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3-Iodotyrosine is a potent inhibitor of tyrosine hydroxylase in vitro, but lacks significant in vivo activity due to deiodination and transamination. On the basis of previous studies with thyroxine analogs, a series of 3-alkyl-amethyltyrosines was synthesized. A 3-Me, Et, or f-Pr substituent was found to have little effect on the tyrosine hydroxylase inhibitory property of -methyltyrosine. A 3-ieri-Bu group, however, caused a marked decrease in inhibitory activity.Numerous attempts have been made to modify tissue catecholamine levels by use of inhibitors of catecholamine biosynthesis. While several enzymatic steps are amenable to pharmacological control, recent interest has focused on inhibitors of tyrosine hydroxylase since this enzyme represents the rate-limiting step in norepinephrine biosynthesis.3

The best scoring molecule, compound 67 showed 53% inhibition of the human Squalene synthase enzyme, isolated from the cell lysates of Human Hepatoma Cell Line, at a dose of 10 mcg with an IC50 value of 9.43 µm.

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