3D-QSAR studies of 1,2-diaryl-1H-benzimidazole derivatives as JNK3 inhibitors with protective effects in neuronal cells

Abstract

JNKs (c-Jun N-terminal kinases) have the potential to serve as a therapeutic target for various inflammatory, vascular, neurodegenerative, metabolic and oncological diseases. In particular, ATP-competitive JNK3 inhibitors act as neuroprotective agents. Here we introduce 1,2-diaryl-1H-benzimidazole derivatives as selective JNK3 inhibitors from among our in-house compounds and describe our elucidation of their SAR using 3D-QSAR models. A predictive CoMFA model (q2=0.795, r2=0.931) and a CoMSIA model (q2=0.700, r2=0.937) were used to describe the non-linearly combined affinity of each functional group in the inhibitors.