Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 1.
The synthesis of a series of novel 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives as well as their 5-HT(2A/2C) and H(1) receptor binding affinities are described. The in vivo activity as potential anxiolytics of the synthesised compounds was measured in a mCPP challenge test. One of the compounds, 2a, proved to be a potent 5-HT(2A/2C) receptor antagonist showing as well oral activity and therefore could be considered as a potential anxiolytic/antidepressant agent.
Andrés
J Ignacio
JI
Janssen-Cilag, Basic Research Centre, Jarama s/n, 45007 Toledo, Spain. jandres@jaces.jnj.com
Alcázar
Jesús
J
Alonso
José M
JM
Díaz
Adolfo
A
Fernández
Javier
J
Gil
Pilar
P
Iturrino
Laura
L
Matesanz
Encarna
E
Meert
Theo F
TF
Megens
Anton
A
Sipido
Victor K
VK
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001381:Azepines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists