Synthesis and structure-activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 1.
The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited potent binding affinity and functional activity at MCH-R1, and good oral bioavailability in rat.
Rowbottom
Martin W
MW
Department of Medicinal Chemistry, Neurocrine Biosciences Inc., San Diego, CA 92130, USA. mrowbottom@neurocrine.com
Vickers
Troy D
TD
Dyck
Brian
B
Grey
Jonathan
J
Tamiya
Junko
J
Zhang
Mingzhu
M
Kiankarimi
Mehrak
M
Wu
Dongpei
D
Dwight
Wesley
W
Wade
Warren S
WS
Schwarz
David
D
Heise
Christopher E
CE
Madan
Ajay
A
Fisher
Andrew
A
Petroski
Robert
R
Goodfellow
Val S
VS
D000818:Animals; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D011759:Pyrrolidines; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor; D014508:Urea