Tetrahydroindazole derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists.

Autor: Matthews JM; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., McNally JJ; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Connolly PJ; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Xia M; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Zhu B; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Black S; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Chen C; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Hou C; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Liang Y; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Tang Y; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†)., Macielag MJ; Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Nov 01; Vol. 26 (21), pp. 5346-5349. Date of Electronic Publication: 2016 Sep 10.
DOI: 10.1016/j.bmcl.2016.09.025
Abstrakt: A series of potent and receptor-selective cannabinoid-1 (CB1) receptor inverse agonists has been discovered. Peripheral selectivity of the compounds was assessed by a mouse tissue distribution study, in which the concentrations of a test compound in both plasma and brain were measured. A number of peripherally selective compounds have been identified through this process. Compound 2p was further evaluated in a 3-week efficacy study in the diet-induced obesity (DIO) mouse model. Beneficial effects on plasma glucose were observed from the compound-treated mice.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: