4-{4-[5-(4,5-Dimethyl-2-nitro-phenyl)-furan-2-ylmethyl]-3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl}-benzoic acid | 1093127-79-7

• 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: 4-{4-[5-(4,5-Dimethyl-2-nitro-phenyl)-furan-2-ylmethyl]-3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl}-benzoic acid
• 英文别名: 4-[4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methyl]-3-methyl-5-oxo-4H-pyrazol-1-yl]benzoic acid
• CAS: 1093127-79-7
• 化学式: C₂₄H₂₁N₃O₆
• 分子量: 447.447
• InChiKey: AQJGYMATQNFUDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  C646?4-[4-[[5-(4,5-二甲基-2-硝基苯基)-2-呋喃基]亚甲基]-4,5-二氢-3-甲基-5-氧代-1H-吡唑-1-基]-苯甲酸 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 4-{4-[5-(4,5-Dimethyl-2-nitro-phenyl)-furan-2-ylmethyl]-3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl}-benzoic acid
  参考文献：
  名称：

  通过破坏涉及自噬相关的蛋白质-蛋白质相互作用发现小分子自噬抑制剂 5

  摘要：

  调节自噬的一种可能策略是破坏在此过程中形成的关键蛋白质-蛋白质相互作用 (PPI)。我们关注的是自噬相关 12 (ATG12)–自噬相关 5 (ATG5)–自噬相关 16-like 1 (ATG16L1) 异源三聚体复合物，它负责 ATG8 从 ATG3 到磷脂酰乙醇胺的易位。在这项工作中，我们发现了一种具有 ( E )-3-(2-furanylmethylene)-2-pyrrolidinone 核心部分 ( T1742 ) 的化合物，该化合物在体外结合试验中阻断了 ATG5–ATG16L1 和 ATG5–TECAIR 相互作用 (IC 50 = 1–2 μM）并且在细胞测定中也表现出自噬抑制。T1742可能的绑定方式通过分子建模预测到ATG5，并合成并测试了一批具有基本相同核心部分的衍生物。这些新合成化合物的体外结合测定和流式细胞术测定的结果大体一致。这项工作验证了我们的中心假设，即涉及

  DOI：

  10.1021/acs.jmedchem.2c01233

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。
• USE OF HISTONE ACETYLTRANSFERASE INHIBITORS AS NOVEL ANTI-CANCER THERAPIES
  申请人：Alani Rhoda Myra

  公开号：US20130142887A1

  公开（公告）日：2013-06-06

  The present invention provides methods for treating cancer comprising inhibiting the activity of p300/CBP histone acetyltransferase (HAT). Also provided are p300/CBP HAT inhibitors for treating a subject having cancer. In addition, the present invention includes biomarkers for p300/CBP HAT inhibition, which are used to i) monitor the effectiveness of cancer therapy, and ii) identify anti-cancer agents for use in combination therapy.

  本发明提供了用于治疗癌症的方法，包括抑制p300/CBP组蛋白乙酰转移酶（HAT）的活性。同时，本发明还提供了用于治疗患有癌症的受试者的p300/CBP HAT抑制剂。此外，本发明包括用于p300/CBP HAT抑制的生物标志物，用于i）监测癌症治疗的有效性，和ii）识别用于联合治疗的抗癌剂。
• Virtual Ligand Screening of the p300/CBP Histone Acetyltransferase: Identification of a Selective Small Molecule Inhibitor
  作者：Erin M. Bowers、Gai Yan、Chandrani Mukherjee、Andrew Orry、Ling Wang、Marc A. Holbert、Nicholas T. Crump、Catherine A. Hazzalin、Glen Liszczak、Hua Yuan、Cecilia Larocca、S. Adrian Saldanha、Ruben Abagyan、Yan Sun、David J. Meyers、Ronen Marmorstein、Louis C. Mahadevan、Rhoda M. Alani、Philip A. Cole

  DOI：10.1016/j.chembiol.2010.03.006

  日期：2010.5

  The histone acetyltransferase (HAT) p300/CBP is a transcriptional coactivator implicated in many gene regulatory pathways and protein acetylation events. Although p300 inhibitors have been reported, a potent, selective, and readily available active-site-directed small molecule inhibitor is not yet known. Here we use a structure-based, in silico screening approach to identify a commercially available pyrazolone-containing small molecule p300 HAT inhibitor, C646. C646 is a competitive p300 inhibitor with a K-i of 400 nM and is selective versus other acetyltransferases. Studies on site-directed p300 HAT mutants and synthetic modifications of C646 confirm the importance of predicted interactions in conferring potency. Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target.
• US8476458B2
  申请人：——

  公开号：US8476458B2

  公开（公告）日：2013-07-02
• US9005670B2
  申请人：——

  公开号：US9005670B2

  公开（公告）日：2015-04-14