1-O-[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] 4-O-tert-butyl butanedioate | 1220780-51-7

• 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: 1-O-[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] 4-O-tert-butyl butanedioate
• CAS: 1220780-51-7
• 化学式: C₂₅H₃₁NO₆
• 分子量: 441.524
• InChiKey: LQVFBQMFHGMAAN-OSMRTBRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-O-[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] 4-O-tert-butyl butanedioate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 morphine-3-hemisuccinate
  参考文献：
  名称：

  Plasma-mediated release of morphine from synthesized prodrugs

  摘要：

  Two morphine prodrugs ('PDA' and 'PDB') were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5-10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine's release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.098
• 作为产物：
  描述：

  单叔丁基琥珀酸酯 、 吗啡 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 1-O-[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] 4-O-tert-butyl butanedioate
  参考文献：
  名称：

  Plasma-mediated release of morphine from synthesized prodrugs

  摘要：

  Two morphine prodrugs ('PDA' and 'PDB') were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5-10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine's release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.098

文献信息

• DENDRIMER CONJUGATES
  申请人：Baker, JR. James R.

  公开号：US20100160299A1

  公开（公告）日：2010-06-24

  The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.

  本发明涉及新型的治疗和诊断树状分子。具体而言，本发明涉及树状分子-连接剂共轭物、其合成方法、包含该共轭物的组合物，以及利用该共轭物的系统和方法（例如，在诊断和/或治疗设置中（例如，用于传递治疗剂、成像和/或靶向剂（例如，在疾病（例如，癌症）诊断和/或治疗、疼痛治疗等方面））。因此，本发明的树状分子-连接剂共轭物还可以包括一个或多个用于靶向、成像、感知和/或提供治疗或诊断材料以及/或监测治疗反应的组分。
• US8889635B2
  申请人：——

  公开号：US8889635B2

  公开（公告）日：2014-11-18
• US8980907B2
  申请人：——

  公开号：US8980907B2

  公开（公告）日：2015-03-17
• Plasma-mediated release of morphine from synthesized prodrugs
  作者：Thommey P. Thomas、Baohua Huang、Ankur Desai、Hong Zong、Xue-min Cheng、Alina Kotlyar、Pascale R. Leroueil、Thomas Dunham、Abraham van der Spek、Brent B. Ward、James R. Baker

  DOI：10.1016/j.bmcl.2010.08.098

  日期：2010.11

  Two morphine prodrugs ('PDA' and 'PDB') were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5-10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine's release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. (C) 2010 Elsevier Ltd. All rights reserved.