1-甲基 3-氧代哌啶-1,4-二羧酸-4-乙酯 | 65202-59-7

• 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 3-氧代哌啶-1,4-二羧酸-4-乙酯
• 中文别名: 1-甲基3-氧代哌啶-1,4-二羧酸-4-乙酯
• 英文名称: 4-ethyl 1-methyl 3-oxopiperidine-1,4-dicarboxylate
• 英文别名: ethyl 1-methoxycarbonyl-3-oxopiperidine-4-carboxylate；4-O-ethyl 1-O-methyl 3-oxopiperidine-1,4-dicarboxylate
• CAS: 65202-59-7
• 化学式: C₁₀H₁₅NO₅
• 分子量: 229.233
• InChiKey: PTKLDHADMDDGDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  1-甲基 3-氧代哌啶-1,4-二羧酸-4-乙酯 在 对甲苯磺酸 、 barium(II) hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 48.0h， 生成 3,3-dimethoxy-1-(methoxycarbonyl)piperidine-4-carboxylic acid
  参考文献：
  名称：

  Optimization of Pyrrolamide Topoisomerase II Inhibitors Toward Identification of an Antibacterial Clinical Candidate (AZD5099)

  摘要：

  AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.

  DOI：

  10.1021/jm500462x
• 作为产物：
  描述：

  N-[3-(ethoxycarbonyl)propyl]glycine ethyl ester hydrochloride 在 potassium tert-butylate 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 1.0h， 生成 1-甲基 3-氧代哌啶-1,4-二羧酸-4-乙酯
  参考文献：
  名称：

  Knight, David W.; Lewis, Neil; Share, Andrew C., Journal of the Chemical Society. Perkin transactions I, 1998, # 22, p. 3673 - 3683

  摘要：

  DOI：

文献信息

• Heterocyclic compounds
  申请人：H. Lundbeck & Co. A/S

  公开号：US04278676A1

  公开（公告）日：1981-07-14

  The compound Ia ##STR1## has been shown to possess GABA-related activity. The invention relates to Ia and derivatives thereof, covered by the formula ##STR2## in which R" is hydrogen, acetyl or a group of the general formula ##STR3## in which R.sub.5 is C.sub.1-8 alkyl; phenyl; phenyl substituted in the 4-position with halogen, lower alkoxy, or lower alkyl; or phenylalkyl in which the phenyl group may be substituted in the 4-position with halogen, lower alkoxy, or lower alkyl; and salts thereof. Novel intermediates for preparing I are ##STR4## in which Alk is a lower alkyl group and Z is hydrogen or an amino-protecting group; ##STR5## wherein Z is hydrogen or an amino-protecting group, T is a group convertible, by hydrolysis, into an oxy group, and Q is a leaving group which, on reaction with hydroxylamine, forms a hydroxamic acid group; ##STR6## wherein Z and T are as defined above; ##STR7## wherein Z is as defined above, and W is hydrogen or a group removable to yield the free hydroxy group, with the proviso that at least one of Z and W is different from hydrogen.

  化合物Ia ##STR1## 已被证实具有与GABA相关的活性。该发明涉及Ia及其衍生物，其公式为 ##STR2## 其中R"为氢、乙酰基或一般式 ##STR3## 中的基团，其中R5为C1-8烷基；苯基；在4位被卤素、较低烷氧基或较低烷基取代的苯基；或苯基烷基，其中苯基在4位可被卤素、较低烷氧基或较低烷基取代；及其盐。用于制备I的新中间体为 ##STR4## 其中Alk为较低烷基基团，Z为氢或氨基保护基团； ##STR5## 其中Z为氢或氨基保护基团，T为可通过水解转化为氧基团的基团，Q为与羟胺反应形成羟胺基团的离去基团； ##STR6## 其中Z和T如上定义； ##STR7## 其中Z如上定义，W为氢或可去除以得到游离羟基团的基团，但至少Z和W中的一个不同于氢。
• Synthesis of 3-isoxazolols revisited. Diketene and (β-ketoesters as starting materials
  作者：Niels Jacobsen、Hans Kolind-Andersen、Jens Christensen

  DOI：10.1139/v84-333

  日期：1984.10.1

  3-Isoxazolols can be made in good yields from β-ketoesters or diketene and hydroxylamine, provided that pH is kept at about 10 throughout the reaction, and that the reaction mixture is quenched with an excess of strong mineral acid. This suppresses the formation of 5-isoxazolones, which are otherwise normally the main products of the reaction.

