(R)-2-(2-fluorophenyl)-4,5-dihydrothiazole-4-carboxylic acid | 1196463-54-3

• 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: (R)-2-(2-fluorophenyl)-4,5-dihydrothiazole-4-carboxylic acid
• 英文别名: (R)-2-(2'-fluorophenyl)-4-carboxy-4,5-dihydrothiazole；(4R)-2-(2-fluorophenyl)-4,5-dihydro-1,3-thiazole-4-carboxylic acid
• CAS: 1196463-54-3
• 化学式: C₁₀H₈FNO₂S
• 分子量: 225.243
• InChiKey: FJLKIBVBYJLHHG-QMMMGPOBSA-N

物化性质

• 沸点：
  416.6±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-(2-fluorophenyl)-4,5-dihydrothiazole-4-carboxylic acid 、 鬼臼毒素 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以75%的产率得到
  参考文献：
  名称：

  Semi-synthesis and anti-lung cancer activity evaluation of aryl dihydrothiazol acyl podophyllotoxin ester derivatives

  摘要：

  S12，17种鬼臼毒素衍生物中最佳的抗癌药物，通过抑制微管聚合表现出增殖抑制作用。

  DOI：

  10.1039/c5ra01871d
• 作为产物：
  描述：

  (R)-2-(2'-fluorophenyl)-4-methoxycarbonyl-4,5-dihydrothiazole 在 sodium hydroxide 作用下， 反应 2.0h， 生成 (R)-2-(2-fluorophenyl)-4,5-dihydrothiazole-4-carboxylic acid
  参考文献：
  名称：

  Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

  摘要：

  通过一种新型的无金属和催化剂方法，设计并合成了 60 个 2-芳基-4,5-二氢噻唑类化合物，其中半胱氨酸和取代苯腈类化合物的产率为 64% 至 89%。标题化合物的结构主要通过核磁共振光谱数据分析得到了证实。抗菌活性测定结果表明，(S)-2-(2′-羟基苯基)-4-羟甲基-4,5-二氢噻唑（7h）和(R)-2-(2′-羟基苯基)-4-羟甲基-4,5-二氢噻唑（7h′）化合物对茄属拉氏菌（Ralstonia solanacearum）、丁香假单胞菌（Pseudomonas syringae pv.最低抑菌浓度为 3.91 μg-mL-1 至 31.24 μg-mL-1。取代基的影响表明，不仅取电子基团会削弱抗菌活性，而且供电子基团也会削弱抗菌活性，除非在 4,5-二氢噻唑类似物的 2-芳基取代基上引入 2′-羟基。扫描电子显微镜（SEM）和脂肪酸暴露实验的结果表明，这些抗菌化合物会影响受试细菌的脂肪酸合成。

  DOI：

  10.3390/molecules201119680

文献信息

• Discovery of 4-Substituted Methoxybenzoyl-aryl-thiazole as Novel Anticancer Agents: Synthesis, Biological Evaluation, and Structure−Activity Relationships
  作者：Yan Lu、Chien-Ming Li、Zhao Wang、Charles R. Ross、Jianjun Chen、James T. Dalton、Wei Li、Duane D. Miller

  DOI：10.1021/jm801449a

  日期：2009.3.26

  ylic acid amides (ATCAA). The antiproliferative activity of the SMART agents against melanoma and prostate cancer cells was improved from μM to low nM range compared with the ATCAA series. The structure−activity relationship was discussed from modifications of “A”, “B”, and “C” rings and the linker. Preliminary mechanism of action studies indicated that these compounds exert their anticancer activity

  由于先导化合物2-芳基噻唑烷-4-羧酸酰胺（ATCAA）的结构修饰，已经发现并合成了一系列4-取代的甲氧基苯甲酰基-芳基-噻唑（SMART）。与 ATCAA 系列相比，SMART 药物对黑色素瘤和前列腺癌细胞的抗增殖活性从 μM 提高到低 nM 范围。从“A”、“B”和“C”环和接头的修饰讨论了构效关系。初步的作用机制研究表明，这些化合物通过抑制微管蛋白聚合发挥其抗癌活性。
• Design, Synthesis, Antifungal Activities and SARs of (<i>R</i>)-2-Aryl-4,5-dihydrothiazole-4-carboxylic Acid Derivatives
  作者：Jingbo Liu、Yuxin Li、Youwei Chen、Xuewen Hua、Yingying Wan、Wei Wei、Haibin Song、Shujing Yu、Xiao Zhang、Zhengming Li

  DOI：10.1002/cjoc.201500619

  日期：2015.11

  natural product 2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid, a series of novel (R)‐2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid derivatives were designed and synthesized. Their structures were characterized by 1H NMR, 13C NMR and HRMS. The single crystal structure of compound 9b was determined by X‐ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results

