[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] [2-[5-(3-chlorophenyl)-4-methyl-2-oxo-1,3-oxazol-3-yl]-2-methylpropyl] carbonate | 908852-26-6

• 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: [(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] [2-[5-(3-chlorophenyl)-4-methyl-2-oxo-1,3-oxazol-3-yl]-2-methylpropyl] carbonate
• CAS: 908852-26-6
• 化学式: C₃₅H₃₉ClN₂O₈
• 分子量: 651.156
• InChiKey: JOJCISXNACYNRF-GMDWMDBXSA-N

物化性质

• 熔点：
  159.50 °C
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] [2-[5-(3-chlorophenyl)-4-methyl-2-oxo-1,3-oxazol-3-yl]-2-methylpropyl] carbonate 在 phosphate buffer 、 Hank's buffer 作用下， 以 水 为溶剂， 生成 羟基1-(3-氯苯基)-2-[(1,1-二甲基乙基)氨基]-1-丙酮盐酸盐 、 5-(3-chlorophenyl)-3-(2-hydroxy-1,1-dimethylethyl)-4-methyloxazolin-2-one 、 6-beta-纳曲醇盐酸盐
  参考文献：
  名称：

  Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6β-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents

  摘要：

  A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was to design and synthesize codrugs for simultaneous treatment of alcohol abuse and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was determined. These codrugs were generally less crystalline when compared to NTX, or NTXOL, as indicated by their lower melting points, and were expected to be more lipid-soluble. Also, the calculated clogP values were found to be higher for the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of the codrugs provided good evidence that they could be efficiently converted to the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to be cleaved enzymatically in vivo to generate the parent drugs, and are considered to be potential candidates for simultaneous treatment of alcohol abuse and tobacco dependence. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.06.018
• 作为产物：
  描述：

  3'-氯丙酮苯 在 溴 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 甲苯 为溶剂， 反应 144.17h， 生成 [(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,7-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] [2-[5-(3-chlorophenyl)-4-methyl-2-oxo-1,3-oxazol-3-yl]-2-methylpropyl] carbonate
  参考文献：
  名称：

  Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6β-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents

  摘要：

  A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was to design and synthesize codrugs for simultaneous treatment of alcohol abuse and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was determined. These codrugs were generally less crystalline when compared to NTX, or NTXOL, as indicated by their lower melting points, and were expected to be more lipid-soluble. Also, the calculated clogP values were found to be higher for the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of the codrugs provided good evidence that they could be efficiently converted to the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to be cleaved enzymatically in vivo to generate the parent drugs, and are considered to be potential candidates for simultaneous treatment of alcohol abuse and tobacco dependence. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.06.018

文献信息

• Enhancing transdermal delivery of opiod antagonists and agonistis using codrugs links to bupropion or hydroxybupropion
  申请人：Stinchcomb Audra L.

  公开号：US20090017102A1

  公开（公告）日：2009-01-15

  The present invention is directed to novel codrugs comprising bupropion or hydroxybupropion and an opioid antagonist or an opioid agonist joined together by chemical bonding. The codrugs provide a significant increase in the transdermal flux across human skin, as compared to the basic opioid antagonist or opioid agonist.

  本发明涉及新颖的共药物，包括由化学键连接的丁丙诺啡或羟基丁丙诺啡与阿片类拮抗剂或阿片类激动剂。与基本的阿片类拮抗剂或阿片类激动剂相比，这些共药物在人类皮肤上的透皮通量有显著提高。