Synthesis and evaluation of 1,1′-hydrocarbylenebis(indazol-3-ols) as potential antimalarial drugs

Abstract

Bis(indazol-3-ol) derivatives (5, 30-38) were prepared by alkylation of 3-alkoxyindazoles with α,ω-dibromides, followed by removal of the O-protecting groups. These compounds were subsequently evaluated as inhibitors of biocrystallization of ferriproto-porphyrin IX (heme) to hemozoin, a Plasmodium detoxification specific process. Most bis(5-nitroindazol-3-ols) were good inhibitors, however, a denitro analogue (38), the intermediate bis(3-al-koxyindazoles) (15-29) as well as bis(indazolin-3-ones) (39-42) were not active, showing the importance of the NO2 and OH groups in the inhibition process. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.