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

共 50 条

[21] First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate
Cinelli, Maris A.
Reidl, Cory T.
Li, Huiying
Chreifi, Georges
Poulos, Thomas L.
Silverman, Richard B.
JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (09) : 4528 - 4554
[22] Optimization of Blood-Brain Barrier Permeability with Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibitors Having a 2-Aminopyridine Scaffold
Do, Ha T.
Li, Huiying
Chreifi, Georges
Poulos, Thomas L.
Silverman, Richard B.
JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (05) : 2690 - 2707
[23] Potent, Highly Selective, and Orally Bioavailable Gem-Difluorinated Monocationic Inhibitors of Neuronal Nitric Oxide Synthase
Xue, Fengtian
Li, Huiying
Delker, Silvia L.
Fang, Jianguo
Martasek, Pavel
Roman, Linda J.
Poulos, Thomas L.
Silverman, Richard B.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (40) : 14229 - 14238
[24] Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase
Xie, Yuanchao
Xu, Dongqing
Huang, Bing
Ma, Xiuli
Qi, Wenbao
Shi, Fangyuan
Liu, Xinyong
Zhang, Yingjie
Xu, Wenfang
JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (20) : 8445 - 8458
[25] Chiral linkers to improve selectivity of double-headed neuronal nitric oxide synthase inhibitors
Jing, Qing
Li, Huiying
Chreifi, Georges
Roman, Linda J.
Martasek, Pavel
Poulos, Thomas L.
Silverman, Richard B.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (20) : 5674 - 5679
[26] Intramolecular hydrogen bonding: A potential strategy for more bioavailable inhibitors of neuronal nitric oxide synthase
Labby, Kristin Jansen
Xue, Fengtian
Kraus, James M.
Ji, Haitao
Mataka, Jan
Li, Huiying
Martasek, Pavel
Roman, Linda J.
Poulos, Thomas L.
Silverman, Richard B.
BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (07) : 2435 - 2443
[27] N-Substituted salicylamides as selective malaria parasite dihydroorotate dehydrogenase inhibitors
Fritzson, Ingela
Bedingfield, Paul T. P.
Sundin, Anders P.
McConkey, Glenn
Nilsson, Ulf J.
MEDCHEMCOMM, 2011, 2 (09) : 895 - 898
[28] Cyclopropyl- and methyl-containing inhibitors of neuronal nitric oxide synthase
Li, Huiying
Xue, Fengtian
Kraus, James M., II
Ji, Haitao
Labby, Kristin Jansen
Mataka, Jan
Delker, Silvia L.
Martasek, Pavel
Roman, Linda J.
Poulos, Thomas L.
Silverman, Richard B.
BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (05) : 1333 - 1343
[29] N-Substituted 4-sulfamoylbenzoic acid derivatives as inhibitors of cytosolic phospholipase A2α
Borecki, Daniel
Lehr, Matthias
MEDICINAL CHEMISTRY RESEARCH, 2022, 31 (06) : 975 - 992
[30] Synthesis of 2-arylindole derivatives and evaluation as nitric oxide synthase and NFκB inhibitors
Yu, Xufen
Park, Eun-Jung
Kondratyuk, Tamara P.
Pezzuto, John M.
Sun, Dianqing
ORGANIC & BIOMOLECULAR CHEMISTRY, 2012, 10 (44) : 8835 - 8847

← 1 2 3 4 5 →