DNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: synthesis and antibacterial activity.
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.
East
Stephen P
SP
Evotec (UK) Ltd, Discovery Services, 114 Milton Park, Abingdon, Oxfordshire OX14 4SA, UK.
White
Clara Bantry
CB
Barker
Oliver
O
Barker
Stephanie
S
Bennett
James
J
Brown
David
D
Boyd
E Andrew
EA
Brennan
Christopher
C
Chowdhury
Chandana
C
Collins
Ian
I
Convers-Reignier
Emmanuelle
E
Dymock
Brian W
BW
Fletcher
Rowena
R
Haydon
David J
DJ
Gardiner
Mihaly
M
Hatcher
Stuart
S
Ingram
Peter
P
Lancett
Paul
P
Mortenson
Paul
P
Papadopoulos
Konstantinos
K
Smee
Carol
C
Thomaides-Brears
Helena B
HB
Tye
Heather
H
Workman
James
J
Czaplewski
Lloyd G
LG
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
D000890:Anti-Infective Agents; D007093:Imidazoles; D011725:Pyridines; D059005:Topoisomerase II Inhibitors; D014230:Triazoles; D000251:Adenosine Triphosphatases; D027101:DNA Topoisomerase IV