| Autor: |
Blumenkopf TA; Wellcome Research Laboratories, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709., Harrington JA, Koble CS, Bankston DD, Morrison RW Jr, Bigham EC, Styles VL, Spector T |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1992 Jun 12; Vol. 35 (12), pp. 2306-14. |
| DOI: |
10.1021/jm00090a022 |
| Abstrakt: |
A series of 2-acetylpyridine thiocarbonohydrazones was synthesized for evaluation as potential antiherpetic agents. The compounds were prepared by the condensation of 2-acetylpyridine with thiocarbonohydrazide followed by treatment with isocyanates or isothiocyanates. Many were found that were potent inactivators of ribonucleotide reductase encoded by HSV-1 and weaker inactivators of human enzyme. Several thiocarbonohydrazones (e.g. 38 and 39) inactivated HSV-1 ribonucleotide reductase at rate constants as much as seven times that of lead compound 2. In general, those substituted with weak electron-attracting groups offered the best combination of potency and apparent selective activity against the HSV-1 enzyme. Seven new thiocarbonohydrazones (21, 25, 31, 36, 38, 39, and 40) were apparently greater than 50-fold more selective than 2 against HSV-1 ribonucleotide reductase versus human enzyme. The results indicated new compounds worthy of further study as potentiators of acyclovir in combination topical treatment of herpes virus infections. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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