A new N-methyl thymine derivative comprising a dihydroxyisobutenyl unit as ligand for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK)

Svjetlana Krištafor; Ivana Novaković; Tatjana Gazivoda Kraljević; Sandra Kraljević Pavelić; Pero Lučin; Yvonne Westermaier; Lucile Pernot; Leonardo Scapozza; Simon M Ametamey; Silvana Raić-Malić

doi:10.1016/j.bmcl.2011.07.115

A new N-methyl thymine derivative comprising a dihydroxyisobutenyl unit as ligand for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK)

Bioorg Med Chem Lett. 2011 Oct 15;21(20):6161-5. doi: 10.1016/j.bmcl.2011.07.115. Epub 2011 Aug 6.

Authors

Svjetlana Krištafor¹, Ivana Novaković, Tatjana Gazivoda Kraljević, Sandra Kraljević Pavelić, Pero Lučin, Yvonne Westermaier, Lucile Pernot, Leonardo Scapozza, Simon M Ametamey, Silvana Raić-Malić

Affiliation

¹ Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, HR-10000 Zagreb, Croatia.

PMID: 21911293
DOI: 10.1016/j.bmcl.2011.07.115

Abstract

Molecular modeling and phosphorylation assay in vitro were employed to select a novel unsaturated 1,3-dihydroxyisobutenyl thymine derivative 6 as ligand for HSV-1 TK which may be of interest as lead for the development of an positron emission tomography (PET) imaging agent. Compound 6 was successfully prepared using modified approaches. A significant improvement over the syntheses involving pathways A and B (1% and 3% overall yield, respectively), was observed using synthetic route C (14% overall yield).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / chemistry*
Antiviral Agents / pharmacology*
Cell Line, Tumor
Herpes Simplex / diagnosis
Herpes Simplex / enzymology*
Herpesvirus 1, Human / enzymology*
Humans
Models, Molecular
Phosphorylation
Positron-Emission Tomography / methods
Thymidine Kinase / metabolism*
Thymine / analogs & derivatives*
Thymine / pharmacology*

Substances

Antiviral Agents
Thymidine Kinase
Thymine