N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase

被引：28

作者：

Maccallini, Cristina ^{[1
]}

Patruno, Antonia ^{[1
]}

Lannutti, Fabio ^{[1
]}

Ammazzalorso, Alessandra ^{[1
]}

De Filippis, Barbara ^{[1
]}

Fantacuzzi, Marialuigia ^{[1
]}

Franceschelli, Sara ^{[2
]}

Giampietro, Letizia ^{[1
]}

Masella, Simona ^{[1
]}

Felaco, Mario ^{[2
]}

Re, Nazzareno ^{[1
]}

Amoroso, Rosa ^{[1
]}

机构：

[1] Univ G DAnnunzio, Dipartimento Sci Farm, I-66100 Chieti, Italy

[2] Univ G DAnnunzio, Dipartimento Sci Movimento Umano, I-66100 Chieti, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

Acetamidines; Isoform selectivity; 2-Methylimidazole derivatives; Nitric oxide synthase (NOS); NOS inhibitors; MECHANISMS; DISEASE; NEUROTOXICITY; DOCKING; BINDING; DESIGN;

D O I：

10.1016/j.bmcl.2010.09.059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-substituted acetamidines and 2-methylimidazole derivatives structurally related to W1400 were synthesized and evaluated as Nitric Oxide Synthase (NOS) inhibitors. Analogs with sterically hindering isopropyl and phenyl substituents on the benzylic carbon connecting the aromatic core of W1400 to the acetamidine nitrogen, showed good inhibitory potency for nNOS (IC(50) = 0.2 and 0.3 mu M) and selectivity over eNOS (500 and 1166) and to a lesser extent over iNOS (50 and 100). A molecular modeling study allowed to shed light on the effects of the structural modifications on the selectivity of the designed inhibitors toward the different NOS isoforms. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6495 / 6499

页数：5

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