3-(tert-butyl)-N-(7-chloroquinolin-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-7-amine | 1010411-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-(tert-butyl)-N-(7-chloroquinolin-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-7-amine
• CAS: 1010411-14-9
• 化学式: C₂₁H₂₂ClN₃O
• 分子量: 367.878
• InChiKey: XTHWAAGEBSMPDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.58
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  37.39
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(tert-butyl)-N-(7-chloroquinolin-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-7-amine 在 盐酸 作用下， 以 水 、 仲丁醇 为溶剂， 生成 2-(tert-butylaminomethyl)-5-(7-chloroquinolin-4-ylamino)phenol hydrochloride
  参考文献：
  名称：

  Candidate Selection and Preclinical Evaluation of N-tert-Butyl Isoquine (GSK369796), An Affordable and Effective 4-Aminoquinoline Antimalarial for the 21st Century

  摘要：

  N-tert-Butyl isoquine (4) (GSK369796) is a 4-aminoquinoline drug candidate selected and developed as part of a public-private partnership between academics at Liverpool, MMV, and GSK pharmaceuticals. This molecule was rationally designed based on chemical, toxicological, pharmacokinetic, and pharmacodynamic considerations and was selected based on excellent activity against Plasmodium falciparum in vitro and rodent malaria parasites in vivo. The optimized chemistry delivered this novel synthetic quinoline in a two-step procedure from cheap and readily available starting materials. The molecule has a full industry standard preclinical development program allowing first into humans to proceed. Employing chloroquine (1) and amodiaquine (2) as comparator molecules in the preclinical plan, the first preclinical dossier of pharmacokinetic, toxicity, and safety pharmacology has also been established for the 4-aminoquinoline antimalarial class. These studies have revealed preclinical liabilities that have never translated into the human experience. This has resulted in the availability of critical information to other drug development teams interested in developing antimalarials within this class.

  DOI：

  10.1021/jm8012618
• 作为产物：
  描述：

  聚合甲醛 、 7-chloro-4-[(3-hydroxyphenyl)amino]quinolinium chloride 、 叔丁胺 以 仲丁醇 为溶剂， 生成 3-(tert-butyl)-N-(7-chloroquinolin-4-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-7-amine
  参考文献：
  名称：

  Candidate Selection and Preclinical Evaluation of N-tert-Butyl Isoquine (GSK369796), An Affordable and Effective 4-Aminoquinoline Antimalarial for the 21st Century

  摘要：

  N-tert-Butyl isoquine (4) (GSK369796) is a 4-aminoquinoline drug candidate selected and developed as part of a public-private partnership between academics at Liverpool, MMV, and GSK pharmaceuticals. This molecule was rationally designed based on chemical, toxicological, pharmacokinetic, and pharmacodynamic considerations and was selected based on excellent activity against Plasmodium falciparum in vitro and rodent malaria parasites in vivo. The optimized chemistry delivered this novel synthetic quinoline in a two-step procedure from cheap and readily available starting materials. The molecule has a full industry standard preclinical development program allowing first into humans to proceed. Employing chloroquine (1) and amodiaquine (2) as comparator molecules in the preclinical plan, the first preclinical dossier of pharmacokinetic, toxicity, and safety pharmacology has also been established for the 4-aminoquinoline antimalarial class. These studies have revealed preclinical liabilities that have never translated into the human experience. This has resulted in the availability of critical information to other drug development teams interested in developing antimalarials within this class.

  DOI：

  10.1021/jm8012618