N-甲基-1-脱氧尻霉素 | 69567-10-8

• 物质功能分类: 有机原料 - 腈类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: N-甲基-1-脱氧尻霉素
• 中文别名: 丙二腈；1,5-二脱氧-1,5-亚氨基-1-甲基-D-山梨醇
• 英文名称: N-methyldeoxynojirimycin
• 英文别名: N-methyl-1-deoxynojirimycin；MOR 14；(2R,3R,4R,5S)-2-(hydroxymethyl)-1-methylpiperidine-3,4,5-triol
• CAS: 69567-10-8
• 化学式: C₇H₁₅NO₄
• 分子量: 177.2
• InChiKey: AAKDPDFZMNYDLR-XZBKPIIZSA-N

物化性质

• 熔点：
  126-128°C
• 沸点：
  367.2±42.0 °C(Predicted)
• 密度：
  1.394±0.06 g/cm3(Predicted)
• 溶解度：
  超声处理轻微溶于甲醇，轻微溶于水
• 稳定性/保质期：
  请远离强酸和强碱。

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• 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

安全信息

• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 储存条件：
  请将药品存放在密封容器中，并置于阴凉、干燥处。务必远离氧化剂。建议在2-8 ºC的条件下保存。

制备方法与用途

生物活性

N-Methylmoranoline (MOR 14) 是 α-糖苷酶 的抑制剂。

体外研究

N-Methylmoranoline 剂量依赖性地减少兔心肌提取物中 α-1,6-糖苷酶 活性。相当大的 N-Methylmoranoline 在心肌中的摄取足以完全抑制 α-1,6-糖苷酶。在预缺血条件下，分别以 25、50 和 100 mg/kg 剂量的 N-Methylmoranoline 处理可剂量依赖性地减少梗死面积，而不改变血压或心率。在 20 分钟和 30 分钟的缺血期间，N-Methylmoranoline 显著增加颗粒组分中 PKC-ε 的水平，并在 30 分钟的缺血期，在细胞质组分中也显著增加。

体内研究

N-Methylmoranoline 减少 α-1,6-糖苷酶 活性至约 20%，减少 10 和 30 分钟内的心肌糖原分解，并减轻乳酸积累。在孤立的鼠心实验中，N-Methylmoranoline 通过抑制糖原分解保护梗死后左室功能障碍。

反应信息

• 作为反应物：
  描述：

  N-甲基-1-脱氧尻霉素 在 双氧水 作用下， 反应 4.0h， 以95%的产率得到N-methyldeoxynojirimycin
  参考文献：
  名称：

  Enzyme-catalyzed aldol condensation for asymmetric synthesis of azasugars: synthesis, evaluation, and modeling of glycosidase inhibitors

  摘要：

  A combined fructose 1,6-diphosphate aldolase reaction and catalytic reductive amination has been used in the asymmetric synthesis of azasugars structurally corresponding to N-acetylglucosamine, N-acetylmannosamine, and deoxyhexoses. The 6-deoxyazasugars were prepared by direct hydrogenolysis of the aldolase product without removal of the 6-phosphate group. Both (R)- and (S)-3-azido-2-acetamidopropanal used as substrates in the aldolase reactions were prepared from the corresponding lipase-resolved 2-hydroxy species followed by formation of an aziridine intermediate and opening of the aziridine with azide. Evaluation of these azasugars and their diastereomerically pure tertiary amine oxides as well as 5-thioglucose and its sulfoxide derivatives as glycosidase inhibitors was carried out. It was found that all synthetic azasugars and 5-thioglucose were strong inhibitors, but oxidation of the ring heteroatom weakened the inhibition. With the aid of molecular modeling and inhibition analysis, a structure-K(i) relation of inhibitors was established which provides useful information for the design of new glycosidase inhibitors.

