(3R,4R,5R)-3-benzyloxy-4-hydroxy-5-hydroxymethyl-piperidine | 161302-92-7

• 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: (3R,4R,5R)-3-benzyloxy-4-hydroxy-5-hydroxymethyl-piperidine
• 英文别名: (3R,4R,5R)-3-benzyloxy-5-hydroxymethyl-piperidin-4-ol；(3R,4R,5R)-3-benzyloxy-5-hydroxymethyl-4-piperidinol；(3R,4R,5R)-3-Benzyloxy-4-hydroxy-5-hydroxymethylpiperidine；(3R,4R,5R)-3-Benzyloxy-5-hydroxymethyl4-piperidinol；(3R,4R,5R)-3-(hydroxymethyl)-5-phenylmethoxypiperidin-4-ol
• CAS: 161302-92-7
• 化学式: C₁₃H₁₉NO₃
• 分子量: 237.299
• InChiKey: VRYOSYRKUMQQTL-JHJVBQTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  61.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,4R,5R)-3-benzyloxy-4-hydroxy-5-hydroxymethyl-piperidine 在 palladium on activated charcoal 盐酸 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 (3R,4R,5R)-1-Dodecyl-5-hydroxymethyl-3,4-piperidinediol
  参考文献：
  名称：

  Iminosugars: potential inhibitors of liver glycogen phosphorylase

  摘要：

  The first synthesis of the single isomers (3R,4R,5R); (3S,4S,5S); (3R,4R,5S) and (3S,4S,5R) of 5-hydroxymethyl-piperidine-3,4-diol from Arecolin is reported, including the synthesis of a series of N-substituted derivatives of the (3R,4R,5R)-isomer (Isofagomine). The inhibitory effect of these isomers as well as of a series of N-substituted derivatives of the (3R,4R,SR)-isomer and selected hydroxypiperidine analogues on liver glycogen phosphorylase (GP) showed that the (3R,4R,5R) configuration was essential for obtaining an inhibitory effect at submicromolar concentration. The results also showed that all three hydroxy groups should be present and could not be substituted, nor were extra OH groups allowed if sub-micromolar inhibition should be obtained. Some inhibitory effect was retained for N-substituted derivatives of Isofagagomine; however, N-substitution always resulted in a loss of activity compared to the parent compound, IC50 values ranging from 1 to 100 muM were obtained for simple alkyl, arylalkyl and benzoylmethyl substituents. Furthermore, we found that it was not enough to assure inhibitory effect to have the (R,,R) configuration. Fagomine, the (2R,3R,4R)-2-hydroxymethylpiperidine-3,4-diol analogue, showed an IC50 value of 200 muM compared to 0.7 muM for Isofagomine. In addition, Isofagomine was able to prevent basal and glucagon stimulated glycogen degradation in cultured hepatocytes with IC50 values of 2-3 muM. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00291-1
• 作为产物：
  描述：

  1,6-anhydro-4-O-benzyl-2-deoxy-2-C-vinyl-β-D-glucopyranose 在 palladium on activated charcoal sodium tetrahydroborate 、 sodium periodate 、 硫酸 、 氨 、 氢气 、 臭氧 作用下， 以 乙醇 为溶剂， 20.0~45.0 ℃ 、3.5 MPa 条件下， 反应 20.48h， 生成 (3R,4R,5R)-3-benzyloxy-4-hydroxy-5-hydroxymethyl-piperidine
  参考文献：
  名称：

  Synthesis of isofagomine, a novel glycosidase inhibitor

  摘要：

  DOI：

  10.1016/s0040-4020(01)89351-0

文献信息

• Synthesis of an 1′-Azasugar Analogue of Maltose
  作者：Vinni Andreassen、Birte Svensson、Mikael Bols

  DOI：10.1055/s-2001-10799

  日期：——

  Methyl 1′-azamaltoside (3) was synthesised from levoglucosane and d-galactose in a 16 step synthesis. Methyl 1′-azamaltoside (3) was found to inhibit glucoamylase with K i of 0.63 μM.

  甲基1′-氮杂麦芽糖苷（3）是通过16步合成法从左旋葡糖酸内酯和D-半乳糖合成得到的。研究发现，甲基1′-氮杂麦芽糖苷（3）能够抑制葡萄糖淀粉酶，其Ki值为0.63微摩尔。
• Heterocyclic compounds
  申请人：Novo Nordisk A/S

  公开号：US06046214A1

  公开（公告）日：2000-04-04

  Novel piperidine compounds are provided, and those compounds are useful in the treatment and/or prevention of diabetes, and especially non-insulin dependent diabetes (NIDDM or type 2 diabetes) including overnight or meal treatment and treatment or prevention of longterm complications, such as retinopathy, neuropathy, nephropathy, and micro- and macroangiopathy; treatment of hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis or myocardial ischemia.

