O-(but-2-ynyl)hydroxylamine | 127298-67-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: O-(but-2-ynyl)hydroxylamine
• 英文别名: O-(but-2-yn-1-yl)hydroxylamine；O-but-2-ynylhydroxylamine
• CAS: 127298-67-3
• 化学式: C₄H₇NO
• 分子量: 85.1057
• InChiKey: KSKWACKJFWWRSR-UHFFFAOYSA-N

物化性质

• 沸点：
  175.5±23.0 °C(Predicted)
• 密度：
  0.968±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 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-(but-2-ynyl)hydroxylamine 以 甲醇 为溶剂， 反应 18.0h， 以51%的产率得到quinuclidin-3-one O-(but-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：

  2-(but-2-yn-1-yloxy)isoindoline-1,3-dione 在 一水合肼 作用下， 反应 0.25h， 生成 O-(but-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

• Catalytic substitution/cyclization sequences of <i>O</i>-substituted Isocyanates: synthesis of 1-alkoxybenzimidazolones and 1-alkoxy-3,4-dihydroquinazolin-2(1<i>H</i>)-ones
  作者：Qiang Wang、Jing An、Howard Alper、Wen-Jing Xiao、André M. Beauchemin

  DOI：10.1039/c7cc07926e

  日期：——

  used in organic synthesis, given their tendency to undergo side reactions (e.g., trimerization). Herein, we show that masked (blocked) O-isocyanate precursors allow one-pot or cascade reaction sequences featuring base-catalyzed substitution with 2-iodoanilines and 2-iodobenzylamines followed by copper-catalyzed cyclization, to form benzimidazolones and 3,4-dihydroquinazolin-2(1H)-ones. This work shows

  考虑到O-取代的异氰酸酯（O-异氰酸酯）易于发生副反应（例如三聚）的趋势，因此很少用于有机合成中。在这里，我们表明，被掩盖的（封闭的）O-异氰酸酯前体允许一锅或级联反应序列，其特征在于用2-碘苯胺和2-碘苄胺进行碱催化的取代，然后进行铜催化的环化反应，形成苯并咪唑酮和3,4-二氢喹唑啉-2（1 H）-ones。这项工作表明，O-异氰酸酯可以作为合成含羟胺杂环的有效构件。
• Coumarin inhibitors of gyrase B with N -propargyloxy-carbamate as an effective pyrrole bioisostere
  作者：Anne-Marie Periers、Patrick Laurin、Didier Ferroud、Jean-Luc Haesslein、Michel Klich、Claudine Dupuis-Hamelin、Pascale Mauvais、Patrice Lassaigne、Alain Bonnefoy、Branislav Musicki

  DOI：10.1016/s0960-894x(99)00654-x

  日期：2000.1

  series of coumarin inhibitors of gyrase B bearing a N-propargyloxycarbamate at C-3' of noviose is presented. Replacement of the 5-methylpyrrole-2-carboxylate of coumarin drugs with an N-propargyloxycarbamate bioisostere leads to analogues with improved antibacterial activity. Analysis of crystal structures of coumarin antibiotics with the 24 kDa N-terminal domain of the gyrase B protein provides a

  介绍了一系列在新出生的C-3'处带有N-炔丙氧基氨基甲酸酯的促旋酶B香豆素抑制剂的合成和体外生物学特性。用N-炔丙氧基氨基甲酸酯生物甾醇替代香豆素药物的5-甲基吡咯-2-羧酸酯可产生具有改善的抗菌活性的类似物。分析具有回旋酶B蛋白的24 kDa N末端结构域的香豆素抗生素的晶体结构，为C-3'N-烷氧基氨基甲酸酯的出色抑制能力提供了一个合理的理由。
• 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.
• Design of [<i>R</i>-(<i>Z</i>)]-(+)-α-(Methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitrile (SB 202026), a Functionally Selective Azabicyclic Muscarinic M1 Agonist Incorporating the <i>N</i>-Methoxy Imidoyl Nitrile Group as a Novel Ester Bioisostere
  作者：Steven M. Bromidge、Frank Brown、Frederick Cassidy、Michael S. G. Clark、Steven Dabbs、Michael S. Hadley、Julie Hawkins、Julia M. Loudon、Christopher B. Naylor、Barry S. Orlek、Graham J. Riley

  DOI：10.1021/jm9702903

  日期：1997.12.1

  Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisostere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile R-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)-(Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.
• 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.