6,7-didehydro-17-(4-methoxybutyl)quinolino[2',3':6,7]morphinan-3,14β-diol

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 6,7-didehydro-17-(4-methoxybutyl)quinolino[2',3':6,7]morphinan-3,14β-diol
• 英文别名: (1R,14S,15S)-25-(4-methoxybutyl)-4,25-diazahexacyclo[13.7.3.01,14.03,12.05,10.017,22]pentacosa-3,5,7,9,11,17(22),18,20-octaene-14,20-diol
• 化学式: C₂₈H₃₂N₂O₃
• 分子量: 444.574
• InChiKey: ADLIDRPYORWYJH-UPRLRBBYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.77
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  65.82
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  6,7-didehydro-17-(4-methoxybutyl)quinolino[2',3':6,7]morphinan-3,14β-diol 在 盐酸 作用下， 以 甲醇 、 氯仿 为溶剂， 以74%的产率得到6,7-didehydro-17-(4-methoxybutyl)quinolino[2',3':6,7]morphinan-3,14β-diol dihydrochloride
  参考文献：
  名称：

  The most effective influence of 17-(3-ethoxypropyl) substituent on the binding affinity and the agonistic activity in KNT-127 derivatives, δ opioid receptor agonists

  摘要：

  We investigated the structure-activity relationship of KNT-127 (opioid delta agonist) derivatives with various 17-substituents which are different in length and size. The 17-substituent in KNT-127 derivatives exerted a great influence on the affinity and agonistic activity for the delta receptor. While the compounds with electron-donating 17-substituents showed higher affinities for the delta receptor than those with electron-withdrawing groups, KNT-127 derivatives with 17-fluoroalkyl groups (the high electron-withdrawing groups) showed high selectivities for the delta receptor among evaluated compounds. In addition, the basicity of nitrogen as well as the structure of the 17-N substituent such as the length and configuration at an asymmetric carbon atom contributed to agonist properties for the delta receptor. Thus, the analog with a 17-(3-ethoxypropyl) group showed the best selectively and potent agonistic activity for the delta receptor among KNT-127 derivatives. These findings should be useful for designing novel delta selective agonists. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.032
• 作为产物：
  描述：

  1-溴-4-甲氧基丁烷 在 盐酸 、 甲烷磺酸 、 丙烷-1-硫醇 、 potassium tert-butylate 、 potassium carbonate 、 sodium iodide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 17.5h， 生成 6,7-didehydro-17-(4-methoxybutyl)quinolino[2',3':6,7]morphinan-3,14β-diol
  参考文献：
  名称：

  The most effective influence of 17-(3-ethoxypropyl) substituent on the binding affinity and the agonistic activity in KNT-127 derivatives, δ opioid receptor agonists

  摘要：

  We investigated the structure-activity relationship of KNT-127 (opioid delta agonist) derivatives with various 17-substituents which are different in length and size. The 17-substituent in KNT-127 derivatives exerted a great influence on the affinity and agonistic activity for the delta receptor. While the compounds with electron-donating 17-substituents showed higher affinities for the delta receptor than those with electron-withdrawing groups, KNT-127 derivatives with 17-fluoroalkyl groups (the high electron-withdrawing groups) showed high selectivities for the delta receptor among evaluated compounds. In addition, the basicity of nitrogen as well as the structure of the 17-N substituent such as the length and configuration at an asymmetric carbon atom contributed to agonist properties for the delta receptor. Thus, the analog with a 17-(3-ethoxypropyl) group showed the best selectively and potent agonistic activity for the delta receptor among KNT-127 derivatives. These findings should be useful for designing novel delta selective agonists. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.10.032

文献信息

• The most effective influence of 17-(3-ethoxypropyl) substituent on the binding affinity and the agonistic activity in KNT-127 derivatives, δ opioid receptor agonists
  作者：Toru Nemoto、Yoshihiro Ida、Yusuke Iihara、Ryo Nakajima、Shigeto Hirayama、Takashi Iwai、Hideaki Fujii、Hiroshi Nagase

  DOI：10.1016/j.bmc.2013.10.032

  日期：2013.12

  We investigated the structure-activity relationship of KNT-127 (opioid delta agonist) derivatives with various 17-substituents which are different in length and size. The 17-substituent in KNT-127 derivatives exerted a great influence on the affinity and agonistic activity for the delta receptor. While the compounds with electron-donating 17-substituents showed higher affinities for the delta receptor than those with electron-withdrawing groups, KNT-127 derivatives with 17-fluoroalkyl groups (the high electron-withdrawing groups) showed high selectivities for the delta receptor among evaluated compounds. In addition, the basicity of nitrogen as well as the structure of the 17-N substituent such as the length and configuration at an asymmetric carbon atom contributed to agonist properties for the delta receptor. Thus, the analog with a 17-(3-ethoxypropyl) group showed the best selectively and potent agonistic activity for the delta receptor among KNT-127 derivatives. These findings should be useful for designing novel delta selective agonists. (C) 2013 Elsevier Ltd. All rights reserved.