(S)-3-butyn-2-ol hydrogen phthalate | 100837-07-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-3-butyn-2-ol hydrogen phthalate
• 英文别名: 1,2-Benzenedicarboxylic acid, mono(1-methyl-2-propynyl) ester, (S)-；2-[(2S)-but-3-yn-2-yl]oxycarbonylbenzoic acid
• CAS: 100837-07-8
• 化学式: C₁₂H₁₀O₄
• 分子量: 218.209
• InChiKey: POOBVOATKBYZQF-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-butyn-2-ol hydrogen phthalate 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 2.0h， 以89%的产率得到(S)-(-)-3-丁炔-2-醇
  参考文献：
  名称：

  Cotterill, Ann S.; Gill, Melvyn; Gimenez, Alberto, Journal of the Chemical Society. Perkin transactions I, 1994, # 22, p. 3269 - 3276

  摘要：

  DOI：
• 作为产物：
  描述：

  1,2-苯二甲酸单(1-甲基-2-丙炔基)酯 生成 (S)-3-butyn-2-ol hydrogen phthalate
  参考文献：
  名称：

  Amide, urea, and carbamate analogs of the muscarinic agent [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride

  摘要：

  A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimulant activity and affinity of the new compounds we studied their ability to increase mean arterial blood pressure (MAP) in the pithed rat and their ability to displace the M1 receptor selective antagonist [H-3]pirenzepine from rabbit sympathetic ganglia. The quaternary ammonium derivatives of 1, but not their corresponding tertiary amines, displayed ganglionic stimulant properties. The urea derivative 14 and the acetamide derivative 18 were almost equipotent to 1 as ganglionic agonists. In addition, 14 and 18 showed only 2- to 3-fold less affinity to ganglionic muscarinic receptors than 1. Introduction of a methyl group in the 1 position of the butynyl chain of 1 and its 4-chlorophenyl analogue increased ganglionic stimulant potency. The resulting (+/-)-9 and (+/-)-11 were the most potent analogues in this study. They were found to be partial agonists and showed 5- and 16-fold higher potency than 1, respectively, in increasing the MAP. They also displayed 6- and 18-fold higher affinity than 1 for ganglionic M1 receptors. The (S)-enantiomers of 9 and 11 were 1.5- and 4.9-fold more potent, respectively, than their antipodes as ganglionic muscarinic stimulants. The C1-methyl-substituted urea and acetamide derivatives (15 and 19) were 1.5- and 3-fold less potent than 1 and displayed several-fold lower affinity for ganglionic M1 receptors. The new quaternary analogues retained the selectivity for ganglionic muscarinic receptors since they produced weak partial agonist effects on the guinea pig ileum and showed several-fold lower nicotinic activity than 1 in the frog rectus abdominis assay.

  DOI：

  10.1021/jm00093a011

文献信息

• Synthesis and pharmacology of the putative novel muscarinic agonist (S)-4-F-MePyMcN [(S)-4-(pyrrolidino)-1-methyl-2-butynyl-N-(4-fluorophenyl) carbamate oxalate]
  作者：Saleh Athmani、Karen N. Bradley、Alan L. Harvey、Edgar Kornisiuk、Diana Jerusalinsky

  DOI：10.1016/s0223-5234(99)80018-x

  日期：1998.12

  (S)-4-F-MePyMcN [(S)-4-(pyrrolidino)-l-methyl-2-butynyl-N-(4-fluorophenyl) carbamate oxalate] has been suggested to be a selective agonist at the M-1 subtype of muscarinic receptor [Lambrecht G. et al., Life Sci. 56 (1995) 815-822]. We synthesized the compound and tested its selectivity for different muscarinic receptors with binding experiments using rat cerebral cortex synaptosomal membranes and cloned human mi to m5 receptors and by functional experiments on rabbit vas deferens preparations. There was little difference in affinity for the compound at the different cloned muscarinic receptors (IC(50)s for displacement of H-3-N-methylscopolamine were 0.7-1.0 mu M). On rabbit vas deferens preparations, (S)-4-F-MePyMcN did reduce twitch responses to electrical stimulation like the known M-1 agonist McN-A-343, but unlike McN-A-343 the compound reduced postsynaptic sensitivity to noradrenaline, ATP and KCl. Because of these additional actions, (s)-4-F-MePyMcN may not be suitable as a tool to study M-1 muscarinic receptors selectively. (C) Elsevier, Paris.
• SMITH, ROGER A.;WHITE, ROBERT L.;KRANTZ, ALLEN, J. MED. CHEM., 31,(1988) N 8, C. 1558-1566
  作者：SMITH, ROGER A.、WHITE, ROBERT L.、KRANTZ, ALLEN

  DOI：——

  日期：——