tert-butyl (2-aminothiazol-4-yl)methylcarbamate | 1146084-66-3

• 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 (2-aminothiazol-4-yl)methylcarbamate
• 英文别名: tert-butyl N-[(2-amino-1,3-thiazol-4-yl)methyl]carbamate
• CAS: 1146084-66-3
• 化学式: C₉H₁₅N₃O₂S
• 分子量: 229.303
• InChiKey: CCJFGPYIZZOZSC-UHFFFAOYSA-N

物化性质

• 沸点：
  407.4±28.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-aminothiazol-4-yl)methylcarbamate 在 4-二甲氨基吡啶 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (2-(1-(4-bromobenzyl)-3-tert-butyl-1H-pyrazole-5-carboxamido)thiazol-4-yl)methylcarbamate
  参考文献：
  名称：

  Structure–activity relationship studies of antiplasmodial aminomethylthiazoles

  摘要：

  Structure-activity relationship (SAR) studies around a previously reported antimalarial aminomethylthiazole pyrazole carboxamide 1 are reported. Several analogues were synthesised and profiled for in vitro antiplasmodial activity against the drug-sensitive Plasmodium falciparum malaria parasite strain, NF54. Although all the reported analogues exhibited inferior in vitro antiplasmodial activity (IC50 = 0.125-173 mu M) relative to compound 1 (IC50 = 0.0203 mu M), one analogue, compound 5a, retained submicromolar activity (IC50 = 0.125 mu M). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.09.071
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 4-(氨基甲基)-1,3-噻唑-2-胺 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以32%的产率得到tert-butyl (2-aminothiazol-4-yl)methylcarbamate
  参考文献：
  名称：

  Structure–activity relationship studies of antiplasmodial aminomethylthiazoles

  摘要：

  Structure-activity relationship (SAR) studies around a previously reported antimalarial aminomethylthiazole pyrazole carboxamide 1 are reported. Several analogues were synthesised and profiled for in vitro antiplasmodial activity against the drug-sensitive Plasmodium falciparum malaria parasite strain, NF54. Although all the reported analogues exhibited inferior in vitro antiplasmodial activity (IC50 = 0.125-173 mu M) relative to compound 1 (IC50 = 0.0203 mu M), one analogue, compound 5a, retained submicromolar activity (IC50 = 0.125 mu M). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.09.071

文献信息

• Novel Orally Active Antimalarial Thiazoles
  作者：Diego González Cabrera、Frederic Douelle、Tzu-Shean Feng、Aloysius T. Nchinda、Yassir Younis、Karen L. White、Quoc Wu、Eileen Ryan、Jeremy N. Burrows、David Waterson、Michael J. Witty、Sergio Wittlin、Susan A. Charman、Kelly Chibale

  DOI：10.1021/jm201108k

  日期：2011.11.10

  An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro antiplasmodial activity [IC50: 0.08 mu M (K1, chloroquine and multidrug resistant strain) and 0.07 mu M (NF54, chloroquine sensitive strain)] and microsomal metabolic stability was identified from whole cell screening of a SoftFocus kinase library. Compound 3 also exhibited in vivo activity in the P. berghei mouse model at 4 x 50 mg/kg administration via the oral route, showing 99.5% activity and 9 days survival and showed low in vitro cytotoxicity. Pharmacokinetic studies in rats revealed good oral bioavailability (51% at 22 mg/kg) with a moderate rate of absorption, reasonable half-life (t(1/2) 3 h), and high volume of distribution with moderately high plasma and blood clearance after IV administration. Toward toxicity profiling, 3 exhibited moderate potential to inhibit CYP1A2 (IC50 = 1.5 mu M) and 2D6 (IC50 = 0.4 mu M) as well as having a potential hERG liability (IC50 = 3.7 mu M).