2‐Alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles: An Overview on Synthetic Strategies and Biological Activity

Abstract

2-Alkylsulfanyl-4(5)-aryl-5(4)-heteroarylimidazoles represent an important class of ATP-competitive protein kinase inhibitors, offering the possibility of multiple interactions with different regions of the target enzyme. The necessity of exploring the effects of diverse chemical decorations around the imidazole core prompted the design of several synthetic routes aimed at achieving both efficiency and flexibility. Additionally, the optimization of established protocols and the extensive use of transition metal-catalyzed cross-coupling reactions have been broadening the spectrum of preparative methodologies within the last decade. This review summarizes the progress in the development of synthetic strategies leading to 2-alkylsulfanyl-4(5)-aryl-5(4)-heteroarylimidazoles and 1-alkyl-2-alkylsulfanyl-4(5)-aryl-5(4)-heteroarylimidazoles and offers a glance at the biological activities of this class of compounds.

Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kinase 3

“…This class of inhibitors counts a large number of examples starting from the precursor SB203580 to the optimized compound LN950 ( Figure 1 ), until reaching derivatives with low single digit nanomolar IC 50 values (a review on this class of compounds has recently been published). 18 As can be seen from Figure 1 , the reported p38α MAPK inhibitors are also able to inhibit the JNK3 with IC 50 values in the submicromolar range, thus offering a suitable starting point for optimization when aiming to target this enzyme. In 2016, we published compound 1a as a balanced dual JNK3/p38α MAPK inhibitor, which served as a precursor for the synthesis of a fluorescent probe used in fluorescence polarization-based binding assays.…”

“…In the last decades, pyridinylimidazoles have encountered a remarkable success in the field of p38α MAPK inhibition. This class of inhibitors counts a large number of examples starting from the precursor SB203580 to the optimized compound LN950 (Figure ), until reaching derivatives with low single digit nanomolar IC 50 values (a review on this class of compounds has recently been published) . As can be seen from Figure , the reported p38α MAPK inhibitors are also able to inhibit the JNK3 with IC 50 values in the submicromolar range, thus offering a suitable starting point for optimization when aiming to target this enzyme.…”

Synthesis and Characterization of Some New 4-Methyl-5-Imidazole Carbaldehyde Derivatives

“…Jadwiga Zabielska-Matejuk et al have synthesized several 1,3-dialkyimidazolium derivatives and studied their antifungal properties to protect wood materials. The synthesized imidazolium salts have been found to inhibit the growth of fungus, in particular Sclerophoma pityophila (19)(20)(21)(22)(23)(24)(25)(26)(27).…”

N1-{4-[2-(Methylthio)-1H-imidazol-5-yl]pyridin-2-yl}benzene-1,4-diamine

“…2-Alkylsulfanylimidazoles represent an important class of kinase inhibitors [1]. Most of the reported compounds belonging to this class have been reported as potent reversible inhibitors of p38α mitogen-activated protein (MAP) kinase displaying IC 50 values down to the low nanomolar range [2][3][4][5][6].…”