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Two alkylating glucocorticoids have been synthesized in order to test the possibility of alkylating glucocorticoid receptors. The title compounds are 9alpha-fluoro-11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione 21-[bis(2-chloroethyl)carbamate] 16,17-acetonide (I) and 11beta,17alpha,21-trihydroxypregn-4-ene-3,20-dione 21-[bis(2-chloroethyl)carbamate] (II), prepared from triamcinolone acetonide and cortisol, respectively, through the reaction of the C-21 hydroxyl group with phosgene and di-2-chloroethylamine in the presence of triethylamine. Both compounds are biologically active as inhibitors of the growth of cultured mouse fibroblasts and are able to compete for the specific binding of radiolabeled triamcinolone acetonide to the L929 cell receptor. The bis(2-chloroethyl)carbamate moiety is capable of reacting with nucleophilic groups as evidenced by the colorimetric reaction with 4-(p-nitrobenzyl)pyridine. Both the interaction with the receptor and inhibition of cell growth by these two glucocorticoids are reversible.

In the present study a series of 3-alkenyl-alpha-methyltyrosines and their corresponding 3-alkyl-and dihydrobenzofuran analogs was synthesized for potential tyrosine hydroxylase (TH) inhibitory activity. The appropriately substituted hydantoins IIIa and IIIb, which were prepared from the corresponding allyloxybenzylhydantoins IIa and IIb through Claisen rearrangement, served as intermediates for the synthesis of these amino acids. TH inhibition was reduced upon either saturation of the double bond in the side chain or cyclization to form the dihydrobenzofuran analogs. Formation of the epoxide had a similar effect. The inhibitory activity of these compounds against aromatic amino acid decarboxylase (AADC) and dopamine beta-hydroxylase (DBH) was also investigated. Unsaturation, in both cases, decreases the inhibitory activity; however, the presence of a free phenolic group appears to be essential for AACD inhibitory activity.