Butyrophenone analogues in the carbazole series as potential atypical antipsychotics: synthesis and determination of affinities at D(2), 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors.
We describe practical and efficient routes for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4H-carbazol-4-ones using the Fischer indole synthesis or palladium-catalysed cyclization methodologies, as well as their affinities for D(2), 5-HT(2A) and 5-HT(2C) receptors, and their activity at the 5-HT(2B) receptor. The most active compounds, 4b (QF 2003B) and 4c (QF 2004B), with a pK(i) (5-HT(2A)/D(2)) ratio of 1.28 show a potential antipsychotic profile according to Meltzer's classification.
Masaguer
C F
CF
Departamento de Química Orgánica, