Imidazole formation cyanamid

The preparation of a pair of iminohydantoins invokes the addition of amide nitrogen to a cyano group for formation of the imidazole ring. The products exhibit unexpectedly quite different biological activities. Reaction of the cyanamide (92-1) from para-chloroaniline and cyanogen bromide with A-methylchloroacetamide (92-2) can be visualized to lead initially to the alkylation product (92-3). Cyclization by addition to the nitrile group then affords clazolamine (92-4) [98], a compound described as a diuretic. 

On account of the requirement of NOS for tetrahy-drobiopterin, two general approaches toward a modulation of NOS activity seem feasible, manipulation of intracellular tetrahydrobiopterin levels and pterin-binding site antagonists. However, recombinant tetrahydrobiopterin-free NOS II catalysed the oxidation of four N-hydroxyguanidines tested by NADPH and O2, with formation of N02 and NOs" at rates between 20 and 80 nmol min" (mg of protein)" (Moali et al. 2001). In the case of N-(4-chlorophenyO-hT-hydroxyguanidine, formation of the corresponding urea and cyanamide was also detected besides that of N02" and NO3". These tetrahydrobiopterin-free NOS Il-dependent reactions were inhibited by modulators of electron transfer in NOS such as thiocitrulline or imidazole. 

---