Identification of 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT2C receptor agonists.
Synthesis and evaluation of the activity of new 4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles as 5-HT(2C) receptor agonists are described. Appropriately substituted, several analogs displayed selectivity against the other 5-HT(2) receptor subtypes of 1 order of magnitude or more. Selectivity was improved for several compounds versus the lead 1, increasing the therapeutic interest in this series of 5-HT(2C) receptor agonists.
Vernalis Research Ltd., Oakdene Court, 613 Reading Road, Wokingham RG41 5UA, UK. stephan.roever@roche.com
S
S
Röver
D R
DR
Adams
A
A
Bénardeau
J M
JM
Bentley
M J
MJ
Bickerdike
A
A
Bourson
I A
IA
Cliffe
P
P
Coassolo
J E P
JE
Davidson
C T
CT
Dourish
P
P
Hebeisen
G A
GA
Kennett
A R
AR
Knight
C S
CS
Malcolm
P
P
Mattei
A
A
Misra
J
J
Mizrahi
M
M
Muller
R H P
RH
Porter
H
H
Richter
S
S
Taylor
S P
SP
Vickers
D000818:Animals; D004435:Eating / Q000187:drug effects*; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D007279:Injections, Subcutaneous; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007211:Indoles; D011719:Pyrazines; D011725:Pyridines; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists