(Z)-5-(5-((1-(3-carboxyphenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)methyl)furan-2-yl)-2-chlorobenzoic acid | 292065-64-6

• 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: (Z)-5-(5-((1-(3-carboxyphenyl)-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)methyl)furan-2-yl)-2-chlorobenzoic acid
• 英文别名: 5-[5-[(Z)-[1-(3-carboxyphenyl)-3-methyl-5-oxopyrazol-4-ylidene]methyl]furan-2-yl]-2-chlorobenzoic acid
• CAS: 292065-64-6
• 化学式: C₂₃H₁₅ClN₂O₆
• 分子量: 450.835
• InChiKey: XZRBYOCWWJMJRZ-BOPFTXTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-肼基苯甲酸 在 甲醇 、 硫酸 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 33.0h， 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

文献信息

• [EN] XPA INHIBITOR COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS INHIBITEURS DE XPA ET LEUR UTILISATION
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2019060260A1

  公开（公告）日：2019-03-28

  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。
• 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。
• 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
• XPA INHIBITOR COMPOUNDS AND THEIR USE
  申请人：Indiana University Research and Technology Corporation

  公开号：EP3684354A1

  公开（公告）日：2020-07-29