title: DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: synthesis and antibacterial activity.
abstract: The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazolo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-positive antibacterial activity and a low resistance frequency.
authors.affiliation: Evotec (UK) Ltd, Discovery Services, 114 Milton Park, Abingdon, Oxfordshire OX14 4SA, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: East
authors.forename: Clara Bantry
authors.initials: CB
authors.lastname: White
authors.forename: Oliver
authors.initials: O
authors.lastname: Barker
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barker
authors.forename: James
authors.initials: J
authors.lastname: Bennett
authors.forename: David
authors.initials: D
authors.lastname: Brown
authors.forename: E Andrew
authors.initials: EA
authors.lastname: Boyd
authors.forename: Christopher
authors.initials: C
authors.lastname: Brennan
authors.forename: Chandana
authors.initials: C
authors.lastname: Chowdhury
authors.forename: Ian
authors.initials: I
authors.lastname: Collins
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Convers-Reignier
authors.forename: Brian W
authors.initials: BW
authors.lastname: Dymock
authors.forename: Rowena
authors.initials: R
authors.lastname: Fletcher
authors.forename: David J
authors.initials: DJ
authors.lastname: Haydon
authors.forename: Mihaly
authors.initials: M
authors.lastname: Gardiner
authors.forename: Stuart
authors.initials: S
authors.lastname: Hatcher
authors.forename: Peter
authors.initials: P
authors.lastname: Ingram
authors.forename: Paul
authors.initials: P
authors.lastname: Lancett
authors.forename: Paul
authors.initials: P
authors.lastname: Mortenson
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papadopoulos
authors.forename: Carol
authors.initials: C
authors.lastname: Smee
authors.forename: Helena B
authors.initials: HB
authors.lastname: Thomaides-Brears
authors.forename: Heather
authors.initials: H
authors.lastname: Tye
authors.forename: James
authors.initials: J
authors.lastname: Workman
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Czaplewski
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors*; D015195:Drug Design; D013293:Enterococcus faecalis / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000737:chemistry; D013211:Staphylococcus aureus / Q000378:metabolism; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014230:Triazoles / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D007093:Imidazoles; D011725:Pyridines; D059005:Topoisomerase II Inhibitors; D014230:Triazoles; D000251:Adenosine Triphosphatases; D027101:DNA Topoisomerase IV