methyl 1-allyl-6-oxo-1,6-dihydropyridine-3-carboxylate | 138042-14-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 1-allyl-6-oxo-1,6-dihydropyridine-3-carboxylate
• 英文别名: Methyl 1-allyl-6-oxo-1,6-dihydropyridine-3-carboxylate；methyl 6-oxo-1-prop-2-enylpyridine-3-carboxylate
• CAS: 138042-14-5
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: ATDAYUCVTVCDSC-UHFFFAOYSA-N

物化性质

• 沸点：
  334.2±42.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-allyl-6-oxo-1,6-dihydropyridine-3-carboxylate 在 2,6-二甲基吡啶 、 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三苯胂 、 叔丁基二甲硅基三氟甲磺酸酯 、 水 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 caesium carbonate 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (11S)-11-[(1R)-2-[[(4S)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-1-hydroxyethyl]-1,12-diazatricyclo[12.3.1.15,9]nonadeca-5(19),6,8,14(18),15-pentaene-13,17-dione
  参考文献：
  名称：

  Hydroxyethylamine-based inhibitors of BACE1: P1–P3 macrocyclization can improve potency, selectivity, and cell activity

  摘要：

  We describe a systematic study of how macrocyclization in the P-1-P-3 region of hydroxyethylamine-based inhibitors of beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE1) modulates in vitro activity. This study reveals that in a number of instances macrocyclization of bis-terminal dienes leads to improved potency toward BACE1 and selectivity against cathepsin D (CatD), as well as greater amyloid beta-peptide (A beta)-lowering activity in HEK293T cells stably expressing APP(SW). However, for several closely related analogs the benefits of macrocyclization are attenuated by the effects of other structural features in different regions of the molecules. X-ray crystal structures of three of these novel macrocyclic inhibitors bound to BACE1 revealed their binding conformations and interactions with the enzyme. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.028
• 作为产物：
  描述：

  1,1,1-三甲基-N-2-丙烯丙胺基硅烷 、 香豆灵酸甲酯 以 乙腈 为溶剂， 反应 72.0h， 以26%的产率得到methyl 1-allyl-6-oxo-1,6-dihydropyridine-3-carboxylate
  参考文献：
  名称：

  Synthese von 2(1H)-Pyridonen aus 2H-Pyran-2-onen

  摘要：

  从2H-吡喃-2-酮合成2(1H)-吡啶酮 5-取代和4,5-二取代的2(1H)-吡啶酮（13个例子）通过将相应的2H-吡喃-2-酮与六甲基二硅氨或烷基（ trimethylsilyl）胺进行胺化反应，在16%-97%的收率下制备了具有甲醛基、酰基、烷氧羧基和三氟甲基的5位取代基。

  DOI：

  10.1055/s-1991-26600

文献信息

• [EN] NOVEL ANTIFUNGAL OXODIHYDROPYRIDINECARBOHYDRAZIDE DERIVATIVE<br/>[FR] NOUVEAU DÉRIVÉ OXODIHYDROPYRIDINECARBOHYDRAZIDE ANTIFONGIQUE
  申请人：DAE WOONG PHARMA

  公开号：WO2015060613A1

  公开（公告）日：2015-04-30

  The present invention relates to novel oxodihydropyridinecarbohydrazide derivatives with excellent antifungal activities, an antifungal composition containing the same, and its use for the prevention and treatment of fungal infectious diseases. The oxodihydropyridinecarbohydrazide derivatives of the present invention have excellent antifungal and fungicidal activities, and thus will be useful for the prevention and treatment of various fungal infections by Candida spp., Aspergillus spp., Cryptococcus neoformans and Trichophyton spp., etc. Additionally, the oxodihydropyridinecarbohydrazide derivatives of the present invention, unlike other fungicidal preparations, can be orally administered.

  本发明涉及具有优异抗真菌活性的新型氧代二氢吡啶羧肼衍生物，含有该衍生物的抗真菌组合物，以及其用于预防和治疗真菌感染疾病。本发明的氧代二氢吡啶羧肼衍生物具有优异的抗真菌和杀真菌活性，因此将对预防和治疗由白色念珠菌属、曲霉菌属、隐球菌新型形态菌和癣菌属等引起的各种真菌感染有用。此外，与其他杀真菌制剂不同，本发明的氧代二氢吡啶羧肼衍生物可以口服给药。
• NOVEL ANTIFUNGAL OXODIHYDROPYRIDINECARBOHYDRAZIDE DERIVATIVE
  申请人：Daewoong Pharmaceutical Co., Ltd.

  公开号：EP3060549A1

  公开（公告）日：2016-08-31
• US9617216B2
  申请人：——

  公开号：US9617216B2

  公开（公告）日：2017-04-11
• Hydroxyethylamine-based inhibitors of BACE1: P1–P3 macrocyclization can improve potency, selectivity, and cell activity
  作者：Lewis D. Pennington、Douglas A. Whittington、Michael D. Bartberger、Steven R. Jordan、Holger Monenschein、Thomas T. Nguyen、Bryant H. Yang、Qiufen M. Xue、Filisaty Vounatsos、Robert C. Wahl、Kui Chen、Stephen Wood、Martin Citron、Vinod F. Patel、Stephen A. Hitchcock、Wenge Zhong

  DOI：10.1016/j.bmcl.2013.05.028

  日期：2013.8

  We describe a systematic study of how macrocyclization in the P-1-P-3 region of hydroxyethylamine-based inhibitors of beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE1) modulates in vitro activity. This study reveals that in a number of instances macrocyclization of bis-terminal dienes leads to improved potency toward BACE1 and selectivity against cathepsin D (CatD), as well as greater amyloid beta-peptide (A beta)-lowering activity in HEK293T cells stably expressing APP(SW). However, for several closely related analogs the benefits of macrocyclization are attenuated by the effects of other structural features in different regions of the molecules. X-ray crystal structures of three of these novel macrocyclic inhibitors bound to BACE1 revealed their binding conformations and interactions with the enzyme. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthese von 2(1<i>H</i>)-Pyridonen aus 2<i>H</i>-Pyran-2-onen
  作者：Vratislav Kvita

  DOI：10.1055/s-1991-26600

  日期：——

  Synthesis of 2(1H)-Pyridones From 2H-Pyran-2-ones 5-Substituted and 4,5-disubstituted 2(1H)-pyridones (13 examples) with formyl, acyl, alkoxycarbonyl, and trifluoromethyl groups in the 5 position were prepared in 16-97% yield by amination of the corresponding 2H-pyran-2-ones with hexamethyldisilazane or alkyl(trimethylsilyl)amines.

  从2H-吡喃-2-酮合成2(1H)-吡啶酮 5-取代和4,5-二取代的2(1H)-吡啶酮（13个例子）通过将相应的2H-吡喃-2-酮与六甲基二硅氨或烷基（ trimethylsilyl）胺进行胺化反应，在16%-97%的收率下制备了具有甲醛基、酰基、烷氧羧基和三氟甲基的5位取代基。