methyl (S)-2-(4-nitrophenyl)-4,5-dihydrooxazole-4-carboxylate | 308846-66-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (S)-2-(4-nitrophenyl)-4,5-dihydrooxazole-4-carboxylate
• 英文别名: methyl (4S)-2-(4-nitrophenyl)-4,5-dihydrooxazole-4-carboxylate；methyl (4S)-2-(4-nitrophenyl)-4,5-dihydro-1,3-oxazole-4-carboxylate
• CAS: 308846-66-4
• 化学式: C₁₁H₁₀N₂O₅
• 分子量: 250.211
• InChiKey: DPCQOTNRLYXKHU-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  93.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-(4-nitrophenyl)-4,5-dihydrooxazole-4-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以98%的产率得到(R)-[2-(4-nitrophenyl)-4,5-dihydrooxazol-4-yl]methanol
  参考文献：
  名称：

  Constrained Analogues of Procaine as Novel Small Molecule Inhibitors of DNA Methyltransferase-1

  摘要：

  Constrained analogues of procaine were synthesized, and their inhibiting activity against DNMT1 was tested. Among them, the most potent compound, derivative 3b, was also able to induce a recognizable demethylation of chromosomal satellite repeats in HL60 human myeloid leukemia cells and thus represents a lead compound for the development of a novel class of non-nucleoside DNMT1 inhibitors.

  DOI：

  10.1021/jm7015705
• 作为产物：
  描述：

  methyl (S)-2-(4-nitrobenzamido)-3-hydroxypropanoate 在 [双(2-甲氧基乙基)胺]三氟化硫 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 methyl (S)-2-(4-nitrophenyl)-4,5-dihydrooxazole-4-carboxylate
  参考文献：
  名称：

  恶唑啉和恶唑苄酯类新型抗结核药物的构效关系

  摘要：

  在天然铁螯合剂（分枝杆菌素）的合成和研究过程中，我们偶然发现一种简单的小分子含恶唑啉中间体3表现出令人惊讶的抗结核活性（平均MIC为7.7 μM）。在此，我们报告了围绕这一打击的 SAR 详细阐述，以及从有效的三步过程衍生的一百种含恶唑啉和恶唑化合物的合成和评估：1）与丝氨酸或苏氨酸形成 β-羟基酰胺； 2)环化得到恶唑啉； 3)脱水得到相应的恶唑。通过这种方法制备的许多化合物显示出具有令人印象深刻的抗结核分枝杆菌活性、极低的毒性和因此高的治疗指数，以及对更顽固的非复制形式的结核分枝杆菌的活性。它们结构的独特性和简单性应该使它们能够进一步优化以满足 ADME（吸收、分布、代谢、排泄）要求。八种最有效的体外化合物的合成得到了扩大，并在小鼠体内感染模型中测试了这些化合物，以评估其功效，然后再进行更精细的化合物设计和优化。

  DOI：

  10.1016/j.ejmech.2009.12.074

文献信息

• [EN] SYNTHESIS OF OXAZOLINE COMPOUNDS<br/>[FR] SYNTHÈSE DE COMPOSÉS D'OXAZOLINE
  申请人：UNIV HONG KONG POLYTECHNIC

  公开号：WO2010015211A1

  公开（公告）日：2010-02-11

  The present invention provides an improved process for preparing an oxazoline compound of the formula: (I) wherein R1 and R2 are independently hydrogen, sulfide, sulfoxide, sulfonyl, optionally substituted lower alkyl, optionally substituted aralkyl, optionally substituted aryl or optionally substituted polycyclic arylyl; or R1 and R2 combined together with the carbon atoms to which they are attached form an optionally substituted fused 6-member aromatic ring provided that R1 and R2 are attached to carbon atoms adjacent to each other; and R3 is hydrogen, sulfide, sulfoxide, sulfonyl, optionally substituted lower alkyl, optionally substituted aralkyl, optionally substituted aryl or optionally substituted polycyclic arylyl; or an enantiomer therof; or an enantiomeric mixture therof; comprising the step of contacting an acylamino alcohol compound to a suitable amount of fluoroalkanesulfonyl fluoride compound and organic basic reagent. By using a fluoroalkanesulfonyl fluoride compound with an organic basic reagent, the present invention efficiently converts acylamino alcohol compounds into highly chemoselective oxazoline compounds with a remarkable variety of substrates, mild conditions and relatively short reaction time.