  DOI：

  10.1021/ja00016a039
• 作为产物：
  描述：

  1-脱氧野尻霉素 在 钯 聚合甲醛 作用下， 以 甲醇 为溶剂， 生成 N-甲基-1-脱氧尻霉素
  参考文献：
  名称：

  1,5-dideoxy-1,5-imino-d-glucitol derivatives

  摘要：

  本发明涉及1,5-二去氧-1,5-亚硝基-D-葡萄糖醇的抗病毒O-酰化衍生物，其中含有一个至四个游离羟基被选自由从三到八个碳原子的羧基脂肪酰基所选择的ω,ω,ω-三氟代烷酰基、从四到八个碳原子的环烷基羧基和从二到十个碳原子的非环烷基羧基的N-烷基或N-芳酰基，其中N-芳酰基被选自p-癸基苯甲酰基、3-(对氯苯氧基)丙酰基、2-(乙酰氧基)苯甲酰基、[1,1'-联苯]-4-基羰基、2-噻吩乙酰基、反式-3-呋喃丙烯酰基、3-甲氧基苯乙酰基和3-(三氟甲基)苯甲酰基，其中N-烷基含有从一个到十四个碳原子，但当N-烷基含有从一个到五个碳原子时，O-酰化基为ω,ω,ω-三氟代烷酰基或环烷基羧基。

  公开号：

  US05144037A1

文献信息

• 1,5-dideoxy-1,5-imino-D-glucitol derivatives
  申请人：G. D. Searle & Co.

  公开号：US05221746A1

  公开（公告）日：1993-06-22

  O-acylated derivatives of 1,5-dideoxy-1,5-imino-D-glucitol are disclosed that contain an N-alkyl or N-aroyl radical in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoro alkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl radical is selected from the group consisting of p-decylbenzoyl, 3-(p-chlorophenoxy)propanoyl, 2-(acetyloxy)benzoyl, [1,1'-biphenyl]-4-ylcarbonyl, 2-thiopheneacetyl, trans-3-furanacryloyl 3-methoxyphenylacetyl and 3-(trifluoromethyl)benzoyl, and wherein the N-alkyl contains from one to fourteen carbon atoms, provided that when N-alkyl contains from one to five carbon atoms the O-acylated groups are .omega.,.omega.,.omega.-trifluoro alkanoyl or carboxylic cycloalkanoyl.

  披露了1,5-二去氧-1,5-亚胺-D-葡萄糖醇的O-酰化衍生物，其中含有一个到四个自由羟基被选自以下羧基烷酰基的羧基烷酰基的N-烷基或N-芳酰基，.omega.，.omega.，.omega.-三氟烷酰基，碳原子数为三至八个，具有四至八个碳原子的羧基环烷酰基和具有两至十个碳原子的羧基无环烷酰基，其中N-芳酰基选自以下羧基苯基，3-(对氯苯氧基)丙酰基，2-(乙酰氧基)苯甲酰基，[1,1'-联苯]-4-基甲酰基，2-噻吩乙酰基，反式-3-呋喃丙烯基3-甲氧基苯乙酰基和3-(三氟甲基)苯甲酰基，其中N-烷基含有一个到十四个碳原子，前提是当N-烷基含有一个到五个碳原子时，O-酰化基团为.omega.，.omega.，.omega.-三氟烷酰基或羧基环烷酰基。
• Antiviral compounds
  申请人：G. D. Searle & Co.

  公开号：US05310745A1

  公开（公告）日：1994-05-10

  A method of inhibiting lentivirus is disclosed which comprises mammalian host susceptible to said lentivirus with a virally inhibitory effective amount of an O-acylated derivative of 1,5-dideoxy-1,5-imino-D-glucitol and their N-alkyl, N-acyl and N-aroyl derivatives in which from one to four of the free hydroxyl groups are O-acylated with carboxylic alkanoyl radicals selected from the group consisting of .omega.,.omega.,.omega.-trifluoroalkanoyl having from three to eight carbon atoms, carboxylic cycloalkanoyl groups having from four to eight carbon atoms and carboxylic acyclic alkanoyl groups having from two to ten carbon atoms, wherein the N-aroyl groups contain from 7 to 14 carbon atoms, the N-acyl groups contain from 4 to 8 carbon atoms and the N-alkyl groups contain from 1 to 14 carbon atoms.

