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http://dx.doi.org/10.13160/ricns.2016.9.1.1

Comparative Molecular Field Analysis of Pyrrolopyrimidines as LRRK2 Kinase Inhibitors  

Balupuri, Anand (Department of Biomedical Sciences, College of Medicine, Chosun University)
Balasubramanian, Pavithra K. (Department of Biomedical Sciences, College of Medicine, Chosun University)
Cho, Seung Joo (Department of Biomedical Sciences, College of Medicine, Chosun University)
Publication Information
Journal of Integrative Natural Science / v.9, no.1, 2016 , pp. 1-9 More about this Journal
Abstract
Leucine rich repeat kinase 2 (LRRK2) is a highly promising target for Parkinson's disease (PD) that affects millions of people worldwide. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of pyrrolopyrimidine-based selective LRRK2 kinase inhibitors. This study was performed to rationalize the structural requirements responsible for the inhibitory activity of these compounds. A reliable 3D-QSAR model was developed using comparative molecular field analysis (CoMFA) technique. The model produced statistically acceptable results with a cross-validated correlation coefficient ($q^2$) of 0.539 and a non-cross-validated correlation coefficient ($r^2$) of 0.871. Robustness of the model was further evaluated by bootstrapping and progressive scrambling analysis. This work could assist in designing more potent LRRK2 inhibitors.
Keywords
Parkinson's Disease; LRRK2 Kinase; Pyrrolopyrimidines; 3D-QSAR; CoMFA;
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