title: 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.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Gothenburg, Kemivägen 10 41296 Gothenburg, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Klein
authors.forename: Peter
authors.initials: P
authors.lastname: Dinér
authors.forename: Dominique
authors.initials: D
authors.lastname: Dorin-Semblat
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
authors.forename: Morten
authors.initials: M
authors.lastname: Grøtli
mesh_terms: 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
chemical_list: 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