In Silico Pharmacology

, 5:9 | Cite as

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

  • Radhakrishnan S. Jisha
  • Lilly Aswathy
  • Vijay H. Masand
  • Jayant M. Gajbhiye
  • Indira G. Shibi
Original Research


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 Q2 values as 0.369, 0.476 and 0.490; \( {\text{R}}_{\text{nev}}^{2} \) values as 0.863, 0.684 and 0.724 and, F values as 23.098, 28.139 and 31.438, respectively. The contour maps produced by the CoMFA and CoMSIA models were used to understand the importance of hydrogen bond donor, acceptor, hydrophobic, steric and electrostatic interactions. The molecular docking studies of these selected compounds with various JAK proteins were carried out and the protein–ligand interactions were also studied. The study concluded that dpp15(s) is a highly potent JAK inhibitor with a very good predicted IC50 value.


Rheumatoid arthritis Janus kinase 2D and 3D QSAR Weka Molecular docking 



Jisha, R.S. is thankful to the University of Kerala, Thiruvananthapuram for providing financial assistance in the form of University Junior Research Fellowship for this work. Aswathy L. is thankful to CSIR, New Delhi for the financial assistance in the form of Senior Research Fellowship.

Supplementary material

40203_2017_29_MOESM1_ESM.docx (275 kb)
Supplementary material 1 (DOCX 274 kb)
40203_2017_29_MOESM2_ESM.docx (31 kb)
Supplementary material 2 (DOCX 30 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Radhakrishnan S. Jisha
    • 1
  • Lilly Aswathy
    • 1
  • Vijay H. Masand
    • 2
  • Jayant M. Gajbhiye
    • 3
  • Indira G. Shibi
    • 1
  1. 1.Department of ChemistrySree Narayana CollegeThiruvananthapuramIndia
  2. 2.Department of ChemistryVidya Bharati CollegeAmravatiIndia
  3. 3.Division of Organic ChemistryCSIR-National Chemical LaboratoryPuneIndia

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