Synthesis and structure-activity relationship of 1H-indole-3-carboxylic acid pyridine-3-ylamides: a novel series of 5-HT2C receptor antagonists.
A novel series of 1H-indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT(2C) receptor. Among them, 1H-indole-3-carboxylic acid[6-(2-chloro-pyridin-3-yloxy)-pyridin-3-yl]-amide (15k) exhibits the highest affinity (IC(50)=0.5 nM) with an excellent selectivity (>2000 times) over other serotonin (5-HT(1A), 5-HT(2A), and 5-HT(6)) and dopamine (D(2)-D(4)) receptors.
Park
Chul Min
CM
Center for Medicinal Chemistry, Drug Discovery Division, Korea Research Institute of Chemical Technology, 100 Chang-dong, Yuseong-gu, Daejeon 305-606, South Korea.
Kim
So Young
SY
Park
Woo Kyu
WK
Park
No Sang
NS
Seong
Churl Min
CM
D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D016466:CHO Cells; D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
C532909:1H-indole-3-carboxylic acid pyridine-3-ylamide; D000588:Amines; D002264:Carboxylic Acids; D007211:Indoles; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D013449:Sulfonamides