1-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)ethanone | 1303709-11-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)ethanone
• 英文别名: 1-[4-Methyl-2-(4-phenylphenyl)-1,3-thiazol-5-yl]ethanone
• CAS: 1303709-11-6
• 化学式: C₁₈H₁₅NOS
• 分子量: 293.389
• InChiKey: CLFDQGKBGOHPHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)ethanone 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 1.0h， 以80%的产率得到1-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)-2-bromoethan-1-one
  参考文献：
  名称：

  Arylthiazole antibiotics targeting intracellular methicillin-resistant Staphylococcus aureus (MRSA) that interfere with bacterial cell wall synthesis

  摘要：

  The promising antibacterial potency of arylthiazole antibiotics is offset by their limited activity against intracellular bacteria (namely methicillin-resistant Staphylococcus aureus (MRSA)), similar to many clinically-approved antibiotics. The failure to target these hidden pathogens is due to the compounds' lack of proper characteristics to accumulate intracellularly. Fine tuning of the size and polar-surface-area of the linking heteroaromatic ring provided a new series of 5-thiazolylarylthiazoles with balanced properties that allow them to sufficiently cross and accumulate inside macrophages infected with MRSA. The most promising compound 4i exhibited rapid bactericidal activity, good metabolic stability and produced over 80% reduction of intracellular MRSA in infected macrophages. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.08.039
• 作为产物：
  描述：

  对苯基苯甲醛 在 劳森试剂 、 盐酸羟胺 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 48.33h， 生成 1-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)ethanone
  参考文献：
  名称：

  ANTIMICROBIAL SUBSTITUTED THIAZOLES AND METHODS OF USE

  摘要：

  披露了对抗MRSA和/或VRSA活性的组合物，并使用这些组合物来治疗微生物感染的方法。

  公开号：

  US20140121249A1

文献信息

• Design, synthesis and bioactivity evaluation of novel pyrazole linked phenylthiazole derivatives in context of antibacterial activity
  作者：Bhautikkumar Patel、Matthew Zunk、Gary Grant、Santosh Rudrawar

  DOI：10.1016/j.bmcl.2021.127853

  日期：2021.5

  investigation into novel classes of antimicrobial agents. This study presents a structure–activity relationship (SAR) rationale for pyrazole linked phenylthiazole analogues as new antibacterial agents. A library of 23 novel pyrazole linked phenylthiazole compounds were synthesised, followed by screening for antimicrobial activity against five bacterial species and two fungi. The most active compound 14b has shown

  耐甲氧西林金黄色葡萄球菌(MRSA) 感染是全球临床和经济上的重大负担。增加对当前抗生素的耐药性需要对新型抗菌剂进行紧急调查。本研究提出了吡唑连接的苯基噻唑类似物作为新型抗菌剂的构效关系 (SAR) 原理。合成了 23 种新型吡唑连接的苯基噻唑化合物库，然后筛选了对五种细菌和两种真菌的抗菌活性。最活跃的化合物14b对革兰氏阳性耐甲氧西林金黄色葡萄球菌显示出有希望的抗菌活性(MRSA, ATCC 43300) 菌株 (MIC 4 μg/mL)。此外，活性吡唑连接的苯基噻唑化合物表现出比标准抗生素更好的毒性特征。总之，这些结果表明，吡唑连接的苯基噻唑支架具有作为进一步研究提供新型抗菌剂的先导物的潜力。
• Investigating the Antibacterial Activity of Biphenylthiazoles against Methicillin- and Vancomycin-Resistant <i>Staphylococcus aureus</i> (MRSA and VRSA)
  作者：Mohamed Hagras、Haroon Mohammad、Mohamed S. Mandour、Youssef A. Hegazy、Adel Ghiaty、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1021/acs.jmedchem.7b00392

