Design, synthesis and enzymatic activity of highly selective human mitochondrial thymidine kinase inhibitors

Authors
Manfredini, S Baraldi, PG Durini, E Porcu, L Angusti, A Vertuani, S Solaroli, N De Clercq, E Karlsson, A Balzarini, J
Citation
S. Manfredini et al., Design, synthesis and enzymatic activity of highly selective human mitochondrial thymidine kinase inhibitors, BIOORG MED, 11(10), 2001, pp. 1329-1332
Citations number
11
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
10
Year of publication
2001
Pages
1329 - 1332
Database
ISI
SICI code
0960-894X(20010521)11:10<1329:DSAEAO>2.0.ZU;2-3
Abstract
Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondr ial thymidine kinase (TK-2) without affecting the closely related herpes si mplex virus type 1 thymidine kinase (HSV-1 TK), varicella-zoster virus thym idine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifuncti onal Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuranosyl moiety and the inhib itory activity. (C) 2001 Elsevier Science Ltd. All rights reserved.