2-(4-chloro-2-butynyl)isoxazolidin-3-one | 191277-31-3

• 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-chloro-2-butynyl)isoxazolidin-3-one
• 英文别名: 3-Isoxazolidinone, 2-(4-chloro-2-butynyl)-；2-(4-chlorobut-2-ynyl)-1,2-oxazolidin-3-one
• CAS: 191277-31-3
• 化学式: C₇H₈ClNO₂
• mdl: MFCD09031497
• 分子量: 173.599
• InChiKey: VPAKRCFQHJKJBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(4-chloro-2-butynyl)isoxazolidin-3-one 以 甲醇 、 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：

  异噁唑啉-3-酮 、 1,4-二氯-2-丁炔 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 2-(4-chloro-2-butynyl)isoxazolidin-3-one
  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

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。
• Novel oxotremorine-related heterocyclic derivatives: Synthesis and in vitro pharmacology at the muscarinic receptor subtypes
  作者：Clelia Dallanoce、Marco De Amici、Elisabetta Barocelli、Simona Bertoni、Bryan L. Roth、Paul Ernsberger、Carlo De Micheli

  DOI：10.1016/j.bmc.2007.09.003

  日期：2007.12

  heterocyclic ligands (6-27) structurally related to Oxotremorine 2 was designed, synthesized and tested at muscarinic receptor subtypes (mAChRs). In the binding experiments at cloned human receptors (hm1-5), compounds 7 and 15 evidenced a remarkable affinity and selectivity for the hm2 subtype. The in vitro functional assays, performed on a selected group of derivatives at M(1), M(2), and M(3) tissue preparations

  在毒蕈碱受体亚型（mAChRs）上设计，合成和测试了一组与Oxotremorine 2结构相关的新型杂环配体（6-27）。在克隆的人类受体（hm1-5）的结合实验中，化合物7和15对hm2亚型表现出显着的亲和力和选择性。在M（1），M（2）和M（3）组织制备物上的一组选定的衍生物上进行的体外功能分析，选出了3-丁炔氧基-5-甲基异恶唑三甲基铵盐7作为有效的非选择性毒蕈碱激动剂[pEC（50）：7.40（M（1）），8.18（M（2））和8.14（M（3））]，而其5-苯基类似物12表现为毒蕈碱拮抗剂，对M（1）子类型[pK（B）：6.88（M（1）），5.95（M（2）），5.53（M（3））]。而且，
• Synthesis and binding affinity of new muscarinic ligands structurally related to oxotremorine
  作者：Paola Conti、Clelia Dallanoce、Marco De Amici、Carlo De Micheli、Bjarke Ebert

  DOI：10.1016/s0960-894x(97)00150-9

  日期：1997.4

  The synthesis and radioligand binding assays of a group of muscarinic ligands related to oxotremorine are reported. The new compounds displayed binding affinities comparable to those of the parent molecule with the exception of the trimethylammonium salt 6, which behaved as a fill muscarinic agonist and showed a pronounced selectivity for M-2 versus M-1 muscarinic receptor subtypes. (C) 1997 Elsevier Science Ltd.
• 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.
• 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.