1,2-dimethoxy-10,11-dihydro-5H-dibenzocyclohepten-5-one | 170244-74-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: 1,2-dimethoxy-10,11-dihydro-5H-dibenzocyclohepten-5-one
• 英文别名: 6,7-Dimethoxytricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaen-2-one
• CAS: 170244-74-3
• 化学式: C₁₇H₁₆O₃
• 分子量: 268.312
• InChiKey: ZBJBVRQWUZCMEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-dimethoxy-10,11-dihydro-5H-dibenzocyclohepten-5-one 在 palladium on activated charcoal 盐酸 、 甲烷磺酸 、 NaBH₄CN 、 氢气 、 sodium hydride 、 二甲基亚砜 、 zinc(II) iodide 作用下， 以 甲醇 、 苯 为溶剂， 反应 31.83h， 生成 N-(trifluoroacetyl)-6,7-dimethoxy-2,3,4,8,9,13b-hexahydro-1H-benzo<6,7>cyclohepta<1,2,3-e,f><3>benzazepine
  参考文献：
  名称：

  Synthesis and Evaluation of 6,7-Dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 6,7-Dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, and 10-(Aminomethyl)-9,10-dihydro-1,2-dihydroxyanthracene as Conformationally Restricted Analogs of .beta.-Phenyldopamine

  摘要：

  The present study was designed to define the geometry of the hydrophobic accessory region for binding of dopamine Dr receptor ligands and to assess the relative importance of ethylamine side chain conformation for receptor affinity. Three compounds, 6,7-dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 4, 6,7-dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, 5, and 10-(aminomethyl)-9,10-dihydro-1 2-dihydroxyanthracene, 6, were synthesized as conformationally restricted analogs of beta-phenyldopamine. Molecular modeling studies were performed to compare these three compounds with the high-affinity D-1 agonists dihydrexidine (DHX), 2, and SKF 38393, 3. The beta-phenyl moieties in the target compounds are constrained by means of either an ethyl (4) or methylene (5 and 6) bridge. The compounds adopt minimum-energy conformations in which the beta-phenyl group is approximately -22 degrees (4), -12 degrees (5), and -30 degrees (6) from coplanarity with the catechol ring. These compounds also embody either a freely rotating (6) or a rigidified gauche (4 and 5) rotameric conformation of the dopamine ethylamine side chain, the latter nearly perfectly superimposible on the benzazepine portion of SKF 38393. Radioligand competition experiments showed that compounds 4, 5, and 6 have only micromolar affinity for both the D-1 and D-2 dopamine receptor subtypes. The low affinity of 4-6, relative to 2 and 3, may be due to improper orientation of the beta-phenyl moiety and provides important information about the three-dimensional orientation of the hydrophobic accessory binding domain of the dopamine D-1 receptor. In addition, the negligible affinity of 6, as compared to 2 and 3, indicates that the rotameric positioning of the ethylamine side chain may not be a primary determinant of receptor affinity.

  DOI：

  10.1021/jm00013a015
• 作为产物：
  描述：

  N-甲基邻甲苯酰胺 在 palladium on activated charcoal sodium hydroxide 、 正丁基锂 、 高氯酸 、 甲烷磺酸 、 氢气 、 phosphorus pentoxide 作用下， 以 乙醇 为溶剂， -10.0~25.0 ℃ 、344.73 kPa 条件下， 反应 68.83h， 生成 1,2-dimethoxy-10,11-dihydro-5H-dibenzocyclohepten-5-one
  参考文献：
  名称：

  Synthesis and Evaluation of 6,7-Dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 6,7-Dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, and 10-(Aminomethyl)-9,10-dihydro-1,2-dihydroxyanthracene as Conformationally Restricted Analogs of .beta.-Phenyldopamine

  摘要：

  The present study was designed to define the geometry of the hydrophobic accessory region for binding of dopamine Dr receptor ligands and to assess the relative importance of ethylamine side chain conformation for receptor affinity. Three compounds, 6,7-dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 4, 6,7-dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, 5, and 10-(aminomethyl)-9,10-dihydro-1 2-dihydroxyanthracene, 6, were synthesized as conformationally restricted analogs of beta-phenyldopamine. Molecular modeling studies were performed to compare these three compounds with the high-affinity D-1 agonists dihydrexidine (DHX), 2, and SKF 38393, 3. The beta-phenyl moieties in the target compounds are constrained by means of either an ethyl (4) or methylene (5 and 6) bridge. The compounds adopt minimum-energy conformations in which the beta-phenyl group is approximately -22 degrees (4), -12 degrees (5), and -30 degrees (6) from coplanarity with the catechol ring. These compounds also embody either a freely rotating (6) or a rigidified gauche (4 and 5) rotameric conformation of the dopamine ethylamine side chain, the latter nearly perfectly superimposible on the benzazepine portion of SKF 38393. Radioligand competition experiments showed that compounds 4, 5, and 6 have only micromolar affinity for both the D-1 and D-2 dopamine receptor subtypes. The low affinity of 4-6, relative to 2 and 3, may be due to improper orientation of the beta-phenyl moiety and provides important information about the three-dimensional orientation of the hydrophobic accessory binding domain of the dopamine D-1 receptor. In addition, the negligible affinity of 6, as compared to 2 and 3, indicates that the rotameric positioning of the ethylamine side chain may not be a primary determinant of receptor affinity.

