Synthesis of imidazole-containing analogues of farnesyl pyrophosphate and evaluation of their biological activity on protein farnesyltransferase

Synthesis and biological evaluation of a new class of triazin–triazoles as potential inhibitors of human farnesyltransferase

“…The activity of newly triazin-triazoles 2a-i was evaluated on human farnesyltransferase (FTase) [62] and on the NCI-60 human tumor cell lines [63,64]. The results are summarized in Tables 2 and 3.…”

“…The obtained solution was stirred at room temperature for 15 h. The residue obtained upon evaporation was purified by flash chromatography (EtOAc/n-heptane) to provide pure (E)-N,N-diethyl-2-(4,6-dimethoxy-1,3,5-triazin-2-yl)ethenamine 18 as an yellow oil in 70 % yield (0.58 g); Rf = 0. 18 [62]. Cell proliferation assay Compounds 2a-i have been tested on a panel of 60 human cancer cell lines at the National Cancer Institute, Rockville, MD.…”

α,β‐Unsaturated 2‐Acyl‐Imidazoles in Asymmetric Biohybrid Catalysis

“…Other syntheses involve the direct addition of the deprotonated form of 13 on an α,β‐unsaturated ester 14 , a carboxylic acid 15 , an acyl chloride 16 or on a Weinreb amide 18 . Similarly, the addition of 13 on an enal 17 followed by an oxidation of the resulting alcohol intermediate can also be envisioned . Ultimately, a tandem aldol/crotonization between aldehyde 19 and N ‐methyl‐2‐acylimidazole 20 or a Wittig reaction with the appropriate phosphorous ylide 21 also leads to the title compound.…”

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

“…Compounds 1a-h, 1j-l, 1p-q, 1s-v, 1x-aa, and 1ff-gg were evaluated for their inhibitory activity against recombinant yeast 35 , human 7 and T. brucei FTases using a fluorescentbased assay 36,37 adapted to 96-well plate format. Results are reported in Table 3.…”

“…The bacteria are harvested by centrifugation (12 min, 8000 rpm) and the pellet frozen at −20°C. To purify the soluble recombinant protein, bacteria were lysed using Dyno Mill (0.2 mm) and purified according to our reported procedure for recombinant human FTase 7 and stored with 5% glycerol at 4°C.…”