New thiazole-based pyrazolo[1,5-a]pyrimidine hybrids: One-pot synthesis of potential MRSA and VRE inhibitors

IF 1.8 3区化学 Q3 CHEMISTRY, ORGANIC

Synthetic Communications Pub Date : 2025-03-08 DOI:10.1080/00397911.2025.2475901

Ahmed A. M. Ahmed (Conceptualization Data curation Formal analysis Funding acquisition Supervision) , Ahmed E. M. Mekky (Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing) , Sherif M. H. Sanad (Investigation Methodology Project administration Resources Software Supervision Validation Visualization Writing – original draft Writing – review & editing)

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引用次数: 0

Abstract

Synthesis of new heterocyclic hybrids that are capable of fighting methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) strains is still a challenging task for organic chemists. In the current study, we examined the protocol involving the reaction of 2-(4-arylthiazol-2-yl)acetonitriles and benzaldehyde in pyridine at reflux for 2 h. The reaction mixture was then treated with 1H-pyrazole-3,5-diamines and heated at reflux for an additional 3-4 h. The reaction afforded 15 new thiazole-linked pyrimidines in good to excellent yields. Product 3e, which is linked to 4-methoxybenzyl and 4-(4-methoxyphenyl)thiazol-2-yl) units at C3 and C6, respectively, displayed the best antibacterial efficacy, especially against Staphylococcus aureus and Enterococcus faecalis, with an MIC/MBC up to 1.8/3.6 µM. Moreover, it possessed comparable efficacy to linezolid with an MIC/MBC of 3.6/7.3 µM against VRE ATCC:51299 and ATCC:51575, whereas it had an MIC/MBC of 7.3/14.6 µM against MRSA ATCC:33591 and ATCC:43300.

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新的噻唑基吡唑[1,5-a]嘧啶杂合体：一锅合成潜在的MRSA和VRE抑制剂

合成能够抵抗耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）菌株的新型杂环杂交体仍然是有机化学家面临的一项具有挑战性的任务。在目前的研究中，我们研究了涉及2-（4-芳基噻唑-2-基）乙腈和苯甲醛在吡啶中回流2小时的反应方案。然后用1h -吡唑-3,5-二胺处理反应混合物，回流加热3-4小时。该反应产生了15种新的噻唑连接嘧啶，收率很高。产物3e在C3和C6分别与4-甲氧基苯基和4-（4-甲氧基苯基）噻唑-2-基连接，抗菌效果最好，特别是对金黄色葡萄球菌和粪肠球菌，其MIC/MBC可达1.8/3.6µM。此外，它对VRE ATCC:51299和ATCC:51575的MIC/MBC为3.6/7.3µM，而对MRSA ATCC:33591和ATCC:43300的MIC/MBC为7.3/14.6µM，与利奈唑胺具有相当的疗效。

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来源期刊

Synthetic Communications 化学-有机化学

CiteScore

4.40

自引率

4.80%

发文量

156

审稿时长

4.3 months

期刊介绍： Synthetic Communications presents communications describing new methods, reagents, and other synthetic work pertaining to organic chemistry with sufficient experimental detail to permit reported reactions to be repeated by a chemist reasonably skilled in the art. In addition, the Journal features short, focused review articles discussing topics within its remit of synthetic organic chemistry.