Synthesis of 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)-substituted pyrazolo[3,4-d]pyrimidin-4-amines via click chemistry: potential inhibitors of the Plasmodium falciparum PfPK7 protein kinase.
Efficient routes to 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)pyrazolo[3,4-d]pyrimidin-4-amines using a one-pot two-step reaction are presented. The two routes give easy access to two different isomers of 1,4-disubstituted triazoles and the target compounds are obtained from a variety of readily available aromatic and aliphatic halides without isolation of potentially unstable organic azide intermediates. Two compounds show activity towards the PfPK7 kinase (IC(50) 10-20 microM) of P. falciparum, the organism responsible for the most virulent form of malaria, and can be regarded as hits useful for further development into lead compounds.
Klein
Michael
M
Department of Chemistry, University of Gothenburg, Kemivägen 10 41296 Gothenburg, Sweden.
Dinér
Peter
P
Dorin-Semblat
Dominique
D
Doerig
Christian
C
Grøtli
Morten
M
D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D010963:Plasmodium falciparum / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis*; D011494:Protein Kinases / Q000187:drug effects; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000588:Amines; D047428:Protein Kinase Inhibitors; D015800:Protozoan Proteins; D011743:Pyrimidines; D014230:Triazoles; D011494:Protein Kinases; C503375:PK7 protein, Plasmodium falciparum; D020929:Mitogen-Activated Protein Kinase Kinases