The discovery and optimization of pyrimidinone-containing MCH R1 antagonists.
Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH R1) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented.
Hertzog
Donald L
DL
Metabolic and Viral Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27707, USA. Donald.L.Hertzog@gsk.com
Al-Barazanji
Kamal A
KA
Bigham
Eric C
EC
Bishop
Michael J
MJ
Britt
Christy S
CS
Carlton
David L
DL
Cooper
Joel P
JP
Daniels
Alex J
AJ
Garrido
Dulce M
DM
Goetz
Aaron S
AS
Grizzle
Mary K
MK
Guo
Yu C
YC
Handlon
Anthony L
AL
Ignar
Diane M
DM
Morgan
Ronda O
RO
Peat
Andrew J
AJ
Tavares
Francis X
FX
Zhou
Huiqiang
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D051379:Mice; D008806:Mice, Inbred AKR; D008958:Models, Molecular; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry
D011744:Pyrimidinones; D011979:Receptors, Pituitary Hormone; D013438:Sulfhydryl Compounds; C092274:melanin-concentrating hormone receptor