Tetrahydroindazole derivatives as potent and peripherally selective cannabinoid-1 (CB1) receptor inverse agonists.
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.
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Jay M
JM
Matthews
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
James J
JJ
McNally
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Peter J
PJ
Connolly
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Mingde
M
Xia
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Bin
B
Zhu
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Shawn
S
Black
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Cailin
C
Chen
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Cuifen
C
Hou
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Yin
Y
Liang
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Yuting
Y
Tang
Janssen Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477, USA(†).
Mark J
MJ
Macielag
D000818:Animals; D054314:Drug Inverse Agonism; D007191:Indazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists
D007191:Indazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2
CB1 receptor; Cannabinoid receptor; Inverse agonist; Peripheral selectivity; Peripherally restricted