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

共 50 条

[11] Rationale for the development of cholinesterase inhibitors as anti-Alzheimer agents
Lahiri, DK
Rogers, JT
Greig, NH
Sambamurti, K
CURRENT PHARMACEUTICAL DESIGN, 2004, 10 (25) : 3113 - 3121
[12] Terpenes as Potential Anti-Alzheimer's Disease Agents
Lima, Elisabete
Medeiros, Jorge
APPLIED SCIENCES-BASEL, 2024, 14 (09):
[13] Simple Choline Esters as Potential Anti-Alzheimer Agents
Alcaro, Stefano
Arcone, Rosaria
Costa, Giosue
De Vita, Daniela
Iannone, Michelangelo
Ortuso, Francesco
Procopio, Antonio
Pasceri, Raffaele
Rotiroti, Domenicantonio
Scipione, Luigi
CURRENT PHARMACEUTICAL DESIGN, 2010, 16 (06) : 692 - 697
[14] Editorial: Advances in drug discovery for anti-Alzheimer's agents
Ismaili, Lhassane
FRONTIERS IN CHEMISTRY, 2022, 10
[15] Discovery of anti-Alzheimer agents from Chinese herbal medicine
Gu, Qiong
Xu, Jun
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2016, 251
[16] Interaction of new anti-Alzheimer's disease agents with cholinesterase
Kamal, MA
Al-Jafari, AA
Greig, NH
JOURNAL OF NEUROCHEMISTRY, 2005, 94 : 168 - 168
[17] Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents
Patel, Dushyant, V
Patel, Nirav R.
Kanhed, Ashish M.
Patel, Sagar P.
Sinha, Anshuman
Kansara, Deep D.
Mecwan, Annie R.
Patel, Sarvangee B.
Upadhyay, Pragnesh N.
Patel, Kishan B.
Shah, Dharti B.
Prajapati, Navnit K.
Murumkar, Prashant R.
Patel, Kirti, V
Yadav, Mange Ram
ACS CHEMICAL NEUROSCIENCE, 2019, 10 (08): : 3635 - 3661
[18] A new investigation for some steroidal derivatives as anti-Alzheimer agents
Abdalla, Mohamed M.
Al-Omar, Mohamed A.
Al-Salahi, Rashad A.
Amr, Abdel-Galil E.
Sabrye, Nermien M.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2012, 51 (1-2) : 56 - 63
[19] Synthesis and characterization of pyrimidines analogues as anti-Alzheimer's agents
Yadav Rakesh
Maan Monika
Yadav Divya
Journal of Chinese Pharmaceutical Sciences, 2017, 26 (11) : 834 - 846
[20] Inhibitors of A beta peptide aggregation as potential anti-Alzheimer agents
Bandiera, T
Lansen, J
Post, C
Varasi, M
CURRENT MEDICINAL CHEMISTRY, 1997, 4 (03) : 159 - 170

← 1 2 3 4 5 →