title: Exploring Left-Hand-Side substitutions in the benzoxazinone series of 4-amino-piperidine bacterial type IIa topoisomerase inhibitors.
abstract: An SAR survey at the C-6 benzoxazinone position of a novel scaffold which inhibits bacterial type IIa topoisomerase demonstrates that a range of small electron donating groups (EDG) and electron withdrawing groups (EWG) are tolerated for antibacterial activity. Cyano was identified as a preferred substituent that affords good antibacterial potency while minimizing hERG cardiac channel activity.
authors.affiliation: Infection Innovative Medicines, AstraZeneca R&D Boston, Waltham, MA 02451, USA. bolin.geng@astrazeneca.com
authors.forename: Bolin
authors.initials: B
authors.lastname: Geng
authors.forename: Janelle
authors.initials: J
authors.lastname: Comita-Prevoir
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Eyermann
authors.forename: Folkert
authors.initials: F
authors.lastname: Reck
authors.forename: Stewart
authors.initials: S
authors.lastname: Fisher
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D048588:Benzoxazines / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D048588:Benzoxazines; D004791:Enzyme Inhibitors; D051638:Ether-A-Go-Go Potassium Channels; D010880:Piperidines; D004250:DNA Topoisomerases, Type II