  3-异噁唑醇可以通过β-酮酸酯或二酮乙烯和羟胺在良好收率下制备，前提是在整个反应过程中保持pH值约为10，并且用过量的强矿酸淬灭反应混合物。这样可以抑制5-异噁唑酮的形成，否则这些通常是反应的主要产物。
• PYRROLE DERIVATIVES WITH ANTIBACTERIAL ACTIVITY
  申请人：Basarab Gregory

  公开号：US20100286181A1

  公开（公告）日：2010-11-11

  Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.

  本文描述了化学式（I）的化合物及其药用可接受的盐。还描述了制备它们的过程，含有它们的药物组合物，它们作为药物的用途以及它们在治疗细菌感染方面的用途。
• 1,2,3,6-Tetrahydroisonicotinic acid and derivatives thereof, methods and starting products for their preparation, and pharmaceutical compositions containing them.
  申请人：Krogsgaard-Larsen, Povl

  公开号：EP0000167A1

  公开（公告）日：1979-01-10

  1,2,3,6-Tetrahydroisonicotinic acid and derivatives thereof, methods and starting products for their preparation, and pharmaceutical compositions containing them. Compounds of formuta is which R" is hydrogen, acetyl or a group wherein R1 is C1-8 alkyl; phenyl; substituted phenyl, phenylalkyl in which the phenyl group may be substituted. R' is hydrogen; C1-8 alkyl; phenyl; substituted phenyl, phenylalkyl, substituted phenylalkyl or idanyl; or R' is a group wherein R2 and R3 are hydrogen; C1-6 alkyl; or phenylalkyl and R4 designates C1-8 alkyl; phenyl; substituted phenyl or phenylalkyl and salts thereof. Intermediates for preparing (1) are in which Z is hydrogen or a protecting group and W is hydrogen or a readily removable group and saits thereof which are subjected to dehydration and in which Z' and W' have the same meaning as and W and salts thereof, which are reacted with appropriate reagents. The compounds (I) exhibit γ-aminobutyric acid related activity and are useful as active ingredients in pharmaceutical compositions. They may additionally contain a minor tranquilizer or a neuroleptic.

  1,2,3,6-四氢异烟酸及其衍生物、制备它们的方法和起始产品，以及含有它们的药物组合物。化合物 其中 R "是氢、乙酰基或一个基团 其中 R1 是 C1-8 烷基；苯基；取代苯基；苯基烷基，其中苯基可被取代。R'是氢；C1-8 烷基；苯基；取代的苯基、苯基烷基、取代的苯基烷基或偶氮苯基；或 R'是一个基团，其中 R2 和 R3 是氢；C1-6 烷基；或苯基烷基，R4 表示 C1-8 烷基；苯基；取代的苯基或苯基烷基及其盐。制备（1）的中间体有 其中 Z 为氢或保护基，W 为氢或易脱去的基团及其经脱水处理的盐，以及 其中 Z'和 W'的含义与 W 及其盐类相同，它们与适当的试剂反应。 化合物（I）具有与γ-氨基丁酸相关的活性，可用作药物组合物中的活性成分。此外，它们还可能含有轻微的镇静剂或神经安定剂。
• Isoxazolo(5,4-c)pyridine derivatives, their preparation and pharmaceutical compositions containing them
  申请人：H.Lundbeck & Co., A/S

  公开号：EP0000338A2

  公开（公告）日：1979-01-24

  Isoxazolo-(5,4-C)-pyridine derivatives of the formula in which R" is hydrogen, acetyl or a group of the formula R5OCO- in which Rs is C1-4-alkyl, phenyl, substituted phenyl; phenylalkyl or substituted phenylalkyl and salts thereof, and intermediates IV, VIII', IX' and V. Compounds (I) may be prepared according to the following reaction scheme: in which Z is hydrogen or a protecting group, T is a group convertible by hydrolysis into an oxo group, Q is a leaving group and W is hydrogen or a group removable to yield the free hydroxy group. Compounds (I) exhibit a y-aminobutyric acid related activity and are useful as active ingredients in pharmaceutical compositions which may, optionally, further contain a minor tranquilizer or a neuroleptic.

  式中的异噁唑-(5,4-C)-吡啶衍生物 其中 R "为氢、乙酰基或式 R5OCO-的基团，其中 Rs 为 C1-4-烷基、苯基、取代苯基；苯基烷基或取代苯基烷基及其盐，以及中间体 IV、VIII'、IX'和 V。 化合物 (I) 可根据以下反应方案制备： 其中 Z 为氢或保护基，T 为可通过水解转化为氧代基团的基团，Q 为离去基团，W 为氢或可去除以产生游离羟基的基团。 化合物(I)具有与 y-氨基丁酸相关的活性，可作为药物组合物中的活性成分，这些药物组合物还可进一步含有轻微的镇静剂或神经安定剂。