An automated, polymer-assisted strategy for the preparation of urea and thiourea derivatives of 15-membered azalides as potential antimalarial chemotherapeutics.
Bioorg Med Chem
; 19(5): 1692-701, 2011 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-21316974
ABSTRACT
A series of 15-membered azalide urea and thiourea derivatives has been synthesized and evaluated for their in vitro antimalarial activity against chloroquine-sensitive (D6), chloroquine/pyremethamine resistant (W2) and multidrug resistant (TM91C235) strains of Plasmodium falciparum. We have developed an effective automated synthetic strategy for the rapid synthesis of urea/thiourea libraries of a macrolide scaffold. Compounds have been synthesized using a solution phase strategy with overall yields of 50-80%. Most of the synthesized compounds had inhibitory effects. The top 10 compounds were 30-65 times more potent than azithromycin, an azalide with antimalarial activity, against all three strains.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Tioureia
/
Ureia
/
Antimaláricos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article