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.
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.
Dickens
J P
JP
Department of Medicinal Chemistry, Searle Research and Development, Buckinghamshire, United Kingdom.
Ellames
G J
GJ
Hare
N J
NJ
Lawson
K R
KR
McKay
W R
WR
Metters
A P
AP
Myers
P L
PL
Pope
A M
AM
Upton
R M
RM
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
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