4-methoxy-2,2-(ethoxycarbonyl)-2,3-dihydro-1H-phenalene | 112892-73-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-methoxy-2,2-(ethoxycarbonyl)-2,3-dihydro-1H-phenalene
• 英文别名: Diethyl 4-methoxy-1,3-dihydrophenalene-2,2-dicarboxylate
• CAS: 112892-73-6
• 化学式: C₂₀H₂₂O₅
• 分子量: 342.392
• InChiKey: FNTGJDUZKXTYNC-UHFFFAOYSA-N

物化性质

• 沸点：
  463.5±45.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methoxy-2,2-(ethoxycarbonyl)-2,3-dihydro-1H-phenalene 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 4-methoxy-2,3-dihydro-1H-phenalene-2-carboxylic acid
  参考文献：
  名称：

  Melatonergic Properties of the (+)- and (−)-Enantiomers of N-(4-Methoxy-2,3-dihydro-1H-phenalen-2-yl)amide Derivatives

  摘要：

  N-(4-Methoxy-2,3-dihydro- 1H-phenalen-2-yl)amide derivatives, conformationally restricted ligands for melatonin receptors, were synthesized by an alternative synthetic method from the corresponding 1,8-naphthalic anhydride which was transformed into the phenalenecarboxylic acid 7. A Curtius reaction on 7 gave the amino compound which was acylated to give compounds 4a-c. The (+)- and (-)-4a-c enantiomers were separated by semipreparative chiral HPLC. Compounds were evaluated for their affinity for chicken brain melatonin receptors in binding assays using 2-[I-125]iodomelatonin and for their potency to light;en the skin of Xenopus laevis tadpoles. The butyramido derivative 4c was the most potent ligand (K-i = 1.7 nM). No enantioselectivity was observed with the enantiomers which were equipotent to the racemic mixture. In contrast to the reference compounds, melatonin, agomelatine (S 20098), and N-[2-(2,7-dimethoxynaphth-1-yl)ethyl]acetamide, which were very potent at Lightening the skin of X. laevis tadpoles, compounds 4a-c were inactive or weakly active (EC50 > 1 mu M). In this bioassay, compound 4a was characterized as a putative antagonist of melatonin receptors.

  DOI：

  10.1021/jm9804937
• 作为产物：
  描述：

  丙二酸二乙酯 、 1,8-Bis(bromomethyl)-2-methoxynaphthalene 在 sodium ethanolate 作用下， 生成 4-methoxy-2,2-(ethoxycarbonyl)-2,3-dihydro-1H-phenalene
  参考文献：
  名称：

  Melatonergic Properties of the (+)- and (−)-Enantiomers of N-(4-Methoxy-2,3-dihydro-1H-phenalen-2-yl)amide Derivatives

  摘要：

  N-(4-Methoxy-2,3-dihydro- 1H-phenalen-2-yl)amide derivatives, conformationally restricted ligands for melatonin receptors, were synthesized by an alternative synthetic method from the corresponding 1,8-naphthalic anhydride which was transformed into the phenalenecarboxylic acid 7. A Curtius reaction on 7 gave the amino compound which was acylated to give compounds 4a-c. The (+)- and (-)-4a-c enantiomers were separated by semipreparative chiral HPLC. Compounds were evaluated for their affinity for chicken brain melatonin receptors in binding assays using 2-[I-125]iodomelatonin and for their potency to light;en the skin of Xenopus laevis tadpoles. The butyramido derivative 4c was the most potent ligand (K-i = 1.7 nM). No enantioselectivity was observed with the enantiomers which were equipotent to the racemic mixture. In contrast to the reference compounds, melatonin, agomelatine (S 20098), and N-[2-(2,7-dimethoxynaphth-1-yl)ethyl]acetamide, which were very potent at Lightening the skin of X. laevis tadpoles, compounds 4a-c were inactive or weakly active (EC50 > 1 mu M). In this bioassay, compound 4a was characterized as a putative antagonist of melatonin receptors.

