Synthesis and antiviral activity of 6-benzoyl-benzoxazolin-2-one and 6-benzoyl-benzothiazolin-2-one derivatives

The synthesis and antiviral activity of an original series of 6-benzoyl-ben zoxazolin-2-one and 6-benzoyl-benzothiazolin-2-one derivatives a re describ ed. Several compounds were found to have a selective inhibitory activity ag ainst human cytomegalovirus (HCMV) and varicella-zoster virus (VZV) in vitr o, being inactive against a variety of other DNA and RNA viruses. 6-(3-fluo robenzoyl)benzoxazolin-2-one, 6-(3-fluorobenzoyl)benzothiazolin-2-one, 6-(3 -bromobenzoyl)benzothiazolin-2-one, 6-(3-iodobenzoyl)benzothiazolin-2-one, 3-methyl-6-(3-fluorobenzoyl)benzothiazolin-2-one, 3-benzyl-6-benzoyl-benzot hiazolin-2-one, 3-benzyl-6-(3-fluorobenzoyl)benzothiazolin-2-one and 3-benz oyl-6-(3-fluorobenzoyl)benzothiazolin-2-one were the most active of the ser ies against HCMV and VZV with a selectivity index (CC50/IC50) ranging from 10 to 20. They displayed similar activity against thymidine kinase competen t (TK+) and deficient (TK-) VZV strains, and also proved to be active again st clinical HCMV isolates that were resistant to ganciclovir (GCV). Time-of -addition experiments revealed a site of interaction with the HCMV replicat ive cycle that may be close or similar to that of GCV and cidofovir (HPMPC) . The compounds showed poor, if any, activity against herpes simplex virus type 1 (HSV-1) and HSV-2, and were not inhibitory against human immunodefic iency virus and other DNA and RNA viruses. Therefore, these compounds may r epresent a novel lead for the development of specific HCMV and VZV drugs.