S22701

• 分子结构分类: 有机化合物 - 苯类化合物 - 非那烯类
• 英文名称: S22701
• 英文别名: N-(4-METHOXY-2,3-DIHYDRO-1H-PHENALEN-2-YL)PROPIONAMIDE；N-(4-methoxy-2,3-dihydro-1H-phenalen-2-yl)propanamide
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: AFVZJQYIPSPCKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-methoxy-2,3-dihydro-1H-phenalene-2-carboxylic acid 在 盐酸 、 sodium azide 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 丙酮 、 甲苯 为溶剂， 反应 5.42h， 生成 S22701
  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

• Synthesis of 2-Amido-2,3-dihydro-1<i>H</i>-phenalene Derivatives as New Conformationally Restricted Ligands for Melatonin Receptors
  作者：Monique Mathé-Allainmat、Florence Gaudy、Sames Sicsic、Anne-Laure Dangy-Caye、Shuren Shen、Béatrice Brémont、Zohra Benatalah、Michel Langlois、Pierre Renard、Philippe Delagrange

  DOI：10.1021/jm960219h

  日期：1996.1.1

  Tetrahydroanthracene, tetrahydrophenanthrene, and tetrahydrophenalene moieties were used to design novel constrained melatoninergic agents. Compounds 1 and 2 were synthesized from the cyclization of the aryl succinic acids 6a,b followed by catalytic reduction, Curtius degradation to the amino derivatives, and acetylation. The phenalene derivatives 3 were prepared by cyclization of the aza lactones of the corresponding alpha-N-acetyl amino acids. The ketone derivatives were reduced directly by catalytic hydrogenation to produce the compounds 3. The different compounds were evaluated in vitro in binding assays using 2-[I-125]iodomelatonin and chicken brain membranes. Melatonin and 2-acetamido-8-methoxytetralin were used as the reference compounds. The results showed the superiority of the dihydrophenalene framework 3 over tho se of tetrahydro anthracene and tetrahydrophenanthrene. 3a had relatively good affinity for melatonin receptors (K-i = 28.7 nM). Introduction of an additional methoxy group gave a derivative (3c) with nanomolar affinity (K-i = 0.7 nM), confirming the existence of a secondary binding site in the receptor which has been described previously. An increase in the affinity was also observed with the propionamido derivative 3e (K-i = 6.0 nM). The potential agonist properties of the compound 3e were evaluated on the dermal melanocytes of Xenopus laevis tadpoles. At the concentration of 2.3 nM (5 x K-i), melatonin gave melanophore index value of 1. Similarly to melatonin, 3e was shown to be a potent agonist of the melanosome aggregation.
• 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.