A triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor (DSM421) with improved drug-like properties for treatment and prevention of malaria

Autor: Phillips, MA, White, KL, Kokkonda, S, Deng, X, White, J, El Mazouni, F, Marsh, KC, Tomchick, DR, Manjalanagara, K, Rudra, KR, Wirjanata, G, Noviyanti, R, Price, R, Marfurt, J, Shackleford, DM, Chiu, FCK, Campbell, M, Jimenez Diaz, MB, Ferrer-Bazaga, S, Angulo-Barturen, I, Martínez-Martínez, MS, Lafuente-Monasterio, MJ, Kaminsky, W, Silue, K, Zeeman, AM, Kocken, C, Leroy, D, Blasco, B, Rossignol, E, Rueckle, T, Matthews, D, Burrows, JN, Waterson, D, Palmer, MJ, Rathod, PK, Charman, SA

The emergence of drug resistant malaria parasites continues to hamper efforts to control this lethal disease. Dihydroorotate dehydrogenase has recently been validated as a new target for the treatment of malaria and a selective inhibitor (DSM265) of

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https://doi.org/10.1021/acsinfecdis.6b00144

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Discovery of 1,3,4-oxadiazoles with slow-action activity against Plasmodium falciparum malaria parasites.

Autor: Andrews KT; Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia. Electronic address: k.andrews@griffith.edu.au., Fisher GM; Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia., Firmin M; Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia., Liepa AJ; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Wilson T; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Gardiner J; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Mohri Y; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Debele E; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Rai A; Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia., Davey AK; Griffith Health Group, Griffith University, Gold Coast, Queensland, 4222, Australia., Masurier A; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Delion A; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Mouratidis AA; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Hutt OE; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia., Forsyth CM; School of Chemistry, Monash University, Clayton, Victoria, 3800, Australia., Burrows JN; Medicines for Malaria Venture, Geneva, Switzerland., Ryan JH; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia. Electronic address: jack.ryan@csiro.au., Riches AG; Commonwealth Scientific and Industrial Research Organization, Biomedical Manufacturing, Clayton, Victoria, 3168, Australia. Electronic address: andrew.riches@csiro.au., Skinner-Adams TS; Institute for Biomedicine and Glycomics, Griffith University, Nathan, Queensland, 4111, Australia. Electronic address: t.skinner-adams@griffith.edu.au.

Publikováno v: European journal of medicinal chemistry [Eur J Med Chem] 2024 Nov 15; Vol. 278, pp. 116796. Date of Electronic Publication: 2024 Aug 28.