N-(5-methoxy-2-indanyl)acetamide | 81593-53-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-(5-methoxy-2-indanyl)acetamide
• 英文别名: N-(5-methoxy-2,3-dihydro-1H-inden-2-yl)acetamide
• CAS: 81593-53-5
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: CEGIWWPLLBWSKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(5-methoxy-2-indanyl)acetamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以60.1%的产率得到N-ethyl-5-methoxy-2-indanylamine hydrochloride
  参考文献：
  名称：

  痉挛剂。I.具有苯乙胺样部分的氨基醇酯。

  摘要：

  制备了一系列苯乙胺的半刚性类似物作为美贝维林的固定反式和顺式类似物，并测试了体外解痉活性。固定的反式类似物比相应的顺式类似物更有效。在该系列中，被认为具有反式构象的四氢-2-萘胺衍生物(2a)具有最强的活性，而被认为具有典型顺式构象的四氢异喹啉衍生物(2g和2h)活性较低。这些结果表明美贝维林的苯乙胺部分采用反式构象来表现解痉活性。

  DOI：

  10.1248/cpb.30.180
• 作为产物：
  描述：

  5-甲氧基-2-氨基茚盐酸盐 、 乙酸酐 以 水 、 溶剂黄146 为溶剂， 反应 1.33h， 以62.9%的产率得到N-(5-methoxy-2-indanyl)acetamide
  参考文献：
  名称：

  痉挛剂。I.具有苯乙胺样部分的氨基醇酯。

  摘要：

  制备了一系列苯乙胺的半刚性类似物作为美贝维林的固定反式和顺式类似物，并测试了体外解痉活性。固定的反式类似物比相应的顺式类似物更有效。在该系列中，被认为具有反式构象的四氢-2-萘胺衍生物(2a)具有最强的活性，而被认为具有典型顺式构象的四氢异喹啉衍生物(2g和2h)活性较低。这些结果表明美贝维林的苯乙胺部分采用反式构象来表现解痉活性。

  DOI：

  10.1248/cpb.30.180

文献信息

• Pharmacokinetic and pharmacodynamic evaluation of 5-methoxy-2-aminoindane (MEAI): A new binge-mitigating agent
  作者：Jakob A. Shimshoni、Eyal Sobol、Ezekiel Golan、Yulius Ben Ari、Orit Gal

  DOI：10.1016/j.taap.2018.02.009

  日期：2018.3

  5-Methoxy-2-aminoindane (MEAI) is a novel psychoactive aminoindane derivative, exerting euphoric, alcohol like tipsy experience and reduced desire to consume alcoholic beverages. Our previous toxicological evaluation of MEAI in rats, clearly indicated MEAI's potential to be further evaluated as a promising binge mitigating agent due to its favorable safety profile. In the light of these observations, we have determined MEAI's pharmacokinetic (PK) profile in rats and evaluated in-vitro its pharmacodynamics (PD) profile. Following oral and intravenous administration of MEAL two metabolites were identified, namely, N-acetyl-MEAI and 5-hydroxy-Nacetyl-Al, arising from N-acetylation and oxidative demethylation. The PK-parameters of MEAI and N-acetyl-MEAI were derived from single i.v. bolus (10 mg/kg) and single oral doses (10 and 90 mg/kg) of MEAT to rats. MEAI displayed extensive total clearance (2.8 L/h/kg) and a very short plasma and brain half-life (0.5-0.7 h). At 10 mg/kg, MEAI displayed low oral bioavailability (25%) and a plasma to brain ratio in the range of 3-5.5, with brain MEAI peak levels attained rapidly. Non-linear pharmacokinetic behavior was observed in the 90 mg/kg oral group, in which the bioavailability increased by 500%. The non-linear behavior was also evident by the significant increase in plasma half-life of MEAI and its metabolite, N-acetyl-MEAI. N-acetyl-MEAI levels in plasma and brain were about ten times lower than the parent compound, indicative of its minor contribution to MEAI's pharmacological effect. MEAI displayed weak to moderate ligand binding inhibition at the 5-HT2B receptor, while the remaining neurochemical targets were unaffected. Further studies, in non-rodent species are required, in-order to assess MEAI's PK and PD profile adequately.