DESIGN AND SYNTHESIS OF SOME NEWER IMIDAZOLYL HETEROCYCLES AS POTENT BTK INHIBITORS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS


R. Priyadarsini, Anandhan Menaka

Abstract


Objective: The rheumatoid arthritis as a global health problem over the past few decades, Emphasizes the need for discovery of new therapeutic disease modifying anti-rheumatoid Arthritis drugs (DMARD’s). Bruton’s tyrosine kinase (BTK) is a cytoplasmic, non-receptor, tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in the development, differentiation and proliferation of B-lineage cells, thus making BTK an efficient therapeutic target for the treatment of rheumatoid arthritis. This prompted us to synthesise a novel series of Imidazolyl Heterocycles as potent BTK (Bruton’s Tyrosine Kinase) inhibitors with alleged Anti-Rheumatoid Arthritis properties.

Methods: Newer BTK inhibitors containing one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD) and three hydrophobic features based on that pharmacophore model for BTK were designed. The designed compounds were sorted by applying ADMET properties, Lipinski rule of five, molecular docking and Novelty prediction to refine the designed ligands. Finally, different five compounds containing Imidazole as the heterocyclic nucleus have been synthesized and characterized by different analytical methods like Chromatographic data, Elemental analysis and Spectral studies by IR, 1H NMR, 13C NMR, GC-MS. Molecular docking studies were performed against BTK using GLIDE 10.2.

Results: Several important hydrogen bonds with BTK were revealed, which include the gatekeeper residue Glu475 and Met477 at the hinge region.

Conclusion: Overall, this study suggests that the proposed ligands are found to be more effective BTK inhibitor as Anti-Rheumatoid arthritis agents.


Keywords


Rheumatoid arthritis, Molecular docking, ADMET properties, BTK inhibitors, Pharmacophore model, Bruton’s tyrosine kinase

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About this article

Title

DESIGN AND SYNTHESIS OF SOME NEWER IMIDAZOLYL HETEROCYCLES AS POTENT BTK INHIBITORS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

Keywords

Rheumatoid arthritis, Molecular docking, ADMET properties, BTK inhibitors, Pharmacophore model, Bruton’s tyrosine kinase

DOI

10.22159/ijcpr.2017.v9i3.19668

Date

05-05-2017

Additional Links

Manuscript Submission

Journal

International Journal of Current Pharmaceutical Research
Vol 9, Issue 3, 2017 Page: 80-83

Online ISSN

0975-7066

Statistics

77 Views | 51 Downloads

Authors & Affiliations

R. Priyadarsini
Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai 03

Anandhan Menaka
Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai 03


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