Exploration of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one derivatives as JAK inhibitors using various in silico techniques.

ABSTRACT: This study focuses on understanding the structural features of 3,6-dihydroimidazo(4,5-d)pyrrolo(2,3-b)pyridin-2(1H)-one (dpp) derivatives to computationally identify new JAK inhibiting compounds. For the purpose, a novel virtual screening strategy, with 2D and 3D-QSAR (CoMFA and CoMSIA), data mining, pharmacophore modeling, ADMET prediction, multi-targeted protein-based docking and inverse QSAR, was employed. The 2D-QSAR equations developed for the JAK3, JAK2 and JAK1 involved five physicochemical descriptors. These descriptors correlate with the anti-RA activity with R² values for JAK3, JAK2 and JAK1 are 0.9811, 0.8620 and 0.9740, respectively. The 3D-QSAR studies such as CoMFA and CoMSIA carried out through PLS analysis of the training set of JAK3, JAK2 and JAK1, gave Q^2<

SUBMITTER: Jisha RS 

PROVIDER: S-EPMC5639824 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature