Synthesis and In Vitro Antibacterial Evaluation of Novel Imidazo[2′, 1′:5, 1]‐1, 2, 4‐triazolo[4, 3‐c]‐quinazoline Derivatives of 5‐Thioxo‐1, 2, 4‐triazole, 4‐Oxothiazolidine, and their Open‐chain Counterparts

Abstract

Two novel series of imidazo[2', 1':5, 1]-1, 2, 4-triazolo[4, 3-c]quinazolines bearing 5-thioxo-1, 2, 4-triazoles, 6a-f, and 4-oxothiazolidines, 7a-f, were synthesized from corresponding thiosemicarbazide derivatives, 5a-f. The stepwise methodology applied to the preparation of compounds 5a-f was initiated with reaction of the parent 3-amino-1, 2, 4-triazolo[4, 3-c]quinazolines, 2, with ethyl 2-chloroacetoacetate resulting in annelation of the imidazole ring to give esters, 3a-c. However, hydrazinolysis of these ester derivatives gave the corresponding acid hydrazides, 4a-c, which on reaction with the appropriate alkyl isothiocyanate yielded compounds 5a-f. In turn, compounds 5, were cyclized with potassium hydroxide or with ethyl bromoacetate to give the corresponding thioxotriazoles 6 and oxothiazolidines 7, respectively. All synthesized compounds were screened for their in vitro antibacterial activity against various Gram-positive and Gram-negative bacteria. Some test compounds were found to possess potent antibacterial activities. Compound, 7f, exhibited much higher potency than the reference standard ciprofloxacin, against both types of bacteria, particularly, Gram-positive organisms.

Design, synthesis, and preliminary evaluation as antimicrobial activity of novel spiro-1, 3-thiazolidine C-acyclic nucleoside analogs

“…IR spectrum showed five absorption bands characterized of acetyl groups around 1730-1754 cm −1 and a broad band for NH group at 3225 cm −1 . Its 1 H NMR spectrum gave data with supports assigned structure and showed that the signals around δ 1.86-2.17 supported for five acetyl group On the other hand, the reaction of compound 4 with 2-oxo-N -(4-sub-phenyl)-propane hydrazonoyl chloride 1b-e under the same reaction condition afforded 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxy-butyl)-3 -acetyl-5 -phenyl/(sub-phenyl)-spiro-[1, 3]-thiazolidine-2,-2 - [1,3,4]thiadiazole 8b-e. The structures of 8b-e were deduced on the basis of analytical and spectral data.…”

“…Thus, the IR spectra for 8b-e revealed the presence of CO group at 1750 cm −1 , and 13 C-NMR showed signals corresponding to N -acetyl groups around 25 ppm for methyl group and 185 ppm for carbonyl group. Also, the reaction of compound 4 with chloro-(4-tolylhydrazono)-ethylacetate 1f afforded 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxybutyl)-3 -ethylcarboxylate-5 -(4-tollyl)-spiro- [1,3]thiazolidine-2,2 -[1,3,4]thiadiazole 8f. The IR spectrum of 8f revealed the presence of C=O (ester) at 1705 cm −1 .…”

“…The structure of the product 4 was established by elemental analyses and spectral data (IR, 1 In continuation of work (9-11) on heteroallenes, we report here an investigation into their 1, 3-dipolar cycloaddition reaction with 1, 3-thiazolidin-2-thione. Thus, stirring 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxybutyl)-thiazolidin-2-thione 4 with C-phenyl-Nphenyl hydrazonyl chloride 1a in refluxing dry chloroform containing triethylamine 3,4]thiadiazole 8a as only one product, as indicated by Thin Layer Chromatography (TLC) (Scheme 3). The formula of the product 8a was established by elemental analyses and spectral data (IR, 1 H and 13 C-NMR, MS).…”

“…The required reactant 5 was prepared from 4 with 3-chloro-pentane-2, 4-dione in ethanolic potassium hydroxide solution, as outlined in Scheme 4. The latter compound 5 was treated with benzenediazonium chloride in ethanol in the presence of sodium acetate, which underwent a Japp-Klingemann reaction (26) and directly yielded the corresponding 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxybutyl)-3 -acetyl-5 -phenyl-spiro- [1,3]thiazolidine-2,2 -[1,-3,4]thiadiazole (8b). Their structure was supported by elemental and spectral ( 1 H, 13 C-NMR, IR, and mass) analyses, which are identical to the data of the structure that is produced from the reaction of 1, 3-thiazolidin-2-thione 3 with benzonitrilium N -phenylimide 1b (Scheme 4).…”

Synthesis and modification of 2-[8-R1-9-R2-10-R3-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetic acids aimed at searching effective substances with the antibacterial and antifungal activity

“…[3]. Some recent publications are devoted to the search of chemotherapeutics among condensed quinazolines, in particular benzimidazo [1,2-c]-, benzthiadiazolimidazo [1,2-c]-, triazolo [1,5-c]-, imidazo, [1,2,4]triazolo [4,3-c]-, triazino [2,3-c]quinazolines [1,2,4,5,7,8,10,[13][14][15][16][17][18]. Highly effective antimicrobial, antifungal, anticancer agents have been found among the compounds mentioned.…”