Title :

Antagonists of the adenosine A(2A) receptor based on a 2-arylbenzoxazole scaffold: Investigation of the C5-and C7-positions to enhance affinity

Author(s) :

Duroux, Romain [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Agouridas, Laurence [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Renault, Nicolas [Auteur]
498252|||Lille Inflammation Research International Center - U 995 [LIRIC] (OLD)
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
El Bakali, Jamal [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Furman, Christophe [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Lille Inflammation Research International Center (LIRIC) - U995
Melnyk, Patricia [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Yous, Said [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Journal title :

European Journal of Medicinal Chemistry

Abbreviated title :

Eur. J. Med. Chem.

Volume number :

144

Pages :

151-163

Publication date :

2018-01-20

ISSN :

0223-5234

English keyword(s) :

Neurodegenerative disease
Benzoxazole
A(2A) receptor
DMPK

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

We have recently reported a series of 2-furoyl-benzoxazoles as potential A adenosine receptor (AR) antagonists. Two hits were identified with interesting pharmacokinetic properties but were find to bind the hAR receptor ...
Show more >We have recently reported a series of 2-furoyl-benzoxazoles as potential A adenosine receptor (AR) antagonists. Two hits were identified with interesting pharmacokinetic properties but were find to bind the hAR receptor in the micromolar-range. Herein, in order to enhance affinity toward the hAR, we explored the C5- and C7-position of hits 1 and 2 based on docking studies. These modifications led to compounds with nanomolar-range affinity (e.g. 6a, Ki = 40 nM) and high antagonist activity (e.g. 6a, IC = 70.6 nM). Selected compounds also exhibited interesting in vitro DMPK (Drug Metabolism and Pharmacokinetics) properties including high solubility and low cytotoxicity. Therefore, the benzoxazole ring appears as a highly effective scaffold for the design of new A antagonists.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Brain Biology & Chemistry (BBC)
Développement et plasticité du cerveau neuro-endocrine
Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:44Z
2024-03-04T15:25:59Z