The identification of pyrimidine-diazabicyclo[3.3.0]octane derivatives as 5-HT2C receptor agonists.
The 5-HT2C receptor has been implicated in the regulation of appetite. As such, small molecule agonists to this receptor may serve as novel therapies to combat obesity. We describe here the identification, synthesis, and SAR of a 5-HT2C agonist from a unique pyrimidine-diazabicyclo[3.3.0]octane series. This compound displayed good potency at the 5-HT2C receptor, modest selectivity relative to other 5-HT2 receptors, and was efficacious in an acute feeding study in rats.
Huck
Bayard R
BR
Athersys, Inc., 3201 Carnegie Ave., Cleveland, OH 44115, USA. brhuck@hotmail.com
Llamas
Luis
L
Robarge
Michael J
MJ
Dent
Thomas C
TC
Song
Jianping
J
Hodnick
William F
WF
Crumrine
Chris
C
Stricker-Krongrad
Alain
A
Harrington
John
J
Brunden
Kurt R
KR
Bennani
Youssef L
YL
D000588:Amines / Q000737:chemistry; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000588:Amines; D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D011743:Pyrimidines; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists