Next Article in Journal
Therapeutic Targeting of Pancreatic Cancer via EphA2 Dimeric Agonistic Agents
Previous Article in Journal
Antibody Targeting of Eph Receptors in Cancer
Previous Article in Special Issue
Correction: McLoughlin, E.C.; O’Boyle, N.M. Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review. Pharmaceuticals 2020, 13, 8
Open AccessCommunication

Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives

1
Normandie Université, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, F-76000 Rouen, France
2
Université de Nantes, Cibles et Médicaments des Infections et du Cancer, IICiMed, EA 1155, F-44000 Nantes, France
3
Station Biologique de Roscoff, Protein Phosphorylation & Human Disease Group, 29680 Roscoff, France
4
Perha Pharmaceuticals, Perharidy Peninsula, 29680 Roscoff, France
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(5), 89; https://doi.org/10.3390/ph13050089
Received: 10 April 2020 / Revised: 1 May 2020 / Accepted: 8 May 2020 / Published: 9 May 2020
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, CK1δ/ε, GSK3α/β, and DYRK1A). As a result, we have identified promising compounds targeting CK1δ/ε and DYRK1A and displaying micromolar and submicromolar IC50 values. View Full-Text
Keywords: microwave-assisted chemistry; protein kinases; CK1; DYRK1A; CDK5; GSK-3 microwave-assisted chemistry; protein kinases; CK1; DYRK1A; CDK5; GSK-3
Show Figures

Graphical abstract

MDPI and ACS Style

Loidreau, Y.; Dubouilh-Benard, C.; Nourrisson, M.-R.; Loaëc, N.; Meijer, L.; Besson, T.; Marchand, P. Exploring Kinase Inhibition Properties of 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine Derivatives. Pharmaceuticals 2020, 13, 89.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop