tert-butyl 4-(tert-butoxycarbonylamino)-5-(2-(2-fluorobenzoyl)phenylamino)-5-oxopentanoate | 1078723-92-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 4-(tert-butoxycarbonylamino)-5-(2-(2-fluorobenzoyl)phenylamino)-5-oxopentanoate
• 英文别名: 4-tert-butoxycarbonylamino-4-[2-(2-fluorobenzoyl)phenylcarbamoyl]-butyric acid tert-butyl ester；tert-butyl (4S)-5-[2-(2-fluorobenzoyl)anilino]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate
• CAS: 1078723-92-8
• 化学式: C₂₇H₃₃FN₂O₆
• 分子量: 500.567
• InChiKey: OUMRUWOJTFDYTR-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(tert-butoxycarbonylamino)-5-(2-(2-fluorobenzoyl)phenylamino)-5-oxopentanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Prevention of Drug-Induced Memory Impairment by Immunopharmacotherapy

  摘要：

  One approach to treating drug abuse uses antidrug antibodies to immunize subjects against the illicit substance rather than administering the CNS site of action. At present, passive vaccination therapeutics that target the specific CNS has recognized efficacy in treating certain gross symptoms of drug misuse, namely, motor activation, self-administration, and overdose. However, the potential for antibodies to prevent drug-induced changes involving finer cognitive processes, such as benzodiazepine-associated amnesia, remains unexplored. To address this concept, a flunitrazepam hapten was synthesized and employed in the generation of a panel of high affinity monoclonal antibodies. Anti-flunitrazepam mAb RCA3A3 (K-d.app = 200 nM) was tested in a mouse model of passive immunization and subsequent mole-equivalent challenge with flunitrazepam. Not only was flunitrazepam-induced sedation prevented but immunization also conferred protection to memory consolidation as assessed through contextual and cued fear conditioning paradigms. These results provide evidence that immunopharmacotherapeutic blockade of drug intoxication also preserves complex cognitive function.

  DOI：

  10.1021/jm800506v
• 作为产物：
  描述：

  叔丁氧羰基-L-谷氨酸-5-叔丁酯 、 2-氨基-2-氟苯甲酮 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.25h， 以80%的产率得到tert-butyl 4-(tert-butoxycarbonylamino)-5-(2-(2-fluorobenzoyl)phenylamino)-5-oxopentanoate
  参考文献：
  名称：

  Prevention of Drug-Induced Memory Impairment by Immunopharmacotherapy

  摘要：

  One approach to treating drug abuse uses antidrug antibodies to immunize subjects against the illicit substance rather than administering the CNS site of action. At present, passive vaccination therapeutics that target the specific CNS has recognized efficacy in treating certain gross symptoms of drug misuse, namely, motor activation, self-administration, and overdose. However, the potential for antibodies to prevent drug-induced changes involving finer cognitive processes, such as benzodiazepine-associated amnesia, remains unexplored. To address this concept, a flunitrazepam hapten was synthesized and employed in the generation of a panel of high affinity monoclonal antibodies. Anti-flunitrazepam mAb RCA3A3 (K-d.app = 200 nM) was tested in a mouse model of passive immunization and subsequent mole-equivalent challenge with flunitrazepam. Not only was flunitrazepam-induced sedation prevented but immunization also conferred protection to memory consolidation as assessed through contextual and cued fear conditioning paradigms. These results provide evidence that immunopharmacotherapeutic blockade of drug intoxication also preserves complex cognitive function.

  DOI：

  10.1021/jm800506v

文献信息

• Prevention of Drug-Induced Memory Impairment by Immunopharmacotherapy
  作者：Jennifer B. Treweek、Chengzao Sun、Alexander V. Mayorov、Longwu Qi、Coree L. Levy、Amanda J. Roberts、Tobin J. Dickerson、Kim D. Janda

  DOI：10.1021/jm800506v

  日期：2008.11.13

  One approach to treating drug abuse uses antidrug antibodies to immunize subjects against the illicit substance rather than administering the CNS site of action. At present, passive vaccination therapeutics that target the specific CNS has recognized efficacy in treating certain gross symptoms of drug misuse, namely, motor activation, self-administration, and overdose. However, the potential for antibodies to prevent drug-induced changes involving finer cognitive processes, such as benzodiazepine-associated amnesia, remains unexplored. To address this concept, a flunitrazepam hapten was synthesized and employed in the generation of a panel of high affinity monoclonal antibodies. Anti-flunitrazepam mAb RCA3A3 (K-d.app = 200 nM) was tested in a mouse model of passive immunization and subsequent mole-equivalent challenge with flunitrazepam. Not only was flunitrazepam-induced sedation prevented but immunization also conferred protection to memory consolidation as assessed through contextual and cued fear conditioning paradigms. These results provide evidence that immunopharmacotherapeutic blockade of drug intoxication also preserves complex cognitive function.