Synthesis of New 1,2,4-Triazole[3,4-b][1,3,4]thiadiazoles Bearing Pyrazole as Potent Antimicrobial Agents

Abstract

Pyrazole and its derivatives represent one of the most active classes of compounds possessing a wide spectrum of biological activities, including antibacterial, 1) antifungal, 2) herbicidal, 3) insecticidal 4) and other biological activities. 5-7)Similarly, the biological activities of various 1,2,4-triazole derivatives and their N-bridged heterocyclic analogs have been widely investigated as antitumor, 8) antiviral, 9) anti-inflammatory, 10) analgesic 11) and antidepressant. 12) 1,2,4-Triazole system is also an important starting material in the synthesis of biologically active heterocycles, which constitute an important class of organic compounds with diverse biological activities, including antiparasitic, analgesic, antibacterial and anti-inflammatory activities. [13][14][15][16][17][18] Further, triazole fused with other heterocyclic rings is also found to possess diverse applications in the field of medicine. [19][20][21][22] The commonly known systems are triazolo-pyridines, 19) triazolo-pyridazines, 20) triazolo-pyrimidines, 21) triazolo-pyrazines, 22) triazolo-triazines 21) and triazolo-thiadiazines. 23) In addition, it has been reported that thiadiazoles exhibit a broad spectrum of biological effectiveness such as anti-parkinsonism, 24) hypoglycaemic, 25) anticancer, 26) anti-inflammatory, 27) anti-asthmatic 28) and anti-hypertensive 29) activities. Inspired by the biological profile of pyrazole, triazole, thiadiazole, and in continuation of our research on biologically active heterocycles, [30][31][32][33][34][35] it was thought worthwhile to synthesize some new heterocyclic compounds containing pyrazole, triazole and thiadiazol rings in one molecular frame work. We report herein the synthesis of a new series of 1,2,4-triazole [3,4-b][1,3,4]thiadiazoles bearing pyrazole and their antimicrobial activity. Results and DiscussionSynthesis The starting material, (E)-2-acetyl-3-(dimethylamino)-2-propenoate (2), was obtained via condensation of ethyl acetoacetate (1) with N,N-dimethyldimethoxymethanamine, 36) which on cyclo-condensation with phenyl hydrazine resulted 5-methyl-1-phenyl-1H-4-pyrazolecarboxylate (3).36) The 5-methyl-1-phenyl-1H-4-pyrazolecarbohydrazide (4) was obtained in 72% yield via hydrazinolysis of compound 3 with hydrazine hydrate. The hydrazide 4 on reaction with carbon disulfide and potassium hydroxide, in ethanol, followed by acidification gave 5-(5-methyl-1-phenyl-1H-4-pyrazolyl)-1,3,4-oxadiazol-2-yl-hydrosulfide (5) in 70% yield. Reaction of 5 with hydrazine hydrate under reflux for 6 h resulted 4-amino-5-(5-methyl-1-phenyl-1H-4-pyrazolyl)-4H-1,2,4-triazol-3-yl-hydrosulfide (6) in 69% yield. The final compounds, 6-(aryl/heteryl)-3-(5-methyl-1-phenyl-1H-4-pyrazolyl)[1,2,4]triazolo [3,4-b] [1,3,4]thiadiazole (7a-j), were synthesized in 66-78% via the reaction of 6 with POCl 3 and the corresponding aryl/heteryl carboxylic acids, in ethanol at reflux temperature for 12 h (Chart 1). The structures of all the newly synthesized compounds were confirmed by their elemental analyses, electron...

Synthesis and Biological Evaluation of Novel Bis[1,2,4]triazolo[3,4-b] [1,3,4]oxadiazoles

“…Owing to the immense importance and varied bioactivities exhibited by triazolo‐oxadiazole and in continuation of our ongoing research on biologically active bis‐heterocyclics , it was thought of interest to accommodate triazole and oxadiazole moieties in a single molecular framework and to obtain new bis‐heterocyclic compounds with potential biological activity. In the present study, we performed the synthesis and biological evaluation of some new bis‐triazolo‐oxadiazoles.…”

Synthesis and Antimicrobial Activity of Linked Heterocyclics Containing Pyrazole and Oxadiazoles

“…In addition, 1,3,4‐oxadiazole derivative were reported to possess significant antibacterial and anti‐inflammatory , tyrosinase inhibitory , antiviral , antihypertensive , cortical muscarinic receptor agonists , herbicidal , Ca 2+ channel blocker , antitumour , anticonvulsant , antielmintic , and antioxidant activities . In view of these reports and in continuation of our ongoing research on the synthesis of new heterocyclic compounds , it was thought of interest to accommodate pyrazole, oxadiazole moieties in a single molecular frame work and to obtain a new class of heterocyclic compounds with potential biological activity. In this article, we wish to report the synthesis of a new class of 3‐(arylaminomethyl)‐5‐(5‐methyl‐1‐phenyl‐1 H ‐4‐pyrazolyl)‐2,3‐dihydro‐1,3,4‐oxadiazole‐2‐thiones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j in good yields from 5‐(5‐methyl‐1‐phenyl‐1 H ‐4‐pyrazolyl)‐1,3,4‐oxadiazol‐2‐ylhydrosulfide 5 (Scheme ) and their evaluated in vitro antibacterial and antifungal activity.…”

Experimental and theoretical investigations on the keto–enol tautomerism of 4-substituted 3-[1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives

“…The 1,2,4-triazole system is present in a great number of compounds characterized by different biological activities, such as: analgesic [8,9] antibacterial [10][11][12][13], fungicidal [14], antinflammatory [15][16][17], antiviral [18,19] and anti-cancer [20][21][22] properties. Based on these facts, many 1,2,4-triazol-5-one derivatives have been synthesized in our laboratory and their biological activities have been investigated [23][24][25][26][27].…”