10-methoxy-2-carboxy-1,2,3,4-tetrahydrophenanthren-4-one | 179041-56-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 10-methoxy-2-carboxy-1,2,3,4-tetrahydrophenanthren-4-one
• 英文别名: 10-methoxy-4-oxo-2,3-dihydro-1H-phenanthrene-2-carboxylic acid
• CAS: 179041-56-6
• 化学式: C₁₆H₁₄O₄
• 分子量: 270.285
• InChiKey: WPZHLBTUGYSVON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-methoxy-2-carboxy-1,2,3,4-tetrahydrophenanthren-4-one 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 70.0 ℃ 、101.32 kPa 条件下， 以83%的产率得到10-methoxy-2-carboxy-1,2,3,4-tetrahydrophenanthrene
  参考文献：
  名称：

  Synthesis of 2-Amido-2,3-dihydro-1H-phenalene Derivatives as New Conformationally Restricted Ligands for Melatonin Receptors

  摘要：

  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.

  DOI：

  10.1021/jm960219h
• 作为产物：
  描述：

  1-methoxy-2-(chloromethyl)naphthalene 在 sodium hydroxide 、 三氯化铝 、 sodium 、 乙酸酐 作用下， 以 硝基苯 为溶剂， 反应 2.08h， 生成 10-methoxy-2-carboxy-1,2,3,4-tetrahydrophenanthren-4-one
  参考文献：
  名称：

  Synthesis of 2-Amido-2,3-dihydro-1H-phenalene Derivatives as New Conformationally Restricted Ligands for Melatonin Receptors

  摘要：

  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.

  DOI：

  10.1021/jm960219h

文献信息

• Amides tricycliques, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：ADIR ET COMPAGNIE

  公开号：EP0737670A1

  公开（公告）日：1996-10-16

  L'invention concerne les composés de formule (I) : dans laquelle R7, R8, Y, n et A sont tels que définis dans la description. Médicaments.

  本发明涉及式 (I) 化合物： 其中 R7、R8、Y、n 和 A 如说明书中所定义。 药物。
• US5712312A
  申请人：——

  公开号：US5712312A

  公开（公告）日：1998-01-27
• US5849781A
  申请人：——

  公开号：US5849781A

  公开（公告）日：1998-12-15
• 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.