Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors

European Journal of Medicinal Chemistry
2016.0

Abstract

Kinases control a diverse set of cellular processes comprising of reversible phosphorylation of proteins. Protein kinases play a pivotal role in human tumor cell proliferation, migration and survival of neoplasia. In the recent past, purine based molecules have emerged as significantly potent kinase inhibitors. In view of their promising potential for the inhibition of kinases, this review article focuses on purines which have progressed as kinase inhibitors during the last five years. A detailed account of the design strategies employed for the synthesis of purine analogs exerting inhibitory effects on diverse kinases has been presented. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the purine analogs for kinase inhibition. The interactions with the amino acid residues responsible for kinase inhibitory potential of purine based molecules have also been discussed. In this assemblage, purine based protein kinase inhibitors patented in the past have also been summarized in the tabular form. This compilation will be of great interest for the researchers working in the area of protein kinase inhibitors.

Knowledge Graph

Similar Paper

Design strategies, structure activity relationship and mechanistic insights for purines as kinase inhibitors
European Journal of Medicinal Chemistry 2016.0
Synthesis and Biological Testing of Purine Derivatives as Potential ATP-Competitive Kinase Inhibitors
Journal of Medicinal Chemistry 2005.0
Exploiting Chemical Libraries, Structure, and Genomics in the Search for Kinase Inhibitors
Science 1998.0
The association between anti-tumor potency and structure-activity of protein-kinases inhibitors based on quinazoline molecular skeleton
Bioorganic & Medicinal Chemistry 2019.0
Molecular hybrids: A five-year survey on structures of multiple targeted hybrids of protein kinase inhibitors for cancer therapy
European Journal of Medicinal Chemistry 2021.0
Aurora kinase inhibitors as potential anticancer agents: Recent advances
European Journal of Medicinal Chemistry 2021.0
Purine derivatives as competitive inhibitors of human erythrocyte membrane phosphatidylinositol 4-kinase
Journal of Medicinal Chemistry 1990.0
A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors
Journal of Medicinal Chemistry 2013.0
Structure-based design and synthesis of novel pseudosaccharine derivatives as antiproliferative agents and kinase inhibitors
European Journal of Medicinal Chemistry 2013.0
Structural Optimization and Structure–Activity Relationships of N<sup>2</sup>-(4-(4-Methylpiperazin-1-yl)phenyl)-N<sup>8</sup>-phenyl-9H-purine-2,8-diamine Derivatives, a New Class of Reversible Kinase Inhibitors Targeting both EGFR-Activating and Resistance Mutations
Journal of Medicinal Chemistry 2012.0