tert-butyl-{5-[1-hydroxyl(2-phenyl)ethyl]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-[1-hydroxyl(2-phenyl)ethyl]thiazol-2-yl}carbamate
• 英文别名: tert-butyl N-[5-(1-hydroxy-2-phenylethyl)-1,3-thiazol-2-yl]carbamate
• 化学式: C₁₆H₂₀N₂O₃S
• 分子量: 320.412
• InChiKey: ALEHZEAAGJQQPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 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-[1-hydroxyl(2-phenyl)ethyl]thiazol-2-yl}carbamate 在 三乙基硅烷 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.25h， 生成 N-(5-phenethylthiazol-2-yl)cyclopentanecarboxamide
  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：

  苯乙醛 、 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35%的产率得到tert-butyl-{5-[1-hydroxyl(2-phenyl)ethyl]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

• Modulators of ATP-Binding Cassette transporters
  申请人：Ruah Sarah Hadida

  公开号：US20080176899A1

  公开（公告）日：2008-07-24

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜传导调节因子（“CFTR”），以及其组成物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
  申请人：Hadida-Ruah Sara Sabina

  公开号：US20110306637A1

  公开（公告）日：2011-12-15

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运蛋白或其片段的调节剂，包括囊性纤维化跨膜传导调节因子（“CFTR”），以及其组合物和使用这些调节剂的方法。本发明还涉及使用这些调节剂治疗ABC转运蛋白介导的疾病的方法。
• Modulators of ATP-binding cassette transporters
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20140080825A1

  公开（公告）日：2014-03-20

  The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

  本发明涉及ATP结合盒（“ABC”）转运体或其片段的调节剂，包括囊性纤维化跨膜传导调节因子（“CFTR”），以及与其相关的组合物和方法。本发明还涉及使用这些调节剂治疗ABC转运体介导的疾病的方法。
• US7977322B2
  申请人：——

  公开号：US7977322B2

  公开（公告）日：2011-07-12
• US8541453B2
  申请人：——

  公开号：US8541453B2

  公开（公告）日：2013-09-24