1.
Chem Pharm Bull (Tokyo)
; 50(8): 1109-13, 2002 Aug.
Artigo
em Inglês
| MEDLINE
| ID: mdl-12192147
RESUMO
The design, synthesis and biological activities of potent pyrazole-based tricyclic CB1 receptor antagonists (2) are described. The key synthetic step involves the ring closure of the lithiated alpha, gamma-keto ester adduct (4). The optimal nitroderivative (28) in this series exhibits a high CB1 receptor affinity (pKi=7.2) as well as very potent antagonistic activity (pA2=8.8) in vitro. The regioselectivity of the pyrazole ring closure is shown to depend strongly on the aromatic substitution pattern of the applied arylhydrazine.