2-nitroimidazol-5-ylmethyl as a potential bioreductively activated prodrug system: reductively triggered release of the PARP inhibitor 5-bromoisoquinolinone.
5-Chloromethyl-1-methyl-2-nitroimidazole reacted efficiently with the anion derived from 5-bromoisoquinolin-1-one to give 5-bromo-2-((1-methyl-2-nitroimidazol-5-yl)methyl)isoquinolin -1-one. Biomimetic reduction effected release of the 5-bromoisoquinolin-1-one. The 2-nitroimidazol-5-ylmethyl unit thus has potential for development as a general prodrug system for selective drug delivery to hypoxic tissues.
Parveen
I
I
Department of Pharmacy & Pharmacology, University of Bath, UK.
Naughton
D P
DP
Whish
W J
WJ
Threadgill
M D
MD
D000643:Ammonium Chloride / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D000860:Hypoxia; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism*; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry* / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry
C121299:5-bromo-2-((1-methyl-2-nitroimidazol-5-yl)methyl)isoquinolin-1-one; C114365:5-bromoisoquinolin-1-one; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011355:Prodrugs; D015363:Quinolones; D000643:Ammonium Chloride; D010165:Palladium; D015032:Zinc