  本发明提供了一种改进的制备氧杂环丙烯酮化合物的方法，其化学式为：(I)，其中R1和R2分别为氢、硫化物、亚氧化物、磺酰基、可选择取代的较低烷基、可选择取代的芳基烷基、可选择取代的芳基或可选择取代的多环芳基；或者R1和R2与它们附着的碳原子结合在一起形成可选择取代的融合6-环芳香环，前提是R1和R2附着在彼此相邻的碳原子上；而R3为氢、硫化物、亚氧化物、磺酰基、可选择取代的较低烷基、可选择取代的芳基烷基、可选择取代的芳基或可选择取代的多环芳基；或其对映体；或其对映体混合物；包括将酰胺醇化合物与适量的氟代烷磺酰氟化合物和有机碱性试剂接触的步骤。通过使用氟代烷磺酰氟化合物和有机碱性试剂，本发明能够高效地将酰胺醇化合物转化为高度化学选择性的氧杂环丙烯酮化合物，适用于多种底物，反应条件温和，反应时间相对较短。
• <i>N</i>-Phenyl-4,5-dibromopyrrolamides and <i>N</i>-Phenylindolamides as ATP Competitive DNA Gyrase B Inhibitors: Design, Synthesis, and Evaluation
  作者：Nace Zidar、Helena Macut、Tihomir Tomašič、Matjaž Brvar、Sofia Montalvão、Päivi Tammela、Tom Solmajer、Lucija Peterlin Mašič、Janez Ilaš、Danijel Kikelj

  DOI：10.1021/acs.jmedchem.5b00775

  日期：2015.8.13

  Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors of its ATP binding subunit, DNA gyrase B (GyrB), have so far not reached clinical use. In the present study, three different series of N-phenyl-4,5-dibromop-yrrolamides and N-phenylindolamides were designed and prepared as potential DNA gyrase B inhibitors. The IC50 values of compounds on DNA gyrase from Escherichia coli were in the low micromolar range, with the best compound, (4-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzoyl)glycine (18a), displaying an IC50 of 450 nM. For this compound, a high-resolution crystal structure in complex with E. coli DNA gyrase B was obtained, revealing details of its binding mode within the active site. The binding affinities. of three compounds with GyrB were additionally evaluated by surface plasmon resonance, and the results were in good agreement with the determined enzymatic activities. For the most promising compounds, the inhibitory activities against DNA gyrase from Staphylococcus aureus and topoisomerases IV from E. coli and S. aureus were determined. Antibacterial activities of the most potent compounds of each series were evaluated against two Gram-positive and two Gram-negative bacterial strains. The results obtained in this study provide valuable information on the binding mode and structure activity relationship of N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides as promising classes of ATP competitive GyrB inhibitors. IC50 =450 nM
• Structure–activity relationship of new anti-tuberculosis agents derived from oxazoline and oxazole benzyl esters
  作者：Garrett C. Moraski、Mayland Chang、Adriel Villegas-Estrada、Scott G. Franzblau、Ute Möllmann、Marvin J. Miller

  DOI：10.1016/j.ejmech.2009.12.074

  日期：2010.5

  During the syntheses and studies of natural iron chelators (mycobactins), we serendipitously discovered that a simple, small molecule, oxazoline-containing intermediate 3 displayed surprising anti-tuberculosis activity (MIC of 7.7 μM, average). Herein we report elaboration of SAR around this hit as well as the syntheses and evaluation of a hundred oxazoline- and oxazole-containing compounds derived from

  在天然铁螯合剂（分枝杆菌素）的合成和研究过程中，我们偶然发现一种简单的小分子含恶唑啉中间体3表现出令人惊讶的抗结核活性（平均MIC为7.7 μM）。在此，我们报告了围绕这一打击的 SAR 详细阐述，以及从有效的三步过程衍生的一百种含恶唑啉和恶唑化合物的合成和评估：1）与丝氨酸或苏氨酸形成 β-羟基酰胺； 2)环化得到恶唑啉； 3)脱水得到相应的恶唑。通过这种方法制备的许多化合物显示出具有令人印象深刻的抗结核分枝杆菌活性、极低的毒性和因此高的治疗指数，以及对更顽固的非复制形式的结核分枝杆菌的活性。它们结构的独特性和简单性应该使它们能够进一步优化以满足 ADME（吸收、分布、代谢、排泄）要求。八种最有效的体外化合物的合成得到了扩大，并在小鼠体内感染模型中测试了这些化合物，以评估其功效，然后再进行更精细的化合物设计和优化。
• Constrained Analogues of Procaine as Novel Small Molecule Inhibitors of DNA Methyltransferase-1
  作者：Sabrina Castellano、Dirk Kuck、Marina Sala、Ettore Novellino、Frank Lyko、Gianluca Sbardella

  DOI：10.1021/jm7015705

  日期：2008.4.1

  Constrained analogues of procaine were synthesized, and their inhibiting activity against DNMT1 was tested. Among them, the most potent compound, derivative 3b, was also able to induce a recognizable demethylation of chromosomal satellite repeats in HL60 human myeloid leukemia cells and thus represents a lead compound for the development of a novel class of non-nucleoside DNMT1 inhibitors.