Synthesis and Investigation of 2-(4-chlorophenyl)-N-(heteroaryl)acetamides

Abstract

Amide functional group can be found in various biologically active molecules, including proteins and naturally existing or synthetic pharmaceutically active ingredients. It can form hydrogen bonding, which further improves solubility and bioavailability. 2-(4-Chlorophenyl)-N-(benzimidazol-2-yl)acetamides constructed following similar procedures can be successfully applied against pathogenic protozoa Trypanosoma cruzi and Trypanosoma brucei.1,2 These protozoa are causative agents of infectious diseases that often progress to chronic ones because there is no reliable treatment. After reviewing the published results, it was decided that it would be interesting to investigate whether the activity of the compounds would improve if the benzimidazole moiety was replaced with a smaller heterocycle – pyridine or thiophene. In collaboration with scientists from Vytautas Magnus University, it was decided to conduct initial studies with non-pathogenic protozoa for safety reasons. The aim of this project was to prepare 2-(4-chlorophenyl)-N-(benzimidazol-2-yl)acetamide analogues with potential activity for in vitro studies against infusoria. For the synthesis of the target compounds, it was chosen to carry out the reactions of 2-(4-chlorophenyl)acetic acid with amino-heterocycles. For carboxylic acid activation a combination of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole was used. To reliably prove the structure of the obtained compounds, spectral analysis IR and NMR (standard and two-dimensional) along with mass spectrometric analysis (MS) methods were used. All compounds prepared for biological studies were purified to at least 97% purity (LC-MS). Key results of primary biotesting data will be presented along with synthesis data.