Premium
Imidazolylpyrrolone‐Based Small Molecules as Anticancer Agents for Renal Cell Carcinoma
Author(s) -
Sousa Ana,
Pontes Olívia,
Andrade Juliana,
Baltazar Fátima,
Costa Marta,
Proença Fernanda
Publication year - 2023
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202200519
Subject(s) - sunitinib , in silico , chemistry , combinatorial chemistry , selectivity , catalysis , stereochemistry , cell culture , cancer , biochemistry , biology , genetics , gene
An in silico study focused on known cancer‐related target proteins, identified a selection of imidazo[4,5‐ b ]pyrrolo[3,4‐ d ]pyridines as potentially active. These compounds were prepared by a novel synthetic approach, designed and developed in‐house, based on the reaction of 5‐amino‐4‐cyanoformimidoyl imidazoles with N ‐substituted cyanoacetamides. The substituted imidazolylpyrrolones obtained, were cyclized intramolecularly to generate the intended imidazo[4,5‐ b ]pyrrolo[3,4‐ d ]pyridines in a process catalyzed by DBU. Treating the imidazolylpyrrolones with an excess of triethyl orthoformate and heating at 80 °C in the presence of acid catalysis led to imidazopyrrolodiazepines. These compounds were screened for their anticancer potential, using the renal cell carcinoma cell line model (A498 and 786‐O cell lines). Two compounds exhibited IC 50 values in the low micromolar range with a good selectivity index, when compared to non‐neoplastic kidney cell line HK2 and the reference compounds rapamycin, cediranib and sunitinib.