4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)amino]-thiophene-3-carboxylic acid | 1082561-02-1

• 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: 4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)amino]-thiophene-3-carboxylic acid
• 英文别名: 4-Ethyl-5-methyl-2-[(4-methylbenzoyl)amino]thiophene-3-carboxylic acid
• CAS: 1082561-02-1
• 化学式: C₁₆H₁₇NO₃S
• 分子量: 303.382
• InChiKey: ZKXHFFRGXJDLLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  94.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  丙醇 、 4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)amino]-thiophene-3-carboxylic acid 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以10%的产率得到n-propyl 4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)-amino]thiophene-3-carboxylate
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of 2-(Acylamino)thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABA_B Receptor

  摘要：

  Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABA(B) receptor by potentiating GTP gamma S stimulation induced by GABA at 2.5 and 25 mu M while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically. Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice. Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.

  DOI：

  10.1021/jm400144w
• 作为产物：
  描述：

  methyl 4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)-amino]thiophene-3-carboxylate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以60%的产率得到4-ethyl-5-methyl-2-[((4-methylphenyl)carbonyl)amino]-thiophene-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of 2-(Acylamino)thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABA_B Receptor

  摘要：

  Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABA(B) receptor by potentiating GTP gamma S stimulation induced by GABA at 2.5 and 25 mu M while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically. Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice. Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.

  DOI：

  10.1021/jm400144w

文献信息

• Synthesis and Pharmacological Characterization of 2-(Acylamino)thiophene Derivatives as Metabolically Stable, Orally Effective, Positive Allosteric Modulators of the GABA_B Receptor
  作者：Claudia Mugnaini、Valentina Pedani、Angelo Casu、Carla Lobina、Alberto Casti、Paola Maccioni、Alessandra Porcu、Daniela Giunta、Stefania Lamponi、Maurizio Solinas、Stefania Dragoni、Massimo Valoti、Giancarlo Colombo、Maria Paola Castelli、Gian Luigi Gessa、Federico Corelli

  DOI：10.1021/jm400144w

  日期：2013.5.9

  Two recently reported hit compounds, COR627 and COR628, underpinned the development of a series of 2-(acylamino)thiophene derivatives. Some of these compounds displayed significant activity in vitro as positive allosteric modulators of the GABA(B) receptor by potentiating GTP gamma S stimulation induced by GABA at 2.5 and 25 mu M while failing to exhibit intrinsic agonist activity. Compounds were also found to be effective in vivo, potentiating baclofen-induced sedation/hypnosis in DBA mice when administered either intraperitoneally or intragastrically. Although displaying a lower potency in vitro than the reference compound GS39783, the new compounds 6, 10, and 11 exhibited a higher efficacy in vivo: combination of these compounds with a per se nonsedative dose of baclofen resulted in shorter onset and longer duration of the loss of righting reflex in mice. Test compounds showed cytotoxic effects at concentrations comparable to or higher than those of GS39783 or BHF177.