that R4 is not unsubstituted thienyl when R2 is trifluoromethyl; or a pharmaceutically acceptable salt thereof.(FR) L'invention se rapporte à une classe de composés de benzènesulfonamide de pyrazolyle utilisés pour traiter les inflammations et les troubles d'ordre inflammatoire. Les composés plus particulièrement étudiés répondent à la formule (II), dans laquelle R2 est choisi entre hydrido, alkyle, haloalkyle, alcoxycarbonyle, cyano, cyanoalkyle, carboxyle, aminocarbonyle, alkylaminocarbonyle, cycloalkylaminocarbonyle, arylaminocarbonyle, carboxyalkylaminocarbonyle, carboxyalkyle, aralcoxycarbonylalkylaminocarbonyle, aminocarbonylalkyle, alcoxycarbonylcyanoalcényle et hydroxyalkyle; R3 est choisi entre hydrido, alkyle, cyano, hydroxyalkyle, cycloalkyle, alkylsulfonyle et halo; R4 est choisi entre aralcényle, aryle, cycloalkyle, cycloalcényle et un groupe hétérocyclique; R4 pouvant être éventuellement substitué en une position apte à être substituée par un ou plusieurs radicaux choisis entre halo, alkylthio, alkylsulfonyle, cyano, nitro, haloalkyle, alkyle, hydroxyle, alcényle, hydroxyalkyle, carboxyle, cycloalkyle, alkylamino, dialkylamino, alcoxycarbonyle, aminocarbonyle, alcoxy, haloalcoxy, sulfamyle, un radical hétérocyclique et amino; à condition que R2 et R3 ne représentent pas tous deux hydrido; que R2 ne représente pas carboxyle ou méthyle quand R3 représente hydrido et quand R4 représente phényle; que R4 ne représente pas triazolyle quand R2 représente méthyle; que R4 ne représente pas aralcényle quand R2 représente carboxyle, aminocarbonyle ou éthoxycarbonyle; que R4 ne représente pas phényle quand R2 représente méthyle et R3 carbonyle; et que R4 ne représente pas thiényle non substitué lorsque R2 représente trifluorométhyle. L'invention se rapporte également à un sel pharmaceutiquement acceptable de ces composés.

  描述了一类用于治疗炎症和炎症相关疾病的吡唑基苯磺酰胺化合物。特别感兴趣的化合物由公式（II）定义，其中R2从氢基，烷基，卤代烷基，烷氧羰基，氰基，氰基烷基，羧基，氨基羰基，烷基氨基羰基，环烷基氨基羰基，芳基氨基羰基，羧基烷基氨基羰基，芳基氧羰基烷基氨基羰基，氨基羰基烷基，烷氧羰基氰基烯基和羟基中选择；其中R3从氢基，烷基，氰基，羟基烷基，环烷基，烷基磺酰和卤素中选择；其中R4从芳烯基，芳基，环烷基，环烯基和杂环中选择；其中R4在可取代位置上可用一个或多个基团进行取代，所述基团从卤素，烷基硫醇，烷基磺酰，氰基，硝基，卤代烷基，烷基，羟基，烯基，羟基烷基，羧基，环烷基，烷基氨基，二烷基氨基，烷氧羰基，氨基羰基，烷氧基，卤代烷氧基，磺酰胺基，杂环和氨基中选择；前提是R2和R3不都是氢基；进一步提供，当R3为氢基且R4为苯基时，R2不是羧基或甲基；进一步提供，当R2为甲基时，R4不是三唑基；进一步提供，当R2为羧基，氨基羰基或乙氧羰基时，R4不是芳烯基；进一步提供，当R2为甲基且R3为羧基时，R4不是苯基；进一步提供，当R2为三氟甲基时，R4不是未取代的噻吩基；或者其药学上可接受的盐。
• Substituted pyrazolyl benzenesulfonamides for the treatment of inflammation
  申请人：G.D. Searle & Co.

  公开号：US20040192930A1

  公开（公告）日：2004-09-30

  A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: 1 wherein R 2 is selected from hydrido, alkyl, haloalkyl, alkoxycaronyl, cyano, cyanoalkyl, carboxyl, aminocaronyl, alkylaminocarbonyl, cycloalklaminocarbonyl, arylaminocarbonyl, carboxyalkylaminocarbonyl, carboxyalkyl, aralkoxycarbonylalkylaminocarbonyl, amioncarbonylalkyl, alkoxycarbonylcyanoalkenyl and hydroxyalkyl; wherein R 3 is selected from hydrido, alkyl, cyano, hydroxyalkyl, cycloalkyl, alkylsulfonyl and halo; and wherein R 4 is selected from aralkenyl, aryl, cycloalkyl, cycloalkenyl and heterocyclic; wherein R 4 is optionally substituted at a substitutable position with one or more radicals selected from halo alkylthio, alkylsulfonyl, cyano, nitro, haloalkyl, alkyl, hydroxyl, alkenyl, hydroxyalkyl, carboxyl, cycloalkyl, alkylamino, dialkylamino, alkoxycarbonyl, aminocarbonyl, alkoxy, haloalkoxy, sulfamyl, heterocyclic and amino; provided R 2 and R 3 are not both hydrido; further provided that R 2 is not carboxyl or methyl when R 3 is hydrido and when R 4 is phenyl; further provided that R 4 is not triazolyl when R 2 is methyl; further provided that R 4 is not arakenyl when R 2 is carboxyl, aminocarbonyl or ethoxycarbonyl; further provided that R 4 is not phenyl when R 2 is methyl and R 3 is carboxyl; and further provided that R 4 is not unsubstituted thienyl when R 2 is trifluoromethyl; or a pharmaceutically-acceptable salt thereof.

  本文描述了一类吡唑基苯磺酰胺化合物，用于治疗炎症和与炎症相关的疾病。特别感兴趣的化合物由公式II:1定义，其中R2从氢，烷基，卤代烷基，烷氧羰基，氰基，氰基烷基，羧基，氨基羧基，烷基氨基羰基，环烷氨基羰基，芳基氨基羰基，羧基烷基氨基羰基，羧基烷基，芳基氧羰基烷基氨基羰基，氨基羰基烷基，烷氧羰基氰基烯基和羟基烷基中选择；其中R3从氢，烷基，氰基，羟基烷基，环烷基，烷基磺酰和卤素中选择；其中R4从芳基烯基，芳基，环烷基，环烯基和杂环中选择；其中R4在可取代位置上可选择一个或多个基团进行取代，所述基团从卤代烷硫基，烷基磺酰，氰基，硝基，卤代烷基，烷基，羟基，烯基，羟基烷基，羧基，环烷基，烷基氨基，二烷基氨基，烷氧羰基，氨基羰基，烷氧基，卤代烷氧基，磺酰胺基，杂环和氨基中选择；前提是R2和R3不同时为氢；进一步提供R2在R3为氢且R4为苯基时不为羧基或甲基；进一步提供当R2为甲基时，R4不为三唑基；进一步提供当R2为羧基，氨基羰基或乙氧羰基时，R4不为芳基烯基；进一步提供当R2为甲基且R3为羧基时，R4不为苯基；进一步提供当R2为三氟甲基时，R4不为未取代的噻吩基；或其药学上可接受的盐。