tert-butyl 7-chloro-4-oxo-3,4-dihydroquinoline-1(2H)-carboxylate | 81892-54-8

• 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: tert-butyl 7-chloro-4-oxo-3,4-dihydroquinoline-1(2H)-carboxylate
• 英文别名: tert-butyl 7-chloro-4-oxo-2,3-dihydroquinoline-1-carboxylate
• CAS: 81892-54-8
• 化学式: C₁₄H₁₆ClNO₃
• 分子量: 281.739
• InChiKey: ATUPZOCVIIIEAU-UHFFFAOYSA-N

物化性质

• 熔点：
  106.7-107.1 °C
• 沸点：
  388.7±42.0 °C(Predicted)
• 密度：
  1.382±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 7-chloro-4-oxo-3,4-dihydroquinoline-1(2H)-carboxylate 在 甲醇 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以87%的产率得到tert-butyl 7-chloro-4-hydroxy-3,4-dihydroquinoline-1(2H)-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
• 作为产物：
  描述：

  7-氯-2,3-二氢喹啉-4-酮 、 二碳酸二叔丁酯 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 以100%的产率得到tert-butyl 7-chloro-4-oxo-3,4-dihydroquinoline-1(2H)-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

• Discovery of novel serine palmitoyltransferase inhibitors as cancer therapeutic agents
  作者：Takuto Kojima、Yasutomi Asano、Osamu Kurasawa、Yasuhiro Hirata、Naoki Iwamura、Tzu-Tshin Wong、Bunnai Saito、Yuta Tanaka、Ryosuke Arai、Kazuko Yonemori、Yasufumi Miyamoto、Yoji Sagiya、Masahiro Yaguchi、Sachio Shibata、Akio Mizutani、Osamu Sano、Ryutaro Adachi、Yoshinori Satomi、Megumi Hirayama、Kazunobu Aoyama、Yuto Hiura、Atsushi Kiba、Shuji Kitamura、Shinichi Imamura

  DOI：10.1016/j.bmc.2018.04.008

  日期：2018.5

  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.