2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution
2-aminopyridines as highly selective inducible nitric oxide synthase inhibitors. Differential binding modes dependent on nitrogen substitution
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DOI：
10.1021/jm031035n
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发表时间：
2004-06-03
影响因子：
7.3
通讯作者：
Wallace, AV
中科院分区：
文献类型：
--
作者：
Connolly, S;Aberg, A;Wallace, AV
4-甲基氨基吡啶（4-MAP）（5）是一种有效但非选择性的一氧化氮合酶（NOS）抑制剂。虽然在这一系列中简单的N-甲基化导致活性差，但更复杂的N-取代，如用4-哌啶氨基甲酸酯或酰胺导致有效的和选择性的诱导型NOS抑制。显然，这些新的抑制剂之间的吡啶环的翻转允许哌啶与不同的残基相互作用，并赋予优异的选择性。
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.