2-<4'-(Dimethylamino)-2'-butinyl>isoxazolidin-3-on | 116445-18-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2-<4'-(Dimethylamino)-2'-butinyl>isoxazolidin-3-on
• 英文别名: 2-(4-Dimethylamino-but-2-ynyl)-isoxazolidin-3-one；2-[4-(dimethylamino)but-2-ynyl]-1,2-oxazolidin-3-one
• CAS: 116445-18-2
• 化学式: C₉H₁₄N₂O₂
• mdl: MFCD09031496
• 分子量: 182.222
• InChiKey: ZDZCQJUIQDQGSU-UHFFFAOYSA-N

物化性质

• 熔点：
  113-116 °C
• 沸点：
  260.6±50.0 °C(Predicted)
• 密度：
  1.128±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-<4'-(Dimethylamino)-2'-butinyl>isoxazolidin-3-on 、 (6-bromohexyl)dimethyl-[3-(1,3-dioxo-1,3-dihydroisoindol-2-yl)propyl]ammonium bromide 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Design, Synthesis, and Action of Oxotremorine-Related Hybrid-Type Allosteric Modulators of Muscarinic Acetylcholine Receptors

  摘要：

  A novel series of muscarinic receptor ligands of the hexamethonio-type was prepared which contained, on one side, the phthalimidopropane or 1,8-naphthalimido-2,2-dimethylpropane moiety typical for subtype selective allosteric antagonists and, on the other, the acetylenic fragment typical for the nonselective orthosteric muscarinic agonists oxotremorine, oxotremorine-M, and related muscarinic agonists. Binding experiments in M-2 receptors using [H-3]N-methylseopolamine as an orthosteric probe proved an allosteric action of both groups of hybrids, 7a-10a and 8b-10b. The difference in activity between a-group and b-group hybrids corresponded with the activity difference between the allosteric parent compounds. In M-1-M-3 muscarinic isolated organ preparations, most of the hybrids behaved as subtype selective antagonists. [S-35]GTP gamma S binding assays using human M-2 receptors overexpressed. in CHO cells revealed that a weak intrinsic efficacy was preserved in 8b-10b. Thus, attaching muscarinic allosteric antagonist moieties to orthosteric muscarinic agonists may lead to hybrid compounds in which functions of both components are mixed.

  DOI：

  10.1021/jm050769s
• 作为产物：
  描述：

  二甲胺 、 2-(4-chloro-2-butynyl)isoxazolidin-3-one 以 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到2-<4'-(Dimethylamino)-2'-butinyl>isoxazolidin-3-on
  参考文献：
  名称：

  新型与oxotremorine和oxotremorine-M有关的衍生物的合成和功能表征。

  摘要：

  合成并测试了与氧代雷莫林和氧代雷莫林-M有关的两个非季铵化（5a-10a）和季铵化衍生物（5b-10b）的亚系列。在三种经典的体外功能测定中，估计了新化合物毒蕈碱受体亚型的激动剂效力：M1兔输精管，M2豚鼠左心房和M3豚鼠回肠。另外，将中毒蕈毒碱作用的发生评估为小鼠腹膜内给药后的致发色活性。在体外测试中，所有衍生物均表现出非选择性毒蕈碱活性，在某些情况下其效力值超过了参考化合物（即8b）。仅对类氧代短发膜样衍生物9a证明了其功能选择性，该衍生物表现为混合的M3激动剂/ M1拮抗剂（pD2 = 5.85； pA2 = 4.76，分别）。在体内试验中，非季铵化合物能够引起中央毒蕈碱作用，其效力与体外观察到的效力顺序平行。

  DOI：

  10.1016/s0968-0896(99)00107-8

文献信息

• Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M
  作者：Clelia Dallanoce、Paola Conti、Marco De Amici、Carlo De Micheli、Elisabetta Barocelli、Milena Chiavarini、Vigilio Ballabeni、Simona Bertoni、Mariannina Impicciatore

  DOI：10.1016/s0968-0896(99)00107-8

  日期：1999.8

  Two subseries of nonquaternized (5a-10a) and quaternized derivatives (5b-10b) related to oxotremorine and oxotremorine-M were synthesized and tested. The agonist potency at the muscarinic receptor subtypes of the new compounds was estimated in three classical in vitro functional assays: M1 rabbit vas deferens, M2 guinea pig left atrium and M3 guinea pig ileum. In addition, the occurrence of central

  合成并测试了与氧代雷莫林和氧代雷莫林-M有关的两个非季铵化（5a-10a）和季铵化衍生物（5b-10b）的亚系列。在三种经典的体外功能测定中，估计了新化合物毒蕈碱受体亚型的激动剂效力：M1兔输精管，M2豚鼠左心房和M3豚鼠回肠。另外，将中毒蕈毒碱作用的发生评估为小鼠腹膜内给药后的致发色活性。在体外测试中，所有衍生物均表现出非选择性毒蕈碱活性，在某些情况下其效力值超过了参考化合物（即8b）。仅对类氧代短发膜样衍生物9a证明了其功能选择性，该衍生物表现为混合的M3激动剂/ M1拮抗剂（pD2 = 5.85； pA2 = 4.76，分别）。在体内试验中，非季铵化合物能够引起中央毒蕈碱作用，其效力与体外观察到的效力顺序平行。
• Die Position 5 im Oxotremorin-Gerüst: Eine zentrale Stelle für die Steuerung der Aktivität am muscarinischen Rezeptor
  作者：René Amstutz、Annemarie Closse、Gernot Gmelin

  DOI：10.1002/hlca.19870700827

  日期：1987.12.16

  Position 5 at the Oxotremorine Skeleton as the Stearing Position for Activity at the Muscarinic Receptors

  Oxotremorine骨架上的位置5作为毒蕈碱受体活性的固定位置
• AMSTUTZ, RENE;CLOSSE, ANNEMARIE;GMELIN, GERNOT, HELV. CHIM. ACTA, 70,(1987) N 8, 2232-2244
  作者：AMSTUTZ, RENE、CLOSSE, ANNEMARIE、GMELIN, GERNOT

  DOI：——

  日期：——
• Design, Synthesis, and Action of Oxotremorine-Related Hybrid-Type Allosteric Modulators of Muscarinic Acetylcholine Receptors
  作者：Teresa Disingrini、Mathias Muth、Clelia Dallanoce、Elisabetta Barocelli、Simona Bertoni、Kerstin Kellershohn、Klaus Mohr、Marco De Amici、Ulrike Holzgrabe

  DOI：10.1021/jm050769s

  日期：2006.1.1

  A novel series of muscarinic receptor ligands of the hexamethonio-type was prepared which contained, on one side, the phthalimidopropane or 1,8-naphthalimido-2,2-dimethylpropane moiety typical for subtype selective allosteric antagonists and, on the other, the acetylenic fragment typical for the nonselective orthosteric muscarinic agonists oxotremorine, oxotremorine-M, and related muscarinic agonists. Binding experiments in M-2 receptors using [H-3]N-methylseopolamine as an orthosteric probe proved an allosteric action of both groups of hybrids, 7a-10a and 8b-10b. The difference in activity between a-group and b-group hybrids corresponded with the activity difference between the allosteric parent compounds. In M-1-M-3 muscarinic isolated organ preparations, most of the hybrids behaved as subtype selective antagonists. [S-35]GTP gamma S binding assays using human M-2 receptors overexpressed. in CHO cells revealed that a weak intrinsic efficacy was preserved in 8b-10b. Thus, attaching muscarinic allosteric antagonist moieties to orthosteric muscarinic agonists may lead to hybrid compounds in which functions of both components are mixed.