Unknown

Dataset Information

0

Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue.

ABSTRACT: Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.

SUBMITTER: Popowycz F 

PROVIDER: S-EPMC3744883 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue.

Popowycz Florence F   Fournet Guy G   Schneider Cédric C   Bettayeb Karima K   Ferandin Yoan Y   Lamigeon Cyrile C   Tirado Oscar M OM   Mateo-Lozano Silvia S   Notario Vicente V   Colas Pierre P   Bernard Philippe P   Meijer Laurent L   Joseph Benoît B  

Journal of medicinal chemistry 20090201 3

Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, comp  ...[more]

Similar Datasets

Unknown Microwave-Assisted Sequential One-Pot Synthesis of 8-Substituted Pyrazolo[1,5-a][1,3,5]triazines.
| S-EPMC8230123 | biostudies-literature
Unknown 4,4-Dimethyl-3,4-dihydro-pyrido[2',3':3,4]pyrazolo-[1,5-a][1,3,5]triazin-2-amine ethanol monosolvate.
| S-EPMC3050164 | biostudies-literature
Unknown Biguanide-Based Synthesis of 1,3,5-Triazine Derivatives with Anticancer Activity and 1,3,5-Triazine Incorporated Calcium Citrate Nanoparticles.
| S-EPMC7919653 | biostudies-literature
Unknown Lateral transfer of genes for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) degradation.
| S-EPMC2681654 | biostudies-literature
Unknown The longstanding challenge of the nanocrystallization of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX).
| S-EPMC5331269 | biostudies-literature
Unknown 2,4,6-Tris(2,4-dimethyl-phen-yl)-1,3,5-triazine.
| S-EPMC3344576 | biostudies-literature
Unknown 2,4-Diamino-6-methyl-1,3,5-triazine ethanol solvate.
| S-EPMC2960281 | biostudies-literature
Unknown 2,4-Diamino-6-methyl-1,3,5-triazine methanol solvate.
| S-EPMC2915324 | biostudies-literature
Unknown Efficient Access to 3,5-Disubstituted 7-(Trifluoromethyl)pyrazolo[1,5-a]pyrimidines Involving SNAr and Suzuki Cross-Coupling Reactions.
| S-EPMC7248703 | biostudies-literature
Unknown Genomic and transcriptomic studies of an RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine)-degrading actinobacterium.
| S-EPMC3485706 | biostudies-literature