Synthesis and biological evaluation of novel N-substituted nipecotic acid derivatives with a cis-alkene spacer as GABA uptake inhibitors.
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
29
11
2018
revised:
15
01
2019
accepted:
23
01
2019
pubmed:
6
2
2019
medline:
15
1
2020
entrez:
6
2
2019
Statut:
ppublish
Résumé
To discover new, potent, and selective inhibitors for the murine gamma-aminobutyric acid transporter 4 (mGAT4), the structure-activity relationship (SAR) study of a new cis-alkene analog family based on DDPM-1457 [(S)-2], which previously showed promising inhibitory potency at and subtype selectivity for mGAT4, was conducted. To uncover the importance of the differences between the trans- and the cis-alkene moiety in the spacer, the present publication describes the synthesis of the new compounds via catalytic hydrogenation with Lindlar's catalyst. The biological results collected by the SAR study revealed that analog rac-7j characterized by a four-instead of a three-carbon atom spacer with a cis double bond applying to the majority of the studied compounds displays a surprisingly high potency at mGAT1 (pIC
Identifiants
pubmed: 30718063
pii: S0968-0896(18)32023-6
doi: 10.1016/j.bmc.2019.01.024
pii:
doi:
Substances chimiques
Alkenes
0
GABA Plasma Membrane Transport Proteins
0
GABA Uptake Inhibitors
0
Gabt4 protein, mouse
0
Nipecotic Acids
0
Tiagabine
Z80I64HMNP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
822-831Informations de copyright
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