O-(1-ethylprop-2-ynyl)hydroxylamine

• 分子结构分类: 有机化合物 - 乙炔化物 - 碳化物
• 英文名称: O-(1-ethylprop-2-ynyl)hydroxylamine
• 英文别名: O-pent-1-yn-3-ylhydroxylamine
• 化学式: C₅H₉NO
• 分子量: 99.1326
• InChiKey: WOVOFTAMBWQSGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-奎宁环酮盐酸盐 、 O-(1-ethylprop-2-ynyl)hydroxylamine 以 甲醇 为溶剂， 反应 18.0h， 以43%的产率得到quinuclidin-3-one O-(1-ethylprop-2-ynyl)oxime hydrochloride
  参考文献：
  名称：

  Quinuclidinone O-Alkynyloximes with muscarinic agonist activity

  摘要：

  A series of quinuclidinone O-alkynyloximes (14-19) were synthesized and evaluated in radioligand displacement assays for binding affinities to M-1-M-3 muscarinic receptors. Radioligand displacement assays were carried out using [H-3] oxotremorine-M and [H-3] pirenzepine on rat cortical tissue and [H-3] N-methylscopolamine on rat heart and submandibulary glands. Two alkynyloximes 15 and 18 had pirenzepine/oxotromorine M ratios which were indicative of muscarinic agonist Ind partial agonist activity, respectively. They were tested for their mnemonic effects in mice using the swimming escape task and found to attenuate scopolamine induced impairment of the task in mice at 2 mg/kg. The results show that the O-alkynyloxime moiety linked to aza-cycles of appropriate size and rigidity (for example quinuclidine and tropane) is a potentially useful muscarinic pharmacophore that can be exploited for the design of muscarinic agonists. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00267-x
• 作为产物：
  描述：

  乙基乙炔基甲醇 在 一水合肼 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 24.25h， 生成 O-(1-ethylprop-2-ynyl)hydroxylamine
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of O-Alkynyloximes of Tropinone and N-Methylpiperidinone as Muscarinic Agonists

  摘要：

  A number of O-alkynyloximes of tropinone and N-methyl-4-piperidinone have been synthesized and evaluated for muscarinic activity. The affinities of these oximes were tested in homogenates of cerebral cortex, heart, and submandibulary glands from rats using [H-3]pirenzepine and [H-3]- N-methylscopolamine as radioligands. The oximes bind to the cortical muscarinic receptors with pK(i) values varying from 3 to 7. Higher binding affinities were observed for the O-alkynyl tropinone oximes than the corresponding piperidinone analogues. Binding to the muscarinic sites in the heart and submandibulary glands was also observed but with lower affinities. Good M-1 subtype selectivity (10-fold or greater) was observed with some oximes (26a, 28a, 32a) at the cortical sites. These oximes also attenuated scopolamine-induced impairment of the water mask task in mice. Functional assays for Ma activity on the rat aorta showed that all oximes possessed M-3 agonist action but M-2 agonist activity was not observed at the endothelium-denuded rabbit aorta. Analysis of the quantitative structure-activity relationship (QSAR) indicated that the Connolly surface area is an important determinant of activity, accounting for 70% of the variation in cortical binding affinity among the oximes.

  DOI：

  10.1021/jm9708588

文献信息

• Quinuclidinone O-Alkynyloximes with muscarinic agonist activity
  作者：Brinda Somanadhan、Weng-Keong Loke、Meng-Kwoon Sim、Mei-Lin Go

  DOI：10.1016/s0968-0896(01)00267-x

  日期：2002.1

  A series of quinuclidinone O-alkynyloximes (14-19) were synthesized and evaluated in radioligand displacement assays for binding affinities to M-1-M-3 muscarinic receptors. Radioligand displacement assays were carried out using [H-3] oxotremorine-M and [H-3] pirenzepine on rat cortical tissue and [H-3] N-methylscopolamine on rat heart and submandibulary glands. Two alkynyloximes 15 and 18 had pirenzepine/oxotromorine M ratios which were indicative of muscarinic agonist Ind partial agonist activity, respectively. They were tested for their mnemonic effects in mice using the swimming escape task and found to attenuate scopolamine induced impairment of the task in mice at 2 mg/kg. The results show that the O-alkynyloxime moiety linked to aza-cycles of appropriate size and rigidity (for example quinuclidine and tropane) is a potentially useful muscarinic pharmacophore that can be exploited for the design of muscarinic agonists. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Synthesis and Pharmacological Characterization of <i>O</i>-Alkynyloximes of Tropinone and <i>N</i>-Methylpiperidinone as Muscarinic Agonists
  作者：Rong Xu、Meng-Kwoon Sim、Mei-Lin Go

  DOI：10.1021/jm9708588

  日期：1998.8.1

  A number of O-alkynyloximes of tropinone and N-methyl-4-piperidinone have been synthesized and evaluated for muscarinic activity. The affinities of these oximes were tested in homogenates of cerebral cortex, heart, and submandibulary glands from rats using [H-3]pirenzepine and [H-3]- N-methylscopolamine as radioligands. The oximes bind to the cortical muscarinic receptors with pK(i) values varying from 3 to 7. Higher binding affinities were observed for the O-alkynyl tropinone oximes than the corresponding piperidinone analogues. Binding to the muscarinic sites in the heart and submandibulary glands was also observed but with lower affinities. Good M-1 subtype selectivity (10-fold or greater) was observed with some oximes (26a, 28a, 32a) at the cortical sites. These oximes also attenuated scopolamine-induced impairment of the water mask task in mice. Functional assays for Ma activity on the rat aorta showed that all oximes possessed M-3 agonist action but M-2 agonist activity was not observed at the endothelium-denuded rabbit aorta. Analysis of the quantitative structure-activity relationship (QSAR) indicated that the Connolly surface area is an important determinant of activity, accounting for 70% of the variation in cortical binding affinity among the oximes.