benzyl 2-phenyloxazole-4-carboxylate | 855405-22-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: benzyl 2-phenyloxazole-4-carboxylate
• 英文别名: 2-phenyl-oxazole-4-carboxylic acid benzyl ester；2-Phenyl-oxazol-4-carbonsaeure-benzylester；benzyl 2-phenyl-1,3-oxazole-4-carboxylate
• CAS: 855405-22-0
• 化学式: C₁₇H₁₃NO₃
• 分子量: 279.295
• InChiKey: IYUMOOMTWILBIL-UHFFFAOYSA-N

物化性质

• 熔点：
  106-107 °C
• 沸点：
  439.8±37.0 °C(Predicted)
• 密度：
  1.217±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 2-phenyloxazole-4-carboxylate 在 1% Pd/C 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 以96%的产率得到2-苯基-4-噁唑羧酸
  参考文献：
  名称：

  N-((1-Benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide as a New Scaffold that Provides Rapid Access to Antimicrotubule Agents: Synthesis and Evaluation of Antiproliferative Activity Against Select Cancer Cell Lines

  摘要：

  A series of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamides was synthesized by copper-catalyzed azide alkyne cycloaddition (CuAAC) and afforded inhibitors of cancer cell growth. For example, compound 13e had an IC50 of 46 nM against MCF-7 human breast tumor cells. Structure activity relationship (SA R) studies demonstrated that (i) meta-phenoxy substitution of the N-1-benzyl group is important for antiproliferative activity and (ii) a variety of heterocyclic substitutions for the aryl group of the arylamide are tolerated. In silico COMPARE analysis of antiproliferative activity against the NCI-60 human tumor cell line panel revealed a correlation to clinically useful antimicrotubule agents such as paclitaxel and vincristine. This in silico correlation was supported by (i) in vitro inhibition of tubulin polymerization, (ii) G(2)/M-phase arrest in HeLa cells as assessed by flow cytometry, and (iii) perturbation of normal microtubule activity in HeLa cells as observed by confocal microscopy. The results demonstrate that N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)arylamide is a readily accessible small molecule scaffold for compounds that inhibit tubulin polymerization and tumor cell growth.

  DOI：

  10.1021/jm1000979
• 作为产物：
  描述：

  L-丝氨酸苄酯盐酸盐 在 三氯溴甲烷 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 为溶剂， 生成 benzyl 2-phenyloxazole-4-carboxylate
  参考文献：
  名称：

  Generation and exploration of new classes of antitubercular agents: The optimization of oxazolines, oxazoles, thiazolines, thiazoles to imidazo[1,2-a]pyridines and isomeric 5,6-fused scaffolds

  摘要：

  Tuberculosis (TB) is a devastating disease resulting in a death every 20 s. Thus, new drugs are urgently needed. Herein we report ten classes of compounds-oxazoline, oxazole, thiazoline, thiazole, pyrazole, pyridine, isoxazole,imidazo[1,2-a] pyridine, imidazo[1,2-a] pyrimidine and imidazo[1,2-c] pyrimidine-which have good (micromolar) to excellent (sub-micromolar) antitubercular potency. The 5,6-fused heteroaromatic compounds were the most potent with MIC's as low as < 0.195 mu M (9 and 11). Overall, the imidazo[1,2-a] pyridine class was determined to be most promising, with potency similar to isoniazid and PA-824 against replicating Mtb H(37)Rv, clinically relevant drug sensitive, multi-and extensively resistant Mtb strains as well as having good in vitro metabolic stability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.025

文献信息

• 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。
• Cornforth, Chemistry of Penicillin
  作者：Cornforth

  DOI：——

  日期：——
• Cornforth et al., Journal of the Chemical Society, 1949, p. 1549,1551
  作者：Cornforth et al.

  DOI：——

  日期：——