ethyl 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate | 107430-36-4

• 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 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate
• 英文别名: 4-(3-methyl-5-oxo-2,5-dihydro-pyrazol-1-yl)-benzoic acid ethyl ester；1-(4-Ethoxycarbonylphenyl)-3-methyl-2-pyrazolin-5-one；1-<4-Ethoxycarbonyl-phenyl>-3-methyl-pyrazolon-(5)>；ethyl 4-(3-methyl-5-oxo-4H-pyrazol-1-yl)benzoate
• CAS: 107430-36-4
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: MYRBZWVVQLOLBF-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 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate 在 aluminum (III) chloride 、 碘苯二乙酸 、 四丁基碘化铵 、 caesium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 diethyl 4,4’-(1,9-dimethyl[1,3]dioxepino[4,5-c:7,6-c’]dipyrazole-3,7-diyl)dibenzoate
  参考文献：
  名称：

  吡唑啉酮衍生物和二氯甲烷参与的 1,3-二氧杂环庚烷-稠合（三环）双吡唑的合成

  摘要：

  描述了一种简单而新颖的合成新型 1,3-二氧杂环庚烷（三环）双吡唑的方法。它涉及以二氯甲烷为亚甲基源的容易获得的吡唑啉酮衍生物的 Cs 2 CO 3介导的O烷基化，然后在温和条件下进行 PhI(OAc) 2介导的分子内氧化二杂芳基偶联。这种可扩展的方案用于制备有价值的新型 1,3-二氧杂环庚烷（三环）双吡唑，可在药物或材料化学中找到应用。

  DOI：

  10.1021/acs.joc.1c03121
• 作为产物：
  描述：

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

  Design and Structure-Guided Development of Novel Inhibitors of the Xeroderma Pigmentosum Group A (XPA) Protein–DNA Interaction

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.7b00780

文献信息

• Methods and Compositions for Modulating P300/CBP Activity
  申请人：Marmorstein Ronen

  公开号：US20100216853A1

  公开（公告）日：2010-08-26

  The present invention relates to a method for identifying compounds that modulate the activity of p300/CBP. Compounds of the invention are identified by designing or screening for a compound which binds to at least one amino acid residue of the newly identified lysine-CoA inhibitor binding site, L1 loop, electronegative pocket, or electronegative groove of the HAT domain of p300/CBP and testing the compound for its ability to modulate the activity of p300/CBP. Compositions and methods for preventing or treating diseases or disorders associated with p300/CBP are also provided as is a method for producing a semi-synthetic HAT domain.

  本发明涉及一种识别调节p300/CBP活性的化合物的方法。该发明的化合物是通过设计或筛选结合至新鉴定的赖氨酸-CoA抑制剂结合位点、L1环、电负性口袋或电负性槽的p300/CBP的HAT结构域的至少一个氨基酸残基的化合物来识别，并测试该化合物调节p300/CBP活性的能力。还提供了用于预防或治疗与p300/CBP相关的疾病或紊乱的组合物和方法，以及一种生产半合成HAT结构域的方法。
• Highly Stereoselective Assembly of Polycyclic Molecules from 1,6-Enynes Triggered by Rhodium(III)-Catalyzed C–H Activation
  作者：Heng Lu、Zhoulong Fan、Chaodong Xiong、Ao Zhang

  DOI：10.1021/acs.orglett.8b01099

  日期：2018.5.18

  An Rh(III)-catalyzed C–H activation of pyrazolones with 1,6-enynes was investigated. The regioselectivity of the C–H activation/alkyne insertion is readily solved by using symmetric enyne coupling partners, and a C–H activation-triggered cascade reaction is realized, which involves alkyne insertion, tautomerization, and double cyclization to offer a class of structurally complex polycyclic architectures

  研究了Rh（III）催化吡唑啉酮与1，6-烯炔的C–H活化。通过使用对称的烯炔偶合剂可轻松解决C–H激活/炔烃插入的区域选择性，并实现了C–H激活触发的级联反应，其中涉及炔烃插入，互变异构和双环化，从而提供了一类结构复杂的多环架构。这种级联反应可在高区域选择性和立体专一性上耐受广泛的底物范围，并在一次操作中提供三个新的化学键和四个手性中心。进行了多环支架的各种衍生化，为产物提供了足够的空间用于进一步的功能转化。
• Synthesis of pyrazolones and pyrazoles via Pd-catalyzed aerobic oxidative dehydrogenation
  作者：Ye-Fu Zhu、Bo-Le Wei、Jiao-Jiao Wei、Wen-Qiong Wang、Wei-Bin Song、Li-Jiang Xuan

  DOI：10.1016/j.tetlet.2019.03.063

  日期：2019.4

  A palladium-catalyzed oxidative dehydrogenation reaction in the presence of AMS and base to synthesize pyrazolones and pyrazoles was identified. This method can be utilized to a wide range of substrates, operates under mild react conditions and can give high yields. We believe it could be used as an alternative protocol for the classical dehydrogenation reactions.

  在AMS和碱存在下，钯催化的氧化脱氢反应得以合成吡唑啉酮和吡唑。该方法可用于多种底物，在温和的反应条件下运行，并能提供高收率。我们相信它可以用作经典脱氢反应的替代方案。
• [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。
• [EN] KU INHIBITORS AND THEIR USE<br/>[FR] INHIBITEURS DE KU ET LEUR UTILISATION
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2017205503A1

  公开（公告）日：2017-11-30

  The present disclosure relates to certain compounds having binding affinity for Ku, and uses thereof. Specifically, the present disclosure relates to the use of Ku inhibitors as described herein in site-specific genome engineering technologies, including but not limited to CRISPR/Cas9, Zinc finger nuclease (ZFN), Transcription activator-like effector nuclease (TALEN), and meganuclease. The present disclosure also relates to kits useful for site-specific genome engineering that include at least one compound as described herein.

  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。