1-carbamoylmethyl-1-azonia-4-aza-bicyclo[2.2.2]octane trifluoromethanesulfonate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-carbamoylmethyl-1-azonia-4-aza-bicyclo[2.2.2]octane trifluoromethanesulfonate
• 英文别名: 1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane salt with trifluoromethanesulfonic acid (1:1)；1-carbamoylmethyl-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate；1-carbamoylmethyl-4-aza-1-azoniabicyclo[2.2.2]-octane trifluoromethane sulfonate；1-carbamoylmethyl-4-aza-1-azonia-bicyclo[2.2.2]octane trifluoromethyl sulfonate；1-carbamoylmethyl-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethane sulfonate；1-Carbamoylmethyl-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethylsulfonate；2-(4-aza-1-azoniabicyclo[2.2.2]octan-1-yl)acetamide;trifluoromethanesulfonate
• 化学式: CF₃O₃S*C₈H₁₆N₃O
• 分子量: 319.305
• InChiKey: MQJUFLDDDLCALJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.33
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-carbamoylmethyl-1-azonia-4-aza-bicyclo[2.2.2]octane trifluoromethanesulfonate 在 Rh on carbon 盐酸 、 氢气 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 (5R,6S)-3-[7-[[4-(2-amino-2-oxoethyl)-1,4-diazoniabicyclo[2.2.2]octan-1-yl]methyl]-9-oxofluoren-3-yl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate;chloride
  参考文献：
  名称：

  Dicationic 2-fluorenonylcarbapenems: Potent anti-MRS agents with improved solubility and pharmacokinetic properties

  摘要：

  The synthesis and biological evaluation of a series of dicationic-substituted 2-fluorenonylcarbapenems is described. This class of compounds showed enhanced water solubility while maintaining potent activity against MRS. Introduction of a beta 1--methyl substituent was found to improve pharmacokinetics. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00567-3
• 作为产物：
  描述：

  三乙烯二胺 以 乙腈 为溶剂， 生成 1-carbamoylmethyl-1-azonia-4-aza-bicyclo[2.2.2]octane trifluoromethanesulfonate
  参考文献：
  名称：

  Practical Synthesis of Anti-Methicillin-Resistant Staphylococcus Aureus (MRSA) Carbapenem L-742,728

  摘要：

  Ani-MRSA carbapenem, L-742,728, has been prepared in large quantity using, the Suzuki-Miyaura cross-coupling as the key reaction. Three approaches have been examined by varying the coupling reaction between carbapenem nucleus A and side chains B, BC, and BCD, wherein BCD represents the fully elaborated side chain. The coupling of A with BCD offers the advantage of convergence and requires fewer chemical steps after installation of the thermally unstable carbapenem skeleton. This key reaction highlights the versatility and efficiency of the Suzuki-Miyaura reaction. This approach offers a general method for the preparation of the 3-aryl carbapenems, which possess strong antibacterial activity against resistant strains.

  DOI：

  10.1021/jo980381n

文献信息

• [EN] NARGENICIN COMPOUNDS AND USES THEREOF AS ANTIBACTERIAL AGENTS<br/>[FR] COMPOSÉS NARGÉNICINE ET LEURS UTILISATIONS DE COMME AGENTS ANTIBACTÉRIENS
  申请人：MERCK SHARP & DOHME

  公开号：WO2016061772A1

  公开（公告）日：2016-04-28

  The present invention relates to novel nargenicin related compounds which can inhibit DnaE and have antibacterial, particularly antimycobacterialactivity against Mycobacterium tuberculosis. The present invention also relates to method for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosis by administering an antimycobacterially effective amount of nargenicin or a nargenicin-related compound and/or their pharmaceutically acceptable salts.

