furan-2-yl(2-methylpiperazin-1-yl)methanone | 146951-80-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: furan-2-yl(2-methylpiperazin-1-yl)methanone
• 英文别名: 1-(Furan-2-carbonyl)-2-methylpiperazine；furan-2-yl-(2-methylpiperazin-1-yl)methanone
• CAS: 146951-80-6
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: ICJBMXSDFQGXKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  furan-2-yl(2-methylpiperazin-1-yl)methanone 、 2-氯-4-氨基-6,7-二甲氧基喹唑啉 以 异戊醇 为溶剂， 反应 72.0h， 以78%的产率得到<4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2-methylpiperazin-1-yl>furan-2-ylmethanone hydrochloride
  参考文献：
  名称：

  Structure-activity relationships in prazosin-related compounds. 2. Role of the piperazine ring on .alpha.-blocking activity

  摘要：

  Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward a-adrenoreceptors. The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the alpha1-adrenoreceptor surface. Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward alpha1-adrenoreceptors. The cis derivative 13 (cyclazosin) was the most potent and selective with an alpha1/alpha2 selectivity ratio value of 7800. The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on alpha1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation. The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats. It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.

  DOI：

  10.1021/jm00058a005
• 作为产物：
  描述：

  2-甲基哌嗪 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 111.0h， 生成 furan-2-yl(2-methylpiperazin-1-yl)methanone
  参考文献：
  名称：

  Structure-activity relationships in prazosin-related compounds. 2. Role of the piperazine ring on .alpha.-blocking activity

  摘要：

  Several prazosin-related compounds have been synthesized and evaluated for their blocking activity toward a-adrenoreceptors. The structural modification performed on the prazosin structure included the replacement of the piperazine ring with 2,3-dialkylpiperazine or 1,2-cyclohexanediamine moieties to characterize a lipophilic binding pocket in the alpha1-adrenoreceptor surface. Cyclohexanediamine derivatives 3-6 were almost devoid of potency and selectivity, whereas dialkylpiperazine compounds 7-14 showed high affinity and selectivity toward alpha1-adrenoreceptors. The cis derivative 13 (cyclazosin) was the most potent and selective with an alpha1/alpha2 selectivity ratio value of 7800. The particular trend of antagonist activity within cis/trans stereoisomeric compounds not only supports the presence of a lipophilic binding area on alpha1-adrenoreceptor surface but also suggests that the lipophilic pocket is endowed with a well-defined size and spatial orientation. The most active compound of the series, 13, was tested also in vivo for antihypertensive activity on spontaneously hypertensive rats. It showed an interesting long-lasting hypotensive effect, very similar to that of doxazosin, which was statistically significant 12 h after oral administration.

  DOI：

  10.1021/jm00058a005

文献信息

• High affinity and low PARP-trapping benzimidazole derivatives as a potential warhead for PARP1 degraders
  作者：Xiaoyu Peng、Yang Li、Junfeng Qu、Lizhi Jiang、Kaiyue Wu、Dan Liu、Yuping Chen、Junmei Peng、Yu Guo、Xuan Cao

  DOI：10.1016/j.ejmech.2024.116405

  日期：2024.5

  toxicity of PARPi, many novel methods have been developed including PROTACs. Being an event-driven technology, PROTACs needs a high affinity, low toxicity warhead with no steric hindrance in binding process. Veliparib shows the lowest PARP-Trapping effect but could hardly to be the warhead of PROTACs because of the strong steric hindrance. Other PARP1 inhibitors showed less steric hindrance but owns high

  PARPi已被探索并应用于治疗多种癌症，效果显着，特别是BRCA1/2突变的卵巢癌、乳腺癌、前列腺癌和胰腺癌。然而，由于PARP-Trapping和长期的临床跟踪，PARPi不可避免地产生耐药性并表现出高毒性。为了克服 PARPi 的耐药性和高毒性，人们开发了许多新方法，包括 PROTAC。作为一种事件驱动技术，PROTAC 需要高亲和力、低毒性的弹头，并且在结合过程中没有空间位阻。 VeliPARib显示出最低的PARP捕获效果，但由于强烈的空间位阻，很难成为PROTAC的弹头。其他 PARP1 抑制剂表现出较小的空间位阻，但具有较高的 PARP 捕获效果。因此，开发具有高PARP1亲和力、低PARP1捕获且无空间位阻的新型弹头将是有价值的。在这项工作中，我们保留苯并咪唑作为基序以保留低PARP1捕获效应，并用芳环取代吡咯以避免PARP1结合洞中的空间位阻。因此，设计并合成了一系列苯并咪