alpha-chymotrypsin and cupferron

O-Alkylation of N-nitroso-N-phenylhydroxylamine ammonium salt (cupferron) was studied for the synthesis of novel nitric oxide (NO) releasing agents. The alkylation occurred regioselectively at the terminal oxygen, leading to a single product N-(alkyloxy)-N'-phenyldiimide N'-oxide as indicated by NMR and X-ray analysis. The O-alkyl derivatives exhibited significantly improved stability compared to their parent compound, cupferron. It was demonstrated that the cupferron O-alkyl derivatives could function as photoreleasing NO donor compounds. N-(N"-acetylphenylalanylmethylenyloxy)-N'-phenyldiimide N'-oxide), which linked the cupferron portion with an amino acid via an acetal moiety, was synthesized as an model NO prodrug where controlled NO release would occur either by increasing pH or by a protease-catalyzed hydrolysis.

Topics: Alkylation; Chymotrypsin; Drug Design; Molecular Structure; Nitric Oxide; Nitric Oxide Donors; Nitrosamines; Structure-Activity Relationship