Inhibition of PDGFR tyrosine kinase activity by a series of novel N-(3-(4-(pyridin-3-yl)-1H-imidazol-2-ylamino)phenyl)amides: a SAR study on the bioisosterism of pyrimidine and imidazole.

摘要

A series of N-(3-(4-(pyridin-3-yl)-1H-imidazol-2-ylamino)phenyl)amides were synthesized and tested for inhibition of PDGFR and FLT3 autophosphorylation. The novel N-(3-(4-(pyridin-3-yl)-1H-imidazol-2-ylamino)phenyl)amides, obtained by replacement of the pyrimidine system in Imatinib (1) with an imidazole ring, exhibit potent inhibitory activity on PDGFR, similar to the parent compound (IC(50) (9e)=0.2 microM; IC(50) Imatinib (1)=0.3 microM). Selectivity hereby seems to be conserved, as shown by the lack of activity on FLT3, a closely related class III receptor tyrosine kinase, which is not affected by the parent compound Imatinib.