2,6-dideoxy-2,6-imino-D-glycero-D-ido-heptononitrile | 78821-34-8

• 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: 2,6-dideoxy-2,6-imino-D-glycero-D-ido-heptononitrile
• 英文别名: 1-α-Cyan-1-desoxynojirimycin；1-α-cyano-1-deoxynojirimycin；1-C-cyano-1-deoxynojirimycin；(2R,3S,4R,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)piperidine-2-carbonitrile
• CAS: 78821-34-8
• 化学式: C₇H₁₂N₂O₄
• 分子量: 188.183
• InChiKey: WPLCPOIAQLRTDR-XUUWZHRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  117
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,6-dideoxy-2,6-imino-D-glycero-D-ido-heptononitrile 在 盐酸 、 sodium tetrahydroborate 、 palladium on activated charcoal 、 三氟化硼乙醚 、 sodium methylate 、 mercury(II) trifluoroacetate 、 dinitrogen tetraoxide 、 碳酸氢钠 、 potassium carbonate 、 三乙胺 、 diborane(6) 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 104.5h， 生成 7-O-β-D-吡喃葡萄糖基-Alpha-后莫野尻霉素
  参考文献：
  名称：

  A facile, practical synthesis of 2,6-dideoxy-2,6-imino-7-O-.beta.-D-glucopyranosyl-D-glycero-L-gulo-heptitol (MDL 25,637)

  摘要：

  DOI：

  10.1021/jo00272a015
• 作为产物：
  描述：

  sodium cyanide 、 5-azido-5-deoxy-α,β-D-glucofuranose 在 三甲基膦 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 5.0h， 以65%的产率得到2,6-dideoxy-2,6-imino-D-glycero-D-ido-heptononitrile
  参考文献：
  名称：

  Concise synthesis of C-1-cyano-iminosugars via a new Staudinger/aza Wittig/Strecker multicomponent reaction strategy

  摘要：

  A new Staudinger/aza Wittig/Strecker multicomponent reaction sequence to C-1-cyano iminoalditols has been developed. When applied to 5-azidodeoxy-D-xylose and -D-glucose as substrates the method leads smoothly in good yield and with excellent stereoselectivity to respectively, 1,5-dideoxy-1,5-imino-D-idurono nitrile and 2,6-didesoxy-2,6-imino-D-glycero-D-ido-heptononitrile. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2014.03.069

文献信息

• Method for the treatment of Pompe disease using 1-deoxynojirimycin and derivatives
  申请人：Mugrage Benjamin

  公开号：US20060264467A1

  公开（公告）日：2006-11-23

  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.

  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。
• 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。
• Synthesis and Evaluation of Homoaza Sugars as Glycosidase Inhibitors
  作者：Chi-Huey Wong、Louis Provencher、John A. Porco、Sang-Hun Jung、Yi-Fong Wang、Lihren Chen、Ruo Wang、Darryl H. Steensma

  DOI：10.1021/jo00111a007

  日期：1995.3

  In an effort to develop transition-state mimetics of the glycosidase-catalyzed reaction, five- and six-membered azasugars and their home-analogs were prepared and tested as inhibitors of glycosidases. Inhibition studies indicate that the fucosyl cationlike, five-membered imine 1 and its reduced form 2 are potent inhibitors of alpha-fucosidase from bovine kidney with respective K-i values of 160 nM and 2 mu M. The five-membered homoaminoazasugar 3 is also a potent inhibitor of the enzyme (K-i = 1.9 x 10(-6) M), while the glucose and mannose-like six-membered homoaminoazasugars 4 and 5 are less potent than the corresponding 1-deoxyazasugars as inhibitors of alpha-glucosidase and alpha-mannosidase, respectively. The primary amino group was placed in an attempt to introduce additional electrostatic interactions in the active site. The inhibitory activities are, however, in the high mu M range. Synthesis of homoazasugars structurally related to a disaccharide and a nucleoside is also described.
• Boeshagen; Geiger; Junge, Angewandte Chemie, 1981, vol. 93, # 9, p. 800 - 801
  作者：Boeshagen、Geiger、Junge

  DOI：——

  日期：——
• ANZEVENO, PETER B.;DANIEL, JOHN K.;CREEMER, LAURA J.;LIU, PAUL S.
  作者：ANZEVENO, PETER B.、DANIEL, JOHN K.、CREEMER, LAURA J.、LIU, PAUL S.

  DOI：——

  日期：——