N-Methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine, a New Cholinesterase and Monoamine Oxidase Dual

被引：57

作者：

Bautista-Aguilera, Oscar M. ^{[1
]}

Samadi, Abdelouahid ^{[1
]}

Chioua, Mourad ^{[1
]}

Nikolic, Katarina ^{[2
]}

Filipic, Slavica ^{[2
]}

Agbaba, Danica ^{[2
]}

Soriano, Elena ^{[3
]}

de Andres, Lucia ^{[4
]}

Isabel Rodriguez-Franco, Maria ^{[4
]}

Alcaro, Stefano ^{[5
]}

Ramsay, Rona R. ^{[6
]}

Ortuso, Francesco ^{[5
]}

Yanez, Matilde ^{[7
]}

Marco-Contelles, Jose ^{[1
]}

机构：

[1] CSIC, Lab Quim Med, IQOG, E-28006 Madrid, Spain

[2] Univ Belgrade, Fac Pharm, Inst Pharmaceut Chem, Belgrade 11000, Serbia

[3] CSIC, SEPCO, IQOG, E-28006 Madrid, Spain

[4] IQM CSIC, Inst Quim Med, Madrid 28006, Spain

[5] Magna Graecia Univ Catanzaro, Dipartimento Sci Salute, I-88100 Catanzaro, Italy

[6] Univ St Andrews, St Andrews KY16 9ST, Fife, Scotland

[7] Univ Santiago de Compostela, Dept Farmacol, Fac Farm, Santiago De Compostela 15782, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 24期

关键词：

ALZHEIMER DRUG CANDIDATES; SELECTIVE INHIBITORS; MAO-A; ACETYLCHOLINESTERASE INHIBITORS; ANTIOXIDANT PROPERTIES; BIOLOGICAL EVALUATION; DIRECTED LIGANDS; B INHIBITION; DISEASE; HYBRIDS;

D O I：

10.1021/jm501501a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

On the basis of N-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (II, ASS234) and QSAR predictions, in this work we have designed, synthesized, and evaluated a number of new indole derivatives from which we have identified N-methyl-N-((1-methyl-5-(3-(1-(2-methylbenzyl)piperidin-4-yl)propoxy)-1H-indol-2-yl)methyl)prop-2-yn-1-amine (2, MBA236) as a new cholinesterase and monoamine oxidase dual inhibitor.

引用

页码：10455 / 10463

页数：9

共 56 条

[1] Polypharmacology: Challenges and Opportunities in Drug Discovery [J].

Anighoro, Andrew ;

Bajorath, Juergen ;

Rastelli, Giulio .

JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (19) :7874-7887

[2] Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease [J].

Bautista-Aguilera, Oscar M. ;

Esteban, Gerard ;

Bolea, Irene ;

Nikolic, Katarina ;

Agbaba, Danica ;

Moraleda, Ignacio ;

Iriepa, Isabel ;

Samadi, Abdelouahid ;

Soriano, Elena ;

Unzeta, Mercedes ;

Marco-Contelles, Jose .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 75 :82-95

[3] Multipotent, Permeable Drug ASS234 Inhibits Aβ Aggregation, Possesses Antioxidant Properties and Protects from Aβ-induced Apoptosis In Vitro [J].

Bolea, Irene ;

Gella, Alejandro ;

Monjas, Leticia ;

Perez, Concepcion ;

Rodriguez-Franco, Maria Isabel ;

Marco-Contelles, Jose ;

Samadi, Abdelouahid ;

Unzeta, Mercedes .

CURRENT ALZHEIMER RESEARCH, 2013, 10 (08) :797-808

[4] Propargylamine-derived multitarget-directed ligands: fighting Alzheimer's disease with monoamine oxidase inhibitors [J].

Bolea, Irene ;

Gella, Alejandro ;

Unzeta, Mercedes .

JOURNAL OF NEURAL TRANSMISSION, 2013, 120 (06) :893-902

[5] Synthesis, Biological Evaluation, and Molecular Modeling of Donepezil and N-[(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine Hybrids as New Multipotent Cholinesterase/Monoamine Oxidase Inhibitors for the Treatment of Alzheimer's Disease [J].

Bolea, Irene ;

Juarez-Jimenez, Jordi ;

de los Rios, Cristobal ;

Chioua, Mourad ;

Pouplana, Ramon ;

Javier Luque, F. ;

Unzeta, Mercedes ;

Marco-Contelles, Jose ;

Samadi, Abdelouahid .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (24) :8251-8270

[6] Alzheimer Disease [J].

Castellani, Rudy J. ;

Rolston, Raj K. ;

Smith, Mark A. .

DM DISEASE-A-MONTH, 2010, 56 (09) :484-546

[7] Targeting beta-amyloid pathogenesis through acetylcholinesterase inhibitors [J].

Castro, Ana ;

Martinez, Ana .

CURRENT PHARMACEUTICAL DESIGN, 2006, 12 (33) :4377-4387

[8] Multi-target-directed ligands to combat neurodegenerative diseases [J].

Cavalli, Andrea ;

Bolognesi, Maria Laura ;

Minarini, Anna ;

Rosini, Michela ;

Tumiatti, Vincenzo ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (03) :347-372

[9]

Copeland R., 2005, EVALUATION ENZYME IN, V1st

[10] Wnt Signaling Pathway, a Potential Target for Alzheimer's Disease Treatment, is Activated by a Novel Multitarget Compound ASS234 [J].

del Pino, Javier ;

Ramos, Eva ;

Bautista Aguilera, Oscar M. ;

Marco-Contelles, Jose ;

Romero, Alejandro .

CNS NEUROSCIENCE & THERAPEUTICS, 2014, 20 (06) :568-570

← 1 2 3 4 5 6 →