Studies on the affinity of 6-[(n-(cyclo)aminoalkyl)oxy]-4H-chromen-4-ones for sigma 1/2 receptors

被引：6

作者：

Deuther-Conrad, Winnie ^{[1
]}

Diez-Iriepa, Daniel ^{[2
]}

Iriepa, Isabel ^{[2
]}

Lopez-Munoz, Francisco ^{[3
,4
]}

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

Guetschow, Michael ^{[6
]}

Marco-Contelles, Jose ^{[7
]}

机构：

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

[2] Univ Alcala, Dept Organ & Inorgan Chem, Ctra Madrid Barcelona,Km 33,6, Madrid 28871, Spain

[3] Camilo Jose Cela Univ Madrid UCJC, Fac Hlth, Madrid, Spain

[4] Hosp 12 Octubre, Res Inst, Neuropsychopharmacol Unit, Madrid, Spain

[5] MG Drug Discovery Consulting, C Nuria 28 2F, Madrid 28034, Spain

[6] Univ Bonn, Pharmaceut Inst, Pharmaceut & Med Chem, Immenburg 4, D-53121 Bonn, Germany

[7] CSIC, IQOG, Lab Med Chem, C Juan de la Cierva 3, Madrid 28006, Spain

来源：

RSC MEDICINAL CHEMISTRY | 2021年 / 12卷 / 06期

关键词：

BIOLOGICAL EVALUATION; ANTAGONISTS; LIGANDS; IDENTIFICATION; SCAFFOLD; AGONISM; BINDING; S1RA;

D O I：

10.1039/d1md00105a

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sigma (sigma) receptors represent attractive targets for the development of potential agents for the treatment of several disorders, including Alzheimer's disease and neuropathic pain. In the search for multitarget small molecules (MSMs) against such disorders, we have re-discovered chromenones as new affine sigma 1/sigma 2 ligands. 6-(4-(Piperidin-1-yl)butoxy)-4H-chromen-4-one (7), a previously identified MSM with potent dual-target activities against acetylcholinesterase and monoamine oxidase B, also exhibited sigma 1/sigma 2 affinity. 6-(3-(Azepan-1-yl)propoxy)-4H-chromen-4-one (20) showed a Ki value for sigma 1 of 27.2 nM (selectivity (sigma 1/sigma 2) = 28), combining the desired sigma 1 receptor affinity with a dual inhibitory capacity against both acetyl- and butyrylcholinesterase. 6-((5-Morpholinopentyl)oxy)-4H-chromen-4-one (12) was almost equipotent to S1RA, an established sigma 1 receptor antagonist.

引用

页码：1000 / 1004

页数：5

共 33 条

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