4-(3-chloro-4-fluoro-phenylsulfanyl)-azetidin-2-one

• 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: 4-(3-chloro-4-fluoro-phenylsulfanyl)-azetidin-2-one
• 英文别名: 4-(3-Chloro-4-fluorophenyl)sulfanylazetidin-2-one；4-(3-chloro-4-fluorophenyl)sulfanylazetidin-2-one
• 化学式: C₉H₇ClFNOS
• 分子量: 231.678
• InChiKey: XHRRMXRDEZNOCM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-chloro-4-fluoro-phenylsulfanyl)-azetidin-2-one 、 异氰酸苄酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以37.5%的产率得到2-(3-chloro-4-fluoro-phenylsulfanyl)-4-oxo-azetidine-1-carboxylic acid benzylamide
  参考文献：
  名称：

  Non-transpeptidase binding arylthioether β-lactams active against Mycobacterium tuberculosis and Moraxella catarrhalis

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2014.11.025
• 作为产物：
  描述：

  4-乙酰氧基-2-氮杂环丁酮 、 3-氯-4氟硫酚 在 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 12.0h， 以56%的产率得到4-(3-chloro-4-fluoro-phenylsulfanyl)-azetidin-2-one
  参考文献：
  名称：

  Non-transpeptidase binding arylthioether β-lactams active against Mycobacterium tuberculosis and Moraxella catarrhalis

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2014.11.025

文献信息

• [EN] SMALL MOLECULE ACTIVATORS AND INHIBITORS OF LECITHIN: CHOLESTEROL ACYLTRANSFERASE<br/>[FR] ACTIVATEURS ET INHIBITEURS DE PETITES MOLÉCULES DE LÉCITHINE-CHOLESTÉROL ACYLTRANSFÉRASE
  申请人：US HEALTH

  公开号：WO2015179293A1

  公开（公告）日：2015-11-26

  The disclosure includes compounds and salts of Formula I, II, and III. The variables R, R0, R1, R10, R11, and R2 are defined herein. Compounds and salts of Formula I, II, and III are useful as modulators of Lecithin: cholesterol acyltransferase (LCAT), a protein that mediates the transfer of fatty acids from lecithin to cholesterol to form cholesterol ester and lysolecithin. LCAT activators of Formula I, II, and III are useful for modulating HDL cholesterol levels and for treating genetic disorders caused by LCAT mutations such as familial LCAT deficiency. Some compounds and salts of Formula I, II, and III are also useful for treating diseases in which LCAT inhibition is desirable, such as lysosomal acid lipase deficiency and Wolman's disease. The disclosure also includes pharmaceutical compositions and method of treatment employing a compound of Formula I, II, or III.

  该披露包括公式I、II和III的化合物和盐。变量R、R0、R1、R10、R11和R2在此处被定义。公式I、II和III的化合物和盐可用作卵磷脂：胆固醇酰基转移酶（LCAT）的调节剂，LCAT是一种介导从卵磷脂向胆固醇转移脂肪酸以形成胆固醇酯和溶血卵磷脂的蛋白质。公式I、II和III的LCAT激活剂可用于调节HDL胆固醇水平，并用于治疗由LCAT突变引起的遗传疾病，如家族性LCAT缺乏症。公式I、II和III的一些化合物和盐也可用于治疗需要LCAT抑制的疾病，如溶酶体酸性脂肪酶缺乏症和沃尔曼氏病。该披露还包括使用公式I、II或III的化合物的药物组合物和治疗方法。
• C4-Phenylthio β-lactams: Effect of the chirality of the β-lactam ring on antimicrobial activity
  作者：Rostislav Kuskovsky、Dina Lloyd、Kriti Arora、Balbina J. Plotkin、Jacalyn M. Green、Helena I. Boshoff、Clifton Barry、Jeffrey Deschamps、Monika I. Konaklieva

  DOI：10.1016/j.bmc.2019.115050

  日期：2019.10

  C4-phenylthio β-lactams are a new family of antibacterial agents that have activity against two phylogenetically distant bacteria – Mycobacterium tuberculosis (Mtb) and Moraxella catarrhalis (M. cat). These compounds are effective against β-lactamase producing Mtb and M. cat unlike the clinically relevant β-lactam antibiotics. The structure-activity relationship for the C4 phenylthio β-lactams has

  C4-苯硫基β-内酰胺类是一个新的抗菌剂家族，对两种系统发育远的细菌（结核分枝杆菌（Mtb）和卡他莫拉菌）具有活性（猫）与临床上相关的β-内酰胺类抗生素不同，这些化合物对产生β-内酰胺酶的Mtb和猫猫有效。C 4苯硫基β-内酰胺的结构活性关系尚未完全确定。在我们实验室的早期工作中，C4-苯硫基取代基对于抗菌活性是必不可少的，而N1氨基甲酰基取代基起着更为微妙的作用。在本研究中，我们研究了C4的立体化学在这些化合物的抗菌活性中的作用。这是通过合成和测试在N1处具有手性氨基甲酸酯基的非对映异构体的抗菌活性来实现的。我们的发现表明，对于获得最佳的抗Mtb和抗M，不需要C4-苯硫基β-内酰胺的严格立体化学。猫的活动。此外，结构-生物活性图与苯硫基的电子需求更紧密相关。此外，Mtb的MIC对生长培养基组成敏感。选择的化合物显示出对非复制性和多药耐药性Mtb的活性。