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Arch Pharm (Weinheim). 1996 Jul;329(7):371-6.

Phenylamino-pyrimidine (PAP) derivatives: a new class of potent and selective inhibitors of protein kinase C (PKC).

Author information

1
CIBA Pharmaceuticals Division, Oncology and Virology Research Department, Ciba-Geigy Limited., Basel, Switzerland.

Abstract

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-alpha (IC50 = 0.79 microM) and not the other subtypes tested. The inhibition constants of PKC-alpha and the antiproliferative effect on T24 human bladder carcinoma cells showed a qualitative correlation, although with some exceptions.

PMID:
8764886
[Indexed for MEDLINE]

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