Journal of medicinal and pharmaceutical chemistry 2009-03-26

4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus.

Sonia De Castro, Carlos García-Aparicio, Graciela Andrei, Robert Snoeck, Jan Balzarini, María-José Camarasa, Sonsoles Velázquez

Index: J. Med. Chem. 52(6) , 1582-91, (2009)

Full Text: HTML

Abstract

We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system. Several 4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives were found to have a selective inhibitory activity against human cytomegalovirus (HCMV) and varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. A structure-activity relationship (SAR) study showed that the presence of a benzyl at the 5 position and a benzyloxy substituent at the 4 position are a prerequisite for anti-HCMV and VZV activity. The novel compounds do not show cross-resistance against a wide variety of mutant drug-resistant HCMV strains, pointing to a novel mechanism of antiviral action.

Related Compounds

  • Naphth(1,8-cd)-1,2...

Related Articles:

Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency. 1. Synthesis and studies on the reactivity toward model nucleophiles of the (13)C-labeled skin sensitizers hex-1-ene- and hexane-1,3-sultones.

2001-01-01

[Chem. Res. Toxicol. 14(1) , 110-7, (2001)]

Studies of the chemical selectivity of hapten, reactivity, and skin sensitization potency. 2. nmr studies of the covalent binding of the (13)c-labeled skin sensitizers 2-[13C]- and 3-[13C]hex-1-ene- and 3-[13C]hexane-1,3-sultones to human serum albumin.

2001-01-01

[Chem. Res. Toxicol. 14(1) , 118-26, (2001)]

DNA adducts of lactones, sultones, acylating agents and acrylic compounds.

1994-01-01

[IARC Sci. Publ. (125) , 179-98, (1994)]

Single injection adjuvant test.

1985-01-01

[Curr. Probl. Dermatol. 14 , 201-7, (1985)]

A rationale for the selection of occlusion to induce and elicit delayed contact hypersensitivity in the guinea pig. A prospective test.

1985-01-01

[Curr. Probl. Dermatol. 14 , 39-58, (1985)]

More Articles...