  提供了新型吡啶类化合物，这些化合物在治疗和/或预防糖尿病方面非常有用，尤其是非胰岛素依赖型糖尿病（NIDDM或2型糖尿病），包括过夜或餐后治疗，以及治疗或预防长期并发症，如视网膜病变、神经病变、肾病、微血管和大血管病变；治疗高血糖、高胆固醇血症、高血压、高胰岛素血症、高脂血症、动脉粥样硬化或心肌缺血。
• Iminosugars as Potential Inhibitors of Glycogenolysis:  Structural Insights into the Molecular Basis of Glycogen Phosphorylase Inhibition
  作者：Nikos G. Oikonomakos、Costas Tiraidis、Demetres D. Leonidas、Spyros E. Zographos、Marit Kristiansen、Claus U. Jessen、Leif Nørskov-Lauritsen、Loranne Agius

  DOI：10.1021/jm060496g

  日期：2006.9.1

  been identified as potent inhibitors of liver glycogen phosphorylase a (IC(50) = 0.4-1.2 microM) and of basal and glucagon-stimulated glycogenolysis (IC(50) = 1-3 microM). The X-ray structures of 5, 9, and its N-3-phenylpropyl analogue 8 in complex with rabbit muscle glycogen phosphorylase (GPb) shows that iminosugars bind tightly at the catalytic site in the presence of the substrate phosphate and

  氨基糖DAB（5），异黄花碱（9）和几种N-取代的衍生物已被确定为肝糖原磷酸化酶a（IC（50）= 0.4-1.2 microM）以及基础和胰高血糖素刺激的糖原分解（IC（ 50）= 1-3 microM）。5、9及其N-3-苯基丙基类似物8​​与兔肌肉糖原磷酸化酶（GPb）的X射线结构表明，亚氨基糖在存在底物磷酸盐的情况下在催化位点紧密结合，并诱导构象变化，表征酶的R-态构象。带电的氮N1与His377的羰基氧（5）处于氢键键合距离之内，并与底物磷酸氧（8和9）发生离子接触。我们的发现表明抑制剂起氧碳鎓离子过渡态类似物的作用。
• [EN] PIPERIDINES AND PYRROLIDINES<br/>[FR] PIPERIDINES ET PYRROLIDINES
  申请人：NOVO NORDISK A/S

  公开号：WO1995024391A1

  公开（公告）日：1995-09-14

  (EN) Compounds (I) and (II), the use of these compounds as medicament, the use of these medicaments in the treatment of diabetes and pharmaceutical compositions containing these compounds.(FR) Composés (I) et (II), leur utilisation comme médicaments, utilisation de ces médicaments pour le traitement du diabète et compositions pharmaceutiques renfermant ces composés.

  (EN) 化合物（I）和（II），这些化合物作为药物的使用，这些药物在糖尿病治疗中的使用以及含有这些化合物的制药组合物。 (FR) 化合物（I）和（II），这些化合物作为药物的使用，这些药物在糖尿病治疗中的使用以及含有这些化合物的制药组合物。
• Glycohydrolase inhibitors, their preparation and use thereof
  申请人：University of Maryland Baltimore County

  公开号：US05844102A1

  公开（公告）日：1998-12-01

  A compound of the formula ##STR1## wherein n, m, and p, which may be the same or different, are a number between 0 and 5; q is a number between 0 and 10; R.sub.1, R.sub.2 R.sub.3 R.sub.4 and R.sub.5, which may be the same or different, are a hydrogen, a hydroxyl, a halogen, a hydrocarbon or an O-hydrocarbon group having between 1 and 6 carbons which is aliphatic, alicyclic or aromatic, or a glycosyl group; and R.sub.4 is a glycosyl group, is disclosed. Nitrogen oxides of such compounds are also included. These novel compounds have been found to be potent glycohydrolase inhibitors. Processes for preparing these novel compounds and methods for their use in the treatment of diabetes mellitus are also provided.

  本发明揭示了一种具有以下式子的化合物：##STR1## 其中n、m和p（可以相同也可以不同）是介于0和5之间的数字；q是介于0和10之间的数字；R.sub.1、R.sub.2、R.sub.3、R.sub.4和R.sub.5（可以相同也可以不同）是氢、羟基、卤素、具有1到6个碳的脂肪族、环烷或芳香族的O-脂肪族基团，或者是糖基团；而R.sub.4则是糖基团。这些化合物的氮氧化物也包括在内。这些新颖的化合物被发现是有效的糖苷酶抑制剂。本发明还提供了制备这些新颖化合物的方法以及在糖尿病治疗中使用它们的方法。