| Autor: |
Corbett, Jeffrey W., Ko, Soo S., Rodgers, James D., Jeffrey, Susan, Bacheler, Lee T., Klabe, Ronald M., Diamond, Sharon, Lai, Chii-Ming, Rabel, Shelley R., Saye, Jo Anne, Adams, Stephen P., Trainor, George L., Anderson, Paul S., Erickson-Viitanen, Susan K. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; December 1999, Vol. 43 Issue: 12 p2893-2897, 5p |
| Abstrakt: |
ABSTRACTA research program targeted toward the identification of expanded-spectrum nonnucleoside reverse transcriptase inhibitors which possess increased potency toward K103N-containing mutant human immunodeficiency virus (HIV) and which maintain pharmacokinetics consistent with once-a-day dosing has resulted in the identification of the 4-cyclopropylalkynyl-4-trifluoromethyl-3,4-dihydro-2(1H)quinazolinones DPC 961 and DPC 963 and the 4-cyclopropylalkenyl-4-trifluoromethyl-3,4-dihydro-2(1H)quinazolinones DPC 082 and DPC 083 for clinical development. DPC 961, DPC 963, DPC 082, and DPC 083 all exhibit low-nanomolar potency toward wild-type virus, K103N and L100I single-mutation variants, and many multiply amino acid-substituted HIV type 1 mutants. This high degree of potency is combined with a high degree of oral bioavailability, as demonstrated in rhesus monkeys and chimpanzees, and with plasma serum protein binding that can result in significant free levels of drug. |
| Databáze: |
Supplemental Index |
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