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Arzneimittelforschung 2007; 57(3): 164-170
DOI: 10.1055/s-0031-1296600
Antibiotics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Improved Oral Bioavailability of Anti-HIV Agent N'-[2-(2-Thiophene)ethyl]-NT-[2-(5-bromopyridyl)]-thiourea (HI-443) in a Novel Lipophilic Formulation

Fatih M. Uckun
1   Paradigm Pharmaceuticals, White Bear Lake, MN, USA
,
Douglas Erbeck
2   Parker Hughes Institute, St. Paul, MN, USA
,
Heather Tibbies
1   Paradigm Pharmaceuticals, White Bear Lake, MN, USA
,
Sanjive Qazi
1   Paradigm Pharmaceuticals, White Bear Lake, MN, USA
2   Parker Hughes Institute, St. Paul, MN, USA
,
Taracad K. Venkatachalam
1   Paradigm Pharmaceuticals, White Bear Lake, MN, USA
› Author Affiliations
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Publication History

Publication Date:
21 December 2011 (online)

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Summary

N'-[2-(2-Thiophene)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea (CAS 258340-15-7, HI-443) is a rationally designed non-nucleoside reverse transcriptase inhibitor (NNRTI) with potent anti-HIV activity at nanomolar concentrations but poor oral bioavailability. Here the identification of a novel oleic acid containing lead formulation of HI-443 is described which resulted in a ~ 10-fold improvement of its oral bioavailability yielding 10-fold higher systemic exposure levels in mice. Formulated HI-443 exhibited a favorable pharmacokinetics and toxicity profile in mice.

Key words

Anti-HIV agent - CAS 258340-15-7 - HI-443 - N'-[2-(2-Thiophene)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea - Non-nucleoside reverse transcriptase inhibitor