The Chemotype of Chromanones as a Privileged Scaffold for Multineurotarget Anti-Alzheimer Agents

被引：4

作者：

Keuler, Tim ^{[1
]}

Lemke, Carina ^{[1
,2
]}

Elsinghorst, Paul W. ^{[1
,2
]}

Iriepa, Isabel ^{[3
]}

Chioua, Mourad ^{[4
]}

Martinez-Grau, Maria Angeles ^{[5
]}

Beadle, Christopher D. ^{[6
]}

Vetman, Tatiana ^{[7
]}

Lopez-Munoz, Francisco ^{[8
]}

Wille, Timo ^{[9
]}

Bartz, Ulrike ^{[10
]}

Deuther-Conrad, Winnie ^{[11
]}

Marco-Contelles, Jose ^{[4
]}

Guetschow, Michael ^{[1
]}

机构：

[1] Univ Bonn, Pharmaceut Inst, Pharmaceut & Med Chem, D-53121 Bonn, Germany

[2] Cent Inst Bundeswehr, Med Serv Munich, D-85748 Garching, Germany

[3] Univ Alcala, Dept Quim Organ & Quim Inorgan, Madrid 28871, Spain

[4] CSIC, IQOG, Lab Med Chem, Madrid 28006, Spain

[5] Eli Lilly & Co, Lilly Res Labs, Madrid 28108, Spain

[6] Eli Lilly & Co, Lilly Res Ctr, Windlesham GU20 6PH, Surrey, England

[7] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

[8] Camilo Jose Cela Univ Madrid UCJC, Fac Hlth, Neuropsychopharmacol Unit, Madrid 28692, Spain

[9] Bundeswehr Inst Pharmacol & Toxicol, D-80937 Munich, Germany

[10] Univ Appl Sci Bonn Rhein Sieg, Dept Nat Sci, D-53359 Rheinbach, Germany

[11] Inst Radiopharmaceut Canc Res, Helmholtz Zentrum Dresden Rossendorf, Dept Neuroradiopharmaceut, D-04318 Leipzig, Germany

来源：

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE | 2022年 / 5卷 / 11期

关键词：

chromanones; Alzheimer?s disease; multineurotarget agents; 1 and ?2 receptors; monoamine oxidases; human cholinesterases; MONOAMINE-OXIDASE; PHARMACOLOGICAL EVALUATION; COGNITIVE DEFICITS; SIGMA(1) RECEPTOR; CRYSTAL-STRUCTURE; INHIBITORS; OPTIMIZATION; DERIVATIVES; LIGANDS; POTENT;

D O I：

10.1021/acsptsci.2c00097

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The multifactorial nature of Alzheimer's disease necessitates the development of agents able to interfere with different relevant targets. A series of 22 tailored chromanones was conceptualized, synthesized, and subjected to biological evaluation. We identified one representative bearing a linker-connected azepane moiety (compound 19) with balanced pharmacological properties. Compound 19 exhibited inhibitory activities against human acetyl-, butyrylcholinesterase and monoamine oxidase-B, as well as high affinity to both the sigma 1 and sigma 2 receptors. Our study provides a framework for the development of further chromanone-based

引用

页码：1097 / 1108

页数：12

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