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

Mi-Hyun Kim; Jae-Sang Ryu; Jung-Mi Hah

doi:10.1016/j.bmcl.2013.01.082

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

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1639-42. doi: 10.1016/j.bmcl.2013.01.082. Epub 2013 Jan 29.

Authors

Mi-Hyun Kim¹, Jae-Sang Ryu, Jung-Mi Hah

Affiliation

¹ Department of Pharmacy, College of Pharmacy, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.

PMID: 23416008
DOI: 10.1016/j.bmcl.2013.01.082

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 (q(2)=0.795, r(2)=0.931) and a CoMSIA model (q(2)=0.700, r(2)=0.937) were used to describe the non-linearly combined affinity of each functional group in the inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzimidazoles / chemistry*
Humans
Kinetics
Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors*
Mitogen-Activated Protein Kinase 10 / metabolism
Neurons / drug effects
Neuroprotective Agents / chemistry*
Neuroprotective Agents / metabolism
Neuroprotective Agents / pharmacology
Protein Binding
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / metabolism
Protein Kinase Inhibitors / pharmacology
Quantitative Structure-Activity Relationship*

Substances

Benzimidazoles
Neuroprotective Agents
Protein Kinase Inhibitors
benzimidazole
Mitogen-Activated Protein Kinase 10