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

Treatment of 1,1-dimethylethyl 1,1-dimethylethoxycarbonylamino)-5-brom opentanoate 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 ami noimadazole 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 b ioreductively activated to a NOS inhibitor in hypoxic solid tumours.