N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors

作者：Fritzson Ingela^*; Bedingfield Paul T P; Sundin Anders P; McConkey Glenn; Nilsson Ulf J

来源：Medchemcomm, 2011, 2(9): 895-898.

DOI：10.1039/c1md00118c

In our continuing program to develop Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors, a series of N-substituted salicylamides were synthesized and their ability to selectively inhibit PfDHODH was examined. The synthetic program was based on 2-hydroxy-N-(2-phenylethyl)benzamide (1) that weakly inhibits both PfDHODH and human DHODH (hDHODH). Structure activity relationships were examined for developing derivatives. Selective PfDHODH inhibitors with improved potency were obtained by introducing a 2,2-diphenylethyl substitution on the salicylamidic nitrogen. Biological activity of the most potent compounds was confirmed on parasite infected cells in vitro.

• 出版日期2011-9