叔丁基(4AS,7AS)-六氢吡咯并[3,4-B][1,4]噁嗪-4(4AH)-羧酸盐 | 1159908-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 叔丁基(4AS,7AS)-六氢吡咯并[3,4-B][1,4]噁嗪-4(4AH)-羧酸盐
• 英文名称: rac-(4aS,7aS)-3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazine-4-carboxylic acid tert-butyl ester
• 英文别名: (4aS,7aS)-3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxaazine-4-carboxylic acid tert-butyl ester；tert-butyl rac-(4aS,7aS)-3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazine-4-carboxylate；(4AS,7AS)-Tert-butyl hexahydropyrrolo[3,4-B][1,4]oxazine-4(4AH)-carboxylate；tert-butyl (4aS,7aS)-3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazine-4-carboxylate
• CAS: 1159908-23-2
• 化学式: C₁₁H₂₀N₂O₃
• 分子量: 228.291
• InChiKey: YLMNCYATSGIUDS-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙基7-氯-8-氰基-1-环丙基-6-氟-4-氧杂-1,4-二氢喹啉-3-羧酸酯 、 叔丁基(4AS,7AS)-六氢吡咯并[3,4-B][1,4]噁嗪-4(4AH)-羧酸盐 在 N,N-二异丙基乙胺 作用下， 以 邻苯二甲酸二甲酯 为溶剂， 反应 6.0h， 以76%的产率得到tert-butyl (4aS,7aS)-6-(8-cyano-1-cyclopropyl-3-ethoxycarbonyl-6-fluoro-4-oxoquinolin-7-yl)-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazine-4-carboxylate
  参考文献：
  名称：

  A novel approach to Finafloxacin hydrochloride (BAY35-3377)

  摘要：

  Finafloxacin hydrochloride, an important clinical compound was synthesized by a novel synthetic approach. An active intermediate ethyl 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate 19 was prepared by a new route. The chiral (S,S')-N-Boc 10 was derived from protected pyrrolidine and the absolute stereochemistry was established by X-ray analysis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.03.051
• 作为产物：
  描述：

  (4aS,7aS)-tert-butyl 6-tosylhexahydropyrrolo[3,4-b][1,4]oxazine-4(4aH)-carboxylate 在 萘 、 sodium 作用下， 以 乙二醇二甲醚 为溶剂， 以55%的产率得到叔丁基(4AS,7AS)-六氢吡咯并[3,4-B][1,4]噁嗪-4(4AH)-羧酸盐
  参考文献：
  名称：

  A novel approach to Finafloxacin hydrochloride (BAY35-3377)

  摘要：

  Finafloxacin hydrochloride, an important clinical compound was synthesized by a novel synthetic approach. An active intermediate ethyl 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate 19 was prepared by a new route. The chiral (S,S')-N-Boc 10 was derived from protected pyrrolidine and the absolute stereochemistry was established by X-ray analysis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.03.051

文献信息

• Synthesis and Structure–Activity Relationship of Thioacetamide-Triazoles against Escherichia coli
  作者：Suresh Dharuman、Miranda J. Wallace、Stephanie M. Reeve、Jürgen B. Bulitta、Richard E. Lee

  DOI：10.3390/molecules27051518

  日期：——

  were more nuanced; the introduction of a methyl branch to the thioacetamide linker substantially decreased antibacterial activity, but the isomeric propionamide and N-benzamide systems retained activity. Changes to the triazole portion of the molecule dramatically decreased the antibacterial activity, further indicating that 1,2,3-triazole is critical for potency. From these studies, we have identified

  由于多重耐药菌株的传播，革兰氏阴性菌引起的感染越来越危险，强调迫切需要具有替代作用模式的新抗生素。我们之前使用抗叶酸靶向筛选确定了一类新型抗菌剂硫代乙酰胺-三唑，并确定了它们的作用方式，这取决于半胱氨酸合酶 A 的激活。在此，我们报告了对抗 E 的详细检查。硫代乙酰胺-三唑的大肠杆菌构效关系。合成了初始命中化合物的类似物，以研究芳基、硫代乙酰胺和三唑部分的贡献。观察到明确的结构-活性关系产生具有优异抑制值的化合物。对芳环的取代通常是最好的耐受性，包括引入噻唑和吡啶杂芳基系统。对中央硫代乙酰胺接头部分的替换更为细微；将甲基支链引入硫代乙酰胺接头显着降低了抗菌活性，但异构丙酰胺和 N-苯甲酰胺系统保留了活性。分子中三唑部分的变化显着降低了抗菌活性，进一步表明 1,2,3-三唑对效力至关重要。从这些研究中，我们确定了具有理想的体外 ADME 特性和体内药代动力学特性的新先导化合物。将甲基支链引入
• Discovery and SAR of 6-Alkyl-2,4-diaminopyrimidines as Histamine H₄ Receptor Antagonists
  作者：Brad M. Savall、Frank Chavez、Kevin Tays、Paul J. Dunford、Jeffery M. Cowden、Michael D. Hack、Ronald L. Wolin、Robin L. Thurmond、James P. Edwards

  DOI：10.1021/jm401727m

  日期：2014.3.27

  This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.