Title :

Development of novel oxazolo[5,4-d]pyrimidines as competitive cb2 neutral antagonists based on scaffold hopping

Author(s) :

Tuo, Wei [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Bollier, Melanie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Chavain, Natascha [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lemaire, Lucas [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Barczyk, Amélie [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dezitter, Xavier [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Klupsch, Frederique [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Szczepanski, Fabien [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Spencer, John [Auteur]
Chavatte, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Millet, Régis [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]

Journal title :

European Journal of Medicinal Chemistry

Abbreviated title :

Eur J Med Chem

Volume number :

146

Pages :

68-78

Publication date :

2018-02-25

ISSN :

1768-3254

English keyword(s) :

Neutral antagonist
oxazolo[5,4-d]pyrimidine
CB2 receptor
Cannabinoid

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

A series of novel oxazolo[5,4-d]pyrimidines was designed via a scaffold hopping strategy and synthesized through a newly developed approach. All these compounds were evaluated for their biological activity toward CB1/CB2 ...
Show more >A series of novel oxazolo[5,4-d]pyrimidines was designed via a scaffold hopping strategy and synthesized through a newly developed approach. All these compounds were evaluated for their biological activity toward CB1/CB2 cannabinoid receptors, their metabolic stability in mice liver microsomes and their cytotoxicity against several cell lines. Eight compounds have been identified as CB2 ligands with Ki values less than 1 μM. It is noteworthy that 2-(2-chlorophenyl)-5-methyl-7-(4-methylpiperazin-1-yl) oxazolo[5,4-d]pyrimidine 47 and 2-(2-chlorophenyl)-7-(4-ethylpiperazin-1-yl)- 5-methyloxazolo[5,4-d]pyrimidine 48 showed CB2 binding affinity in the nanomolar range and significant selectivity over CB1 receptors. Interestingly, functionality studies imply that they behave as competitive neutral antagonists. Moreover, all tested compounds are devoid of cytotoxicity toward several cell lines, including Chinese hamster ovary cells (CHO) and human colorectal adenocarcinoma cells HT29.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-30T10:27:22Z
2024-03-18T13:52:39Z