  日期：2017.5.11

  Phenylthiazoles were reported previously as a new scaffold with antibacterial activity against an array of multidrug-resistant staphylococci. However, their promising antibacterial activity was hampered in large part by their short half-life due to excessive hepatic clearance. Close inspection of the structure-activity-relationships (SARs) of the phenylthiazoles revealed two important structural features necessary for antibacterial activity (a nitrogenous and a lipophilic component). Incorporating the nitrogenous part within a pyrimidine ring resulted in analogues with a prolonged half-life, while the biphenyl moiety revealed the most potent analogue 1b. In this study, advantageous moieties have been combined to generate a new hybrid scaffold of 5-pyrimidinylbiphenylthiazole with the objective of enhancing both anti-MRSA activity and drug-like properties. Among the 37 tested biphenylthiazoles, piperazinyl-containing derivatives 10, 30, and 36 were the most potent analogues with MIC values as low as 0.39 mu g/mL. Additionally, 36 exhibited significant improvement in stability to hepatic metabolism.
• Discovery and Characterization of Potent Thiazoles versus Methicillin- and Vancomycin-Resistant <i>Staphylococcus aureus</i>
  作者：Haroon Mohammad、Abdelrahman S. Mayhoub、Adil Ghafoor、Muhammad Soofi、Ruba A. Alajlouni、Mark Cushman、Mohamed N. Seleem

  DOI：10.1021/jm401905m

  日期：2014.2.27

  Methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) infections are growing global health concerns. Structure-activity relationships of phenylthiazoles as a new antimicrobial class have been addressed. We present 10 thiazole derivatives that exhibit strong activity against 18 clinical strains of MRSA and VRSA with acceptable PK profile. Three derivatives revealed an advantage over vancomycin by rapidly eliminating MRSA growth within 6 h, and no derivatives are toxic to HeLa cells at 11 mu g/mL.
• Development of Biphenylthiazoles Exhibiting Improved Pharmacokinetics and Potent Activity Against Intracellular<i>Staphylococcus aureus</i>
  作者：Mohamed Hagras、Nader S. Abutaleb、Noha M. Elhosseiny、Tamer M. Abdelghany、Mariam Omara、Mohamed M. Elsebaei、Marwa Alhashimi、Allison B Norvil、Mark I Gutay、Humaira Gowher、Ahmed S. Attia、Mohamed N. Seleem、Abdelrahman S. Mayhoub

  DOI：10.1021/acsinfecdis.0c00137

  日期：2020.11.13

  Exploring the structure-activity relationship (SAR) at the cationic part of arylthiazole antibiotics revealed hydrazine as an active moiety. The main objective of the study is to overcome the inherited toxicity associated with the free hydrazine. A series of hydrocarbon bridges was inserted in between the groups, to separate the two amino groups. Hence, the aminomethylpiperidine-containing analog 16 was identified as a new promising antibacterial agent with efficient antibacterial and pharmacokinetic profiles. Briefly, compound 16 outperformed vancomycin in terms of the antibacterial spectrum against vancomycin-resistant staphylococcal and enterococcal strains with minimum inhibitory concentrations (MICs) ranging from 2 to 4 μg/mL, which is a faster bactericidal mode of action, completely eradicating the high staphylococcal burden within 6-8 h, and it has a unique ability to completely clear intracellular staphylococci. In addition, the initial pharmacokinetic assessment confirmed the high metabolic stability of compound 16 (biological half-life >4 h); it had a good extravascular distribution and maintained a plasma concentration higher than the average MIC value for over 12 h. Moreover, compound 16 significantly reduced MRSA burden in an in vivo MRSA skin infection mouse experiment. These attributes collectively suggest that compound 16 is a good therapeutic candidate for invasive staphylococcal and enterococcal infections. From a mechanistic point of view, compound 16 inhibited undecaprenyl diphosphate phosphatase (UppP) with an IC₅₀ value of 29 μM.
• US9353072B2
  申请人：——

  公开号：US9353072B2

  公开（公告）日：2016-05-31