1,4-二噁-7-氮杂螺[4.5]癸烷-7,10-二羧酸 10-乙酯 7-甲酯 | 65202-60-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 中文名称: 1,4-二噁-7-氮杂螺[4.5]癸烷-7,10-二羧酸 10-乙酯 7-甲酯
• 英文名称: 10-ethyl 7-methyl 1,4-dioxa-7-azaspiro[4.5]decane-7,10-dicarboxylate
• 英文别名: 1,4-dioxa-7-aza-spiro[4.5]decane-7,10-dicarboxylic acid 10-ethyl ester 7-methyl ester；ethyl 1-methoxycarbonyl-3-oxopiperidine-4-carboxylate ethylene acetal；6-O-ethyl 9-O-methyl 1,4-dioxa-9-azaspiro[4.5]decane-6,9-dicarboxylate
• CAS: 65202-60-0
• 化学式: C₁₂H₁₉NO₆
• 分子量: 273.286
• InChiKey: JCSIMGKOBJIXLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  74.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,4-二噁-7-氮杂螺[4.5]癸烷-7,10-二羧酸 10-乙酯 7-甲酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 (2-hydroxymethyl-1,3-dithian-2-yl)-(1-methoxycarbonyl-3,3-ethylenedioxy-4-piperidyl)-ketone
  参考文献：
  名称：

  Haefliger; Revesz; Maurer, European Journal of Medicinal Chemistry, 1984, vol. 19, # 2, p. 149 - 156

  摘要：

  DOI：
• 作为产物：
  描述：

  1-甲基 3-氧代哌啶-1,4-二羧酸-4-乙酯 在 对甲苯磺酸 作用下， 以 乙二醇 、 乙酸乙酯 、 苯 为溶剂， 以65%的产率得到1,4-二噁-7-氮杂螺[4.5]癸烷-7,10-二羧酸 10-乙酯 7-甲酯
  参考文献：
  名称：

  Heterocyclic compounds

  摘要：

  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。

  公开号：

  US04278676A1

文献信息

• 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。
• 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。
• Isoxazolo(5,4-C)pyridines
  申请人：H.Lundbeck & Co., A/S

  公开号：EP0027279A1

  公开（公告）日：1981-04-22

  The compound wherein Z is hydrogen or an amino-protecting group 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, is a novel intermediate for preparing compound I. The invention covered bytheformula in which R" is hydrogen, acetyl or a group of the general formula VII in which R5 is C1-8 alkyl; phenyl; phenyl substituted in the 4-position with halogen, Ci-4 alkoxy, or C1-4 alkyl; or phenylalkyl in which the phenyl group may be substituted in the 4-position with halogen, lower alkoxy, or lower alkyl. Compound I, in which R" is hydrogen, possesses GABA-related activity.

  其中 Z 是氢或氨基保护基团，W 是氢或可产生游离羟基的基团，但 Z 和 W 中至少有一个不同于氢，该化合物是制备化合物 I 的新型中间体。 本发明包括以下式子，其中 R" 是氢、乙酰基或通式 VII 的基团，其中 R5 是 C1-8 烷基；苯基；在 4 位被卤素、Ci-4 烷氧基或 C1-4 烷基取代的苯基；或苯基烷基，其中苯基可在 4 位被卤素、低级烷氧基或低级烷基取代。 其中 R" 是氢的化合物 I 具有 GABA 相关活性。
• 3-Piperidinone-4-carboxylic acid derivatives
  申请人：H.Lundbeck & Co., A/S

  公开号：EP0028017A1

  公开（公告）日：1981-05-06

  The compounds in which Alk is a lower alkyl group and Z is hydrogen or an amino-protecting group: 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; wherein Z and T are as defined above, are novel intermediates for preparing compound I. in which R" is hydrogen, acetyl or a group of the general formula VII in which R5 is Ci-8 alkyl; phenyl; phenyl substituted in the 4-position with halogen, C1-4 alkoxy, or Ci-4 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. The compound I, in which R" is hydrogen, possesses GABA-related activity.

  化合物 其中 Alk 为低级烷基，Z 为氢或氨基保护基团： 其中 Z 是氢或氨基保护基，T 是可通过水解转化为氧基的基团，Q 是与羟胺反应后形成羟肟酸基的离去基团； 其中 Z 和 T 如上定义，是制备化合物 I 的新型中间体。 其中 R "是氢、乙酰基或通式 VII 的基团 其中 R5 是 Ci-8 烷基；苯基；在 4 位被卤素、C1-4 烷氧基或 Ci-4 烷基取代的苯基；或苯基烷基，其中苯基可在 4 位被卤素、低级烷氧基或低级烷基取代；及其盐类。其中 R "为氢的化合物 I 具有 GABA 相关活性。
• Optimization of Pyrrolamide Topoisomerase II Inhibitors Toward Identification of an Antibacterial Clinical Candidate (AZD5099)
  作者：Gregory S. Basarab、Pamela J. Hill、C. Edwin Garner、Ken Hull、Oluyinka Green、Brian A. Sherer、P. Brian Dangel、John I. Manchester、Shanta Bist、Sheila Hauck、Fei Zhou、Maria Uria-Nickelsen、Ruth Illingworth、Richard Alm、Mike Rooney、Ann E. Eakin

  DOI：10.1021/jm500462x

  日期：2014.7.24

  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.