Phenylacetyl-/Trolox- Amides: Synthesis, Sigma-1, HDAC-6, and Antioxidant Activities.
Trolox
antioxidant
drug-likeness
histone-deacetylase-6
phenylacetic
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Oct 2023
18 Oct 2023
Historique:
received:
21
09
2023
revised:
07
10
2023
accepted:
13
10
2023
medline:
30
10
2023
pubmed:
28
10
2023
entrez:
28
10
2023
Statut:
epublish
Résumé
In search of novel multi-mechanistic approaches for treating Alzheimer's disease (AD), we have embarked on synthesizing single small molecules for probing contributory roles of the following combined disease targets: sigma-1 (σ-1), class IIb histone deacetylase-6 (HDAC-6), and oxidative stress (OS). Herein, we report the synthesis and partial evaluation of 20 amides (i.e., phenylacetic and Trolox or 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid derivatives). Target compounds were conveniently synthesized via amidation by either directly reacting acyl chlorides with amines or condensing acids with amines in the presence of coupling agents 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b] pyridinium 3-oxide hexafluorophosphate (HATU) or 1,1'-carbonyldiimidazole (CDI). Overall, this project afforded compound
Identifiants
pubmed: 37894975
pii: ijms242015295
doi: 10.3390/ijms242015295
pmc: PMC10607876
pii:
doi:
Substances chimiques
Antioxidants
0
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
S18UL9710X
Amides
0
Chromans
0
Amines
0
Histone Deacetylase Inhibitors
0
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : 1SC3GM140980-03
Pays : United States
Références
Neurosci Biobehav Rev. 2022 Jan;132:1114-1136
pubmed: 34736882
Med Res Rev. 2021 Mar;41(2):770-784
pubmed: 32656815
Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):87-92
pubmed: 11134513
ChemMedChem. 2021 May 6;16(9):1336-1359
pubmed: 33428327
Iran J Pharm Res. 2014 Fall;13(4):1165-72
pubmed: 25587304
Biochem Pharmacol. 2012 Sep 15;84(6):756-65
pubmed: 22728920
EMBO J. 2003 Mar 3;22(5):1168-79
pubmed: 12606581
Curr Med Chem. 2022;29(9):1474-1502
pubmed: 34477503
J Med Chem. 2018 Jul 26;61(14):6056-6074
pubmed: 29940115
Adv Exp Med Biol. 2017;964:133-152
pubmed: 28315269
Acta Pharm Sin B. 2022 Oct;12(10):3891-3904
pubmed: 36213537
Front Neurosci. 2019 Aug 28;13:862
pubmed: 31551669
Drug Discov Today Technol. 2004 Dec;1(4):337-41
pubmed: 24981612
J Med Chem. 2004 Jan 15;47(2):467-74
pubmed: 14711316
Drug Discov Today Technol. 2015 Nov;18:38-48
pubmed: 26723891
Ageing Res Rev. 2022 May;77:101619
pubmed: 35395415
Molecules. 2023 Mar 02;28(5):
pubmed: 36903567
Beilstein J Org Chem. 2015 May 05;11:638-46
pubmed: 26124866
Bioorg Med Chem Lett. 2016 Dec 15;26(24):5916-5919
pubmed: 27839917
Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19599-604
pubmed: 19884510
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
pubmed: 11259830
Front Cell Dev Biol. 2021 Aug 05;9:704298
pubmed: 34422824
J Alzheimers Dis. 2017;57(4):1105-1121
pubmed: 28059794
J Med Chem. 2020 Nov 12;63(21):12460-12484
pubmed: 32608981
Mol Neurobiol. 2021 Nov;58(11):5649-5666
pubmed: 34383254
J Enzyme Inhib Med Chem. 2012 Oct;27(5):666-72
pubmed: 21899491
Molecules. 2011 Jul 25;16(8):6232-42
pubmed: 21788931
Front Pharmacol. 2019 May 31;10:519
pubmed: 31214020
J Med Chem. 2019 Nov 14;62(21):9824-9836
pubmed: 31603678
J Biomed Sci. 2017 Sep 16;24(1):74
pubmed: 28917260
Eur J Med Chem. 2023 Mar 5;249:115163
pubmed: 36716640
Org Biomol Chem. 2016 Oct 14;14(38):9046-54
pubmed: 27605448
J Biol Chem. 1990 Oct 5;265(28):17174-9
pubmed: 2211619
FEBS J. 2013 Feb;280(3):775-93
pubmed: 23181831
J Chem Inf Model. 2022 May 23;62(10):2387-2397
pubmed: 35467871
Chem Commun (Camb). 2015 Oct 1;51(76):14365-8
pubmed: 26268790
J Med Chem. 1992 Nov 13;35(23):4464-72
pubmed: 1447746
Org Lett. 2013 Feb 1;15(3):642-5
pubmed: 23330785
Mol Neurodegener. 2013 Jan 29;8:7
pubmed: 23356410