Supramolecular architecture in sulfonylurea, sulfonyldiurea and sulfonyltriurea drugs: Synthesis, X-ray structure and Hirshfeld surface analysis

Sulfonylureas provide a useful motif for carrying donor and acceptor sites capable of hydrogen bonding. These are a prominent class of therapeutic agents in the pharmaceutical industry. However, the use of aryl sulfonyl oligomers in drug discovery, supramolecular chemistry and crystal engineering are unexplored. This motivated us to design, synthesize and understand the structural features of aryl sulfonylurea oligomers ( n = 1?3). Here, we report the synthesis and spectroscopic characterization details such as 1 H NMR, 13 C NMR, mass spectrometry and single-crystal X-ray diffraction analysis for three sulfonylurea oligomer derivatives. Further, the molecular packing analysis of three derivatives reveals the significance of N ?H...O and C ?H...O intra and intermolecular hydrogen bonding. These hydrogen bonding contacts enable the sulfonylurea derivatives to form 2D framework/architecture. We quantify various intermolecular interactions in these derivatives by Hirshfeld analysis and 2D fingerprint plots. We have performed in-silico docking studies against Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) to rationalize the binding affinity of title compounds. ? 2021 Elsevier B.V. All rights reserved.

Automated summary

Sulfonylureas serve as a useful motif for carrying donor and acceptor sites capable of hydrogen bonding, making them a prominent class of therapeutic agents in the pharmaceutical industry. However, the potential applications of aryl sulfonyl oligomers in drug discovery, supramolecular chemistry, and crystal engineering have not been fully explored. Through synthesis, spectroscopic characterization, and molecular packing analysis, the structural features of aryl sulfonylurea oligomers and their ability to form 2D framework through hydrogen bonding contacts have been investigated. In-silico docking studies against Plasmodium falciparum prolyl-tRNA synthetase were conducted to rationalize the binding affinity of the compounds.