Phenylamino‐pyrimidines represent a novel class of inhibitors of the protein kinase C with a high degree of selectivity versus other serine/threonine and tyrosine kinases. Steady state kinetic analysis of N‐(3‐[1‐imidazolyl]‐phenyl)‐4‐(3‐pyridyl)‐2‐pyrimidinamine (5), which showed potent inhibitory activity, revealed competitive kinetics relative to ATP. The adjacent H‐bond acceptor of the pyrimidine moiety next to an H‐bond donor of the phenylamine was found to be crucial for inhibitory activity. N‐(3‐Nitro‐phenyl)‐4‐(3‐pyridyl)‐2‐pyrimidinamine (7) preferentially inhibited PKC‐α (IC₅₀ = 0.79 μM) and not the other subtypes tested. The inhibition constants of PKC‐α and the antiproliferative effect on T24 human bladder carcinoma cells showed a qualitative correlation, although with some exceptions.