10-hydroxy-8-methyl-1,2,3,4-tetrahydro-chromeno[3,4-c]pyridin-5-one | 27296-61-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 10-hydroxy-8-methyl-1,2,3,4-tetrahydro-chromeno[3,4-c]pyridin-5-one
• 英文别名: 10-Hydroxy-8-methyl-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one
• CAS: 27296-61-3
• 化学式: C₁₃H₁₃NO₃
• 分子量: 231.251
• InChiKey: LPUUVYJUIMSPNK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴丙炔 、 10-hydroxy-8-methyl-1,2,3,4-tetrahydro-chromeno[3,4-c]pyridin-5-one 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 生成 1,2,3,4-四氢-10-羟基-8-甲基-3-(2-丙炔基)-5H-[1]苯并吡喃并[3,4-c]吡啶-5-酮
  参考文献：
  名称：

  Drugs derived from cannabinoids. 1. Nitrogen analogs, benzopyranopyridines and benzopyranopyrroles

  摘要：

  Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.

  DOI：

  10.1021/jm00226a001
• 作为产物：
  描述：

  1-苄基-3-乙氧羰基-4-哌啶酮盐酸盐 在 palladium on activated charcoal 硫酸 、 氢气 、 三氯氧磷 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 生成 10-hydroxy-8-methyl-1,2,3,4-tetrahydro-chromeno[3,4-c]pyridin-5-one
  参考文献：
  名称：

  Drugs derived from cannabinoids. 1. Nitrogen analogs, benzopyranopyridines and benzopyranopyrroles

  摘要：

  Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.

  DOI：

  10.1021/jm00226a001

文献信息

• Discovery of a Potent, Selective, and Orally Available MTHFD2 Inhibitor (DS18561882) with in Vivo Antitumor Activity
  作者：Junya Kawai、Tadashi Toki、Masahiro Ota、Hidekazu Inoue、Yoshimi Takata、Takashi Asahi、Makoto Suzuki、Takashi Shimada、Kaori Ono、Kanae Suzuki、Sachiko Takaishi、Hitoshi Ohki、Satoshi Matsui、Shinji Tsutsumi、Yasuhide Hirota、Kiyoshi Nakayama

  DOI：10.1021/acs.jmedchem.9b01113

  日期：2019.11.27

  isozyme-selective MTHFD2 inhibitor, DS18561882 (2). Through investigation of the substituents on our tricyclic coumarin scaffold (1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one), MTHFD2 inhibitory activity was shown to be elevated by incorporating an amine moiety at the 8-position and a methyl group at the 7-position of the initial lead 1. X-ray structure analysis revealed that a key interaction for enhanced

  我们报告了一种有效的和同工酶选择性MTHFD2抑制剂DS18561882（2）的发现。通过研究我们的三环香豆素骨架上的取代基（1,2,3,4-四氢色素[3,4- c ]吡啶-5-酮），MTHFD2的抑制活性通过在第8位引入胺部分而提高-位置和初始铅1的7位上的甲基。X射线结构分析表明，增强效能的关键相互作用是NAD +辅因子的胺部分和二磷酸酯连接基之间形成盐桥。此外，用邻位磺酰胺代替苯甲酸1显着改善了针对人类乳腺癌细胞系的细胞通透性和基于细胞的生长抑制。如此优化的DS18561882在同类小鼠中显示出最强的基于细胞的活性（GI 50 = 140 nM），良好的口服药代动力学特征，从而在口服小鼠异种移植模型中抑制了肿瘤的生长。