| Autor: |
S K, Balani, M E, Goldman, L R, Kauffman, S L, Varga, J A, O'Brien, S J, Smith, T V, Olah, H G, Ramjit, T W, Schorn, S M, Pitzenberger |
| Rok vydání: |
1993 |
| Předmět: |
|
| Zdroj: |
Drug metabolism and disposition: the biological fate of chemicals. 21(4) |
| ISSN: |
0090-9556 |
| Popis: |
Rhesus monkeys were dosed orally with 10 mg/kg 5-chloro-3-phenylthioindole-2-carboxamide (L-734,005), a nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, in polyethylene glycol 300. Plasma samples from these monkeys demonstrated greater bioactivity in an HIV-1 reverse transcriptase inhibition assay than anticipated from the parent compound concentrations as determined by an HPLC-UV assay. One major and three minor metabolites, as well as the parent compound, were detected in the plasma. One of the minor metabolites was determined to be several-fold more active, and the major metabolite one-half as active as the parent compound in the inhibition assay. Identical metabolites were formed during an incubation of L-734,005 with rat liver microsomes. The most active minor metabolite was identified as a sulfone analog (L-737,126) of the parent compound by NMR and MS analyses. The less active major metabolite and two relatively inactive minor metabolites were similarly identified as the sulfoxide, 4-hydroxythiophenyl and 6-hydroxyindole analogs of L-734,005. The synthetic sulfone analog was highly potent against HIV-1, with a 95% inhibitory concentration of 3.0 nM for the spread of virus infection in a cell culture. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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