  本发明涉及一种新型的纳尔吉霉素相关化合物，可以抑制DnaE并具有抗细菌作用，特别是对结核分枝杆菌具有抗菌活性。本发明还涉及一种抑制分枝杆菌细胞生长的方法，以及通过给予纳尔吉霉素或纳尔吉霉素相关化合物及/或其药学上可接受的盐的抗结核菌有效量来治疗结核分枝杆菌感染的方法。
• A Practical and Efficient Preparation of the Releasable Naphthosultam Side Chain of a Novel Anti-MRSA Carbapenem
  作者：Ross A. Miller、Guy R. Humphrey、David R. Lieberman、Scott S. Ceglia、Derek J. Kennedy、Edward J. J. Grabowski、Paul J. Reider

  DOI：10.1021/jo991490k

  日期：2000.3.1

  A practical large-scale synthesis of the naphthosultam-based side chain of the anti-MRSA antibiotic 1 has been achieved in 29% overall yield over seven steps from 1-methylnaphthalene. The synthesis was completed without the use of protecting groups, featuring a novel naphthosultam annelation, a chemoselective acid-catalyzed triflation, and the use of a novel naphthosultam dianion to effect functionalization

  从1-甲基萘经过七个步骤，已实现了大规模合成抗-MRSA抗生素1的萘甲舒坦基侧链的方法，总收率达29％。无需使用保护基团即可完成合成，该保护基团具有新型的萘并硫酸氢呋喃脱嵌，化学选择性酸催化的三氟甲基磺酸盐化以及使用新型的萘并硫酸氢根二价阴离子通过苄基金属化作用实现功能化。
• Carbapenem antibacterial compounds, compositions containing such compounds and methods of treatment
  申请人：Merck & Co., Inc.

  公开号：US06346526B1

  公开（公告）日：2002-02-12

  Compounds of formula I: as well as pharmaceutically acceptable salts thereof useful as carbapenem antibacterial agents are disclosed wherein X is CH2 or C═O.

  公开了式I的化合物及其药学上可接受的盐，其作为碳青霉烯类抗菌剂有用，其中X为CH2或C═O。
• [EN] 1- beta -METHYL-CARBAPENEM, COMPOSITIONS CONTAINING SAME AND METHODS OF USE<br/>[FR] 1- beta -METHYLE-CARBAPENEM, COMPOSITIONS CONTENANT CE COMPOSE ET SES PROCEDES D'UTILISATION
  申请人：MERCK & CO., INC.

  公开号：WO1995021841A1

  公开（公告）日：1995-08-17

  (EN) A carbapenem antibiotic of formula (I) is disclosed. The variable (a) represents a counterion. Pharmaceutical compositions and methods of use are also disclosed.(FR) L'invention se rapporte à un antibiotique à base de carbapenem de la formule (I). La variable (a) représente un contre-ion. L'invention se rapporte également aux compositions pharmaceutiques et aux procédés d'utilisation de ce composé.

  一种化学式为(I)的碳青霉烯类抗生素被揭示。变量(a)代表一个反离子。还揭示了药物组成和使用方法。
• [EN] CARBAPENEM ANTIBACTERIAL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT<br/>[FR] COMPOSES ANTIBACTERIENS A BASE DE CARBAPENEM, COMPOSITIONS CONTENANT DE TELS COMPOSES ET METHODES DE TRAITEMENT
  申请人：MERCK & CO., INC.

  公开号：WO1997040048A1

  公开（公告）日：1997-10-30

  (EN) The present invention relates to carbapenem antibacterial agents in which the carbapenem nucleus is substituted at the 2-position with a naphthosultam linked through a CH2 group. The naphthosultam is further substituted with various substituent groups including at least one cationic group. The compounds are represented by formula (I). Pharmaceutical compositions and methods of use are also included.(FR) Agents antibactériens à base de carbapénem dans lesquels le noyau carbapénem est substitué en position 2 par un naphtosultame lié par l'intermédiaire d'un groupe CH2. Le naphtosultame est lui-même substitué par divers groupes de substitution, dont au moins un groupe cationique. Ces composés répondent à la formule (I). Des compositions pharmaceutiques et des procédés d'utilisation sont également décrits.

  (中文) 本发明涉及一种碳青霉烯抗菌剂，其中碳青霉烯核在2位被萘磺酰胺通过CH2基连接取代。萘磺酰胺还进一步被各种取代基取代，包括至少一个阳离子基团。该化合物由式(I)表示。还包括制药组合物和使用方法。