2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution.

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Connolly S, Aberg A, Arvai A, Beaton HG, Cheshire DR, Cook AR, Cooper S, Cox D, Hamley P, Mallinder P, Millichip I, Nicholls DJ, Rosenfeld RJ, St-Gallay SA, Tainer J, Tinker AC, Wallace AV

2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution.

J Med Chem. 2004 Jun 3;47(12):3320-3.

PubMed ID

15163211 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE	Nitric oxide synthase, inducible	IC 50 (nM)	37	N/A	N/A	Details
4-({4-[(4-methoxypyridin-2-yl)amino]piperidin-1-yl}carbonyl)benzonitrile	Nitric oxide synthase, inducible	IC 50 (nM)	71	N/A	N/A	Details
ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE	Nitric oxide synthase 3	IC 50 (nM)	50000	N/A	N/A	Details
ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE	Nitric oxide synthase, inducible	IC 50 (nM)	350	N/A	N/A	Details