  根据天然产物2-芳基-4-5,5-二氢噻唑-4-羧酸的结构，设计和合成了一系列新颖的（R）-2-芳基-4,5-二氢噻唑-4-羧酸衍生物。它们的结构通过1 H NMR，13 C NMR和HRMS表征。化合物9b的单晶结构通过X射线衍射分析确定。首次评估了抗真菌活性。生物测定结果表明，大多数化合物表现出中等至良好的抗真菌活性。化合物13a（对Cercospora arachidicola Hori），13d（对链格孢菌（Alternaria solani））的抗真菌活性和16e（与花生油茶（Cercospora arachidicola Hori）相比）分别为61.9％，67.3％和61.9％，高于商品杀真菌剂百菌清和多菌灵中的16e。此外，化合物13d对测试的7种真菌表现出优异的抗真菌活性（在50 µg？mL下，分别为66.7％，77.3％，63.0％，87.9％，70.0％，70.0％和80
• Synthesis of aryl dihydrothiazol acyl shikonin ester derivatives as anticancer agents through microtubule stabilization
  作者：Hong-Yan Lin、Zi-Kang Li、Li-Fei Bai、Shahla Karim Baloch、Fang Wang、Han-Yue Qiu、Xue Wang、Jin-Liang Qi、Raong-Wu Yang、Xiao-Ming Wang、Yong-Hua Yang

  DOI：10.1016/j.bcp.2015.04.021

  日期：2015.7

  The high incidence of cancer and the side effects of traditional anticancer drugs motivate the search for new and more effective anticancer drugs. In this study, we synthesized 17 kinds of aryl dihydrothiazol acyl shikonin ester derivatives and evaluated their anticancer activity through MTT assay. Among them, C13 showed better antiproliferation activity with IC50 = 3.14 +/- 0.21 mu M against HeLa cells than shikonin (IC50 = 5.75 +/- 0.47 mu M). We then performed PI staining assay, cell cycle distribution, and cell apoptosis analysis for C13 and found that it can cause cell arrest in G2/M phase, which leads to cell apoptosis. This derivative can also reduce the adhesive ability of HeLa cells. Docking simulation and confocal microscopy assay results further indicated that C13 could bind well to the tubulin at paclitaxel binding site, leading to tubulin polymerization and mitotic disruption. (C) 2015 Elsevier Inc. All rights reserved.
• Semi-synthesis and anti-lung cancer activity evaluation of aryl dihydrothiazol acyl podophyllotoxin ester derivatives
  作者：Hong-Yan Lin、Li-Fei Bai、Fang Wang、Xun Wu、Lu-Jing Han、Shahla Karim Baloch、Yong-Hua Yang、Xiao-Ming Wang

  DOI：10.1039/c5ra01871d

  日期：——

  S12, the best anticancer agent among the 17 podophyllotoxin derivatives, showed a proliferative inhibition effect via inhibiting tubulin polymerization.

  S12，17种鬼臼毒素衍生物中最佳的抗癌药物，通过抑制微管聚合表现出增殖抑制作用。
• Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action
  作者：Fangfang Tan、Baojun Shi、Jian Li、Wenjun Wu、Jiwen Zhang

  DOI：10.3390/molecules201119680

  日期：——

  Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2′-hydroxyphenyl)-4-hydroxy-methyl- 4,5-dihydrothiazole (7h) and (R)-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h′) exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs) ranging from 3.91 to 31.24 μg·mL−1. The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2′-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM) and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria.

  通过一种新型的无金属和催化剂方法，设计并合成了 60 个 2-芳基-4,5-二氢噻唑类化合物，其中半胱氨酸和取代苯腈类化合物的产率为 64% 至 89%。标题化合物的结构主要通过核磁共振光谱数据分析得到了证实。抗菌活性测定结果表明，(S)-2-(2′-羟基苯基)-4-羟甲基-4,5-二氢噻唑（7h）和(R)-2-(2′-羟基苯基)-4-羟甲基-4,5-二氢噻唑（7h′）化合物对茄属拉氏菌（Ralstonia solanacearum）、丁香假单胞菌（Pseudomonas syringae pv.最低抑菌浓度为 3.91 μg-mL-1 至 31.24 μg-mL-1。取代基的影响表明，不仅取电子基团会削弱抗菌活性，而且供电子基团也会削弱抗菌活性，除非在 4,5-二氢噻唑类似物的 2-芳基取代基上引入 2′-羟基。扫描电子显微镜（SEM）和脂肪酸暴露实验的结果表明，这些抗菌化合物会影响受试细菌的脂肪酸合成。