New insights into the binding mode of pyridine-3-carboxamide inhibitors of E. coli DNA gyrase |
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| Affiliation: | 1. School of Chemistry and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK;2. Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK;1. University of Uludag, Faculty of Science and Arts, Department of Chemistry, 16059 Bursa, Turkey;2. Thamar University, Faculty of Medicine and Health Sciences, Department of Pharmacy, Dhamar, Yemen;1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 ZuChongZhi Road, Shanghai 201203, China;2. School of Pharmacy, Xinxiang Medical University, 601 Jisui Avenue, Xinxiang, Henan 453003, China;1. Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach an der Riss, Germany;2. Central Nervous System Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach an der Riss, Germany;3. Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach an der Riss, Germany;1. Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, Andhra Pradesh, India;2. Dr Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India;3. Zephase Therapeutics (An Incubated Company at the Dr Reddy’s Institute of Life Sciences), University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India |
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| Abstract: | Previously we have reported on a series of pyridine-3-carboxamide inhibitors of DNA gyrase and DNA topoisomerase IV that were designed using a computational de novo design approach and which showed promising antibacterial properties. Herein we describe the synthesis of additional examples from this series aimed specifically at DNA gyrase, along with crystal structures confirming the predicted mode of binding and in vitro ADME data which describe the drug-likeness of these compounds. |
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