  DOI：

  10.1021/jm9804937

文献信息

• 2,3-Dihydro-1H-phenalene-2-amino compounds as anti-psychotic drugs
  申请人：THE UPJOHN COMPANY

  公开号：EP0234113A1

  公开（公告）日：1987-09-02

  2-3-Dihydro-1H-phenalene-2-amino compounds of the formula some of which are new, e.g., 2-3-dihydro-2-(N,N-di-n-propylamino)-1H-phenalen-5-ol, and pharmaceutically acceptable salts of such compounds have been found to be useful anti-psychotic drug compounds.

  已发现 2-3-二氢-1H-苯丙烯-2-氨基化合物（其中一些是新式化合物，如 2-3-二氢-2-（N,N-二正丙基氨基）-1H-苯丙烯-5-醇）以及此类化合物的药学上可接受的盐类是有用的抗精神病药物化合物。
• [EN] 2,3-DIHYDRO-1H-PHENALENE-2-AMINO COMPOUNDS AS ANTI-PSYCHOTIC DRUGS
  申请人：THE UPJOHN COMPANY

  公开号：WO1987004153A1

  公开（公告）日：1987-07-16

  (EN) 2,3-Dihydro-1H-phenalene-2-amino compounds of formula (I), some of which are new, e.g., 2,3-dihydro-2-(N,N-di-n-propylamino)-1H-phenalen-5-ol, and pharmaceutically acceptable salts of such compounds have been found to be useful anti-psychotic drug compounds.(FR) On a découvert que des composés de 2,3-dihydro-1H-phénalène-2-amine ayant la formule (I), dont certains sont de nouveaux composés, tels que 2,3-dihydro-2-(N,N-di-n-propylamino)-1H-phénalène-5-ol, et leurs sels pharmaceutiquement acceptables, constituent des composés utiles pour des médicaments anti-psychotiques.

  具有化学式（I）的2,3-双氢-1H-苯并吡咯-2-氨化合物，其中有些是新型化合物，例如2,3-双氢-2-(N,N-二-n-丙基氨基)-1H-苯并吡咯-5-ol，以及这种化合物的药用上可接受的盐类被发现是有用的抗精神病药物。
• 2,3-DIHYDRO-1H-PHENALENE-2-AMINO COMPOUNDS AS ANTI-PSYCHOTIC DRUGS
  申请人：THE UPJOHN COMPANY

  公开号：EP0288477A1

  公开（公告）日：1988-11-02
• Melatonergic Properties of the (+)- and (−)-Enantiomers of <i>N</i>-(4-Methoxy-2,3-dihydro-1<i>H</i>-phenalen-2-yl)amide Derivatives
  作者：Carole Jellimann、Monique Mathé-Allainmat、Jean Andrieux、Pierre Renard、Philippe Delagrange、Michel Langlois

  DOI：10.1021/jm9804937

  日期：1999.3.1

  N-(4-Methoxy-2,3-dihydro- 1H-phenalen-2-yl)amide derivatives, conformationally restricted ligands for melatonin receptors, were synthesized by an alternative synthetic method from the corresponding 1,8-naphthalic anhydride which was transformed into the phenalenecarboxylic acid 7. A Curtius reaction on 7 gave the amino compound which was acylated to give compounds 4a-c. The (+)- and (-)-4a-c enantiomers were separated by semipreparative chiral HPLC. Compounds were evaluated for their affinity for chicken brain melatonin receptors in binding assays using 2-[I-125]iodomelatonin and for their potency to light;en the skin of Xenopus laevis tadpoles. The butyramido derivative 4c was the most potent ligand (K-i = 1.7 nM). No enantioselectivity was observed with the enantiomers which were equipotent to the racemic mixture. In contrast to the reference compounds, melatonin, agomelatine (S 20098), and N-[2-(2,7-dimethoxynaphth-1-yl)ethyl]acetamide, which were very potent at Lightening the skin of X. laevis tadpoles, compounds 4a-c were inactive or weakly active (EC50 > 1 mu M). In this bioassay, compound 4a was characterized as a putative antagonist of melatonin receptors.