ASSOCIATED CONTENT Supporting Information. Supporting information includes: Quinolone screening summary Full experimental for all intermediates. Metabolite identification report for MTC420. Molecular formula strings. This material is available free of charge via the Internet at http://pubs.acs.org. ACKNOWLEDGMENT Peter Webborn, Mark Wenlock and Stefan Kavanagh (Astrazeneca) are thanked for their assistance in providing predicted and measured DMPK data. in vitro ABBREVIATIONS TB tuberculosis, MDR multi-drug resistant, XDR extensively drug resistant, Mtb – – – – NADH - Nicotinamide adenine dinucleotide, ETC electron Mycobacterium tuberculosis, – transport chain, ATP - Adenosine triphosphate, ETF electron transferring flavoprotein, FRD – – fumarate reductase, nar nitrate reductase, HTS high throughput screen, DMPK drug – – – metabolism and pharmacokinetics, SAR structure activity relationship, DMF dimethyl – – formamide, GSK Glaxosmithkline, NBS succinamide, DCM dichloromethane, N-bromo – – – PCC - pyridinium chlorochromate, EDC -1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, NHS
ASSOCIATED CONTENT Supporting Information. Supporting information includes: Quinolone screening summary Full experimental for all intermediates. Metabolite identification report for MTC420. Molecular formula strings. This material is available free of charge via the Internet at http://pubs.acs.org. ACKNOWLEDGMENT Peter Webborn, Mark Wenlock and Stefan Kavanagh (Astrazeneca) are thanked for their assistance in providing in vitro predicted and measured DMPK data. ABBREVIATIONS TB – tuberculosis, MDR – multi-drug resistant, XDR – extensively drug resistant, Mtb – Mycobacterium tuberculosis, NADH - Nicotinamide adenine dinucleotide, ETC – electron transport chain, ATP - Adenosine triphosphate, ETF – electron transferring flavoprotein, FRD – fumarate reductase, nar – nitrate reductase, HTS – high throughput screen, DMPK – drug metabolism and pharmacokinetics, SAR – structure activity relationship, DMF – dimethyl formamide, GSK – Glaxosmithkline, NBS – N-bromo succinamide, DCM – dichloromethane, PCC - pyridinium chlorochromate, EDC -1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, NHS