Synthesis and Antimalarial Activities of a Diverse Set of Triazole‐Containing Furamidine Analogues

Abstract

Four different series of triazole diamidines have been prepared by the Pinner method from the corresponding triazole dinitriles. Copper-catalyzed "click chemistry" was used for the synthesis of 1,4- and 4,5-substituted triazoles, aryl magnesium acetylide reagents for the 1,5-substituted triazoles, with a thermal dipolar addition reaction employed for the 2,4-substituted triazoles. In vitro antimalarial activity against two different PfCRT-modified parasite lines (Science 2002, 298, 210-213) of Plasmodium falciparum and inhibition of hemozoin formation were determined for each compound. Several diamidines with potent nanomolar antimalarial activities were identified, and selected molecules were resynthesized as their diamidoxime triazole prodrugs. One of these prodrugs, OB216, proved to be highly potent in vivo with an ED50 value of 5 mg kg(-1) (po) and an observed 100 % cure rate (CD100) of just 10 mg kg(-1) by oral (po) administration in mice infected with P. vinckei.

Structure‐Based Design, Synthesis, and Biological Evaluation of Triazole‐Based smHDAC8 Inhibitors

“…In the first step of the synthetic route, the triazole ring was established by performing Cu(I)‐catalyzed [3+2]‐cycloadditions . The reaction of methyl propiolate ( 3 ) with various azides ( 4 a – g ) was carried out at ambient temperature in a 1 : 1 mixture of water and tert ‐butanol in the presence of copper(II) sulfate and sodium ascorbate giving access to triazole derivatives 5 a – g (Scheme ).…”

Unpacking the Pathogen Box—An Open Source Tool for Fighting Neglected Tropical Disease

“…synthesised a small series of triazole compounds, and found the 2 hydrochloride salt of 72 to be active against chloroquine sensitive and resistant P. falciparum as well as active against P. vinkei ‐infected mice when administered intraperitoneally. The N‐methoxylated prodrug of 72 ( 73 , OB216) was curative in this mouse model when administered orally …”

Evaluation of free radical scavenging capacity of methoxy containing-hybrids of thiosemicarbazone-triazole and their influence on glucose transport

“…A triazole is a five-membered aromatic ring which contains at least one nitrogen atom and another heteroatom such as nitrogen, oxygen, or sulphur in the ring. Triazole derivatives are known to have antifungal, antibacterial, anticancer, antimalaria, anti-inflammatory activities [ 9 – 14 ]. Derivatives of triazole have also been reported to protect pancreatic β cells against endoplasmmic reticulum stress-mediated dysfunction and death [ 15 ].…”