M. Aouad
May 4, 2017
Citations
0
Influential Citations
25
Citations
Journal
Organic Preparations and Procedures International
Abstract
Indoles are one of the most prevalent classes of pharmacologically active azoles and have found applications as antibacterial, antifungal, anti-mycobacterial, antiviral, anti-HIV, antitumor and anticonvulsant agents. Among these, some 1H-indole-2,3-dione (isatin) compounds incorporating a 1,2,3-triazole scaffold were recently found to exhibit significant antimalarial and anticancer activities. The 1,2,3-triazole ring system is a common structural motif for a number of chemotherapeutic agents that have exhibited remarkable biological potential in areas that include antitubercular, anti-inflammatory, antifungal, antibacterial, and anticancer activities. Recent advances in modern heterocyclic chemistry have introduced the 1,2,3-triazole moiety as a connecting spacer to link two pharmacophore sites together and generate original bifunctional drugs. Conversely, the piperidine, morpholine and piperazine moieties are key structural units in drug design due to their insertion into several drug molecules, including thioridazine, linezolid, levofloxacin, trifluoroperazine, gatifloxacin, itraconazole, posaconazole and eperezolid. In view of the fact that the presence of two pharmacophoric sites in one molecule could generate relevant compounds with increased medicinal potentialities, the present study reports the click synthesis and antimicrobial screening of novel isatin-1,2,3-triazoles appended with piperidine, morpholine or piperazine moieties connected via a methylene and/or an acetyl linkage. Two classes of isatin-1,2,3-triazole hybrids were synthesized by the Cu(I)-mediated click chemistry approach via regioselective addition of the N-propargylated isatin 1 with different cyclic secondary amine azides 2a-h (Scheme 1) or by the addition of azidoacetyl isatin 5 with various propargylated cyclic secondary amines 6a-h (Scheme 2). For that purpose, isatin was used as a starting material, which, when treated with propargyl bromide in the presence of NaH and DMF, yielded the precursor N-propargylated isatin.