Synthesis of novel 2-pyrrolidinone and pyrrolidine derivatives and study of their inhibitory activity against autotaxin enzyme.
2-pyrrolidinones
Autotaxin
Inhibitor
Pyrrolidines
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
09
10
2019
revised:
11
11
2019
accepted:
13
11
2019
pubmed:
23
12
2019
medline:
28
1
2021
entrez:
23
12
2019
Statut:
ppublish
Résumé
Autotaxin (ATX), a glycoprotein (~125 kDa) isolated as an autocrine motility factor from melanoma cells, belongs to a seven-membered family of ectonucleotide pyrophosphatase/phosphodiesterase (ENPP), and exhibits lysophospholipase D activity. ATX is responsible for the hydrolysis of lysophosphatidylcholine (LPC) to produce the bioactive lipid lysophosphatidic acid (LPA), which is upregulated in a variety of pathological inflammatory conditions, including fibrosis, cancer, liver toxicity and thrombosis. Given its role in human disease, the ATX-LPA axis is an interesting target for therapy, and the development of novel potent ATX inhibitors is of great importance. In the present work a novel class of ATX inhibitors, optically active derivatives of 2-pyrrolidinone and pyrrolidine heterocycles were synthesized. Some of them exhibited interesting in vitro activity, namely the hydroxamic acid 16 (IC
Identifiants
pubmed: 31864778
pii: S0968-0896(19)31728-6
doi: 10.1016/j.bmc.2019.115216
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Pyrrolidines
0
Phosphoric Diester Hydrolases
EC 3.1.4.-
alkylglycerophosphoethanolamine phosphodiesterase
EC 3.1.4.39
pyrrolidine
LJU5627FYV
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115216Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.