Acetic acid-driven one-pot synthesis of 4,7-dihydro-[1,2,3]thiadiazolo[5,4-b]pyridine-6-carboxamides and Pharmacological Evaluations

• Published in: ChemMedChem p. e202400595
• Main Authors: Bhalodiya, Savan S, Parmar, Mehul P, Patel, Chirag D, Patel, Subham G, Vala, Disha P, Suresh, Nandhakumar, Jayachandran, Bhuvaneshwari, Arumugam, Madankumar, Narayan, Mahesh, Patel, Hitendra M
• Format: Journal Article
• Language: English
• Published: Germany 12.10.2024
• Subjects: antimicrobial; Multicomponent reaction; 4,7-dihydro-[1,2,3]thiadiazolo[5,4-b]pyridine-6-carboxamides; Molecular Docking; catalyst-free
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.202400595

A diverse set of 4,7-dihydro-[1,2,3]thiadiazolo[5,4-b]pyridine-6-carboxamides 4(a-o) were synthesized via a one-pot reaction of 5-amino[1,2,3]thiadiazole, various aromatic aldehydes, and different acetoacetanilides, using glacial acetic acid as the solvent and without the need for any catalysts. The resulting compounds were obtained in moderate to good yields. All the newly synthesized compounds were evaluated for their antimicrobial activity. Among them, compound 4e demonstrated superior efficacy against Salinivibrio proteolyticus strain of Gram-(-Ve)-bacteria compared to ciprofloxacin. Compound 4d exhibited the highest potency against the fungal strain Candida albicans surpassing Amphotericin B. 4d and 4e's physicochemical characteristics were assessed. According to docking analysis, DHTDAPy 4e shows the higher binding affinity of -7.2 kcal moL-1 in the binding cavity of the receptor. These findings illustrate the safety and tolerability as well as the potency of newly syntehsized DHTDAPy against the fungal and bacterial infections.