N-cyclopropylmethyl-1-deoxynojirimycin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-cyclopropylmethyl-1-deoxynojirimycin
• 英文别名: (2R,3R,4R,5S)-1-(cyclopropylmethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: KWBAIPASFIBUNH-UTINFBMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  84.2
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-脱氧野尻霉素 、 环丙甲醛 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 48.25h， 生成 N-cyclopropylmethyl-1-deoxynojirimycin
  参考文献：
  名称：

  Method for the treatment of Pompe disease using 1-deoxynojirimycin and derivatives

  摘要：

  本发明提供了一种通过将酶与一种特定的药理伴侣接触来增加体外和体内突变型或野生型α葡萄糖苷酶酶活性的方法，该药理伴侣是1-去氧诺吉霉素的衍生物。该发明还提供了一种通过给予1-去氧诺吉霉素衍生物的伴侣小分子化合物来治疗庞贝病的方法。1-去氧诺吉霉素衍生物在N或C1位置被取代。还提供了与替代α葡萄糖苷酶基因或酶的联合治疗方法。

  公开号：

  US20060264467A1

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、-OCF3、-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、-CF3、-OCF3 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。
• Enzymatic replacement therapy and antisense therapy for pompe disease
  申请人：Erasmus University Medical Center Rotterdam

  公开号：US10993995B2

  公开（公告）日：2021-05-04

  The present invention is direct to the treatment of Pompe disease by administration of an enzyme or nucleic acid encoding for said enzyme suitable for Enzyme Replacement Therapy for Pompe disease in combination with the administration of an antisense oligomeric compound that modulates the splicing of acid alpha-glucosidase (GAA) gene.

  本发明直接用于庞贝氏症的治疗，其方法是通过施用一种酶或编码所述酶的核酸，并结合施用一种可调节酸性α-葡萄糖苷酶（GAA）基因剪接的反义寡聚化合物，这种酶或核酸适用于庞贝氏症的酶替代疗法。
• 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
• THERAPY REGIMENS, DOSING REGIMENS AND STABLE MEDICAMENTS FOR THE TREATMENT OF POMPE DISEASE
  申请人：Do Hung V.

  公开号：US20100119502A1

  公开（公告）日：2010-05-13

  The present application provides a method for treating Pompe disease in a subject in need thereof, that includes a method of administering to the subject a GAA enzyme in combination with an ASSC for the GAA enzyme. The present application also provides methods for increasing the in vitro and in vivo stability of a GAA enzyme formulation.
• TREATMENT OF POMPE DISEASE WITH SPECIFIC PHARMACOLOGICAL CHAPERONES AND MONITORING TREATMENT USING SURROGATE MARkERS
  申请人：Wustman Brandon

  公开号：US20110189710A1

  公开（公告）日：2011-08-04

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