3-(azetidin-3-yl)-1,4-dihydroquinazolin-2-one | 337910-03-9

• 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: 3-(azetidin-3-yl)-1,4-dihydroquinazolin-2-one
• 英文别名: 3-(Azetidin-3-yl)-1,2,3,4-tetrahydroquinazolin-2-one
• CAS: 337910-03-9
• 化学式: C₁₁H₁₃N₃O
• 分子量: 203.244
• InChiKey: OYZRDGBOCXDONT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-甲酰基哌啶-1-羧酸乙酯 、 3-(azetidin-3-yl)-1,4-dihydroquinazolin-2-one 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以66%的产率得到ethyl 4-{[3-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)azetidin-1-yl]methyl}piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of dihydroquinazolinone derivatives as potent, selective, and CNS-penetrant M1 and M4 muscarinic acetylcholine receptors agonists

  摘要：

  We designed and synthesized a series of dihydroquinazolinone derivatives as selective M-1 and M-4 muscarinic acetylcholine receptors agonists. Introduction of the N-carbethoxy piperidine unit into a HTS hit compound followed by optimization of the amine linker and the carbamoyl moiety led to the identification of compound 1 as a potential candidate. The identified compound 1 showed high selectivity for M-1 and M-4 muscarinic acetylcholine receptors with M-4 partial agonistic activity. In addition, compound 1 showed good brain penetration and reversed methamphetamine-induced hyperlocomotion in rats (ED50 = 3.0 mg/kg, sc). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.032

文献信息

• Discovery of dihydroquinazolinone derivatives as potent, selective, and CNS-penetrant M1 and M4 muscarinic acetylcholine receptors agonists
  作者：Yoshiharu Uruno、Yasuko Konishi、Atsushi Suwa、Kentaro Takai、Kengo Tojo、Tomokazu Nakako、Mutsuko Sakai、Takeshi Enomoto、Harumi Matsuda、Atsushi Kitamura、Takaaki Sumiyoshi

  DOI：10.1016/j.bmcl.2015.09.032

  日期：2015.11

  We designed and synthesized a series of dihydroquinazolinone derivatives as selective M-1 and M-4 muscarinic acetylcholine receptors agonists. Introduction of the N-carbethoxy piperidine unit into a HTS hit compound followed by optimization of the amine linker and the carbamoyl moiety led to the identification of compound 1 as a potential candidate. The identified compound 1 showed high selectivity for M-1 and M-4 muscarinic acetylcholine receptors with M-4 partial agonistic activity. In addition, compound 1 showed good brain penetration and reversed methamphetamine-induced hyperlocomotion in rats (ED50 = 3.0 mg/kg, sc). (C) 2015 Elsevier Ltd. All rights reserved.