Synthesis of Deuterated Endochin ‐Like Quinolones

A prodrug of antimalarial drug candidateELQ-300 is currently in preclinical development, requiring the availability of isotopically labeled analogs. A suitable method for isotopic labeling of these compounds has not yet been reported. Here, we describe a method for the deuteration ofELQ-300 and its prodrug using deuterated acetic acid. ABSTRACTMalaria continues to be a serious and debilitating disease. The emergence and spread of high-level resistance to multiple antimalarial drugs byPlasmodium falciparum has brought about an urgent need for new treatments that will be active against multidrug resistant malaria infections. One such treatment,ELQ-331 (MMV-167), an alkoxy carbonate prodrug of 4(1H)-quinoloneELQ-300, is currently in preclinical development with the Medicines for Malaria Venture. Clinical development ofELQ-331 or similar compounds will require the availability of isotopically labeled analogs. Unfortunately, a suitable method for the deuteration of these important compounds was not found in the literature. Here, we describe a facile and scalable method for the deuteration of 4(1H)-quinoloneELQ-300, its alkoxycarbonate prodrugELQ-331, and their respective N-oxides using deuterated acetic acid.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research