3-(benzyloxy)-17-(cyclopropylmethyl)-14-hydroxy-6β-(N,N-dimethylcarbamate)-4,5α-epoxymorphinan | 1166387-51-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 3-(benzyloxy)-17-(cyclopropylmethyl)-14-hydroxy-6β-(N,N-dimethylcarbamate)-4,5α-epoxymorphinan
• CAS: 1166387-51-4
• 化学式: C₃₀H₃₆N₂O₅
• 分子量: 504.626
• InChiKey: QQWZJDCVKIBJSU-INUSXLDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  71.47
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-17-(cyclopropylmethyl)-14-hydroxy-6β-(N,N-dimethylcarbamate)-4,5α-epoxymorphinan 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以40%的产率得到dimethyl-6beta-Naltrexamate
  参考文献：
  名称：

  Design, synthesis, and characterization of 6β-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes

  摘要：

  Since the mu opioid receptor (MOR) is known to be involved in the therapeutically relevant pathways leading to the manifestation of pain and addiction, we are currently studying the specific structural characteristics that promote antagonism at the MOR. The opiates 6 beta-naltrexol and 6 beta-naltrexamide function as neutral antagonists in in vitro and in vivo systems previously exposed to morphine, and are under investigation as improved treatments for narcotic dependence. In this research, we synthesized and characterized carbamate and sulfonate ester derivates of 6 beta-naltrexol that do not contain a protic group at C-6, and evaluated these compounds for opioid receptor affinity. In vitro receptor subtype (mu, kappa, and delta opioid receptors) binding data of the carbamate and sulfonate derivatives is reported. All four compounds synthesized exhibited affinity for the MOR better than the standard 6 beta-naltrexol HCl. Based on K-i data, the order of MOR affinity is as follows: 9 > 13 > 14 > 10 > 6 beta-naltrexol HCl. Carbamate 9 and tosylate 13 displayed subnanomolar affinity for the MOR, while 10 was the most mu-selective compound synthesized. In conclusion, our data indicate that the absence of a hydrogen-bond donor on the C-6 oxygen enhances rather than impedes the in vitro affinity of naltrexol derivatives for the MOR. Additionally, data also suggest that increasing the bulk around C-6 may allow control of subtype selectivity within these compound series. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.095
• 作为产物：
  描述：

  3-(benzyloxy)-4,5α-epoxy-6β,14-dihydroxy-17-(cyclopropylmethyl)morphinan 、 二甲氨基甲酰氯 在 吡啶 作用下， 以47%的产率得到3-(benzyloxy)-17-(cyclopropylmethyl)-14-hydroxy-6β-(N,N-dimethylcarbamate)-4,5α-epoxymorphinan
  参考文献：
  名称：

  Design, synthesis, and characterization of 6β-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes

  摘要：

  Since the mu opioid receptor (MOR) is known to be involved in the therapeutically relevant pathways leading to the manifestation of pain and addiction, we are currently studying the specific structural characteristics that promote antagonism at the MOR. The opiates 6 beta-naltrexol and 6 beta-naltrexamide function as neutral antagonists in in vitro and in vivo systems previously exposed to morphine, and are under investigation as improved treatments for narcotic dependence. In this research, we synthesized and characterized carbamate and sulfonate ester derivates of 6 beta-naltrexol that do not contain a protic group at C-6, and evaluated these compounds for opioid receptor affinity. In vitro receptor subtype (mu, kappa, and delta opioid receptors) binding data of the carbamate and sulfonate derivatives is reported. All four compounds synthesized exhibited affinity for the MOR better than the standard 6 beta-naltrexol HCl. Based on K-i data, the order of MOR affinity is as follows: 9 > 13 > 14 > 10 > 6 beta-naltrexol HCl. Carbamate 9 and tosylate 13 displayed subnanomolar affinity for the MOR, while 10 was the most mu-selective compound synthesized. In conclusion, our data indicate that the absence of a hydrogen-bond donor on the C-6 oxygen enhances rather than impedes the in vitro affinity of naltrexol derivatives for the MOR. Additionally, data also suggest that increasing the bulk around C-6 may allow control of subtype selectivity within these compound series. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.095