1-甲基-1,,3,6-四氢吡啶-3-羧酸甲酯 | 86447-15-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 1-甲基-1,,3,6-四氢吡啶-3-羧酸甲酯
• 英文名称: (3RS)-methyl 1-methyl-1,,3,6-tetrahydropyridine-3-carboxylate
• 英文别名: methyl 1-methyl-1,2,3,6-tetrahydro-pyridine-3-carboxylate；methyl N-methyl-1,2,3,6-tetrahydropyridine-3-carboxylate；methyl 1-methyl-1,2,3,6-tetrahydro-3-pyridine carboxylate；methyl 1-methyl-1,2,3,6-tetrahydropyridine-3-carboxylate；3-Pyridinecarboxylic acid, 1,2,3,6-tetrahydro-1-methyl-, methyl ester；methyl 1-methyl-3,6-dihydro-2H-pyridine-3-carboxylate
• CAS: 86447-15-6
• 化学式: C₈H₁₃NO₂
• 分子量: 155.197
• InChiKey: LGPGDOKRMJRCLE-UHFFFAOYSA-N

物化性质

• 沸点：
  199.2±40.0 °C(Predicted)
• 密度：
  1.045±0.06 g/cm3(Predicted)
• 保留指数：
  1170.8

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-甲基-1,,3,6-四氢吡啶-3-羧酸甲酯 在 四氧化锇 、 lithium aluminium tetrahydride 、 水 、 氧化-4-甲基吗啉一水合物 作用下， 以 四氢呋喃 、 丙酮 、 叔丁醇 为溶剂， 反应 121.5h， 生成 (3R,4S)-5-Hydroxymethyl-1-methyl-piperidine-3,4-diol
  参考文献：
  名称：

  Synthesis of (±)-isofagomine and its stereoisomers from arecoline

  摘要：

  (±)-Isofagomine (1) 及其所有立体异构体都是由异甲氧苄啶通过简短的合成方法制备的。异构化后的异胆碱双键不再与羧基共轭，酯还原成（羟甲基）四氢吡啶 5，经过烯烃二羟基化、分离和 N-去甲基化后得到 1 及其异构体。

  DOI：

  10.1039/a909472e
• 作为产物：
  描述：

  槟榔碱 在 盐酸 、 lithium diisopropyl amide 作用下， 生成 1-甲基-1,,3,6-四氢吡啶-3-羧酸甲酯
  参考文献：
  名称：

  Synthesis of analogues of GABA. VIII. Selective a-alkylation and γ-halogenation of the dianion from α,β-unsaturated nipecotic acid derivatives

  摘要：

  1,2,3,6-四氢吡啶-3-羧酸 (3) 酸 (3) 是 GABA 摄取抑制剂尼泊金酸 (1) 的 β、γ 不饱和衍生物。 的β，γ-不饱和衍生物。 通过二锂 盐脱共轭，合成了受 N-叔丁氧羰基保护的 中间体 (6)。用烷基化剂或醛取代中间体 烷基化剂或醛取代，得到的主要是 a-烷基化产物，但用 N-氯代丁二酰亚胺进行氯化则提供了一条通向 γ-取代的不饱和氨基酸 (13a)。

  DOI：

  10.1071/ch9830601

文献信息

• 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。
• 3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles
  申请人：Sterling Drug Inc.

  公开号：US05068234A1

  公开（公告）日：1991-11-26

  2-R.sub.2 -R.sub.4 -substituted-3-R.sub.3 -CO-1-[(C-attached-N-herteryl)-(Alk).sub.n ]-1H-indoles useful as analgesic, anti-rheumatic, anti-inflammatory or anti-glaucoma agents.

  2-R.sub.2 -R.sub.4 -取代的-3-R.sub.3 -CO-1-[(C-连接的-N-杂环)-(Alk).sub.n ]-1H-吲哚可用作镇痛、抗风湿、抗炎或抗青光眼药剂。
• Tetrahydroisoxazolo(4,5-c)pyridine derivatives and preparation thereof
  申请人：H. LUNDBECK A/S

  公开号：EP0126654A1

  公开（公告）日：1984-11-28

  Tetrahydroisoxazolo[4,5-c]pyridine derivatives of the formula: individual isomers and pharmaceutically acceptable acid addition salts thereof, wherein R1 is hydrogen, alkyl or phenyl-lower alkyl, in which the phenyl group may be substituted with halogen, lower alkyl or lower alkoxy; R2 is alkyl, alkenyl, alkynyl or phenyl-lower alkyl, in which the phenyl group may be substituted with halogen, lower alkyl or lower alkoxy; and R4 is hydrogen or alkyl. The compounds are prepared by different methods. The compounds have been found to posses strong acetylcholine agonistic activity in pharmacological tests and having few undesired side effects. Pharmaceutical compositions of said compounds, and methods for the treatment of diseases involving acetylcholine malfunction are described.

  式中的四氢异恶唑并[4,5-c]吡啶衍生物：单个异构体及其药学上可接受的酸加成盐，其中 R1 是氢、烷基或苯基-低级烷基，其中苯基可被卤素、低级烷基或低级烷氧基取代；R2 是烷基、烯基、炔基或苯基-低级烷基，其中苯基可被卤素、低级烷基或低级烷氧基取代；R4 是氢或烷基。 这些化合物通过不同的方法制备。 在药理试验中发现，这些化合物具有很强的乙酰胆碱激动活性，并且几乎没有不良副作用。 描述了上述化合物的药物组合物以及治疗涉及乙酰胆碱功能失调的疾病的方法。
• 3-Arylcarbonyl-1H-indoles useful as therapeutic agents
  申请人：STERLING WINTHROP INC.

  公开号：EP0444451A2

  公开（公告）日：1991-09-04

  2-R₂-R₄-substituted-3-R₃-CO-1-[(C-attached-N-heteryl)-(Alk)n]-1H-indoles useful as analgesic, anti-rheumatic, anti-inflammatory or anti-glaucoma agents.

  2-R₂-R₄-取代的-3-R₃-CO-1-[(C-连接的-N-庚基)-(烷基)n]-1H-吲哚，可用作镇痛剂、抗风湿剂、消炎剂或抗青光眼剂。
• Iminosugars: potential inhibitors of liver glycogen phosphorylase
  作者：Palle Jakobsen、Jane M Lundbeck、Marit Kristiansen、Jens Breinholt、Helle Demuth、Jan Pawlas、Maria P Torres Candela、Birgitte Andersen、Niels Westergaard、Karsten Lundgren、Naoki Asano

  DOI：10.1016/s0968-0896(00)00291-1

  日期：2001.3

  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.