1-[2-[(Heteroarylmethoxy)aryl]carbamoyl]indolines are selective and orally active 5-HT2C receptor inverse agonists.
Bisarylmethoxyethers have been identified with nanomolar 5-HT2C affinity and selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 1, 2, 8, 12, 14 and 18 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function and their therapeutic potential is currently under further investigation.
Bromidge
S M
SM
SmithKline Beecham Pharmaceuticals, Discovery Research, Harlow, Essex, UK. steve_bromidge-1@sbphrd.com
Davies
S
S
Duckworth
D M
DM
Forbes
I T
IT
Jones
G E
GE
Jones
J
J
King
F D
FD
Blackburn
T P
TP
Holland
V
V
Kennett
G A
GA
Lightowler
S
S
Middlemiss
D N
DN
Riley
G J
GJ
Trail
B
B
Wood
M D
MD
D000631:Aminopyridines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015195:Drug Design; D007211:Indoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000631:Aminopyridines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists