N-benzyl-2-oxoazetidine-1-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: N-benzyl-2-oxoazetidine-1-carboxamide
• 英文别名: N-benzylcarbamoylazetidin-2-one
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: RKFBLIRNEMKIAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-氮杂环丁酮 、 异氰酸苄酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以66%的产率得到N-benzyl-2-oxoazetidine-1-carboxamide
  参考文献：
  名称：

  C-4取代基激活β-内酰胺支架对丝氨酸蛋白酶和氢氧根离子的效率。

  摘要：

  通常认为在单bactams C-4处有一个离去基团是这些酰化剂基于机制抑制人白细胞弹性蛋白酶的必要条件。我们报告说，N-氨基甲酰基单bactams的碱性水解和弹性蛋白酶失活的二级速率常数与C-4上离去基团的pKa无关。实际上，这些取代基发挥的作用纯粹是感应性的：N-氨基甲酰基-3,3-二乙基单bactams C-4处的吸电子取代基可提高碱性水解和弹性蛋白酶的失活速率，哈米特pI值分别为3.4和2.5。 ，表明在过渡态中产生负电荷。当与化学过程相比时，这些pI值之间的大小差异与酶促反应的较早过渡状态一致。这些结果表明，弹性蛋白酶失活的限速步骤是四面体中间体的形成，并且β-内酰胺开环与离去基团离开C-4不协调。即使不存在与主要识别位点相互作用所需的C-3乙基，单bactamulfones仍然是有效的弹性蛋白酶抑制剂。对于一种这样的化合物，已经通过X射线晶体学检查了涉及猪胰弹性蛋白酶的1：1酶抑

  DOI：

  10.1039/b706622h

文献信息

• The efficiency of C-4 substituents in activating the β-lactam scaffold towards serine proteases and hydroxide ion
  作者：Jalmira Mulchande、Luísa Martins、Rui Moreira、Margarida Archer、Tania F. Oliveira、Jim Iley

  DOI：10.1039/b706622h

  日期：——

  that second-order rate constants for the alkaline hydrolysis and elastase inactivation by N-carbamoyl monobactams are independent of the pKa of the leaving group at C-4. Indeed, the effect exerted by these substituents is purely inductive: electron-withdrawing substituents at C-4 of N-carbamoyl-3,3-diethylmonobactams increase the rate of alkaline hydrolysis and elastase inactivation, with Hammett pI

  通常认为在单bactams C-4处有一个离去基团是这些酰化剂基于机制抑制人白细胞弹性蛋白酶的必要条件。我们报告说，N-氨基甲酰基单bactams的碱性水解和弹性蛋白酶失活的二级速率常数与C-4上离去基团的pKa无关。实际上，这些取代基发挥的作用纯粹是感应性的：N-氨基甲酰基-3,3-二乙基单bactams C-4处的吸电子取代基可提高碱性水解和弹性蛋白酶的失活速率，哈米特pI值分别为3.4和2.5。 ，表明在过渡态中产生负电荷。当与化学过程相比时，这些pI值之间的大小差异与酶促反应的较早过渡状态一致。这些结果表明，弹性蛋白酶失活的限速步骤是四面体中间体的形成，并且β-内酰胺开环与离去基团离开C-4不协调。即使不存在与主要识别位点相互作用所需的C-3乙基，单bactamulfones仍然是有效的弹性蛋白酶抑制剂。对于一种这样的化合物，已经通过X射线晶体学检查了涉及猪胰弹性蛋白酶的1：1酶抑
• Synthesis and evaluation of N1/C4-substituted β-lactams as PPE and HLE inhibitors
  作者：Stéphane Gérard、Moreno Galleni、Georges Dive、Jacqueline Marchand-Brynaert

