An automated, polymer-assisted strategy for the preparation of urea and thiourea derivatives of 15-membered azalides as potential antimalarial chemotherapeutics

作者：Hutinec Antun^*; Rupcic Renata; Ziher Dinko; Smith Kirsten S; Milhous Wilbur; Ellis William; Ohrt Colin; Schoenfeld Zrinka Ivezic

来源：Bioorganic & Medicinal Chemistry, 2011, 19(5): 1692-1701.

DOI：10.1016/j.bmc.2011.01.030

• Antimalarial
• Azalide
• Ureas
• Thiourea
• Automated parallel synthesis
• Plasmodium falciparum

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.

• 出版日期2011-3-1