1-甲基-4-羟基-哌啶-4-二羧酸甲酯 | 21667-71-0

• 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: 1-甲基-4-羟基-哌啶-4-二羧酸甲酯
• 英文名称: 4-hydroxy-4-(methoxycarbonyl)-1-methylpiperidine
• 英文别名: 4-hydroxy-4-methoxycarbonyl-1-methylpiperidine；4-(methoxycarbonyl)-1-methyl-4-piperidinol；4-hydroxy-1-methyl-piperidine-4-carboxylic acid methyl ester；1-Methyl-4-carbomethoxy-4-peridol；Methyl 4-hydroxy-1-methylpiperidine-4-carboxylate
• CAS: 21667-71-0
• 化学式: C₈H₁₅NO₃
• mdl: MFCD28142389
• 分子量: 173.212
• InChiKey: TWKGNGYMVZKLCJ-UHFFFAOYSA-N

物化性质

• 沸点：
  242.6±40.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-甲基-4-羟基-哌啶-4-二羧酸甲酯 在 lithium aluminium tetrahydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 4.5h， 生成 2-ethyl-8-methyl-1,3-dioxa-8-azaspiro<4,5>decane
  参考文献：
  名称：

  2-甲基-1,3-二氧杂萘并[4.5]癸烷是新型毒蕈碱胆碱能激动剂。

  摘要：

  在过去的几年中，已经开发出许多非季铵毒蕈碱激动剂，但是大多数现有化合物（例如槟榔碱，RS-86，AF-30）在受体储备有限的组织中对胆碱能受体表现为弱的部分激动剂。目前的论文描述了AF-30类似物的合成和生化评估，其被设计为具有足够的构象自由度以允许更大的受体柔性并因此具有激活作用。新的化合物和重要的标准品在新的生化分析中进行了测试，旨在测量每种化合物的受体亲和力和内在活性，以及​​它们刺激大鼠大脑皮层磷脂酰肌醇更新的能力。已显示两种氮杂螺旋十二烷（5a和5b）具有比AF-30大得多的预测功效。

  DOI：

  10.1021/jm00397a039

文献信息

• NEW PIPERIDINE DERIVATIVES
  申请人：Ackermann Jean

  公开号：US20110028515A1

  公开（公告）日：2011-02-03

  Compounds of formula (I) as well as pharmaceutically acceptable salts thereof can be used in the form of pharmaceutical compositions, wherein A 1 , A 2 , R 1 , R 2 , R 3 and R 4 have the significance given in claim 1.

  化合物的化学式（I） 以及其药学上可接受的盐可以用于制成药物组合物的形式，其中A 1 ，A 2 ，R 1 ，R 2 ，R 3 和R 4 具有权利要求中给定的含义。
• Central Cholinergic Agents. III. Synthesis of 2-Alkoxy-2,8-diazaspiro(4.5)decane-1,3-diones as Muscarinic Agonists.
  作者：Yuji ISHIHARA、Hidehumi YUKIMASA、Masaomi MIYAMOTO、Giichi GOTO

  DOI：10.1248/cpb.40.1177

  日期：——

  and tested for muscarinic receptor binding affinity using [3H]pirenzepine and [3H]oxotremorine M as ligands. They were also evaluated for agonistic activities in the guinea pig ileum assay. 2-Methoxy- 2,8-diazaspiro[4.5]decane-1,3-dione (1i) was found to be a relatively M1 selective agonist. It reversed CO2-induced impairment of passive avoidance response with long duration of action, but also displayed

  合成了一系列的2-烷氧基-2,8-二氮杂螺[4.5]癸烷-1,3-二酮和相关化合物，并以[3H]哌仑西平和[3H]氧代苯甲酸M作为配体测试了毒蕈碱受体的结合亲和力。还通过豚鼠回肠试验评估了它们的激动活性。发现2-甲氧基-2,8-二氮杂螺[4.5]癸烷-1,3-二酮（1i）是相对M1选择性的激动剂。它以较长的作用时间逆转了CO2引起的被动回避反应的损害，但在低剂量时也表现出外周效应。为了最小化这些副作用，我们提出了将1i与毒蕈碱拮抗剂结合的想法。因此，检查了1i的氨基甲酸酯连接的共轭物（1u）与甲基阿托品。
• [EN] ΡΡΑRγ MODULATORS AND METHODS OF USE<br/>[FR] MODULATEURS DE ΡΡΑRγ ET MÉTHODES D'UTILISATION
  申请人：EISAI R&D MANGEMENT CO LTD

  公开号：WO2022099144A1

  公开（公告）日：2022-05-12

  Disclosed herein are novel PPARy modulators of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the same, and methods of using the same, in particular for the treatment of cancers.

  本文公开了一种新型的PPARy调节剂，其化学式为（I），以及其药学上可接受的盐，包含它们的制药组合物，以及使用它们的方法，特别是用于治疗癌症的方法。
• Synthesis and structure-activity studies of a series of spirooxazolidine-2,4-diones: 4-oxa-analogs of the muscarinic agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione
  作者：Shinichi Tsukamoto、Masato Ichihara、Fumikazu Wanibuchi、Shinji Usuda、Kazuyuki Hidaka、Masatomi Harada、Toshinari Tamura

  DOI：10.1021/jm00068a005

  日期：1993.8

  A series of spirooxazolidine-2,4-dione derivatives related to the putative M, agonist 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dione (RS86; 1) were synthesized. The compounds were evaluated as cholinergic agents in in vitro binding assays and in in vivo pharmacological tests including antiamnesic effects using scopolamine-treated mice, hypothermia, and salivation in mice. Four compounds (5a,c,f and 17a) exhibited affinity for cortical M1 receptors and reversed scopolamine-induced impairment of mouse passive avoidance tasks, as did 1. Among these compounds, only 5a exhibited M1-receptor stimulating activity in pithed rats. Structural requirements for muscarinic activity in this series of spirooxazolidine-2,4-dione derivatives were as strict as those reported for spirosuccinimide derivatives including 1. The antiamnesic dose of 3-ethyl-8-methyl-1-oxa-3,8-diazaspiro[4.5]decane-2,4-dione (5a) was 2 orders of magnitude lower than the doses inducing hypothermia and salivation, in contrast to 1 for which the former dose was only 5-10-fold lower than the latter. These results suggest that the 8-azaspiro[4.5]decane skeleton represents a useful template for designing new muscarinic agonists as antidementia drugs.
• SAUNDERS, JOHN;SHOWELL, GRAHAM A.;SNOW, ROGER J.;BAKER, RAYMOND;HARLEY, E+, J. MED. CHEM., 31,(1988) N 2, 486-491
  作者：SAUNDERS, JOHN、SHOWELL, GRAHAM A.、SNOW, ROGER J.、BAKER, RAYMOND、HARLEY, E+

  DOI：——

  日期：——