4-(4,5-二氢-1,2-恶唑-3-基氧基)-2-丁炔-1-醇 | 247079-77-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 中文名称: 4-(4,5-二氢-1,2-恶唑-3-基氧基)-2-丁炔-1-醇
• 英文名称: 3-(4-hydroxy-2-butynyl)oxy-Δ²-isoxazoline
• 英文别名: 2-Butyn-1-OL, 4-[(4,5-dihydro-3-isoxazolyl)oxy]-；4-(4,5-dihydro-1,2-oxazol-3-yloxy)but-2-yn-1-ol
• CAS: 247079-77-2
• 化学式: C₇H₉NO₃
• mdl: MFCD18813536
• 分子量: 155.153
• InChiKey: VAYCMHLSEXCAGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4,5-二氢-1,2-恶唑-3-基氧基)-2-丁炔-1-醇 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 3-[4-(2-methyl-1H-imidazol-1-yl)-2-butynyl]oxy-Δ²-isoxazoline
  参考文献：
  名称：

  Synthesis and in vitro pharmacology of novel heterocyclic muscarinic ligands

  摘要：

  A set of novel heterocyclic ligands (7a-9a, 7b-9b, and 9c) structurally related to oxotremorine 2 was designed, synthesized, and tested at muscarinic receptor subtypes. In the binding experiments at cloned hm1-5, the presence of the 2-methylimidazole/2-methyl-3-alkylimidazolium moiety in place of the pyrrolidine ring revealed, in derivatives 8a, 8b, and 9c, a moderate selectivity for some receptor subtypes. The functional in vitro assays yielded results that correlated closely to binding data. In general, on passing from agonists bearing the pyrrolidine moiety to their analogues carrying the 2-methylimidazole function, the overall pharmacological efficacy profile is shifted from agonism toward partial agonism. The insertion of the 2-methyl-3-alkylimidazolium moiety advances the effect such that the compounds are pure antagonists. Quite similarly, chiral 3-oxo-Delta(2)-isoxazoline (+/-)-10 behaved as a weak antagonist unable to discriminate the different muscarinic receptor subtypes.

  DOI：

  10.1016/s0014-827x(03)00113-7
• 作为产物：
  描述：

  丁炔二醇 、 3-硝基-4,5-二氢异噁唑 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以51%的产率得到4-(4,5-二氢-1,2-恶唑-3-基氧基)-2-丁炔-1-醇
  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。
• Synthesis and in vitro pharmacology of novel heterocyclic muscarinic ligands
  作者：Marco De Amici、Paola Conti、Ezio Fasoli、Elisabetta Barocelli、Vigilio Ballabeni、Simona Bertoni、Mariannina Impicciatore、Bryan L Roth、Paul Ernsberger、Carlo De Micheli

  DOI：10.1016/s0014-827x(03)00113-7

  日期：2003.9

  A set of novel heterocyclic ligands (7a-9a, 7b-9b, and 9c) structurally related to oxotremorine 2 was designed, synthesized, and tested at muscarinic receptor subtypes. In the binding experiments at cloned hm1-5, the presence of the 2-methylimidazole/2-methyl-3-alkylimidazolium moiety in place of the pyrrolidine ring revealed, in derivatives 8a, 8b, and 9c, a moderate selectivity for some receptor subtypes. The functional in vitro assays yielded results that correlated closely to binding data. In general, on passing from agonists bearing the pyrrolidine moiety to their analogues carrying the 2-methylimidazole function, the overall pharmacological efficacy profile is shifted from agonism toward partial agonism. The insertion of the 2-methyl-3-alkylimidazolium moiety advances the effect such that the compounds are pure antagonists. Quite similarly, chiral 3-oxo-Delta(2)-isoxazoline (+/-)-10 behaved as a weak antagonist unable to discriminate the different muscarinic receptor subtypes.