Development of novel oxazolo[5,4-d]pyrimidines as competitive CB2 neutral antagonists based on scaffold hopping - Archive ouverte HAL
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2018

Development of novel oxazolo[5,4-d]pyrimidines as competitive CB2 neutral antagonists based on scaffold hopping

Résumé

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.

Dates et versions

hal-03328250 , version 1 (29-08-2021)

Identifiants

Citer

Wei Tuo, Mélanie Bollier, Natascha Leleu-Chavain, Lucas Lemaire, Amélie Barczyk, et al.. Development of novel oxazolo[5,4-d]pyrimidines as competitive CB2 neutral antagonists based on scaffold hopping. European Journal of Medicinal Chemistry, 2018, 146, pp.68-78. ⟨10.1016/j.ejmech.2018.01.034⟩. ⟨hal-03328250⟩
143 Consultations
0 Téléchargements

Altmetric

Partager

More