4-[(S)-5-((amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl)-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester | 1221593-68-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-[(S)-5-((amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl)-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-[(S)-5-([amino-[2,2,4,6,7-pentarnethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl]-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester；4-[(S)-5-([amino-[2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl]-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester；4-[(S)-5-({amino-[2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl}-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester；4-[(S)-5-({Amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl}-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]piperazine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[(2S)-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-(naphthalen-2-ylsulfonylamino)pentanoyl]piperazine-1-carboxylate
• CAS: 1221593-68-5；1276540-64-7
• 化学式: C₃₈H₅₂N₆O₈S₂
• 分子量: 784.998
• InChiKey: WSAQRNGFHDHUMN-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  54
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  207
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-[(S)-5-((amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl)-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 生成 2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonic acid 1-amino-1-[(S)-4-(naphthalene-2-sulfonylamino)-5-oxo-5-piperazin-1-yl-pentylamino]-meth-(E)-ylideneamide
  参考文献：
  名称：

  Compositions Comprising Enzyme-Cleavable Phenol-Modified Opioid Prodrugs and Inhibitors Thereof

  摘要：

  提供了药物组合物及其使用方法，其中药物组合物包括一种苯酚修饰的阿片类前药，该前药提供酶控制释放苯酚类阿片类药物，并且包括与介导苯酚修饰的阿片类前药酶控制释放的酶相互作用的酶抑制剂，以调节苯酚修饰的阿片类前药的酶解。

  公开号：

  US20110262360A1
• 作为产物：
  描述：

  (S)-3-amino-2-tert-butoxycarbonylaminopropionic acid 在 NaOH 、 1-羟基苯并三唑 作用下， 以 四氢呋喃 、 氯仿 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-[(S)-5-((amino-[(E)-2,2,4,6,7-pentamethyl-2,3-dihydro-benzofuran-5-sulfonylimino]-methyl)-amino)-2-(naphthalene-2-sulfonylamino)-pentanoyl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PRODRUGS OF ACTIVE AGENTS AND INHIBITORS THEREOF

  摘要：

  本公开提供了药物组合物及其使用方法，其中药物组合物包括一种前药，该前药提供酶控释放药物的能力，以及一种酶抑制剂，与介导前药中药物酶控释放的酶相互作用，以减弱前药的酶解作用。该公开提供了包括酶抑制剂和含有酶可切割基团的前药的药物组合物，当切割时，促进药物释放。

  公开号：

  US20110262359A1

文献信息

• [EN] COMPOSITIONS COMPRISING ENZYME-CLEAVABLE OPIOID PRODRUGS AND INHIBITORS THEREOF<br/>[FR] COMPOSITIONS COMPRENANT DES PROMÉDICAMENTS OPIACÉS CLIVABLES PAR ENZYME ET LEURS INHIBITEURS
  申请人：PHARMACOFORE INC

  公开号：WO2011133149A1

  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。
• [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：Jenkins Thomas E.

  公开号：US20110262355A1

  公开（公告）日：2011-10-27

  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.

  提供的药物组合物及其使用方法，其中药物组合物包括一种阿片类药物的前药，该前药提供酶控释放的阿片类药物，以及一种酶抑制剂，该酶抑制剂与介导阿片类药物前药酶控释放的酶相互作用，以减弱对阿片类药物前药的酶切。
• [EN] COMPOSITIONS COMPRISING TRYPSIN-CLEAVABLE AMPHETAMINE PRODRUGS AND INHIBITORS THEREOF<br/>[FR] COMPOSITIONS COMPRENANT DES PROMÉDICAMENTS DE TYPE AMPHÉTAMINE CLIVABLES PAR TRYPSINE ET LEURS INHIBITEURS
  申请人：PHARMACOFORE INC

  公开号：WO2011133347A1

  公开（公告）日：2011-10-27

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

  提供药物组合物及其使用方法，其中药物组合物包括一种苯丙胺前药，可提供苯丙胺或苯丙胺类似物的酶控释放。该组合物还可以包括一个酶抑制剂，与介导苯丙胺前药中的苯丙胺或苯丙胺类似物的酶相互作用，以减弱苯丙胺前药的酶解裂。
• [EN] COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PHENOL-MODIFIED TAPENTADOL PRODRUG<br/>[FR] COMPOSITIONS COMPRENANT UN PROMÉDICAMENT DE TAPENTADOL MODIFIÉ PHÉNOL CLIVABLE PAR ENZYME
  申请人：PHARMACOFORE INC

  公开号：WO2011133178A1

  公开（公告）日：2011-10-27

  A method of providing a patient with controlled release of tapentadol using a prodrug capable, upon enzymatic activation and intramolecular cyclization, of releasing tapentadol 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 tapentadol from the prodrug so as to modify enzymatic cleavage of the prodrug. Also included are methods to use such compounds and pharmaceutical compositions.

  本发明揭示了一种利用能够在酶的活化和分子内环化时释放tapentadol的前药来为患者提供控制释放tapentadol的方法。该公开还提供了这种前药化合物和包含这种化合物的药物组合物。这种药物组合物可以选择性地包括与酶相互作用以调节从前药中释放tapentadol的酶控制释放的酶抑制剂，以修改前药的酶切割。还包括使用这种化合物和药物组合物的方法。