title: Pyrrolamide DNA gyrase inhibitors: optimization of antibacterial activity and efficacy.
abstract: The pyrrolamides are a new class of antibacterial agents targeting DNA gyrase, an essential enzyme across bacterial species and inhibition results in the disruption of DNA synthesis and subsequently, cell death. The optimization of biochemical activity and other drug-like properties through substitutions to the pyrrole, piperidine, and heterocycle portions of the molecule resulted in pyrrolamides with improved cellular activity and in vivo efficacy.
authors: Infection Innovative Medicines Unit, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. brian.sherer@astrazeneca.com
authors: Brian A
authors: BA
authors: Sherer
authors: Kenneth
authors: K
authors: Hull
authors: Oluyinka
authors: O
authors: Green
authors: Gregory
authors: G
authors: Basarab
authors: Sheila
authors: S
authors: Hauck
authors: Pamela
authors: P
authors: Hill
authors: James T
authors: JT
authors: Loch
authors: George
authors: G
authors: Mullen
authors: Shanta
authors: S
authors: Bist
authors: Joanna
authors: J
authors: Bryant
authors: Ann
authors: A
authors: Boriack-Sjodin
authors: Jon
authors: J
authors: Read
authors: Nancy
authors: N
authors: DeGrace
authors: Maria
authors: M
authors: Uria-Nickelsen
authors: Ruth N
authors: RN
authors: Illingworth
authors: Ann E
authors: AE
authors: Eakin
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001665:Binding Sites; D018360:Crystallography, X-Ray; D027081:DNA Gyrase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011758:Pyrroles; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase