1,2-dimethoxy-6-methanesulfonyl-5,6,6a,7-tetrahydro-4H-benzo[de][1,3]benzodioxolo[5,6-g]quinoline | 1241834-05-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: 1,2-dimethoxy-6-methanesulfonyl-5,6,6a,7-tetrahydro-4H-benzo[de][1,3]benzodioxolo[5,6-g]quinoline
• 英文别名: 18,19-Dimethoxy-13-methylsulfonyl-5,7-dioxa-13-azapentacyclo[10.7.1.02,10.04,8.016,20]icosa-1(20),2,4(8),9,16,18-hexaene
• CAS: 1241834-05-8
• 化学式: C₂₀H₂₁NO₆S
• 分子量: 403.456
• InChiKey: QNHBDNRZLCNOBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  82.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (+/-)-Nornantenine 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以55%的产率得到1,2-dimethoxy-6-methanesulfonyl-5,6,6a,7-tetrahydro-4H-benzo[de][1,3]benzodioxolo[5,6-g]quinoline
  参考文献：
  名称：

  Affinity of aporphines for the human 5-HT2A receptor: Insights from homology modeling and molecular docking studies

  摘要：

  Analogs of nantenine were docked into a modeled structure of the human 5-HT2A receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K-e) data. The GOLD docking algorithm when used with a homology model of 5-HT2A, based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT2A receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2010.06.043

文献信息

• Affinity of aporphines for the human 5-HT2A receptor: Insights from homology modeling and molecular docking studies
  作者：Stevan Pecic、Pooja Makkar、Sandeep Chaudhary、Boojala V. Reddy、Hernan A. Navarro、Wayne W. Harding

  DOI：10.1016/j.bmc.2010.06.043

  日期：2010.8

  Analogs of nantenine were docked into a modeled structure of the human 5-HT2A receptor using ICM Pro, GLIDE, and GOLD docking methods. The resultant docking scores were used to correlate with observed in vitro apparent affinity (K-e) data. The GOLD docking algorithm when used with a homology model of 5-HT2A, based on a bovine rhodopsin template and built by the program MODELLER, gives results which are most in agreement with the in vitro results. Further analysis of the docking poses among members of a C1 alkyl series of nantenine analogs, indicate that they bind to the receptor in a similar orientation, but differently than nantenine. Besides an important interaction between the protonated nitrogen of the C1 alkyl analogs and residue Asp155, we identified Ser242, Phe234, and Gly238 as key residues responsible for the affinity of these compounds for the 5-HT2A receptor. Specifically, the ability of some of these analogs to establish a H-bond with Ser242 and hydrophobic interactions with Phe234 and Gly238 appears to explain their enhanced affinity as compared to nantenine. Published by Elsevier Ltd.