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A new series of arylmethylene hydrazine derivatives bearing 1,3-dimethylbarbituric moiety 7a–o were designed, synthesized, and evaluated for their in vitro urease inhibitory activity. All the title compounds displayed high anti-urease activity, with IC50 values in the range of 0.61 ± 0.06–4.56 ± 0.18 µM as compared to the two standard inhibitors hydroxyurea (IC50 = 100 ± 0.15 μM) and thiourea (IC50 = 23 ± 1.7 μM). Among the synthesized compounds, compound 7h with 2-nitro benzylidene group was found to be the most potent compound. Kinetic study of this compound revealed that it is a mix-mode inhibitor against urease. Evaluation of the interaction modes of the synthesized compounds in urease active site by molecular modeling revealed that that compounds with higher urease inhibitor activity (7h, 7m, 7c, 7l, 7i, and 7o, with IC50 of 0.61, 0.86, 1.2, 1.34, 1.33, 1.94 μM, respectively) could interact with higher number of residues, specially Arg609, Cys592 (as part of urease active site flap) and showed higher computed free energy, while compounds with lower urease activity (7f, 7n, 7g, and 7a with IC50 of 3.56, 4.56, 3.62 and 4.43 μM, respectively) and could not provide the proper interaction with Arg609, and Cys592 as the key interacting residues along with lower free binding energy. MD investigation revealed compound 7h interacted with Arg609 and Cys592 which are of the key residues at the root part of mobile flap covering the active site. Interacting with the mentioned residue for a significant amount of time, affects the flexibility of the mobile flap covering the active site and causes inhibition of the ureolytic activity. Furthermore, in silico physico-chemical study of compounds 7a–o predicted that all these compounds are drug-likeness with considerable orally availability.

A new series of quinoxalin-1,3,4-oxadiazole (10a-l) derivatives was synthesized and evaluated against some metabolic enzymes including human carbonic anhydrase (hCA) isoenzymes I and II (carbonic anhydrases I and II), cholinesterase (acetylcholinesterase and butyrylcholinesterase), and α-glucosidase. Obtained data revealed that all the synthesized compounds were more potent as compared with the used standard inhibitors against studied target enzymes. Among the synthesized compounds, 4-fluoro derivative (10f) against hCA I, 4-chloro derivative (10i) against hCA II, 3-fluoro derivative (10e) against acetylcholinesterase and butyrylcholinesterase, and 3-bromo derivative (10k) against α-glucosidase were the most potent compounds with inhibitory activity around 1.8- to 7.37-fold better than standard inhibitors. Furthermore, docking studies of these compounds were performed at the active site of their target enzymes.

The present review offers an apt summary of amide bond formation with carboxylic acid substrates by taking advantage of several methods. Carboxamides can be regarded as a substantial part of organic and medicinal chemistry due to their utility in synthesizing peptides, lactams, and more than 25% of familiar drugs. Moreover, they play a leading role in the synthesis of bioactive products with anticancer, antifungal, and antibacterial properties. The data are arranged based on the type and amount of reagents used to conduct amidation and are also divided into the following categories: catalytic amidation of carboxylic acids, non-catalytic amidation, and transamidation.

A highly regioselective hydrocarbonylation of phenylacetylene with thiols and alcohols was developed using metal carbonyls/diazabicyclo[2.2.2]octane (DABCO) system at 100 °C in DMF. The use of Mo(CO)6 and thiols in the presence of DABCO was applied as an efficient Pd-free method for hydrothiocarbonylation of phenylacetylene into trans-α,β-cinamyl thioesters in excellent yields (88–98%). Similar reaction using Fe(CO)5/ROH/DABCO system resulted into high yield synthesis of trans-α,β-cinamyl esters (87–98%). These reactions were conducted under mild reaction conditions without the need to use gaseous CO or any phosphine ligand and palladium catalyst.