2,2-dimethyl-4,9-dioxo-3,11-dioxa-5,8-diazatridecan-13-oic acid

• 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: 2,2-dimethyl-4,9-dioxo-3,11-dioxa-5,8-diazatridecan-13-oic acid
• 英文别名: 2,2-Dimethyl-4,9-dioxo-3,11-dioxa-5,8-diazatridecan-13-oic acid；2-[2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylamino]-2-oxoethoxy]acetic acid
• 化学式: C₁₁H₂₀N₂O₆
• 分子量: 276.29
• InChiKey: FBZSEHDKBRFMEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-4,9-dioxo-3,11-dioxa-5,8-diazatridecan-13-oic acid 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(14-(((4αS,7S,7αR,12βS)-4α,9-dihydroxy-3-methyl-2,3,4,4α,5,6,7,7α-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)amino)-5,10,14-trioxo-3,12-dioxa-6,9-diazatetradecan-1-oyl)piperidin-4-yl)-4-methyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Bivalent Ligands That Target μ Opioid (MOP) and Cannabinoid1 (CB₁) Receptors Are Potent Analgesics Devoid of Tolerance

  摘要：

  Given that mu opioid (MOP) and canabinoid (CB1) receptors are colocalized in various regions of the central nervous system and have been reported to associate as heteromer (MOP-CB1) in cultured cells, the possibility of functional, endogenous MOP CB1 in nociception and other pharmacologic effects has been raised. As a first step in investigating this possibility, we have synthesized a series of bivalent ligands 1-5 that contain both mu agonist and CB1 antagonist pharmacophores for use as tools to study the functional interaction between MOP and CB1 receptors in vivo. Immunofluorescent studies on HEK293 cells coexpressing both receptors suggested 5 (20-atom spacer) to be the only member of the series that bridges the protomers of the heteromer. Antinociceptive testing in mice revealed 5 to be the most potent member of the series. As neither a mixture of monovalent ligands 9 + 10 nor bivalents 2-5 produced tolerance in mice, MOR-CB1 apparently is not an important target for reducing tolerance.

  DOI：

  10.1021/jm4005219
• 作为产物：
  描述：

  二甘醇酐 、 N-叔丁氧羰基-1,2-乙二胺 在 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 18.0h， 以85%的产率得到2,2-dimethyl-4,9-dioxo-3,11-dioxa-5,8-diazatridecan-13-oic acid
  参考文献：
  名称：

  通过改变发育序列的微环境，改善“困难肽”的固相肽合成

  摘要：

  通过将商业AMP聚合物与2- [2-（2-（2-氨基乙基氨基）-2-氧乙氧基]乙酸接枝，制备了三种与间隔基，环境和微环境模型有关的树脂。所有树脂均高载量并用Rink-酰胺连接基官能化。介绍了用Fmoc / t- Bu化学方法在制备的树脂上对经典困难序列ACP（65-74）的比较合成。“微环境”模型树脂可提供最高纯度（98％）的粗肽。

  DOI：

  10.1016/j.tetlet.2006.07.053

文献信息

• [EN] ANALGESIC CONJUGATES<br/>[FR] CONJUGUÉS ANALGÉSIQUES
  申请人：UNIV MINNESOTA

  公开号：WO2014124317A1

  公开（公告）日：2014-08-14

  The invention provides analgesic conjugates having a mu opioid receptor agonist linked to a mGluR5 antagonist, and to methods for producing analgesia using such compounds.

  该发明提供了一种镇痛共轭物，其中包含与mGluR5拮抗剂连接的mu阿片受体激动剂，并提供了使用这种化合物产生镇痛作用的方法。
• ANALGESIC CONJUGATES
  申请人：PORTOGHESE Philip

  公开号：US20150374836A1

  公开（公告）日：2015-12-31

  The invention provides analgesic conjugates having a mu opioid receptor agonist linked to a mGluR 5 antagonist, and to methods for producing analgesia using such compounds.

  本发明提供了一种镇痛偶联物，其中包括一个与mu型阿片受体激动剂连接的mGluR5拮抗剂，并提供了使用这些化合物产生镇痛的方法。
• Peptide-containing linkers for antibody-drug conjugates
  申请人：Mersana Therapeutics, Inc.

  公开号：US11135307B2

  公开（公告）日：2021-10-05

  The present disclosure relates generally to antibody-drug conjugates comprising peptide-containing linkers and to methods of using these conjugates as therapeutics and/or diagnostics. Also disclosed herein are peptide-containing scaffolds useful to conjugate with a targeting moiety (e.g., an antibody), a drug, or both to produce the antibody-drug conjugates.

  本公开一般涉及包含含肽连接体的抗体-药物共轭物，以及将这些共轭物用作治疗和/或诊断的方法。本文还公开了用于与靶向分子（如抗体）、药物或两者共轭以产生抗体-药物共轭物的含肽支架。
• [EN] PEPTIDE-CONTAINING LINKERS FOR ANTIBODY-DRUG CONJUGATES<br/>[FR] LIEURS CONTENANT DES PEPTIDES POUR DES CONJUGUÉS ANTICORPS-MÉDICAMENT
  申请人：MERSANA THERAPEUTICS INC

  公开号：WO2018098269A3

  公开（公告）日：2018-06-28
• PEPTIDE-CONTAINING LINKERS FOR ANTIBODY-DRUG CONJUGATES
  申请人：Mersana Therapeutics, Inc.

  公开号：US20180154018A1

  公开（公告）日：2018-06-07

  The present disclosure relates generally to antibody-drug conjugates comprising peptide-containing linkers and to methods of using these conjugates as therapeutics and/or diagnostics. Also disclosed herein are peptide-containing scaffolds useful to conjugate with a targeting moiety (e.g., an antibody), a drug, or both to produce the antibody-drug conjugates.