Portal de Periódicos da CAPES

2-Aminopyridines as Highly Selective Inducible Nitric Oxide Synthase Inhibitors. Differential Binding Modes Dependent on Nitrogen Substitution

2004; American Chemical Society; Volume: 47; Issue: 12 Linguagem: Inglês

10.1021/jm031035n

1520-4804

Stephen Connolly, Anders Åberg, A.S. Arvai, Haydn G. Beaton, David R. Cheshire, Anthony R. Cook, Sally L. Cooper, David Cox, Peter Hamley, P.R. Mallinder, Ian Millichip, David Nicholls, R.J. Rosenfeld, Stephen A. St-Gallay, John A. Tainer, Alan C. Tinker, A.V. Wallace,

Metal-Catalyzed Oxygenation Mechanisms

4-Methylaminopyridine (4-MAP) (5) is a potent but nonselective nitric oxide synthase (NOS) inhibitor. While simple N-methylation in this series results in poor activity, more elaborate N-substitution such as with 4-piperidine carbamate or amide results in potent and selective inducible NOS inhibition. Evidently, a flipping of the pyridine ring between these new inhibitors allows the piperidine to interact with different residues and confer excellent selectivity.