title: S-2-amino-5-(2-nitroimidazol-1-yl)pentanoic acid: a model for potential bioreductively activated prodrugs for inhibitors of nitric oxide synthase (NOS) activity.
abstract: Treatment of 1,1-dimethylethyl S-(2-1,1-dimethylethoxycarbonylamino)-5-bromopentanoate with 1-potassio-2-nitroimidazole, followed by deprotection, afforded S-2-amino-5-(2-nitroimidazol-1-yl)pentanoic acid, which was reduced to S-2-amino-5-(2-aminoimidazol-1-yl)pentanoic acid. This aminoimadazole inhibited rat brain nitric oxide synthase (NOS) activity 3.2 times more potently than did the nitro analogue. Thus S-2-amino-5-(2-nitroimidazol-1-yl)pentanoic acid is a potent prodrug which may be bioreductively activated to a NOS inhibitor in hypoxic solid tumours.
authors.affiliation: Division of Experimental Oncology, MRC Radiobiology Unit, Chilton, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ulhaq
authors.forename: M A
authors.initials: MA
authors.lastname: Naylor
authors.forename: E C
authors.initials: EC
authors.lastname: Chinje
authors.forename: M D
authors.initials: MD
authors.lastname: Threadgill
authors.forename: I J
authors.initials: IJ
authors.lastname: Stratford
mesh_terms: D000818:Animals; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007093:Imidazoles; D011355:Prodrugs; D019001:Nitric Oxide Synthase