title: 2-Chloro-1-(2,4-dichlorophenyl)-3-(1H-imidazol-1-yl)-2-phenylpropan-1-one hydrochloride, a novel, nonmutagenic antibacterial with specific activity against anaerobic bacteria.
abstract: 1-(2,4-Dichlorophenyl)-2-phenylpropen-1-one (2) is identified as a potent antibacterial agent. A compound, 2-chloro-1-(2,4-dichlorophenyl)-3-(1H-imidazol-1-yl)-2-phenylpropan++ +-1-one (5) has been designed with the intention of its acting as a pro-drug, liberating the lethal species 2 specifically within the target anaerobic bacterial cell following bioreduction by bacterial ferredoxin or related electron transfer proteins. The synthesis and biological activity of 5 is described and compared with the activities of the analogous alpha-bromo ketone 6 and alpha-fluoro ketone 7. Synthesis of 6, 7, and the corresponding alpha-hydroxy ketone 11 is also described.
authors.affiliation: Department of Medicinal Chemistry, Searle Research and Development, Buckinghamshire, United Kingdom.
authors.forename: J P
authors.initials: JP
authors.lastname: Dickens
authors.forename: G J
authors.initials: GJ
authors.lastname: Ellames
authors.forename: N J
authors.initials: NJ
authors.lastname: Hare
authors.forename: K R
authors.initials: KR
authors.lastname: Lawson
authors.forename: W R
authors.initials: WR
authors.lastname: McKay
authors.forename: A P
authors.initials: AP
authors.lastname: Metters
authors.forename: P L
authors.initials: PL
authors.lastname: Myers
authors.forename: A M
authors.initials: AM
authors.lastname: Pope
authors.forename: R M
authors.initials: RM
authors.lastname: Upton
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D002722:Chlorobenzenes / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008795:Metronidazole / Q000494:pharmacology; D009152:Mutagenicity Tests; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000081248:Allylbenzene Derivatives
chemical_list: D000475:Alkenes; D000900:Anti-Bacterial Agents; D002722:Chlorobenzenes; D007093:Imidazoles; D008795:Metronidazole; D011355:Prodrugs; C070450:1-(2,4-dichlorophenyl)-2-phenylpropen-1-one; D000081248:Allylbenzene Derivatives; C070452:2-chloro-1-(2,4-dichlorophenyl)-3-(1H-imidazol-1-yl)-2-phenylpropan-1-one