874813-68-0Relevant academic research and scientific papers
Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum
Anderson, Marc O.,Sherrill, John,Madrid, Peter B.,Liou, Ally P.,Weisman, Jennifer L.,DeRisi, Joseph L.,Guy, R. Kiplin
, p. 334 - 343 (2007/10/03)
A parallel synthetic strategy to the 9-aminoacridine scaffold of the classical anti-malarial drug quinacrine (2) is presented. The method features a new route to 9-chloroacridines that utilizes triflates of salicylic acid derivatives, which are commercially available in a variety of substitution patterns. The route allows ready variation of the two diversity elements present in this class of molecules: the tricyclic aromatic heterocyclic core, and the disubstituted diamine sidechain. In this study, a library of 175 compounds was designed, although only 93 of the final products had purities acceptable for screening. Impurity was generally due to incomplete removal of 9-acridones (18), a degradation product of the 9-chloroacridine synthetic intermediates. The library was screened against two strains of Plasmodium falciparum, including a model of the drug-resistant parasite, and six novel compounds were found to have IC50 values in the low nanomolar range.
