In vivo Pharmacokinetics, Metabolism, Toxicity, and Anti-HIV Activity of N'-[2-(2-Thiophene)ethyl]-N'-[2-(5-bromopyridyl)]thiourea (HI-443), a Potent Non-nucleoside Inhibitor of HIV Reverse Transcriptase
| Autor: | Douglas Erbeck, Taracad K. Venkatachalam, Fatih M. Uckun, Heather E. Tibbles |
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| Rok vydání: | 2011 |
| Předmět: |
Pyridines
Mice SCID Pharmacology Rats Sprague-Dawley Mice chemistry.chemical_compound Pharmacokinetics In vivo Drug Discovery medicine Animals Tissue Distribution Chromatography High Pressure Liquid biology Reverse-transcriptase inhibitor Thiourea Reproducibility of Results Biological activity Blood Proteins biology.organism_classification Virology Reverse transcriptase Blood Cell Count Rats chemistry Rats Inbred Lew Area Under Curve Injections Intravenous Lentivirus Toxicity Microsomes Liver Reverse Transcriptase Inhibitors Female Half-Life Protein Binding medicine.drug |
| Zdroj: | Arzneimittelforschung. 57:483-496 |
| ISSN: | 1616-7066 0004-4172 |
| DOI: | 10.1055/s-0031-1296636 |
| Popis: | N'-[2-(2-Thiophene)ethyl]-N'-[2-(5bromopyridyl)]thiourea (CAS 258340-15-7, HI-443) is a potent non-nucleoside inhibitor of HIV reverse transcriptase (NNRTI) that was rationally designed as a candidate anti-HIV agent. The purpose of the present study was to examine the in vivo pharmacokinetics, metabolism, toxicity, and anti-HIV activity of HI-443. HI-443 was very well tolerated in CD-1 mice and Lewis rats without any detectable toxicity at single parenteral bolus dose levels as high as 80 mg/kg. Intraperitoneally administered HI-443 exhibited anti-HIV activity in the Hu-PBL-SCID mouse surrogate model for hunnan AIDS at a non-toxic daily dose level of 10-20 mg/kg. These preclinical research studies provide the basis for future preclinical studies and clinical development of HI-443 as a new NNRTI candidate. |
| Databáze: | OpenAIRE |
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