Discovery of 4-(dimethylamino)quinazolines as potent and selective antagonists for the melanin-concentrating hormone receptor 1.
A series of 4-(dimethylamino)quinazoline based antagonists of the melanin-concentrating hormone receptor 1 (MCH-R1) is described. This series was derived from a lead compound, AR129330, identified by HTS of a GPCR-directed library using a functional assay with a constitutively activated (CART) form of the receptor. The preliminary optimization resulted in the identification of compounds 20, 21, and 23.
Kanuma
Kosuke
K
Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama, Saitama 331-9530, Japan.
Omodera
Katsunori
K
Nishiguchi
Mariko
M
Funakoshi
Takeo
T
Chaki
Shigeyuki
S
Semple
Graeme
G
Tran
Thuy-Anh
TA
Kramer
Bryan
B
Hsu
Debbie
D
Casper
Martin
M
Thomsen
Bill
B
Beeley
Nigel
N
Sekiguchi
Yoshinori
Y
D002460:Cell Line; D006801:Humans; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D011799:Quinazolines; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor