methyl 8-chloroquinoxaline-6-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl 8-chloroquinoxaline-6-carboxylate
• 英文别名: Methyl 8-chloroquinoxaline-6-carboxylate
• 化学式: C₁₀H₇ClN₂O₂
• 分子量: 222.631
• InChiKey: ZZFRCVUHEMKBFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-chloroquinoxaline-6-carboxylate 在 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 N-((3S,4R)-1-((8-chloroquinoxalin-6-yl)carbonyl)-3-phenylpiperidin-4-yl)-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  ACYLATED 4-AMINOPIPERIDINES AS INHIBITORS OF SERINE PALMITOYLTRANSFERASE

  摘要：

  公开号：

  EP3287441B1
• 作为产物：
  描述：

  methyl 3,4-diamino-5-chlorobenzoate 、 草酸醛 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以98%的产率得到methyl 8-chloroquinoxaline-6-carboxylate
  参考文献：
  名称：

  Discovery of novel serine palmitoyltransferase inhibitors as cancer therapeutic agents

  摘要：

  We pursued serine palmitoyltransferase (SPT) inhibitors as novel cancer therapeutic agents based on a correlation between SPT inhibition and growth suppression of cancer cells. High-throughput screening and medicinal chemistry efforts led to the identification of structurally diverse SPT inhibitors 4 and 5. Both compounds potently inhibited SPT enzyme and decreased intracellular ceramide content. In addition, they suppressed cell growth of human lung adenocarcinoma HCC4006 and acute promyelocytic leukemia PL-21, and displayed good pharmacokinetic profiles. Reduction of 3-ketodihydrosphingosine, the direct downstream product of SPT, was confirmed under in vivo settings after oral administration of compounds 4 and 5. Their anti-tumor efficacy was observed in a PL-21 xenograft mouse model. These results suggested that SPT inhibitors might have potential to be effective cancer therapeutics. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.008

文献信息

• Heterocyclic compound
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US10189785B2

  公开（公告）日：2019-01-29

  The present invention relates to a compound which can be useful for the treatment or prevention of SPT-related diseases including cancer and congenital diseases associated with sphingolipid accumulation (including Niemann-Pick disease).

  本发明涉及一种化合物，该化合物可用于治疗或预防与 SPT 有关的疾病，包括癌症和与鞘脂蓄积有关的先天性疾病（包括尼曼-皮克病）。
• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3530655B1

  公开（公告）日：2022-02-09