Synthesis and .BETA.-lactamase inhibitory activity of 6-((1-heteroarylthioethyl-1,2,3-triazol4-yl)methylene)-penam sulfones.

Abstract

The synthesis of /Mactamase inhibitory activity of a series of sodium 6-[(l-heteroarylthioethyll ,2,3-triazol-4-yl)methylene]penicillanate 1 , 1-dioxides are described. Their activity was compared with tazobactam and sulbactam. The Z-isomers were moreactive than the Is-isomers. The in vitro activity of the Z-isomers of the phenylthiadiazole derivatives (13a and 15a) was better than sulbactam against the tested /Mactamases and comparable to tazobactam especially against TEM-2 and cephalosporinase. But their synergistic activity with five antibiotics was inferior to tazobactam.A successful approach to overcoming the bacterial resistance to /Mactam antibiotics caused by /Mactamase production is to develop agents that can inhibit the action of the /Mactamase. The success of clavulanic acid1} stimulated extensive research leading to the discovery of other /Mactamase inhibitors such as sulbactam2) and tazobactam3). A number of 6-(substituted methylene)penams have been reported in the literature4'5) as potent inhibitors of cell free /Mactamases, but were ineffective in synergistic antibacterial tests probably because of poor penetration through the bacterial cell wall. More recently, 6-triazolylmethylenepenem (1)6'7), BRL-42715, has been shown to be a very potent inhibitor of most bacterial /Mactamases including the class I /Mactamase, which is resistant to other /Mactamase inhibitors.

Synthesis of Functionalized Bicyclic Triazoles from Chiral Aziridines

“…In conclusion, we developed a new method for the preparation of enantiomerically pure cis-and trans-3-substituted-5-amino-4-hydroxy-5,6-dihydro-4H-pyrrolo[1,2-c] [1,2,3]triazole from the sequential reactions including a regioselective ring-opening of 1-aziridine-2-yl-propargylic alcohols by azidotrimethylsilane and intramolecular 1,3-dipolar cycloaddition between alkyne and azide.…”

“…The importance of triazoles found in many biologically active products has been emphasized in organic chemistry. They consist of essential structural backbone of various pharmaceuticals with anti-HIV, 1 antimicrobial, 2 blactamase inhibitory, 3 antiviral and antiepileptic 4 activities. Therefore, methodologies for the preparations of triazoles have attracted much attention from both academia and industry.…”

Selective Synthesis of 2-(1,2,3-Triazoyl) Quinazolinones through Copper-Catalyzed Multicomponent Reaction

“…Other examples are Rufinamide ® [27] and Tazobactam ® [28], that having anticonvulsant and antibiotic activities, respectively (Figure 1). Some 1,2,3-triazole-based compounds have shown antibacterial [29][30][31], anticancer [32], antifungal [33,34], antiviral [35], among others [36,37]. Efficient methods to access highly functionalized 1,2,3-triazoles include the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction [38,39] and the organocatalyzed [3+2] cycloaddition reactions via the generation of enamines, also known as Ramachary-Bressy-Wang organocatalytic azide-ketone [3+2]-cycloaddition (OrgAKC) [40][41][42].…”

Synthesis, Molecular Docking, and Preliminary Evaluation of 2‐(1,2,3‐Triazoyl)benzaldehydes As Multifunctional Agents for the Treatment of Alzheimer's Disease

“…The development of novel and effective methods for the synthesis of highly functionalized 1,2,3‐triazoles therefore remains an important challenge in synthetic organic chemistry. These compounds have a broad range of biological activities, such as antibacterial, antifungal, antiviral, β‐lactamase . As example, the synthetic QTC‐4‐MeOBnE A exerts therapeutic effect through multiple pathways involved in AD .…”