tert-butyl (3Z)-3-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (3Z)-3-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate
• 英文别名: tert-butyl 3-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate
• 化学式: C₁₄H₂₃NO₄
• 分子量: 269.341
• InChiKey: ADHUSARVCHQJCU-LUAWRHEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  磷酰基乙酸三乙酯 、 N-叔丁氧羰基-3-哌啶酮 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.08h， 以8.86 g的产率得到tert-butyl (3E)-3-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: Highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate

  摘要：

  A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, Substituted at the 2-position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Attachment of the charged entity using an N-ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.039

文献信息

• Chemokine receptor binding heterocyclic compounds with enhanced efficacy
  申请人：——

  公开号：US20030220341A1

  公开（公告）日：2003-11-27

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  这项发明涉及由一个核心氮原子环绕着三个侧链基团的杂环化合物，其中三个侧链基团中的两个最好是苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N，并且可选地含有额外的环。这些化合物与趋化因子受体结合，包括CXCR4和CCR5，并且表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护作用。
• Cycloaddition Strategies for the Synthesis of Diverse Heterocyclic Spirocycles for Fragment‐Based Drug Discovery
  作者：Thomas A. King、Hannah L. Stewart、Kim T. Mortensen、Andrew J. P. North、Hannah F. Sore、David R. Spring

  DOI：10.1002/ejoc.201900847

  日期：2019.9

  benefited from the advances made in fragment‐based drug discovery (FBDD) with more than 30 fragment‐derived drugs currently marketed or progressing through clinical trials. The success of fragment‐based drug discovery is entirely dependent upon the composition of the fragment screening libraries used. Heterocycles are prevalent within marketed drugs due to the role they play in providing binding interactions;

  近年来，制药行业受益于基于片段的药物发现 (FBDD) 的进步，目前有 30 多种片段衍生药物已上市或正在进行临床试验。基于片段的药物发现的成功完全取决于所使用的片段筛选文库的组成。杂环化合物在市售药物中普遍存在，因为它们在提供结合相互作用方面发挥着作用；因此，杂环片段是 FBDD 文库的重要组成部分。目前的筛选文库主要是扁平的、富含sp2的化合物，这主要是由于它们的合成易处理性，尽管更多的三维支架表现出优异的理化性质。在此，我们报告了许多生物学相关的片段状杂环螺环的高效路线。在复杂性生成的[3+2]-环加成中探索了使用缺电子和富电子2原子供体，以通过市售起始材料分3步提供产品。所得化合物从合成一开始就通过包含合成句柄来进行进一步的片段加工。
• [EN] CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS WITH ENHANCED EFFICACY<br/>[FR] COMPOSES HETEROCYCLIQUES A EFFICACITE ACCRUE SE FIXANT SUR LES RECEPTEURS DE LA CHIMIOKINE
  申请人：ANORMED INC

  公开号：WO2003055876A1

  公开（公告）日：2003-07-10

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  本发明涉及由一个核心氮原子和三个侧链基团组成的杂环化合物，其中三个侧链基团中的两个首选为苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N并可选择性地含有其他环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并对人免疫缺陷病毒（HIV）感染靶细胞表现出保护作用。
• CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS WITH ENHANCED EFFICACY
  申请人：BRIDGER Gary

  公开号：US20080167341A1

  公开（公告）日：2008-07-10

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  该发明涉及由一个核心氮原子和三个侧链基团组成的杂环化合物，其中三个侧链基团中有两个是苯并咪唑甲基和四氢喹啉基，第三个侧链基团含有N，并且可以含有额外的环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并且表现出对人类免疫缺陷病毒（HIV）感染靶细胞的保护效果。
• Chemokine Receptor Binding Heterocyclic Compounds With Enhanced Efficacy
  申请人：Genzyme Corporation

  公开号：US20150038509A1

  公开（公告）日：2015-02-05

  The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).

  该发明涉及杂环化合物，其由一个核心氮原子和三个下垂基团组成，其中三个下垂基团中的两个优选为苯并咪唑甲基和四氢喹啉基，第三个下垂基团含有N，并且可以包含其他环。这些化合物结合趋化因子受体，包括CXCR4和CCR5，并且对人类免疫缺陷病毒（HIV）感染目标细胞具有保护作用。