Design and synthesis of orally-active and selective azaindane 5HT2c agonist for the treatment of obesity.
Based on our original pyrazine hit, CP-0809101, novel conformationally-restricted 5HT2c receptor agonists with 2-piperazin-azaindane scaffold were designed. Synthesis and structure-activity relationship (SAR) studies are described with emphasis on optimization of the selectivity against 5HT2a and 5HT2b receptors with excellent 2c potency. Orally-active and selective compounds were identified with dose-responsive in vivo efficacy in our pre-clinical food intake model.
Liu
Kevin K-C
KK
Pfizer Global Research and Development, Chemistry Department, 10770 Science Center Drive, La Jolla, CA 92120, United States. kevin.k.liu@pfizer.com
Cornelius
Peter
P
Patterson
Terrell A
TA
Zeng
Yuan
Y
Santucci
Stephanie
S
Tomlinson
Elizabeth
E
Gibbons
Colleen
C
Maurer
Tristan S
TS
Marala
Ravi
R
Brown
Janice
J
Kong
Jimmy X
JX
Lee
Eunsun
E
Werner
Wendy
W
Wenzel
Zane
Z
Vage
Chandra
C
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004285:Dogs; D015195:Drug Design; D000882:Haplorhini; D006801:Humans; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019440:Anti-Obesity Agents; D001372:Aza Compounds; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists