2-chloro-N-(7-chloro-1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-4-yl)benzamide

• 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: 2-chloro-N-(7-chloro-1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-4-yl)benzamide
• 英文别名: 2-chloro-N-[7-chloro-1-(3,4-dimethoxybenzoyl)-3,4-dihydro-2H-quinolin-4-yl]benzamide
• 化学式: C₂₅H₂₂Cl₂N₂O₄
• 分子量: 485.367
• InChiKey: VTGGRIZFDBXPGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-氯-2,3-二氢喹啉-4-酮 在 盐酸 、 甲醇 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 叠氮磷酸二苯酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 55.0h， 生成 2-chloro-N-(7-chloro-1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-4-yl)benzamide
  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：EP3287441A1

  公开（公告）日：2018-02-28

  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：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）。
• ACYLATED 4-AMINOPIPERIDINES AS INHIBITORS OF SERINE PALMITOYLTRANSFERASE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP3287441B1

  公开（公告）日：2021-06-09
• 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.