2,2-Dimethyl-5-(4-phenylbutanoyl)-1,3-dioxane-4,6-dione

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,2-Dimethyl-5-(4-phenylbutanoyl)-1,3-dioxane-4,6-dione
• 英文别名: 2,2-dimethyl-5-(4-phenylbutanoyl)-1,3-dioxane-4,6-dione
• 化学式: C₁₆H₁₈O₅
• 分子量: 290.316
• InChiKey: WMOVYRIMXPYNJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2-Dimethyl-5-(4-phenylbutanoyl)-1,3-dioxane-4,6-dione 以 乙醇 为溶剂， 反应 4.0h， 生成 ethyl 3-oxo-6-phenylhexanoate
  参考文献：
  名称：

  新型AKR1C3抑制剂6-氨基-4-苯基-1,4-二氢吡喃并[2,3 - c ]吡唑-5-甲腈的筛选，合成，晶体结构和分子基础

  摘要：

  AKR1C3是去势抵抗性前列腺癌的有希望的治疗靶标。在本文中，对内部文库的评估发现取代的吡喃并吡唑是AKR1C3抑制剂的新型支架。初步的SAR探索确定其衍生化合物19d是最有前途的化合物，其IC 50为50在23个合成分子中的0.160μM。晶体结构研究表明，吡喃并吡唑支架的结合方式与目前的抑制剂不同。C4-苯基取代基上的羟基，甲氧基和硝基一起将抑制剂锚定在氧阴离子位点上，而支架的核心则显着增大，但部分占据了具有丰富氢键相互作用的SP口袋。令人惊讶的是，该抑制剂经历了构象变化，以适应AKR1C3及其同源蛋白AKR1C1。我们的结果表明，在合理设计选择性AKR1C3抑制剂时，应同时考虑受体和抑制剂的构象变化。从分子动力学模拟获得的详细结合特征有助于最终阐明6-氨基-4-苯基-1的分子基础，c ]吡唑-5-腈作为AKR1C3抑制剂，这将有助于将来合理的抑制剂设计和结构优化。

  DOI：

  10.1016/j.bmc.2018.10.044
• 作为产物：
  描述：

  丙二酸环(亚)异丙酯 、 4-苯基丁酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 2,2-Dimethyl-5-(4-phenylbutanoyl)-1,3-dioxane-4,6-dione
  参考文献：
  名称：

  Indole-based novel small molecules for the modulation of bacterial signalling pathways

  摘要：

  基于吲哚的N-酰化l-同型丝氨酸内酯（AHL）类似物被开发为革兰氏阴性细菌烟草霉菌的群体感应（QS）抑制剂，并可用作新型抗微生物药剂。

  DOI：

  10.1039/c4ob02096k

文献信息

• Synthesis of antimicrobial glucosamides as bacterial quorum sensing mechanism inhibitors
  作者：Nripendra N. Biswas、Tsz Tin Yu、Önder Kimyon、Shashidhar Nizalapur、Christopher R. Gardner、Mike Manefield、Renate Griffith、David StC. Black、Naresh Kumar

  DOI：10.1016/j.bmc.2016.12.024

  日期：2017.2

  Bacteria communicate with one another and regulate their pathogenicity through a phenomenon known as quorum sensing (QS). When the bacterial colony reaches a threshold density, the QS system induces the production of virulence factors and the formation of biofilms, a powerful defence system against the host's immune responses. The glucosamine monomer has been shown to disrupt the bacterial QS system by inhibiting autoinducer (AI) signalling molecules such as the acyl-homoserine lactones (AHLs). In this study, the synthesis of acetoxy-glucosamides 8, hydroxy-glucosamides 9 and 3-oxo-glucosamides 12 was performed via the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC center dot HCl) and N, N'-dicyclohexylcarbodiimide (DCC) coupling methods. All of the synthesized compounds were tested against two bacterial strains, P. aeruginosa MH602 (LasI/R-type QS) and E. coli MT102 (LuxI/R-type QS), for QS inhibitory activity. The most active compound 9b showed 79.1% QS inhibition against P. aeruginosa MH602 and 98.4% against E. coli MT102, while compound 12b showed 64.5% inhibition against P. aeruginosa MH602 and 88.1% against E. coli MT102 strain at 2 mM concentration. The ability of the compounds to inhibit the production of the virulence factor pyocyanin and biofilm formation in the P. aeruginosa (PA14) strain was also examined. Finally, computational docking studies were performed with the LasR receptor protein. (C) 2016 Elsevier Ltd. All rights reserved.