Novel indole based hybrid oxadiazole scaffolds with N-(substituted-phenyl)butanamides: synthesis, lineweaver–burk plot evaluation and binding analysis of potent urease inhibitors

Abstract

In the study presented herein, 4-(1H-indol-3-yl)butanoic acid (1) was sequentially transformed in the first phase into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3) and 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4) as a nucleophile.

Bi‐heterocyclic benzamides as alkaline phosphatase inhibitors: Mechanistic comprehensions through kinetics and computational approaches

“…The 4‐methylphenyl group attached with a nitrogen atom was thoroughly corroborated by two quaternary signals at δ 136.56 (C‐1″″) and 132.57 (C‐4″″), two methine signals at δ 128.88 (C‐2″″ & C‐6″″) and 120.31 (C‐3″″ & C‐5″″), along with one methyl signal at δ 20.46 (CH 3 ‐4″″). In the up‐field region of the spectrum, three signals at δ 26.48 (C‐2′), 24.26 (C‐1′), and 23.81 (C‐3′) were characteristic for three connected methylenes, which were joining the indole moiety with heterocyclic oxadiazole core in the molecule . The salient connectivities in the carbon skeleton of this molecule were thoroughly substantiated by its HMBC spectrum.…”

“…The other three quaternary carbons appearing at δ 136.29 (C‐8), 127.00 (C‐9), and 113.22 (C‐3) ppm were attributes of the indole core. The methine carbon resonances appearing at δ 122.49 (C‐2), 120.86 (C‐6), 118.18 (C‐7), 118.16 (C‐5), 111.35 (C‐4) were also coherent with the indole moiety . The dually substituted 4‐yl‐methylbenzamido group was confirmed by its discrete resonances, one for a carbonyl group at δ 164.90 (C‐8‴), other four signals at δ 140.19 (C‐4‴), 134.35 (C‐1‴), 128.93 (C‐3‴ & C‐5‴), 127.80 (C‐2‴ & C‐6‴), and one signal of methylene group at δ 35.34 (C‐7‴) .…”

“…The salts of these acids were partitioned to the aqueous layer while the resulted ester to the organic phase during solvent extraction. Thus, ethyl 4‐(1 H ‐indol‐3‐yl)butanoate ( 2 ) was obtained as brownish liquid (solid at refrigeration) . The second step was performed to convert this ethyl ester to respective carbohydrazide, 3 , by the nucleophillic hydrazine in the presence of an organic solvent like methanol and refluxed for 14 h. Thus, 4‐(1 H ‐indol‐3‐yl)butanohydrazide ( 3 ) was obtained as a light brown‐colored solid .…”

“…The product was isolated by solvent extraction using chloroform (50 mL × 3). The solvent was distilled off and the required ester, 2 , was obtained as reddish brown liquid …”

“…Our group has already reported lead compounds based on indole and oxadiazole scaffold as enzyme inhibitors, and the current study was expanded to explore new therapeutic potentials of such hybrid molecules as alkaline phosphatase inhibitors. In silico studies were also carried out to ascertain different types of interactions with active pocket of enzyme.…”