  本发明揭示了一种抑制慢病毒的方法，包括将哺乳动物宿主暴露于所述慢病毒的有效抑制量的1,5-二去氧-1,5-亚胺-D-葡萄糖醇的O-酰化衍生物及其N-烷基，N-酰基和N-芳酰衍生物中，其中从一个到四个自由羟基被选自由三至八个碳原子的羧基烷酰基的.omega.，.omega.，.omega.-三氟烷酰基，含有四至八个碳原子的环烷基羧基和含有两至十个碳原子的无环烷基羧基，其中N-芳酰基含有七至十四个碳原子，N-酰基含有四至八个碳原子，N-烷基含有一至十四个碳原子。
• Process for preparing 1-deoxynojirimycin and N-derivatives thereof
  申请人：Bayer Aktiengesellschaft

  公开号：US04806650A1

  公开（公告）日：1989-02-21

  A process for preparing a 1-deoxynojirimycin of the formula ##STR1## in which R is hydrogen, optionally substituted alkyl or aralkyl, which comprises converting D-glucose to an aminosorbitol ##STR2## protecting the amino group of the aminosorbitol with an alkalinically detachable group to form the protected compound of the formula ##STR3## in which X is an alkalinically detachable protective group, microbiologically oxidizing the protected compound to an oxidation product of the formula ##STR4## alkalinically splitting off the protective group X to form an aminosorbose of the formula ##STR5## and reducing the aminosorbose.

  一种制备式为##STR1##的1-去氧诺基霉素的方法，其中R是氢，可选择性地取代的烷基或芳基，包括将D-葡萄糖转化为氨基山梨醇##STR2##，保护氨基山梨醇的氨基团以形成式为##STR3##的保护化合物，其中X是碱性可分离的保护基团，微生物氧化保护化合物以得到氧化产物的方法，其化学式为##STR4##，碱性地去除保护基团X以形成山梨醛胺##STR5##，并还原山梨醛胺。
• Inhibition of intestinal .ALPHA.-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives.
  作者：Yoshiaki YOSHIKUNI

  DOI：10.1271/bbb1961.52.121

  日期：——

  Moranoline (1-deoxynojirimycin) isolated from mulberry root bark (Mori Cortex), is a potent intestinal α-glucosidase inhibitor. The IC50 values for sucrase and maltase in various animals ranged around 10-7M. Postprandial hyperglycemia in sucrose-, starch-, or maltose-loaded rats was significantly supressed by simultaneous administration of moranoline in doses over 6 mg/kg. In contrast to the potent inhibition of intestinal α-glucosidase, the inhibition of β-glucosidase, glucoamylase, and α-amylase was weak. Among the N-substituted alkyl derivatives of moranoline, the methyl and ethyl derivatives had more potent hypoglycemic activity than moranoline in sucrose- or starch-loaded rat models. Nojirimycin, or 2, 5-dihydroxymethyl 3, 4-dihydroxypyrrolidine (DMDP), which structurally resembles moranoline, only weakly inhibited α-glucosidase but strongly inhibited β-glucosidase.

  莫拉诺林（1-脱氧诺吉霉素）从桑树根皮（桑皮）中提取，是一种有效的肠道α-葡萄糖苷酶抑制剂。不同动物中蔗糖酶和麦芽糖酶的IC50值大约在10-7M左右。在接受蔗糖、淀粉或麦芽糖负荷的老鼠中，同时给予剂量超过6 mg/kg的莫拉诺林能够显著抑制餐后高血糖。与肠道α-葡萄糖苷酶的强效抑制形成对比，β-葡萄糖苷酶、葡萄糖淀粉酶和α-淀粉酶的抑制效应较弱。在莫拉诺林的N取代烷基衍生物中，甲基和乙基衍生物在蔗糖或淀粉负荷的老鼠模型中显示出比莫拉诺林更强的降血糖活性。诺吉霉素或2, 5-二羟甲基-3, 4-二羟吡咯烷（DMDP），与莫拉诺林在结构上相似，仅弱抑制α-葡萄糖苷酶，但对β-葡萄糖苷酶的抑制影响较强。
• 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。