Evaluation of bromovinyldeoxyuridine-related compounds in the treatment of experimental herpes simplex keratitis

Abstract

Several newly synthesized compounds, all structurally related to the highly potent and selective antiherpes agent bromovinyldeoxyuridine ( [E]-5-[2-bromovinyl]-2'-deoxyuridine), have been evaluated for their healing effect on herpes simplex virus type 1 keratitis in rabbits. These novel compounds included chloroethyldeoxyuridine (5-[2-chloroethyl]-2'-deoxyuridine), trifluoropropenyldeoxyuridine ( [E]-5-[3,3,3-trifluoro-1-propenyl]-2'-deoxyuridine), bromovinylaminodideoxyuridine ( [E]-5-[2-bromovinyl]-3'-amino-2',3'-dideoxyuridine), bromovinylarabinofuranosyluracil ( [E]-5-[2-bromovinyl]-1-beta-D-arabinofuranosyluracil), and glycylbromovinyldeoxyuridine (5'-O-aminoacetyl-[E]-5-[2-bromovinyl]-2'-deoxyuridine). Bromovinylaminodideoxyuridine and trifluoropropenyldeoxyuridine did not promote a significant healing of herpes simplex keratitis. Bromovinylarabinofuranosyluracil markedly reduced the severity of keratitis, but to a significantly lesser extent than bromovinyldeoxyuridine. Finally, chloroethyldeoxyuridine and glycylbromovinyldeoxyuridine caused a pronounced healing effect on herpes simplex keratitis, comparable to that obtained with bromovinyldeoxyuridine. Chloroethyldeoxyuridine was even slightly better than bromovinyldeoxyuridine, but the difference in their healing effect was not statistically significant.