Novel Bi-heterocycles as potent inhibitors of Urease and less cytotoxic agents: 3-({5-((2-amino-1,3-thiazol-4-yl)methyl)-1,3,4-oxadiazol-2-yl}sulfanyl)-N-(un/substituted-phenyl) propanamides

• Published in: Iranian Journal of Pharmaceutical Research
• Main Author: Abbasi M.A.; Ramzan M.S.; Aziz-Ur-Rehman; Siddiqui S.Z.; Hassan M.; Shah S.A.A.; Ashraf M.; Shahid M.; Seo S.-Y.
• Format: Article
• Language: English
• Published: Iranian Journal of Pharmaceutical Research 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085346036&doi=10.22037%2fijpr.2019.13084.11362&partnerID=40&md5=42f727fe97faa359f68a1c84b3a321a0

The synthesis of a novel series of bi-heterocyclic propanamides, 7a-l, was accomplished by S-substitution of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol (3). The synthesis was initiated from ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) which was converted to corresponding hydrazide, 2, by hydrazine hydrate in methanol. The refluxing of hydrazide, 2, with carbon disulfide in basic medium, resulted in 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4- oxadiazol-2-thiol (3). A series of electrophiles, 6a-l, was synthesized by stirring un/substituted anilines (4a-l) with 3-bromopropanoyl chloride (5) in a basic aqueous medium. Finally, the targeted compounds, 7a-l, were acquired by stirring 3 with newly synthesized electrophiles, 6a-l, in DMF using LiH as a base and an activator. The structures of these bi-heterocyclic propanamides were confirmed through spectroscopic techniques, such as IR,1H-NMR,13C-NMR, and EI-MS. These molecules were tested for their urease inhibitory potential, whereby, the whole series exhibited very promising activity against this enzyme. Their cytotoxic behavior was ascertained through hemolysis and it was observed that all these were less cytotoxic agents. The in-silico molecular docking analysis of these molecules was also in full agreement with their in-vitro enzyme inhibition data. © 2020, Iranian Journal of Pharmaceutical Research. All rights reserved.