Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives.
Pharmaceuticals (Basel)
; 13(5)2020 May 09.
Article
in En
| MEDLINE
| ID: mdl-32397570
ABSTRACT
We previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave irradiation in an eco-friendly approach. In order to explore more in-depth the pharmacological interest in such tricyclic skeletons, the central five member ring, i.e., thiophène or furan, was replaced by a pyrrole to afford 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives inspired from harmine. The inhibitory potency of the final products was determined against four protein kinases (CDK5/p25, CK1ï¤/ε, GSK3ï¡ï¯ï¢ï¬ and DYRK1A). As a result, we have identified promising compounds targeting CK1ï¤/ε and DYRK1A and displaying micromolar and submicromolar IC50 values.
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Pharmaceuticals (Basel)
Year:
2020
Document type:
Article
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