Hopfner, Sarah M.Lee, Bei ShiKalia, Nitin P.Miller, Marvin J.Pethe, KevinMoraski, Garrett C.2022-12-292022-12-292021-09Hopfner, S.M.; Lee, B.S.; Kalia, N.P.; Miller, M.J.; Pethe, K.; Moraski, G.C. Syntheses and Structure–Activity Relationships of N-Phenethyl-Quinazolin-4-yl-Amines as Potent Inhibitors of Cytochrome bd Oxidase in Mycobacterium tuberculosis. Appl. Sci. 2021, 11, 9092. https:// doi.org/10.3390/app111990922076-3417https://scholarworks.montana.edu/handle/1/17548The development of cytochrome bd oxidase (cyt-bd) inhibitors are needed for comprehensive termination of energy production in Mycobacterium tuberculosis (Mtb) to treat tuberculosis infections. Herein, we report on the structure-activity-relationships (SAR) of 22 new N-phenethyl-quinazolin-4-yl-amines that target cyt-bd. Our focused set of compounds was synthesized and screened against three mycobacterial strains: Mycobacterium bovis BCG, Mycobacterium tuberculosis H37Rv and the clinical isolate Mycobacterium tuberculosis N0145 with and without the cytochrome bcc:aa3 inhibitor Q203 in an ATP depletion assay. Two compounds, 12a and 19a, were more active against all three strains than the naturally derived cyt-bd inhibitor aurachin D.en-UScc-byhttps://creativecommons.org/licenses/by/4.0/tuberculosisdrug developmentstructure-activityrelationshipsquinazolineenergy metabolismcytochrome bd oxidaseArticle