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Titolo:
Synthesis and antiviral activity of novel anti-VZV 5-substituted uracil nucleosides with a cyclopropane sugar moiety
Autore:
Onishi, T; Mukai, C; Nakagawa, R; Sekiyama, T; Aoki, M; Suzuki, K; Nakazawa, H; Ono, N; Ohmura, Y; Iwayama, S; Okunishi, M; Tsuji, T;
Indirizzi:
Ajinomoto Co Inc, Pharmaceut Res Labs, Kawasaki, Kanagawa 2108681, Japan Ajinomoto Co Inc Kawasaki Kanagawa Japan 2108681 Kanagawa 2108681, Japan
Titolo Testata:
JOURNAL OF MEDICINAL CHEMISTRY
fascicolo: 2, volume: 43, anno: 2000,
pagine: 278 - 282
SICI:
0022-2623(20000127)43:2<278:SAAAON>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
VARICELLA-ZOSTER VIRUS; ACID RELATED-COMPOUNDS; HERPES-SIMPLEX VIRUS; BIOLOGICAL-ACTIVITIES; ANALOGS; POTENT; AGENT; DERIVATIVES; (E)-5-(2-BROMOVINYL)URACIL; PYRIMIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Tsuji, T Ajinomoto Co Inc, Pharmaceut Res Labs, 1-1 Suzuki Cho, Kawasaki, Kanagawa 2108681, Japan Ajinomoto Co Inc 1-1 Suzuki Cho Kawasaki Kanagawa Japan 2108681 n
Citazione:
T. Onishi et al., "Synthesis and antiviral activity of novel anti-VZV 5-substituted uracil nucleosides with a cyclopropane sugar moiety", J MED CHEM, 43(2), 2000, pp. 278-282

Abstract

A series of 5-substituted uracil nucleoside derivatives with a 1(1'S,2'R)-[1',2'-bis(hydroxymethyl)-cycloproplyl]methyl group as an acyclosugar moiety were synthesized and evaluated for their anti-herpetic activities. Among the compounds synthesized, (E)-5-halovinyluracil derivatives showed superior anti-varicella tester virus (VZV) activity over acyclovir (ACV) but were less potent than ACV against herpes symplex virus type-1 (HSV-1). IC50 values for the VZV Kawaguchi strain were 0.027 for Br, 0.070 for Cl, and 0.054 mu g/mL for I derivatives and 3.4 mu g/mL for ACV. The most potent compound, (1'S,2'R)-5-[(E)-2-bromoethenyl]-1-[[1', (hydroxymethyl)cycloprop-1'-yl]methyl]-2,4-(1H,3H)-pyrimidinedione (3a), was 40-60-fold more potent than ACV against clinical isolates of VZV. It showed good oral bioavailability in rats (68.5%) and, unlike (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU), did not result in the release of (E)-5-(2-bromovinyl)uracil (BVU), a potent dihydropyrimidine dehydrogenase inhibitor, in plasma after oral administration.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 08:09:49