Synthesis and pharmacological effects of 3-methyl tyrphostin (2-cyano- 3-[4-hydroxyphenyl]-2-butenethioamide): A new protein tyrosine kinase inhibitor

A novel tyrphostin (2-cyano-3-[4-hydroxyphenyl]-2-butenethioamide) (CHB) with a methyl group adjacent to the aromatic ring has been synthesized. The new compound inhibits the autophosphorylation of the platelet-derived growth factor receptor kinase and the phosphorylation of phosphatidylinositol 3- kinase by this receptor kinase with an IC₅₀ of approximately 1 μM. It also decreased the proliferation of a cell line transformed with the keratinocyte growth factor kinase but had no effect on the parent NIH/3T3 cells. Neither cyclic adenosine monophosphate-dependent protein kinase nor protein kinase C activities were affected by the new tyrphostin.