Novel Bi-heterocycles as Potent Inhibitors of Urease and LessCytotoxic Agents: 3-({5-((2-Amino-1,3-thiazol-4-yl)methyl)-1,3,4-oxadiazol-2-yl}sulfanyl)-N-(un/substituted-phenyl)propanamides

The synthesis of a novel series of bi-heterocyclic propanamides, 7a-l, was accomplishedby s-substitution of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol (3). thesynthesis was initiated from ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) which was convertedto 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/substitutedanilines (4a-l) with 3-bromopropanoyl chloride (5) in a basic aqueous medium. finally, the targetedcompounds, 7a-l, were acquired by stirring 3 with newly synthesized electrophiles, 6a-l, in dmfusing lih as a base and an activator. the structures of these bi-heterocyclic propanamides wereconfirmed through spectroscopic techniques, such as ir, ^1h-nmr, ^13c-nmr, and ei-ms. thesemolecules were tested for their urease inhibitory potential, whereby, the whole series exhibited verypromising activity against this enzyme. their cytotoxic behavior was ascertained through hemolysisand it was observed that all these were less cytotoxic agents. the in-silico molecular dockinganalysis of these molecules was also in full agreement with their in-vitro enzyme inhibition data.