title: 2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion.
abstract: A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyrazines has been used to probe the structure-activity relationships of these inhibitors, which show potential as antibacterial agents.
authors.affiliation: Department of Chemistry, UCL, 20, Gordon Street, London WC1H 0AJ, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Sayer
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London WC1E 7HX, UK.
authors.forename: Karin
authors.initials: K
authors.lastname: Walldén
authors.affiliation: Department of Chemistry, UCL, 20, Gordon Street, London WC1H 0AJ, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pesnot
authors.affiliation: Department of Chemistry, UCL, 20, Gordon Street, London WC1H 0AJ, UK.
authors.forename: Frederick
authors.initials: F
authors.lastname: Campbell
authors.affiliation: Wolfson Institute for Biomedical Research, UCL, The Cruciform Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gane
authors.affiliation: Wolfson Institute for Biomedical Research, UCL, The Cruciform Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Michela
authors.initials: M
authors.lastname: Simone
authors.affiliation: Department of Chemistry, UCL, 20, Gordon Street, London WC1H 0AJ, UK.
authors.forename: Hans
authors.initials: H
authors.lastname: Koss
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London WC1E 7HX, UK.
authors.forename: Floris
authors.initials: F
authors.lastname: Buelens
authors.affiliation: Department of Chemistry, UCL, 20, Gordon Street, London WC1H 0AJ, UK.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Boyle
authors.affiliation: Wolfson Institute for Biomedical Research, UCL, The Cruciform Building, Gower Street, London WC1E 6BT, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Selwood
authors.affiliation: Institute of Structural and Molecular Biology, UCL and Birkbeck, Malet Street, London WC1E 7HX, UK.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Waksman
authors.affiliation: Department of Chemistry, UCL, 20, Gordon Street, London WC1H 0AJ, UK. Electronic address: a.b.tabor@ucl.ac.uk.
authors.forename: Alethea B
authors.initials: AB
authors.lastname: Tabor
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D006090:Gram-Negative Bacteria / Q000378:metabolism; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007093:Imidazoles; D011719:Pyrazines; C556838:imidazo(1,2-a)pyrazine
keywords: 8-Amino imidazo[1,2-a]pyrazine; ATPase inhibitor; Bacterial type IV secretion system; HP0525