N-Substituted Nipecotic Acids as (S)-SNAP-5114 Analogues with Modified Lipophilic Domains.
Dose-Response Relationship, Drug
Enzyme Inhibitors
/ chemical synthesis
GABA Uptake Inhibitors
/ chemical synthesis
HEK293 Cells
Humans
Hydrophobic and Hydrophilic Interactions
Molecular Structure
N-Acetylglucosaminyltransferases
/ antagonists & inhibitors
Nipecotic Acids
/ chemical synthesis
Structure-Activity Relationship
GABA uptake inhibitors
mGAT4
medicinal chemistry
neurochemistry
structure-activity relationships
Journal
ChemMedChem
ISSN: 1860-7187
Titre abrégé: ChemMedChem
Pays: Germany
ID NLM: 101259013
Informations de publication
Date de publication:
06 05 2020
06 05 2020
Historique:
received:
20
12
2019
revised:
26
02
2020
pubmed:
19
3
2020
medline:
21
5
2021
entrez:
19
3
2020
Statut:
ppublish
Résumé
Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC
Identifiants
pubmed: 32187815
doi: 10.1002/cmdc.201900719
pmc: PMC7317212
doi:
Substances chimiques
Enzyme Inhibitors
0
GABA Uptake Inhibitors
0
Nipecotic Acids
0
MGAT4A protein, human
EC 2.4.1.-
N-Acetylglucosaminyltransferases
EC 2.4.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
756-771Informations de copyright
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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