  DOI：10.1016/j.bmc.2003.10.009

  日期：2004.1

  4-(Alkylamino)carbonyl-1-(alkoxy)carbonyl-2-azetidinones (9-11) have been prepared in five steps from 4-(benzyloxy)carbonyl-1-(t-butyidimethyl)silyl-2-azetidinone (1). The P-lactam reactivity of 9 has been established by H-1 NMR experiment. Compound 11 was a good reversible inhibitor of PPE and HLE. Based on theoretical design, series of 2-azetidinones (12-17) and 4(alkoxy)carbonyl-2-azetidinones (18-21) bearing various carbonyl (ester, thiolester, amide) and thiocarbonyl (thioamide) functionalities at position N1 were similarly prepared. In the absence of C4-substituent, the compounds were inactive against elastases. On the other hand, 4-(benzyloxy)carbonyl-1-(ethylthioxy)carbonyl-2-azetidinone (19) and 4-(benzyloxy)carbonyl-1-(benzylamino)-thiocarbonyl-2-azetidinone (21) were both good reversible inhibitors, but acting most probably via different mechanisms (enzymic processing of the exocyclic ester function or beta-lactam ring opening). (C) 2003 Elsevier Ltd. All rights reserved.
• AZETIDINONE DERIVATIVES FOR THE TREATMENT OF HCMV INFECTIONS
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP1021404A1

  公开（公告）日：2000-07-26
• [EN] AZETIDINONE DERIVATIVES FOR THE TREATMENT OF HCMV INFECTIONS<br/>[FR] DERIVES D'AZETIDINONE POUR LE TRAITEMENT D'INFECTIONS HCMV
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：WO1999018071A1

  公开（公告）日：1999-04-15

  (EN) A compound of formula (1) wherein Y is S or O; R1 is C1-6 alkyl; (C0-6 alkyl)aryl; (C0-6 alkyl)Het; or R1 is an amino acid analog or dipeptide analog of formula (I) wherein R2 is H, C1-10 alkyl; or an amide or ester group; A is C6-10 aryl, Het or CH-R3 wherein R3 is C1-6 alkyl or (C0-4 alkyl)aryl; and Z is H, C1-6 alkyl, or an acyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy, or benzyloxy; and R5 is alkyl, cycloalkyl, carboxyl group; an aryl; Het or Het(lower alkyl); or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with phenyl or C(O)OCH2-phenyl, said phenyl ring optionally mono- or di-substituted with among others C(O)OR7 wherein R7 is lower alkyl or phenyl (lower alkyl); or a therapeutically acceptable acid addition salt thereof.(FR) L'invention concerne un composé de formule (1) dans laquelle Y désigne S ou O; R1 désigne un alkyle C1-6; (alkyl C0-6)aryle; (alkyl C0-6)Het; ou R1 désigne un analogue d'acide aminé ou analogue dipeptidique de la formule (I) dans laquelle R2 désigne H, alkyle C1-10; ou un groupe amide ou ester; A désigne un aryle C6-10, Het ou CH-R3 où R3 désigne un alkyle C1-6 ou (alkyl C0-4)aryle; et Z désigne H, alkyle C1-6 ou un acyle; R4 désigne l'hydrogène, un alkyle inférieur, méthoxy, éthoxy ou benzyloxy; et R5 désigne un alkyle, cycloalkyle, groupe carboxyle, un aryle; Het ou Het(alkyle inférieur); ou R4 et R5 pris ensemble avec l'atome d'azote auquel ils sont liés forment un cycle contenant de l'azote éventuellement substitué par phényle ou C(O)OCH2-phényle; ledit cycle phényle éventuellement mono- ou di-substitué par entre autres C(O)OR7 où R7 désigne un alkyle inférieur ou phényl(alkyle inférieur); ou un de ses sels d'addition d'acide thérapeutiquement acceptable.
• Non-transpeptidase binding arylthioether β-lactams active against Mycobacterium tuberculosis and Moraxella catarrhalis
  作者：Tim N. Beck、Dina Lloyd、Rostislav Kuskovsky、Jeanette Minah、Kriti Arora、Balbina J. Plotkin、Jacalyn M. Green、Helena I. Boshoff、Clifton Barry、Jeffrey Deschamps、Monika I. Konaklieva

  DOI：10.1016/j.bmc.2014.11.025

  日期：2015.2

  The prevalence of drug resistance in both clinical and community settings as a consequence of alterations of biosynthetic pathways, enzymes or cell wall architecture is a persistent threat to human health. We have designed, synthesized, and tested a novel class of non-transpeptidase, beta-lactamase resistant monocyclic beta-lactams that carry an arylthio group at C4. These thioethers exhibit inhibitory and cidal activity against serine beta-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n = 8) beta-lactamase producing Moraxella catarrhalis clinical isolates. (C) 2014 Elsevier Ltd. All rights reserved.