2-氨基吡啶作为高选择性诱导型一氧化氮合酶抑制剂。取决于氮取代的不同结合模式。

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

作者信息

Connolly Stephen, Aberg Anders, Arvai Andrew, Beaton Haydn G, Cheshire David R, Cook Anthony R, Cooper Sally, Cox David, Hamley Peter, Mallinder Phil, Millichip Ian, Nicholls David J, Rosenfeld Robin J, St-Gallay Stephen A, Tainer John, Tinker Alan C, Wallace Alan V

机构信息

Medicinal Chemistry, Discovery BioScience, Molecular Biology and Physical and Metabolic Sciences Departments, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leics LE11 5RH, U.K.

出版信息

J Med Chem. 2004 Jun 3;47(12):3320-3. doi: 10.1021/jm031035n.

DOI:10.1021/jm031035n

PMID:15163211

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.

摘要

4-甲基氨基吡啶（4-MAP）（5）是一种强效但非选择性的一氧化氮合酶（NOS）抑制剂。虽然该系列中的简单N-甲基化导致活性较差，但更复杂的N-取代，如与4-哌啶氨基甲酸酯或酰胺反应，则会产生强效且选择性的诱导型NOS抑制作用。显然，这些新抑制剂之间吡啶环的翻转使得哌啶能够与不同的残基相互作用并具有出色的选择性。