N-((S)-1-{2-[(dihydrocodein-6-enyloxycarbonyl)-methylamino]-ethylcarbamoyl-4-guanidino}-butyl)-malonamic acid | 1276121-96-0

• 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: N-((S)-1-{2-[(dihydrocodein-6-enyloxycarbonyl)-methylamino]-ethylcarbamoyl-4-guanidino}-butyl)-malonamic acid
• 英文别名: N-(S)-1-(2-((dihydrocodein-6-enyloxycarbonyl)-methylamino)-ethylcarbamoyl-4-guanidino-bulyl)-malonamic acid；3-[[(2S)-1-[2-[[(4R,4aR,7aR,12bS)-9-methoxy-3-methyl-2,4,4a,5,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]oxycarbonyl-methylamino]ethylamino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-oxopropanoic acid
• CAS: 1276121-96-0
• 化学式: C₃₁H₄₃N₇O₈
• 分子量: 641.725
• InChiKey: IEGJTNORZGIEKP-VZBCWKSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  46
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  211
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-((S)-1-{2-[(dihydrocodein-6-enyloxycarbonyl)-methylamino]-ethylcarbamoyl-4-guanidino}-butyl)-malonamic acid 在 盐酸 作用下， 以 乙醚 、 乙腈 为溶剂， 生成 N-((S)-1-{2-[(dihydrocodein-6-enyloxycarbonyl)-methylamino]-ethylcarbamoyl-4-guanidino}-butyl)-malonamic acid hydrochloride
  参考文献：
  名称：

  [EN] COMPOSITIONS COMPRISING ENZYME-CLEAVABLE OPIOID PRODRUGS AND INHIBITORS THEREOF
  [FR] COMPOSITIONS COMPRENANT DES PROMÉDICAMENTS OPIACÉS CLIVABLES PAR ENZYME ET LEURS INHIBITEURS

  摘要：

  本公开提供了一种药物组合物及其使用方法，其中所述药物组合物包含一种前药，该前药能够提供通过酶控释放的药物，以及一种酶抑制剂，该酶抑制剂与介导从该前药酶控释放药物的酶相互作用，以减弱前药的酶裂解。本公开还提供了包含酶抑制剂和含酶可裂解基团的前药的药物组合物，所述酶可裂解基团在裂解时有助于药物的释放。

  公开号：

  WO2011133149A1
• 作为产物：
  描述：

  二氢可待因酮 在 盐酸 、 双(三甲基硅烷基)氨基钾 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 间甲酚 、 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-) 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.41h， 生成 N-((S)-1-{2-[(dihydrocodein-6-enyloxycarbonyl)-methylamino]-ethylcarbamoyl-4-guanidino}-butyl)-malonamic acid
  参考文献：
  名称：

  [EN] COMPOSITIONS COMPRISING ENZYME-CLEAVABLE OPIOID PRODRUGS AND INHIBITORS THEREOF
  [FR] COMPOSITIONS COMPRENANT DES PROMÉDICAMENTS OPIACÉS CLIVABLES PAR ENZYME ET LEURS INHIBITEURS

  摘要：

  本公开提供了一种药物组合物及其使用方法，其中所述药物组合物包含一种前药，该前药能够提供通过酶控释放的药物，以及一种酶抑制剂，该酶抑制剂与介导从该前药酶控释放药物的酶相互作用，以减弱前药的酶裂解。本公开还提供了包含酶抑制剂和含酶可裂解基团的前药的药物组合物，所述酶可裂解基团在裂解时有助于药物的释放。

  公开号：

  WO2011133149A1

文献信息

• [EN] COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PRODRUGS OF ACTIVE AGENTS AND INHIBITORS THEREOF<br/>[FR] COMPOSITIONS COMPRENANT DES PROMÉDICAMENTS CLIVABLES PAR ENZYME DE PRINCIPES ACTIFS ET LEURS INHIBITEURS
  申请人：PHARMACOFORE INC

  公开号：WO2011133150A1

  公开（公告）日：2011-10-27

  The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.

  本公开提供了一种药物组合物及其使用方法，其中所述药物组合物包含一种前药，该前药能够提供通过酶控释放的药物，以及一种酶抑制剂，该酶抑制剂与介导药物从该前药通过酶控释放的酶相互作用，以减弱前药的酶切。本公开还提供了一种包含酶抑制剂和前药的药物组合物，所述前药包含一个酶可切割的部分，切割后可促进药物的释放。
• Compositions Comprising Enzyme-Cleavable Opioid Prodrugs and Inhibitors Thereof
  申请人：Signature Therapeutics, Inc.

  公开号：US20150297736A1

  公开（公告）日：2015-10-22

  Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an opioid prodrug that provides enzymatically-controlled release of an opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the opioid from the opioid prodrug so as to attenuate enzymatic cleavage of the opioid prodrug.

  提供了药物组合物及其使用方法，其中药物组合物包括鸦片类药物前药，该前药提供酶控制释放鸦片类药物，以及酶抑制剂，该酶抑制剂与介导鸦片类药物前药酶控制释放的酶相互作用，以减弱鸦片类药物前药的酶解。
• Compositions comprising enzyme-cleavable ketone-modified opioid prodrugs and optional inhibitors thereof
  申请人：Signature Therapeutics, Inc.

  公开号：US10028945B2

  公开（公告）日：2018-07-24

  A method of providing a patient with controlled release of ketone-containing opioid using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing the ketone-containing opioid is disclosed. The disclosure also provides such prodrug compounds and pharmaceutical compositions comprising such compounds. Such pharmaceutical compositions can optionally include an enzyme inhibitor that interacts with the enzyme(s) to mediate the enzymatically-controlled release of the ketone-containing opioid from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions.

  本发明公开了一种使用原药的方法，这种原药能够在酶活化和分子内环化后释放含酮阿片类药物，为患者提供控释含酮阿片类药物。本公开还提供了此类原药化合物和包含此类化合物的药物组合物。此类药物组合物可选择性地包括一种酶抑制剂，该酶抑制剂与酶相互作用，介导含酮阿片类药物从原药中的酶控释放，从而改变原药的酶裂解。此外，还包括使用此类化合物和药物组合物的方法。
• COMPOSITIONS COMPRISING ENZYME-CLEAVABLE KETONE-MODIFIED OPIOID PRODRUGS AND OPTIONAL INHIBITORS THEREOF
  申请人：Signature Therapeutics, Inc.

  公开号：EP2475429B1

  公开（公告）日：2015-07-29
• Compositions Comprising Enzyme-Cleavable Ketone-Modified Opioid Prodrugs and Optional Inhibitors Thereof
  申请人：Signature Therapeutics, Inc.

  公开号：US20170119754A1

  公开（公告）日：2017-05-04

  A method of providing a patient with controlled release of ketone-containing opioid using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing the ketone-containing opioid is disclosed. The disclosure also provides such prodrug compounds and pharmaceutical compositions comprising such compounds. Such pharmaceutical compositions can optionally include an enzyme inhibitor that interacts with the enzyme(s) to mediate the enzymatically-controlled release of the ketone-containing opioid from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions.