Scheme 2. Trifluoromethylation of arenes with well-defined sources of CuCF 3 , described by the groups of Vicic, [10a] Grushin, [10b] and Hartwig, [10c, d] (top) and of Grushin [11] (bottom). Bpin = pinacolylboryl.Scheme 3. CÀH trifluoromethylation, described by the groups of Yu [12] (top) and Liu [13a] and Qing [13b] (bottom).Scheme 4. CÀH radical trifluoromethylation of (hetero)arenes according to Nagib and MacMillan [14] (top) and Baran et al. [15] (bottom).

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.