Synthesis and pharmacophore modeling of novel quinazolines bearing a biologically active sulfonamide moiety

Abstract

In the present work, interaction of the strategic starting material, methyl 2-isothiocyanatobenzoate (1), with sulfa drugs resulted in the formation of methyl 2-[3-(4-(N-substituted sulfamoyl)phenyl)thioureido] benzoates 2-5, which upon reaction with hydrazine hydrate afforded N-amino derivatives 6-9. Triazoloquinazoline derivatives 10-18 were obtained via reaction of compounds 6-8 with aromatic aldehydes. Also, the reaction of compound 8 with formic acid gave the corresponding triazoloquinazoline derivative 19. Triazinoquinazoline derivatives 22, 23 were obtained via reaction of N-amino derivatives 6 or 8 with ethyl chloroacetate. Interaction of 6 with diethyloxalate yielded triazoloquinazoline 26. The synthesized compounds were screened for their in vitro antimicrobial activities and some of them exhibited promising antibacterial activity compared to ampicillin as positive control. Compounds that revealed significant activity are able to satisfy effectively the proposed pharmacophore geometry.

An environmentally friendly approach for the synthesis of quinazolinone sulfonamide

“…Quinazolinone sulfonamides are considered as hybrid molecules which have been identified as biological active compounds and they showed extended biological activities, such as cancer chemotherapeutic agents [42][43][44], antimicrobial [45], and diuretic [46] activities ( Fig. 1).…”

Quinazolin-4(3H)-ones: A Tangible Synthesis Protocol via an Oxidative Olefin Bond Cleavage Using Metal-Catalyst Free Conditions

“…Quinazolinone heterocycles are an important class of fundamental building blocks in modern organic synthesis with recognized importance in natural products, bioactive compounds and pharmaceutical industry. A broad range of medicinal properties are reported for quinazolinones, such as anticancer [23][24][25][26][27], antibacterial [28][29][30], antifungal [31][32][33][34][35], antimalarial [36], antiviral [37,38] as well as anti-microbial cholinesterase inhibitors [39,40], making quinazolinone a privileged class of N-containing heterocyclic scaffolds ( Figure 1). Due to diverse biological applications in pharmaceutical industry numerous synthetic methodologies were developed for the synthesis of quinazolinones [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58].…”

Synthesis of some novel quinazolin‐4(3H)‐one hybrid molecules as potent urease inhibitors

“…In recent years, considerable evidence has been found on the importance of quinazolinone derivatives in the pharmaceutical chemistry . For example, they have attracted attention as an important nucleus in the class of therapeutic agents because of their wide range of biological activities .…”