(2S,3S)-3-[[[(1R)-3-methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-oxiranecarboxylic acid | 81739-94-8

• 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: (2S,3S)-3-[[[(1R)-3-methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-oxiranecarboxylic acid
• 英文别名: Loxistatin Acid (E-64C)；(2R,3R)-3-[[(2R)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid
• CAS: 81739-94-8
• 化学式: C₁₅H₂₆N₂O₅
• 分子量: 314.382
• InChiKey: SCMSYZJDIQPSDI-IJLUTSLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-[[[(1R)-3-methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-oxiranecarboxylic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3R)-3-[[(2R)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carbonyl chloride
  参考文献：
  名称：

  WO2007/38772

  摘要：

  公开号：
• 作为产物：
  描述：

  (2S,3S)-3-[[[(1R)-3-methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-oxiranecarboxylic acid ethyl ester 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 以99%的产率得到(2S,3S)-3-[[[(1R)-3-methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-oxiranecarboxylic acid
  参考文献：
  名称：

  Design, Synthesis and Evaluation of d-Homophenylalanyl Epoxysuccinate Inhibitors of the Trypanosomal Cysteine Protease Cruzain

  摘要：

  The binding modes of E-64c to papain combined with molecular modeling and ligand design using the crystal structure of cruzain have been used to develop new, potent D-Homophenylalanyl epoxysuccinate inhibitors of cruzain, the major cysteine protease of Trypanosoma cruzi. The most potent inhibitor 47 contains an O-benzyl hydroxamate unit and is highly specific for cruzain relative to other cysteine proteases tested. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00882-6

文献信息

• Novel Drugs for Dementia
  申请人：Ternansky Robert

  公开号：US20080227806A1

  公开（公告）日：2008-09-18

  The invention is directed to compounds that are prodrugs containing a chemical delivery system (CDS) moiety and a cysteine protease inhibitor moiety. The CDS moiety targets the prodrug to the brain or central nervous system. The cysteine protease inhibitor inhibits cysteine proteases upon release from the prodrug. Cysteine protease inhibitors are effective for treating dementia, Alzheimer's disease and vascular dementia. Targeting the brain or central nervous system offers significant advantages in treating these conditions and diseases. A preferred CDS prodrug is a dihydrotrigoneline CDS moiety coupled to an epoxysuccinyl peptide cysteine protease inhibitor moiety.

  本发明涉及一种含有化学递送系统（CDS）基团和半胱氨酸蛋白酶抑制剂基团的前药化合物。CDS基团将前药定位于大脑或中枢神经系统。半胱氨酸蛋白酶抑制剂在从前药中释放后抑制半胱氨酸蛋白酶。半胱氨酸蛋白酶抑制剂对治疗痴呆症、阿尔茨海默病和血管性痴呆症有效。定位于大脑或中枢神经系统在治疗这些疾病和症状方面具有显著的优势。首选的CDS前药是将二氢三角线CDS基团与环氧丙酰肽半胱氨酸蛋白酶抑制剂基团耦合。
• [EN] NOVEL DRUGS FOR DEMENTIA<br/>[FR] NOUVEAUX MEDICAMENTS CONTRE LA DEMENCE
  申请人：TERNANSKY ROBERT

  公开号：WO2007038772A1

  公开（公告）日：2007-04-05

  [EN] The invention is directed to compounds that are prodrugs containing a chemical delivery system (CDS) moiety and a cysteine protease inhibitor moiety. The CDS moiety targets the prodrug to the brain or central nervous system. The cysteine protease inhibitor inhibits cysteine proteases upon release from the prodrug. Cysteine protease inhibitors are effective for treating dementia, Alzheimer's disease and vascular dementia. Targeting the brain or central nervous system offers significant advantages in treating these conditions and diseases. A preferred CDS prodrug is a dihydrotrigoneline CDS moiety coupled to an epoxysuccinyl peptide cysteine protease inhibitor moiety.
  [FR] L'invention concerne des composés qui sont des promédicaments contenant un fragment de système de délivrance chimique ("chemical delivery system" ou CDS) et un fragment d'inhibiteur de cystéine protéase. Le fragment CDS cible le promédicament sur le cerveau ou le système nerveux central. L'inhibiteur de cystéine protéase inhibe les cystéine protéases lors de la libération du promédicament. Les inhibiteurs de cystéine protéase sont efficaces dans le traitement de la démence, de la maladie d'Alhzheimer et de la démence vasculaire. Le ciblage du cerveau ou du système nerveux central offre des avantages significatifs dans le traitement de ces états et maladies. Un médicament CDS préféré est composé d'un fragment CDS de dihydrotrigoneline couplé à un fragment d'inhibiteur de cystéine protéase de peptide d'époxysuccinile.
• WO2007/38772
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis and Evaluation of d-Homophenylalanyl Epoxysuccinate Inhibitors of the Trypanosomal Cysteine Protease Cruzain
  作者：William R Roush、Alejandro Alvarez Hernandez、James H McKerrow、Paul M Selzer、Elizabeth Hansell、Juan C Engel

  DOI：10.1016/s0040-4020(00)00882-6

  日期：2000.12

  The binding modes of E-64c to papain combined with molecular modeling and ligand design using the crystal structure of cruzain have been used to develop new, potent D-Homophenylalanyl epoxysuccinate inhibitors of cruzain, the major cysteine protease of Trypanosoma cruzi. The most potent inhibitor 47 contains an O-benzyl hydroxamate unit and is highly specific for cruzain relative to other cysteine proteases tested. (C) 2000 Elsevier Science Ltd. All rights reserved.