5-(cyclohexylmethyl)-2-thiazolamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(cyclohexylmethyl)-2-thiazolamine
• 英文别名: 5-(Cyclohexylmethyl)-1,3-thiazol-2-amine；5-(cyclohexylmethyl)-1,3-thiazol-2-amine
• 化学式: C₁₀H₁₆N₂S
• 分子量: 196.316
• InChiKey: JDZALRHOIRRVPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(cyclohexylmethyl)-2-thiazolamine 、 3-环己基丙酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.25h， 以60%的产率得到N-[5-(cyclohexylmethyl)thiazol-2-yl]-3-cyclohexanepropanamide
  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：

  环己烷基甲醛 在 三乙基硅烷 、 正丁基锂 、 三氟乙酸 作用下， 以 氘代四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 5-(cyclohexylmethyl)-2-thiazolamine
  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

• 一种合成5-亚甲基取代的噻唑-2-胺衍生物的新方法
  申请人：成都分迪药业有限公司

  公开号：CN115260181A

  公开（公告）日：2022-11-01

  本发明提供了一种合成5‑亚甲基取代的噻唑‑2‑胺衍生物的新方法，经锂化反应然后同时脱羟基和保护基的二步反应，合成得到5‑亚甲基取代的噻唑‑2‑胺衍生物；本发明的合成方法，整个合成路线步骤短，副反应少，转化率和收率高，原料购买便宜易得，应用底物广泛，操作条件温和，安全性高，有利于放大生产和产业化推广应用。