alpha-cyano-4-trifluoromethyl(benzyl)-DNJ | 915278-73-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: alpha-cyano-4-trifluoromethyl(benzyl)-DNJ
• 英文别名: 2-[4-(trifluoromethyl)phenyl]-2-[(2R,3R,4R,5S)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]acetonitrile
• CAS: 915278-73-8
• 化学式: C₁₅H₁₇F₃N₂O₄
• 分子量: 346.306
• InChiKey: JQZCGAATHLYEHR-ZLMOABSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  9

文献信息

• A method for the treatment of pompe disease using 1-deoxynojirimycin and derivatives
  申请人：Amicus Therapeutics, Inc.

  公开号：EP2932982A1

  公开（公告）日：2015-10-21

  A combination therapy for use in the treatment of Pompe Disease, the combination therapy comprising a 1-deoxynojirimycin (DNJ) derivative and acid α-glucosidase (Gaa), wherein the DNJ derivative comprises a compound of the formula: where R1 is H or a straight or branched alkyl, cycloalkyl, alkenyl, alkoxyalkyl or aminoalkyl containing 1-12 carbon atoms, an aryl, alkylaryl, heteroaryl, or heteroaryl alkyl containing 5-12 ring atoms, where R1 is optionally substituted with one or more -OH, -COOH, -Cl, -F, -CF3,-OCF3, -O-C(=O)N-(alkyl)2; R2 is H; a straight or branched alkyl, cycloalkyl, alkenyl, alkylaryl, or alkoxyalkyl, containing 1 - 9 carbon atoms or aryl containing 5 - 12 carbon atoms, wherein R2 is optionally substituted with -OH, -COOH, -CF3, -OCF3 or a heterocyclic ring; and at least one of R1 and R2 is not H; or a pharmaceutically acceptable salt thereof, wherein the DNJ derivative is used for increasing the activity of Gaa enzyme in a cell, at a concentration at or below the IC50 value for inhibition of intestinal Gaa; and wherein the DNJ derivative is not 1-deoxynojirimycin or α-homonojirimycin.

  一种用于治疗庞贝氏症的组合疗法，该组合疗法包括 1-脱氧野尻霉素 (DNJ) 衍生物和酸α-葡萄糖苷酶 (Gaa)，其中 DNJ 衍生物包括式中化合物： 其中 R1 是 H 或含有 1-12 个碳原子的直链或支链烷基、环烷基、烯基、烷氧基烷基或氨基烷基，含有 5-12 个环原子的芳基、烷芳基、杂芳基或杂芳基烷基，其中 R1 可任选地被一个或多个 -OH、-COOH、-Cl、-F、-CF3、-O 、-O-C(=O)N-(烷基)2 取代；R2 是 H；含有 1-9 个碳原子的直链或支链烷基、环烷基、烯基、烷芳基或烷氧基烷基，或含有 5-12 个碳原子的芳基，其中 R2 可任选被-OH、-COOH、- 、-O 或杂环取代；且 R1 和 R2 中至少有一个不是 H； 或其药学上可接受的盐、 其中DNJ衍生物用于增加细胞中Gaa酶的活性，其浓度达到或低于抑制肠道Gaa的IC50值；其中DNJ衍生物不是1-脱氧野尻霉素或α-所罗门野尻霉素。
• A METHOD FOR THE TREATMENT OF POMPE DISEASE USING 1-DEOXYNOJIRIMYCIN AND DERIVATIVES
  申请人：Amicus Therapeutics, Inc.

  公开号：EP1896083B1

  公开（公告）日：2016-03-02
• METHOD FOR THE TREATMENT OF POMPE DISEASE USING 1-DEOXYNOJIRIMYCIN DERIVATIVES
  申请人：AMICUS THERAPEUTICS, INC.

  公开号：US20180221357A1

  公开（公告）日：2018-08-09

  The present invention provides a method for increasing the activity of a mutant or wild-type α-glucosidase enzyme in vitro and in vivo by contacting the enzyme with a specific pharmacological chaperone which is a derivative of 1-deoxynojirimycin. The invention also provides a method for the treatment of Pompe disease by administration of chaperone small molecule compound which is a derivative of 1-deoxynojirimycin. The 1-deoxynojirimycin derivative is substituted at the N or C1 position. Combination therapy with replacement α-glucosidase gene or enzyme is also provided.
• US9181184B2
  申请人：——

  公开号：US9181184B2

  公开（公告）日：2015-11-10
• [EN] TREATMENT OF POMPE DISEASE WITH SPECIFIC PHARMACOLOGICAL CHAPERONES AND MONITORING TREATMENT USING SURROGATE MARKERS<br/>[FR] TRAITEMENT DE LA MALADIE DE POMPE AU MOYEN DE CHAPERONES PHARMACOLOGIQUES SPÉCIFIQUES, ET TRAITEMENT DE SURVEILLANCE UTILISANT DES CRITÈRES DE SUBSTITUTION
  申请人：AMICUS THERAPEUTICS INC

  公开号：WO2009114679A2

  公开（公告）日：2009-09-17

  Provided is a method of monitoring the treatment of Pompe disease with specific pharmacological chaperones using systemic and/or cellular surrogate markers.