The inhibition on the tyrosine kinases c Abl and c Src suggests a higher potential for treatment of solid cancers. The dual kinase inhibitors had been located active against a large panel of tumour cell lines such as human Doxorubicin solubility and murine lung, hepatoma and colon cancer cell lines. Remedy with these experimental drugs led to growth arrest and induction of apoptosis. Strategies Chemistry Starting materials had been bought from Aldrich Italia. Melting factors had been determined with a Bu?chi 530 apparatus and are uncorrected. IR spectra had been measured in KBr having a Perkin Elmer 398 spectrophotometer. 1H NMR spectra had been recorded inside a 2SO resolution on a Varian Gemini 200 instrument. Chemical shifts are reported as d relative to TMS as internal regular, J in Hz. 1H patterns are described applying the following abbreviations: s singlet, d doublet, t triplet, q quartet, quint quintex, sx sextet, m multiplet, br broad. All compounds had been tested for purity by TLC. Analyses for C, H, N, S were inside 60.3% in the theoretical worth. Synthesis on the dual kinase inhibitors The synthesis of compounds 11 23 has already been reported, when the synthesis of compounds four and 5 is depicted in figure five.
The 1 six thioxo 1,5,6,7 tetrahydro 4H pyrazolopyrimidin four one 1, ready in accordance with this procedure, was alkylated on the C6 sulphur atom making use of the suitable alkyl bromide and anhydrous K2CO3 in anhydrous dimethylformamide at room temperature.
The six alkylthio derivatives 2a b had been in turn chlorinated with all the Vilsmeier complicated, in CHCl3 at reflux for 8 h to get Androgen Receptor Antagonists the dichloro analogues 3a b in good yield just after chromatography purification on a Florisil column. The desired pyrazolopyrimidine 4 was obtained by reaction amongst 3a and 3 chloroaniline in ethanol at reflux for four h although the analogue 5 was obtained by reaction of 3b with phenylethylamine in anhydrous toluene at rt for two days. Compounds 9 and ten were ready as described in figure 6. The 5 amino 1 1H pyrazole four carboxamide six, prepared based on our procedure, was treated with sodium ethoxide and ethyl acetate in absolute ethanol at reflux for 6 h to afford the 1 six methyl 1,five dihydro 4H pyrazolopyrimidin four one 7, that was in turn chlorinated using the Vilsmeier complex, in refluxing CHCl3 at reflux for 12 h to obtain the dichloro derivative 8. Reaction with the latter together with the suitable aniline in absolute ethanol at reflux for four h gave the preferred compounds 9 and ten. General procedure for the synthesis of 6 1 1,5 dihydro 4H pyrazolopyrimidin four ones. Amixture of 1 six thioxo 1,five,six,7 tetrahydro 4H pyrazolopyrimidin 4 one 1, the suitable alkyl bromide and anhydrous K2CO3 in anhydrous DMF was stirred at room temperature for 8 h.