title: 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.
abstract: 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.
authors.affiliation: Institute of Pharmacy, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany. siavosh.mahboobi@chemie.uni-regensburg.de <siavosh.mahboobi@chemie.uni-regensburg.de>
authors.forename: Siavosh
authors.initials: S
authors.lastname: Mahboobi
authors.forename: Andreas
authors.initials: A
authors.lastname: Sellmer
authors.forename: Asma
authors.initials: A
authors.lastname: Eswayah
authors.forename: Sigurd
authors.initials: S
authors.lastname: Elz
authors.forename: Andrea
authors.initials: A
authors.lastname: Uecker
authors.forename: Frank-D
authors.initials: FD
authors.lastname: Böhmer
mesh_terms: D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D011743:Pyrimidines; C099852:PDGF receptor tyrosine kinase; D017479:Receptors, Platelet-Derived Growth Factor; C030986:pyrimidine