1,6-Dihydro-5(4H)-pyrimidinone O-methyloxime monohydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1,6-Dihydro-5(4H)-pyrimidinone O-methyloxime monohydrochloride
• 英文别名: (Z)-N-methoxy-4,6-dihydro-1H-pyrimidin-5-imine;hydrochloride
• 化学式: C₅H₉N₃O*ClH
• 分子量: 163.607
• InChiKey: ADVAKSBZOSKXII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.04
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,6-Dihydro-5(4H)-pyrimidinone O-methyloxime monohydrochloride 在 盐酸 、 硼烷-三甲胺络合物 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以38%的产率得到O-Methyl-N-(1,4,5,6-tetrahydro-pyrimidin-5-yl)-hydroxylamine; hydrochloride
  参考文献：
  名称：

  Synthesis, and In vitro and In vivo muscarinic pharmacological properties of a series of 1,6-Dihydro-5-(4 H )-pyrimidinone oximes

  摘要：

  A series of 1,6-dihydro-5-(4H)-pyrimidinone oxime derivatives I was synthesized (Scheme 1, Tables 1 and 2) and tested for muscarinic activity (Table 3) in receptor binding assays using [H-3]-oxotremorine-M (Oxo-M) and [H-3]-pirenzepine pirenzepine (Pz) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies that measured their potencies to inhibit the binding of Oxo-M and Pz. Preferential inhibition of Oxo-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. The series produced a wide range of active compounds with differing degrees of selectivity in M-1, M-2, and M-3 functional models. Several compounds that have mixed agonist/antagonist profiles were able to reduce cholinergic-related cognitive impairments in models of mnemonic function. Substitutions (I, e.g. R-2 or R-3 = Me) at the 1,6-dihydro-5-(4H)pyrimidine ring disrupted binding and efficacy, whereas systematic variation of the oximes substituent R1 resulted in various degrees of potency and selectivity dependent on the nature of the substitution. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00074-1
• 作为产物：
  描述：

  甲氧基胺盐酸盐 、 1,3-diamino-acetone; hydrochloride 以 甲醇 为溶剂， 以850 mg (36%)的产率得到1,6-Dihydro-5(4H)-pyrimidinone O-methyloxime monohydrochloride
  参考文献：
  名称：

  Tetrahydropyrimidine derivatives

  摘要：

  该发明涉及具有式I的四氢吡咯烷衍生物 ##STR1## 其中R.sub.1是氢；R.sub.2是氢、较低的烷基基团或较低的酰基；或R.sub.1和R.sub.2一起表示键；R.sub.3是氢、较低的烃基团，可选择地用卤素、CN、芳基或COR.sub.7取代；R.sub.4是氢、较低的烷基(烯基)基团或芳基；R.sub.5是氢、氨基、较低的烷基取代的氨基或较低的烷基基团；R.sub.6是氢或甲基；R.sub.7是氨基、较低的烷基取代的氨基或较低的烷基基团；或其药学上可接受的盐。本发明的化合物具有肌碱性质，可用于治疗认知障碍和胆碱缺乏症的治疗。

  公开号：

  US05470856A1

文献信息

• US5470856A
  申请人：——

  公开号：US5470856A

  公开（公告）日：1995-11-28
• Synthesis, and In vitro and In vivo muscarinic pharmacological properties of a series of 1,6-Dihydro-5-(4 H )-pyrimidinone oximes
  作者：Ralf Plate、Marc J.M. Plaum、Peter Pintar、Christan G. Jans、Thijs de Boer、Fred A. Dijcks、Ge Ruigt、John S. Andrews

  DOI：10.1016/s0968-0896(98)00074-1

  日期：1998.9

  A series of 1,6-dihydro-5-(4H)-pyrimidinone oxime derivatives I was synthesized (Scheme 1, Tables 1 and 2) and tested for muscarinic activity (Table 3) in receptor binding assays using [H-3]-oxotremorine-M (Oxo-M) and [H-3]-pirenzepine pirenzepine (Pz) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies that measured their potencies to inhibit the binding of Oxo-M and Pz. Preferential inhibition of Oxo-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. The series produced a wide range of active compounds with differing degrees of selectivity in M-1, M-2, and M-3 functional models. Several compounds that have mixed agonist/antagonist profiles were able to reduce cholinergic-related cognitive impairments in models of mnemonic function. Substitutions (I, e.g. R-2 or R-3 = Me) at the 1,6-dihydro-5-(4H)pyrimidine ring disrupted binding and efficacy, whereas systematic variation of the oximes substituent R1 resulted in various degrees of potency and selectivity dependent on the nature of the substitution. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Tetrahydropyrimidine derivatives
  申请人：Akzo Nobel N.V.

  公开号：US05470856A1

  公开（公告）日：1995-11-28

  The invention is concerned with a tetrahydropyrimidine derivative having formula I ##STR1## wherein R.sub.1 is hydrogen; R.sub.2 is hydrogen, a lower alkyl group, or lower acyl; or R.sub.1 and R.sub.2 represent together a bond; R.sub.3 is hydrogen, a lower hydrocarbon group optionally substituted with halogen, CN, aryl, or COR.sub.7 ; R.sub.4 is hydrogen, a lower alk(en)yl group, or aryl; R.sub.5 is hydrogen, amino, lower alkyl substituted amino, or a lower alkyl group; and R.sub.6 is hydrogen or methyl; R.sub.7 is amino, lower alkyl substituted amino, or a lower alkyl group; or a pharmaceutically acceptable salt thereof. The compounds of this invention have muscarinic properties and can be used for the treatment of cognition disorders, and for the treatment of cholinergic deficiencies.

  该发明涉及具有式I的四氢吡咯烷衍生物 ##STR1## 其中R.sub.1是氢；R.sub.2是氢、较低的烷基基团或较低的酰基；或R.sub.1和R.sub.2一起表示键；R.sub.3是氢、较低的烃基团，可选择地用卤素、CN、芳基或COR.sub.7取代；R.sub.4是氢、较低的烷基(烯基)基团或芳基；R.sub.5是氢、氨基、较低的烷基取代的氨基或较低的烷基基团；R.sub.6是氢或甲基；R.sub.7是氨基、较低的烷基取代的氨基或较低的烷基基团；或其药学上可接受的盐。本发明的化合物具有肌碱性质，可用于治疗认知障碍和胆碱缺乏症的治疗。