1-(2-甲氧基苯基)吡唑-4-甲酸 | 1015845-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(2-甲氧基苯基)吡唑-4-甲酸
• 中文别名: 1-(2-甲氧基苯基)-1H-吡唑-4-羧酸
• 英文名称: 1-(2-Methoxyphenyl)-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-(2-methoxyphenyl)pyrazole-4-carboxylic acid
• CAS: 1015845-77-8
• 化学式: C₁₁H₁₀N₂O₃
• 分子量: 218.212
• InChiKey: GETIPSHEOZTBRP-UHFFFAOYSA-N

物化性质

• 沸点：
  423.1±25.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  1-(2-甲氧基苯基)吡唑-4-甲酸 、 Methyl 4-aminobut-2-enoate;2,2,2-trifluoroacetic acid 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  一种基于片段的方法来发现半胱氨酸蛋白酶的不可逆共价抑制剂

  摘要：

  报道了一种新的基于片段的药物发现方法，该方法不可逆地将类药物片段束缚在催化半胱氨酸上。我们将亲电试剂连接到 100 个片段上，而亲电试剂的反应性没有显着改变。质谱分析发现了半胱氨酸蛋白酶木瓜蛋白酶的三种非肽抑制剂。鉴定出的化合物显示出不可逆抑制剂的特征。不可逆的束缚系统也显示出特异性：三种鉴定出的木瓜蛋白酶抑制剂不与 UbcH7、USP08 或带有 GST 标签的人类鼻病毒 3C 蛋白酶共价反应。

  DOI：

  10.1021/jm500345q

文献信息

• Selective Inhibition of DNA Polymerase β by a Covalent Inhibitor
  作者：Shelby C. Yuhas、Daniel J. Laverty、Huijin Lee、Ananya Majumdar、Marc M. Greenberg

  DOI：10.1021/jacs.1c02453

  日期：2021.6.2

  has been closely linked to cancer. Selective inhibitors of this enzyme are lacking. Inspired by DNA lesions produced by antitumor agents that inactivate Pol β, we have undertaken the development of covalent small-molecule inhibitors of this enzyme. Using a two-stage process involving chemically synthesized libraries, we identified a potent irreversible inhibitor (14) of Pol β (KI = 1.8 ± 0.45 μM, kinact

  DNA 聚合酶 β (Pol β) 在 DNA 修复中起着至关重要的作用，并且与癌症密切相关。缺乏这种酶的选择性抑制剂。受使 Pol β 失活的抗肿瘤剂产生的 DNA 损伤的启发，我们着手开发这种酶的共价小分子抑制剂。使用涉及化学合成文库的两阶段过程，我们确定了Pol β的有效不可逆抑制剂 ( 14 ) ( K I = 1.8 ± 0.45 μM, k inact = (7.0 ± 1.0) × 10 –3 s –1 )。抑制剂14比其他 DNA 聚合酶选择性地灭活 Pol β。用14处理的 Pol β 胰蛋白酶消化物的 LC-MS/MS 分析鉴定了聚合酶结合位点内共价修饰的两个赖氨酸，其中一个先前被确定在DNA结合中起作用。荧光各向异性实验表明，用14预处理 Pol β可防止 DNA 结合。在野生型小鼠胚胎成纤维细胞 (MEF) 中使用前抑制剂 ( pro - 14 ) 的实验表明，抑制剂
• [EN] ACYL PIPERAZINE DERIVATIVES AS TTX-S BLOCKERS<br/>[FR] DÉRIVÉS D'ACYLPIPÉRAZINE À TITRE DE BLOQUEURS DE TTX-S
  申请人：RAQUALIA PHARMA INC

  公开号：WO2012020567A1

  公开（公告）日：2012-02-16

  The present invention relates to acyl piperazine derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

  本发明涉及酰基哌嗪衍生物，具有阻断电压门控钠通道（如TTX-S通道）活性的特性，可用于治疗或预防涉及电压门控钠通道的疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及电压门控钠通道的疾病中使用这些化合物和组合物。
• Acyl Piperazine Derivatives as TTX-S Blockers
  申请人：Morita Mikiko

  公开号：US20130150356A1

  公开（公告）日：2013-06-13

  The present invention relates to acyl piperazine derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

  本发明涉及酰基哌嗪衍生物，具有阻断电压门控钠通道（TTX-S通道）的活性，并且在治疗或预防涉及电压门控钠通道的疾病和疾病方面非常有用。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗涉及电压门控钠通道的疾病中使用这些化合物和组合物的用途。
• ARYL CARBOXAMIDE DERIVATIVES AS TTX-S BLOCKERS
  申请人：Yamagishi Tatsuya

  公开号：US20120232052A1

  公开（公告）日：2012-09-13

  The present invention relates to aryl carboxamide derivatives of formula (I), wherein Ar 1 is phenyl; Ar 2 is aryl; n is 1-4; X is —O—, —S—, —SO— or —SO 2 —, a prodrug thereof or a pharmaceutically acceptable salt thereof, which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of such disorders and diseases as pain in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases as pain in which voltage gated sodium channels are involved.

  本发明涉及公式（I）的芳基羧酰胺衍生物，其中Ar1是苯基；Ar2是芳基；n为1-4；X为—O—、—S—、—SO—或—SO2—，其前体药物或其药学上可接受的盐，具有阻断电压门控钠通道如TTX-S通道的活性，并在治疗或预防涉及电压门控钠通道的疾病和疾病，如疼痛方面中有用。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗涉及电压门控钠通道的疾病和疾病，如疼痛方面的使用。
• Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain
  作者：Danielle McShan、Stefan Kathman、Brittiney Lowe、Ziyang Xu、Jennifer Zhan、Alexander Statsyuk、Ifedayo Victor Ogungbe

  DOI：10.1016/j.bmcl.2015.08.074

  日期：2015.10

  Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads. (C) 2015 Elsevier Ltd. All rights reserved.