5-(2-Pyrimidinyl)-imidazo[1,2-a]pyridines are antibacterial agents targeting the ATPase domains of DNA gyrase and topoisomerase IV.
Dual inhibitors of bacterial gyrB and parE based on a 5-(2-pyrimidinyl)-imidazo[1,2-a]pyridine template exhibited MICs (microg/mL) of 0.06-64 (Sau), 0.25-64 (MRSA), 0.06-64 (Spy), 0.06-64 (Spn), and 0.03-64 (FQR Spn). Selected examples were efficacious in mouse sepsis and lung infection models at <50mg/kg (PO dosing).
Starr
Jeremy T
JT
Pfizer Global Research and Development, 445 Eastern Point Rd., Groton, CT 06340, United States. Jeremy.Starr@pfizer.com
Sciotti
Richard J
RJ
Hanna
Debra L
DL
Huband
Michael D
MD
Mullins
Lisa M
LM
Cai
Hongliang
H
Gage
Jeffrey W
JW
Lockard
Mandy
M
Rauckhorst
Mark R
MR
Owen
Robert M
RM
Lall
Manjinder S
MS
Tomilo
Mark
M
Chen
Huifen
H
McCurdy
Sandra P
SP
Barbachyn
Michael R
MR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D027081:DNA Gyrase / Q000378:metabolism*; D027101:DNA Topoisomerase IV / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D018805:Sepsis / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007093:Imidazoles; D011725:Pyridines; D011743:Pyrimidines; C029899:imidazole; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; C030986:pyrimidine