| Autor: |
M P, Wentland, R B, Perni, P H, Dorff, R P, Brundage, M J, Castaldi, J A, Carlson, T R, Bailey, S C, Aldous, P M, Carabateas, E R, Bacon, R K, Kullnig, D C, Young, M G, Woods, S D, Kingsley, K A, Ryan, D, Rosi, M L, Drozd, F J, Dutko |
| Rok vydání: |
1997 |
| Předmět: |
|
| Zdroj: |
Drug design and discovery. 15(1) |
| ISSN: |
1055-9612 |
| Popis: |
Novel antiherpetic 3-quinolinecarboxamides were discovered as part of a drug discovery program at Sterling Winthrop Inc. A major goal of this research was to identify novel non-nucleoside agents possessing activity against acyclovir resistant herpes simplex virus. From screening compound libraries in an HSV-2 plaque reduction assay, 1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarboxamide (1) emerged as an attractive lead structure. By modifying the quinoline ring at the 1-, 2-, 3-, 4-, and 7-positions, analogues were identified that have up to 5-fold increased in vitro potency relative to acyclovir. In a single dose mouse model of infection the 1-(4-FC6H4) analogue 17, one of the most potent derivatives in vitro, displayed comparable oral antiherpetic efficacy to acyclovir at 1/16 the dose; in a multiple dose regimen, however, it was 2-fold less potent. Mechanism of action studies indicate that these new compounds interact with a different, as yet undefined, molecular target than acyclovir. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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