O-(pent-2-ynyl)hydroxylamine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: O-(pent-2-ynyl)hydroxylamine
• 英文别名: O-pent-2-ynylhydroxylamine
• 化学式: C₅H₉NO
• 分子量: 99.1326
• InChiKey: KITGTUKUPBYKSM-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：
  1
• 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-(pent-2-ynyl)hydroxylamine 以 甲醇 为溶剂， 反应 18.0h， 以52%的产率得到quinuclidin-3-one O-(pent-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-戊炔-1-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-(pent-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

• Identification of an oxime-containing C-glucosylarene as a potential inhibitor of sodium-dependent glucose co-transporter 2
  作者：Mao-Chia Yuan、Teng-Kuang Yeh、Chiung-Tong Chen、Jen-Shin Song、Yu-Chen Huang、Tsung-Chih Hsieh、Chung-Yu Huang、Yu-Ling Huang、Min-Hsien Wang、Szu-Huei Wu、Chun-Hsu Yao、Yu-Sheng Chao、Jinq-Chyi Lee

  DOI：10.1016/j.ejmech.2017.11.019

  日期：2018.1

  hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management. In this study, twenty-seven aryl C-glycosides bearing a C=N/C−N linkage at the glucosyl C6 position were designed, synthesized and evaluated for their inhibitory activity against human SGLT2 (hSGLT2). Compounds with good hSGLT2

  用可通过抑制钠依赖性葡萄糖共转运蛋白2（SGLT2）阻断肾脏葡萄糖再吸收的药物治疗高血糖症，是治疗糖尿病的一种新方法。在这项研究中，设计，合成和评估了在葡萄糖基C6位置带有C = N / C-N键的27个芳基C-糖苷对人SGLT2（hSGLT2）的抑制活性。进一步研究了具有良好hSGLT2抑制作用的化合物，以确定它们对hSGLT1的选择性。其中，选择五个代表性的芳基C-糖苷进行药代动力学分析。肟2a被确定具有最有希望的药代动力学特性，并被选择用于体内葡萄糖尿和血浆葡萄糖水平的研究，发现它与dapagliflozin（1）表现出可比的功效。此外，未发现2a表现出明显的细胞毒性（CC 50  > 50μM）或人类以太相关基因（hERG）抑制（在10μM时抑制2％）。综上所述，这些努力最终导致了肟2a作为潜在SGLT2抑制剂的发现。
• 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.