Novel carbazole derivatives as NPY Y1 antagonists.
The synthesis of a series of carbazole derivatives and their SAR at the NPY Y1 receptor is described. Modulation of physicochemical properties by appropriate decoration led to the identification of a high-affinity NPY Y1 antagonist that shows high brain penetration and modest oral bioavailability.
Leslie
Colin P
CP
GlaxoSmithKline Medicines Research Centre, Via A. Fleming 4, Verona 37135, Italy. colin.p.leslie@gsk.com
Di Fabio
Romano
R
Bonetti
Francesca
F
Borriello
Manuela
M
Braggio
Simone
S
Dal Forno
Giovanna
G
Donati
Daniele
D
Falchi
Alessandro
A
Ghirlanda
Damiano
D
Giovannini
Riccardo
R
Pavone
Francesca
F
Pecunioso
Angelo
A
Pentassuglia
Giorgio
G
Pizzi
Domenica A
DA
Rumboldt
Giovanna
G
Stasi
Luigi
L
D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D002227:Carbazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D003412:Cricetulus; D006207:Half-Life; D007202:Indicators and Reagents; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D002227:Carbazoles; D007202:Indicators and Reagents; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor