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

Mi Hyun Kim, Jae Sang Ryu, Jung Mi Hah

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	1639-1642
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2013.01.082
State	Published - 15 Mar 2013

Bibliographical note

Funding Information:
This work was supported by the Hanyang University Research Fund ( HY-2012-N ).

Keywords

1,2-Diaryl-1H-benzimidazole
3D-QSAR
JNK inhibitors
Neuroprotective agents
Receptor-guided alignment

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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.",

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AU - Ryu, Jae Sang

AU - Hah, Jung Mi

N1 - Funding Information: This work was supported by the Hanyang University Research Fund ( HY-2012-N ).

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

Abstract

Bibliographical note

Keywords

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