ethyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate | 354997-99-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate
• 英文别名: ethyl 3-(3-methyl-5-oxo-4H-pyrazol-1-yl)benzoate
• CAS: 354997-99-2
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: AQZWDEVQKKEAMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate 在 甲醇 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 (Z)-5-(5-((1-(3-carboxyphenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)methyl)furan-2-yl)-2-chlorobenzoic acid
  参考文献：
  名称：

  [EN] KU INHIBITORS AND THEIR USE
  [FR] INHIBITEURS DE KU ET LEUR UTILISATION

  摘要：

  本公开涉及具有与Ku结合亲和力的某些化合物及其用途。具体而言，本公开涉及在位点特异性基因组工程技术中使用如本文所述的Ku抑制剂，包括但不限于CRISPR/Cas9、锌指核酸酶（ZFN）、转录激活因子样效应核酸酶（TALEN）和巨核核酸酶。本公开还涉及用于位点特异性基因组工程的工具包，其中包括至少一种如本文所述的化合物。

  公开号：

  WO2017205503A1
• 作为产物：
  描述：

  3-肼基苯甲酸 在 硫酸 、 溶剂黄146 作用下， 反应 24.0h， 生成 ethyl 3-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate
  参考文献：
  名称：

  [EN] XPA INHIBITOR COMPOUNDS AND THEIR USE
  [FR] COMPOSÉS INHIBITEURS DE XPA ET LEUR UTILISATION

  摘要：

  本公开涉及具有与XPA结合亲和力的某些化合物及其用途。具体而言，本公开涉及在治疗癌症的方法中使用如此描述的XPA抑制剂。

  公开号：

  WO2019060260A1

文献信息

• Identification of non-substrate-like glycosyltransferase inhibitors from library screening: pitfalls & hits
  作者：Masaki Ema、Yong Xu、Sebastian Gehrke、Gerd K. Wagner

  DOI：10.1039/c7md00550d

  日期：——

  initial structure–activity relationships in this series, and to establish the target selectivity of the most potent inhibitor over two other glycosyltransferases. Our results provide insights into the activity of this class of non-substrate-like glycosyltransferase inhibitors, and highlight important general pitfalls for inhibitor screening against this enzyme family. Key elements of our experimental design

  细菌糖基转移酶是开发新型抗生素和抗毒剂的潜在目标。大多数现存的糖基转移酶抑制剂是药物开发潜力有限的底物类似物。因此，对于药物化学，药物发现和化学糖生物学，鉴定替代抑制剂的化学型引起了极大的兴趣。我们描述了生化糖基转移酶测定法的应用，以筛选包含三个不同化学支架（核苷，类固醇和5-甲基吡唑-3-酮）的小化合物文库，用于对抗脑膜炎奈瑟氏球菌的保留α-1,4-半乳糖基转移酶LgtC。虽然在核苷和类固醇系列中未观察到真正的LgtC抑制活性，但在5-甲基吡唑-3-一系列中命中率最高的化合物显示出较低的微摩尔活性。我们调整了我们的测定方案，以开发该系列中的初始结构-活性关系，并建立了对两种其他糖基转移酶的最有效抑制剂的目标选择性。我们的结果提供了对这类非底物样糖基转移酶抑制剂的活性的见解，并强调了针对该酶家族进行抑制剂筛选的重要一般性陷阱。从理论上讲，我们的实验设计的关键要素，包括经过验证的用于抑制剂筛
• XPA inhibitor compounds and their use
  申请人：INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION

  公开号：US11207296B2

  公开（公告）日：2021-12-28

  The present disclosure relates to certain compounds having binding affinity for XPA, and uses thereof. Specifically, the present disclosure relates to the use of XPA inhibitors as described herein in in methods of treating cancer.

  本公开涉及某些对 XPA 具有结合亲和力的化合物及其用途。 具体而言，本公开涉及本文所述的 XPA 抑制剂在治疗癌症方法中的用途。
• Discovery and Optimization of 1,3,4-Trisubstituted-pyrazolone Derivatives as Novel, Potent, and Nonsteroidal Farnesoid X Receptor (FXR) Selective Antagonists
  作者：Huang Huang、Ying Yu、Zhenting Gao、Yong Zhang、Chenjing Li、Xing Xu、Hui Jin、Wenzhong Yan、Ruoqun Ma、Jin Zhu、Xu Shen、Hualiang Jiang、Lili Chen、Jian Li

  DOI：10.1021/jm3002718

  日期：2012.8.23

  LBVS of 12480 in-house compounds, followed by HTRF assay, resulted in one nonsteroidal compound (11) with antagonistic activity against FXR (69.01 +/- 11.75 mu M). On the basis of 11, 26 new derivatives (12a-z) were designed and synthesized accordingly. Five derivatives (12f-g, 12p, 12u, and 12y) showed better antagonistic activities against FXR than compound 11. Remarkably, the most potent derivative, 12u (8.96 +/- 3.62 mu M), showed antagonistic capability approximately 10 times and 8-fold higher than that of the control (GS) and the starting compound 11, respectively. 12u was further confirmed to have high binding affinity with FXR alpha LBD, FXR specificity over six other nuclear receptors, and potent antagonistic activity against FXR in two cell testing platforms. 12u strongly suppressed the regulating effects of CDCA on FXR target genes. The therapeutic potential of 12u was identified by lowering the contents of triglyceride and cholesterol in human hepatoma HepG2 cells and in the cholesterol-fed C57BL/6 mices.
• Design and Structure-Guided Development of Novel Inhibitors of the Xeroderma Pigmentosum Group A (XPA) Protein–DNA Interaction
  作者：Navnath S. Gavande、Pamela VanderVere-Carozza、Akaash K. Mishra、Tyler L. Vernon、Katherine S. Pawelczak、John J. Turchi

  DOI：10.1021/acs.jmedchem.7b00780

  日期：2017.10.12

  XPA is a unique and essential protein required for the nucleotide excision DNA repair pathway and represents a therapeutic target in oncology. Herein, we are the first to develop novel inhibitors of the XPA-DNA interaction through structure-guided drug design efforts. Ester derivatives of the compounds 1 (X80), 22, and 24 displayed excellent inhibitory activity (IC50 of 0.82 +/- 0.18 mu M and 1.3 +/- 0.22 mu M, respectively) but poor solubility. We have synthesized novel amide derivatives that retain potency and have much improved solubility. Furthermore, compound 1 analogs exhibited good specificity for XPA over RPA (replication protein A), another DNA-binding protein that participates in the nucleotide excision repair (NER) pathway. Importantly, there were no significant interactions observed by the X80 class of compounds directly with DNA. Molecular docking studies revealed a mechanistic model for the interaction, and these studies could serve as the basis for continued analysis of structure-activity relationships and drug development efforts of this novel target.
• KU INHIBITORS AND THEIR USE
  申请人：Indiana University Research & Technology Corporation

  公开号：EP3463371B1

  公开（公告）日：2022-02-23