  DOI：

  10.1021/jm00013a015

文献信息

• Tricyclic steroid hormone nuclear receptor modulators
  申请人：Coghlan Joseph Michael

  公开号：US20060063759A1

  公开（公告）日：2006-03-23

  The present invention relates to methods of treating pathological disorders susceptible to steroid hormone nuclear receptor modulation comprising administering to a patient in need thereof an effective amount of a compound of the formula (I): or a pharmaceutically acceptable salt thereof. In addition, the present invention provides novel pharmaceutical compounds of Formula (I), including the pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions which comprise as an active ingredient a compound of Formula (I).

  本发明涉及治疗对类固醇激素核受体调节敏感的病理性疾病的方法，包括向需要治疗的患者施用化合物（I）的有效量或其药学上可接受的盐。此外，本发明提供了公式（I）的新型药物化合物，包括其药学上可接受的盐，以及含有公式（I）化合物作为活性成分的药物组合物。
• TRICYCLIC STEROID HORMONE NUCLEAR RECEPTOR MODULATORS
  申请人：Coghlan Michael Joseph

  公开号：US20090149445A1

  公开（公告）日：2009-06-11

  The present invention relates to methods of treating pathological disorders susceptible to steroid hormone nuclear receptor modulation comprising administering to a patient in need thereof an effective amount of a compound of the formula: or a pharmaceutically acceptable salt thereof. In addition, the present invention provides novel pharmaceutical compounds of Formula I, including the pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions which comprise as an active ingredient a compound of Formula I.

  本发明涉及治疗容易受到类固醇激素核受体调节的病理性疾病的方法，包括向需要治疗的患者施用化合物的有效量，该化合物的公式为：或其药学上可接受的盐。此外，本发明提供了公式I的新型药物化合物，包括其药学上可接受的盐，以及含有公式I化合物作为活性成分的药物组合物。
• US7411072B2
  申请人：——

  公开号：US7411072B2

  公开（公告）日：2008-08-12
• [EN] TRICYCLIC STEROID HORMONE NUCLEAR RECEPTOR MODULATORS<br/>[FR] MODULATEURS TRICYCLIQUES DU RECEPTEUR NUCLEAIRE DES HORMONES STEROIDIENNES
  申请人：LILLY CO ELI

  公开号：WO2004052847A2

  公开（公告）日：2004-06-24

  The present invention relates to methods of treating pathological disorders susceptible to steroid hormone nuclear receptor modulation comprising administering to a patient in need thereof an effective amount of a compound of the formula (I): or a pharmaceutically acceptable salt thereof. In addition, the present invention provides novel pharmaceutical compounds of Formula (I), including the pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions which comprise as an active ingredient a compound of Formula (I).
• Synthesis and Evaluation of 6,7-Dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 6,7-Dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, and 10-(Aminomethyl)-9,10-dihydro-1,2-dihydroxyanthracene as Conformationally Restricted Analogs of .beta.-Phenyldopamine
  作者：Scott E. Snyder、Felix A. Aviles-Garay、Ratna Chakraborti、David E. Nichols、Val J. Watts、Richard B. Mailman

  DOI：10.1021/jm00013a015

  日期：1995.6

  The present study was designed to define the geometry of the hydrophobic accessory region for binding of dopamine Dr receptor ligands and to assess the relative importance of ethylamine side chain conformation for receptor affinity. Three compounds, 6,7-dihydroxy-2,3,4,8,9,13b-hexahydro-1H-benzo[6,7]cyclohepta[1,2,3-ef][3]benzazepine, 4, 6,7-dihydroxy-1,2,3,4,8,12b-hexahydroanthr[10,4a,4-cd]azepine, 5, and 10-(aminomethyl)-9,10-dihydro-1 2-dihydroxyanthracene, 6, were synthesized as conformationally restricted analogs of beta-phenyldopamine. Molecular modeling studies were performed to compare these three compounds with the high-affinity D-1 agonists dihydrexidine (DHX), 2, and SKF 38393, 3. The beta-phenyl moieties in the target compounds are constrained by means of either an ethyl (4) or methylene (5 and 6) bridge. The compounds adopt minimum-energy conformations in which the beta-phenyl group is approximately -22 degrees (4), -12 degrees (5), and -30 degrees (6) from coplanarity with the catechol ring. These compounds also embody either a freely rotating (6) or a rigidified gauche (4 and 5) rotameric conformation of the dopamine ethylamine side chain, the latter nearly perfectly superimposible on the benzazepine portion of SKF 38393. Radioligand competition experiments showed that compounds 4, 5, and 6 have only micromolar affinity for both the D-1 and D-2 dopamine receptor subtypes. The low affinity of 4-6, relative to 2 and 3, may be due to improper orientation of the beta-phenyl moiety and provides important information about the three-dimensional orientation of the hydrophobic accessory binding domain of the dopamine D-1 receptor. In addition, the negligible affinity of 6, as compared to 2 and 3, indicates that the rotameric positioning of the ethylamine side chain may not be a primary determinant of receptor affinity.