2-(2-hydroxyphenyl)-5-methyloxazole-4-carboxylic acid | 53669-44-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2-hydroxyphenyl)-5-methyloxazole-4-carboxylic acid
• 英文别名: Asteroidic acid；2-(2-Hydroxyphenyl)-5-methyl-oxazole-4-carboxylic acid；2-(2-hydroxyphenyl)-5-methyl-1,3-oxazole-4-carboxylic acid
• CAS: 53669-44-6
• 化学式: C₁₁H₉NO₄
• 分子量: 219.197
• InChiKey: FBCDPRRYLBFICD-UHFFFAOYSA-N

物化性质

• 熔点：
  243-244 °C
• 沸点：
  449.7±55.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-hydroxyphenyl)-5-methyloxazole-4-carboxylic acid 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 (S)-methyl 6-(N-(hydroxy)acetamido)-2-(2-(2-hydroxyphenyl)-5-methyloxazole-4-carboxamido)hexanoate
  参考文献：
  名称：

  Syntheses of Amamistatin Fragments and Determination of Their HDAC and Antitumor Activity

  摘要：

  Amamistatins A and B are natural products found to have anti-proliferative effects against MCF-7, A549, and MKN45 human tumor cell lines (IC(50) 0.24-0.56 mu M). It was proposed that their activity was due to histone deacetylase (HDAC) inhibition mediated by the N-formyl-N-hydroxy lysine moiety. Amamistatin B fragment analogs were synthesized and screened for biological activity. These compounds were modest HDAC inhibitors and showed antitumor activity against MCF-7 and PC-3 human tumor cells.

  DOI：

  10.1021/ol070382e
• 作为产物：
  描述：

  2-苄氧基苯甲酸 在 palladium on activated charcoal 氢气 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， -20.0~20.0 ℃ 、101.33 kPa 条件下， 反应 7.0h， 生成 2-(2-hydroxyphenyl)-5-methyloxazole-4-carboxylic acid
  参考文献：
  名称：

  Syntheses of Amamistatin Fragments and Determination of Their HDAC and Antitumor Activity

  摘要：

  Amamistatins A and B are natural products found to have anti-proliferative effects against MCF-7, A549, and MKN45 human tumor cell lines (IC(50) 0.24-0.56 mu M). It was proposed that their activity was due to histone deacetylase (HDAC) inhibition mediated by the N-formyl-N-hydroxy lysine moiety. Amamistatin B fragment analogs were synthesized and screened for biological activity. These compounds were modest HDAC inhibitors and showed antitumor activity against MCF-7 and PC-3 human tumor cells.

  DOI：

  10.1021/ol070382e

文献信息

• Syntheses and Biological Activity of Amamistatin B and Analogs
  作者：Kelley A. Fennell、Ute Möllmann、Marvin J. Miller

  DOI：10.1021/jo7020532

  日期：2008.2.1

  Structurally related mycobactins affect the growth of both mycobacterial and human cells through interference with iron chelation. To further probe the biological activity of this class of compounds, the total syntheses of amamistatin B and two analogs were completed, and the synthetic samples were screened for tumor cell growth inhibition, HDAC inhibition, and Mycobacterium tuberculosis growth inhibition

  从诺卡氏菌菌株中分离得到的天然产物Amamistatins A和B对三种人类肿瘤细胞系表现出生长抑制作用（IC 50 0.24-0.56μM）。与结构相关的分支杆菌素通过干扰铁螯合影响分支杆菌和人细胞的生长。为了进一步探查这类化合物的生物活性，完成了阿米他汀B和两种类似物的总合成，并对合成样品进行了肿瘤细胞生长抑制，HDAC抑制和结核分枝杆菌生长抑制的筛选。Amamistatin B（15）和非对映异构体18均对MCF-7细胞具有活性（IC 500.12-0.20μM），对PC-3电池则更低（IC 50 8-13μM ）。Amamistatin B仅适度抑制结核分枝杆菌的生长（MIC 47μM ），但表现出耻垢分枝杆菌和其他细菌的生长促进作用。
• 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。
• Syntheses and studies of amamistatin B analogs reveals that anticancer activity is relatively independent of stereochemistry, ester or amide linkage and select replacement of one of the metal chelating groups
  作者：Chunrui Wu、Patricia A. Miller、Marvin J. Miller

  DOI：10.1016/j.bmcl.2011.01.084

  日期：2011.5

  A series of analogs of the amamistatin natural products was designed and synthesized to facilitate additional anticancer structure-activity relationships. The results indicate that the anticancer activity is relatively independent of stereochemistry, ester or amide linkage and replacement of the oxazoline/oxazole based iron-binding group with a catechol. (C) 2011 Elsevier Ltd. All rights reserved.
• Syntheses of Amamistatin Fragments and Determination of Their HDAC and Antitumor Activity
  作者：Kelley A. Fennell、Marvin J. Miller

  DOI：10.1021/ol070382e

  日期：2007.4.1

  Amamistatins A and B are natural products found to have anti-proliferative effects against MCF-7, A549, and MKN45 human tumor cell lines (IC(50) 0.24-0.56 mu M). It was proposed that their activity was due to histone deacetylase (HDAC) inhibition mediated by the N-formyl-N-hydroxy lysine moiety. Amamistatin B fragment analogs were synthesized and screened for biological activity. These compounds were modest HDAC inhibitors and showed antitumor activity against MCF-7 and PC-3 human tumor cells.