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.
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Bayard R
BR
Huck
Luis
L
Llamas
Michael J
MJ
Robarge
Thomas C
TC
Dent
Jianping
J
Song
William F
WF
Hodnick
Chris
C
Crumrine
Alain
A
Stricker-Krongrad
John
J
Harrington
Kurt R
KR
Brunden
Youssef L
YL
Bennani
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