(+/-)-methyl 2-(2,3-dihydro-5-methoxybenzofuran-3-yl)acetate | 93772-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (+/-)-methyl 2-(2,3-dihydro-5-methoxybenzofuran-3-yl)acetate
• 英文别名: 5-methoxy-2,3-dihydro-3-benzofuranacetic acid methylester；Methyl 5-Methoxy-2,3-dihydrobenzofuran-3-acetate；methyl 2-(5-methoxy-2,3-dihydro-1-benzofuran-3-yl)acetate
• CAS: 93772-89-5
• 化学式: C₁₂H₁₄O₄
• 分子量: 222.241
• InChiKey: UEYJPVIIMYMORG-UHFFFAOYSA-N

物化性质

• 沸点：
  292.0±33.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-methyl 2-(2,3-dihydro-5-methoxybenzofuran-3-yl)acetate 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 (+/-)-2-(5-methoxy-2,3-dihydrobenzofuran-3-yl)ethyl p-toluenesulfonate
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of a Series of Geometrically Constrained 5-HT_2A/2C Receptor Ligands

  摘要：

  In studies of the SAR of phenethylamine-type serotonin 5-HT2A receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT1A, 5-HT2A, and 5-HT2C receptors. The benzofuran-containing analogues, 6a and 6b, had significantly higher affinity for the 5-HT receptors tested than did the benzodi-hydrofuran-containing compounds, 4a, 4b, 5a, and 5b. The most potent compound (8-bromo-6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane, 6b, had K-i values for displacement of [I-125] -DOI from 5-HT2A and 5-HT2C cloned rat receptors of 2.6 and 1.1 nM, respectively. Despite their high affinity, the compounds of this naphthofuran series lacked high intrinsic activity at the 5-HT2A receptor as measured using the phosphoinositide hydrolysis assay. The most potent compound in vitro, 6b, was tested in the two-lever drug discrimination assay in rats trained to discriminate LSD from saline, and failed to substitute, a result typical for compounds with low intrinsic activity. Thus, although conformational constraint has led to high-affinity 5-HT2A ligands with partial agonist activity, all of the spatial and steric properties of the ligand necessary for full receptor activation have not yet been identified.

  DOI：

  10.1021/jm030064v
• 作为产物：
  描述：

  2,5-二甲氧基苯甲酸 在 palladium on activated charcoal 草酰氯 、 氢气 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 乙醇 、 氯仿 、 甲苯 、 苯 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 100.0h， 生成 (+/-)-methyl 2-(2,3-dihydro-5-methoxybenzofuran-3-yl)acetate
  参考文献：
  名称：

  取代萘并呋喃为致幻剂苯乙胺-麦角灵杂合分子，具有意想不到的毒蕈碱拮抗活性。

  摘要：

  合成了一系列取代的消旋萘并呋喃，作为两种主要的典型致幻药物类别（苯乙胺和色胺/麦角灵）的“混合”分子。尽管据推测这些新药可能对5-羟色胺5-HT2A / 2C受体亚型具有很高的亲和力，但仍观察到了对毒蕈碱受体的出乎意料的亲和力。最初合成用于本研究的化合物为（+/-）-抗-和合成-4-氨基-6-甲氧基-2a，3,4,5-四氢-2H-萘[1,8-bc]呋喃（4a ，b）和它们的8-溴衍生物4c，d。首先在训练中区分盐水与LSD酒石酸盐（0. 08 mg / kg）的大鼠中，分析了溴化伯胺4c，d在双杠杆药物歧视（DD）范式中的活性。还有4c 评估d在克隆的人5-HT 2A，5-HT 2B和5-HT 2C受体上与激动剂和拮抗剂放射性配体竞争的能力。在这些初步分析中发现顺式非对映异构体具有最高活性后，N-烷基化类似物syn-N，N-N-二甲基-4-氨基-6-甲氧基-2a，3,4,5-四氢-2H-萘并[1

  DOI：

  10.1021/jm980076u

文献信息

• CNS affecting 5-oxy-3-aminomethyl-dihydro-benzofurans and benzothiophenes
  申请人：H. Lundbeck A/S

  公开号：US04847254A1

  公开（公告）日：1989-07-11

  The present invention relates to 3-aminomethyl derivatives of indane, dihydrobenzofurane, dihydrobenzothiophene, and indoline, acid addition salts thereof, isomers thereof, methods of preparation, pharmaceutical compositions and method of treating CNS-disorders such as schizophrenia, Parkinson's disease, depression, anxiety, migraine and senile dementia, or in the cure of cardiovascular diseases, by administering such a derivative.

