tert-butyl (5-(hydroxy(phenyl)methyl)thiazol-2-yl)carbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl (5-(hydroxy(phenyl)methyl)thiazol-2-yl)carbamate
• 英文别名: tert-butyl N-[5-[hydroxy(phenyl)methyl]-1,3-thiazol-2-yl]carbamate
• 化学式: C₁₅H₁₈N₂O₃S
• 分子量: 306.386
• InChiKey: APIAHQDYWLDBPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (5-(hydroxy(phenyl)methyl)thiazol-2-yl)carbamate 在 三乙基硅烷 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(5-benzylthiazol-2-yl)chromane-3-carboxamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

  摘要：

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.006
• 作为产物：
  描述：

  苯甲醛 、 噻唑-2-氨基甲酸叔丁酯 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以59%的产率得到tert-butyl (5-(hydroxy(phenyl)methyl)thiazol-2-yl)carbamate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

  摘要：

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.006

文献信息

• Design and synthesis of aminothiazole based Hepatitis B Virus (HBV) capsid inhibitors
  作者：Ting Pan、Yanchao Ding、Liyang Wu、Liting Liang、Xin He、Qianwen Li、Chuan Bai、Hui Zhang

  DOI：10.1016/j.ejmech.2019.01.059

  日期：2019.3

  The capsid assembly is an essential step for Hepatitis B Virus (HBV) life cycle and is an important target for anti-HBV drug development. In this report, we identified a hit compound with aminothiazole structure by the high throughput screening (HTS) which inhibited the interaction of HBV capsid protein within the cells. The structure hopping and SAR studies of the hit compound afforded compound 79

  衣壳装配是乙肝病毒（HBV）生命周期的重要步骤，并且是抗HBV药物开发的重要目标。在本报告中，我们通过抑制细胞内HBV衣壳蛋白相互作用的高通量筛选（HTS），鉴定了具有氨基噻唑结构的命中化合物。对该化合物的结构跳跃和SAR研究提供了具有强大的抗HBV复制活性和良好的基本药物样性质的化合物79。工作机理研究表明，化合物79可以通过杂芳基二氢嘧啶（HAP）支架与已知HBV衣壳抑制剂的相似结合位点结合，通过相似的疏水相互作用但具有不同的氢键。该化合物在细胞培养物中或在没有明显急性毒性的小鼠中均对HBV产生有效的抑制作用。我们建议对该化合物的进一步开发可能会导致靶向HBV衣壳装配的新型有效抗HBV抑制剂。
• Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans
  作者：Ahmed Khalil、Jessica A. Edwards、Chad A. Rappleye、Werner Tjarks

  DOI：10.1016/j.bmc.2014.12.006

  日期：2015.2

  Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4-0.8 mu M) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother. 2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC(50)s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure-activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC(50)s of 0.4 mu M. For these analogues, SIs of 92 to > 100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity. (C) 2014 Elsevier Ltd. All rights reserved.