title: 5-(2-Pyrimidinyl)-imidazo[1,2-a]pyridines are antibacterial agents targeting the ATPase domains of DNA gyrase and topoisomerase IV.
abstract: 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).
authors.affiliation: Pfizer Global Research and Development, 445 Eastern Point Rd., Groton, CT 06340, United States. Jeremy.Starr@pfizer.com
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Starr
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Sciotti
authors.forename: Debra L
authors.initials: DL
authors.lastname: Hanna
authors.forename: Michael D
authors.initials: MD
authors.lastname: Huband
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mullins
authors.forename: Hongliang
authors.initials: H
authors.lastname: Cai
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Gage
authors.forename: Mandy
authors.initials: M
authors.lastname: Lockard
authors.forename: Mark R
authors.initials: MR
authors.lastname: Rauckhorst
authors.forename: Robert M
authors.initials: RM
authors.lastname: Owen
authors.forename: Manjinder S
authors.initials: MS
authors.lastname: Lall
authors.forename: Mark
authors.initials: M
authors.lastname: Tomilo
authors.forename: Huifen
authors.initials: H
authors.lastname: Chen
authors.forename: Sandra P
authors.initials: SP
authors.lastname: McCurdy
authors.forename: Michael R
authors.initials: MR
authors.lastname: Barbachyn
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D011725:Pyridines; D011743:Pyrimidines; C029899:imidazole; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; C030986:pyrimidine