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Synthesis, Biological Evaluations and 18F-Radiolabeling of C-6 Substituted Thymine Derivatives

The novel C-6 substituted pyrimidine derivatives were designed and synthesized by multistep synthetic strategy involving nucleophilic addition of lithiated 2, 4-dimethoxy-5, 6-dimethylpyrimidine to 1, 3-bis(benzyloxy)propan-2-one, radical deoxygenation, N-methylation and deprotection of methoxy and benzyl groups to give the 6-(1, 3-dihydroxyisobutyl)-1-methylthymine and its corresponding unsaturated structural congener. The target molecules, which were selectively phosphorylated by herpes simplex virus type-1 thymidine kinase (HSV-1 TK) and not by human TK, exhibited good binding affinities for viral TK and no cytotoxicities [1]. Thus, they fulfilled the necessary requirements for their application as tracer molecules for non-invasive TK imaging by positron emission tomography (PET). [1] Johayem A., Raić-Malić, S., Lazzati, K., Schubiger P.A., Scapozza, L., Ametamey, S., Chem. & Biodiv. 3 (2006) 274 ; Raić-Malić S., Johayem A., Ametamey S., Batinac S., De Clercq E., Folkers G., Scapozza L., 23 Nucleosides, Nucleotides & Nucleic Acids (2004) 1707.

C-6 Substituted Thymine Derivatives; 18F-Radiolabeling; Positron Emission Tomography

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