  本发明涉及吲烷、二氢苯并呋喃、二氢苯并噻吩和吲哚啉的3-氨基甲基衍生物，其酸加成盐、异构体、制备方法、药物组合物以及通过施用此类衍生物治疗中枢神经系统疾病如精神分裂症、帕金森病、抑郁症、焦虑症、偏头痛和老年痴呆症，或在治疗心血管疾病中的方法。
• Electron impact mass spectrometry of some 2,3-dihydro-1-benzofuran-3-acetic acids
  作者：Pierfrancesco Bravo、Calimero Ticozzi、Sergio Daolio、Pietro Traldi、Enrico Vecchi

  DOI：10.1002/oms.1210200112

  日期：1985.1

  AbstractThe mass spectrometric behaviour of four 2,3‐dihydro‐1‐benzofuran‐3‐acetic acids has been studied in detail with the aid of exact mass measurements, linked scans, collisionally activated decomposition, mass analysed ion kinetic energy spectra and labelling experiments. Unusual fragmentation pathways are emphasized for which mechanisms are proposed.
• Bravo, Pierfrancesco; Gentile, Anna; Ticozzi, Calimero, Gazzetta Chimica Italiana, 1984, vol. 114, # 3/4, p. 89 - 92
  作者：Bravo, Pierfrancesco、Gentile, Anna、Ticozzi, Calimero

  DOI：——

  日期：——
• Synthesis and Pharmacological Characterization of a Series of Geometrically Constrained 5-HT_2A/2C Receptor Ligands
  作者：James J. Chambers、Jason C. Parrish、Niels H. Jensen、Deborah M. Kurrasch-Orbaugh、Danuta Marona-Lewicka、David E. Nichols

  DOI：10.1021/jm030064v

  日期：2003.7.1

  In studies of the SAR of phenethylamine-type serotonin 5-HT2A receptor agonists, substituted conformationally constrained tetrahydronaphthofurans were designed to investigate the optimal conformation of the 2-aminoethyl moiety. These compounds were tested using in vitro assays for affinity at 5-HT1A, 5-HT2A, and 5-HT2C receptors. The benzofuran-containing analogues, 6a and 6b, had significantly higher affinity for the 5-HT receptors tested than did the benzodi-hydrofuran-containing compounds, 4a, 4b, 5a, and 5b. The most potent compound (8-bromo-6-methoxy-4,5-dihydro-3H-naphtho[1,8-bc]furan-5-yl)aminomethane, 6b, had K-i values for displacement of [I-125] -DOI from 5-HT2A and 5-HT2C cloned rat receptors of 2.6 and 1.1 nM, respectively. Despite their high affinity, the compounds of this naphthofuran series lacked high intrinsic activity at the 5-HT2A receptor as measured using the phosphoinositide hydrolysis assay. The most potent compound in vitro, 6b, was tested in the two-lever drug discrimination assay in rats trained to discriminate LSD from saline, and failed to substitute, a result typical for compounds with low intrinsic activity. Thus, although conformational constraint has led to high-affinity 5-HT2A ligands with partial agonist activity, all of the spatial and steric properties of the ligand necessary for full receptor activation have not yet been identified.
• Substituted Naphthofurans as Hallucinogenic Phenethylamine−Ergoline Hybrid Molecules with Unexpected Muscarinic Antagonist Activity
  作者：Aaron P. Monte、Danuta Marona-Lewicka、Mechelle M. Lewis、Richard B. Mailman、David B. Wainscott、David L. Nelson、David E. Nichols

  DOI：10.1021/jm980076u

  日期：1998.6.1

  have the highest activity in these preliminary assays, the N-alkylated analogues syn-N,N-dimethyl-4-amino-6-methoxy-2a,3,4, 5-tetrahydro-2H-naphtho[1,8-bc]furan (4e) and syn-N, N-dipropyl-4-amino-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1, 8-bc]furan (4f) were prepared and assayed for their affinities at [3H]ketanserin-labeled 5-HT2A and [3H]-8-OH-DPAT-labeled 5-HT1A sites. All of the molecules tested

  合成了一系列取代的消旋萘并呋喃，作为两种主要的典型致幻药物类别（苯乙胺和色胺/麦角灵）的“混合”分子。尽管据推测这些新药可能对5-羟色胺5-HT2A / 2C受体亚型具有很高的亲和力，但仍观察到了对毒蕈碱受体的出乎意料的亲和力。最初合成用于本研究的化合物为（+/-）-抗-和合成-4-氨基-6-甲氧基-2a，3,4,5-四氢-2H-萘[1,8-bc]呋喃（4a ，b）和它们的8-溴衍生物4c，d。首先在训练中区分盐水与LSD酒石酸盐（0. 08 mg / kg）的大鼠中，分析了溴化伯胺4c，d在双杠杆药物歧视（DD）范式中的活性。还有4c 评估d在克隆的人5-HT 2A，5-HT 2B和5-HT 2C受体上与激动剂和拮抗剂放射性配体竞争的能力。在这些初步分析中发现顺式非对映异构体具有最高活性后，N-烷基化类似物syn-N，N-N-二甲基-4-氨基-6-甲氧基-2a，3,4,5-四氢-2H-萘并[1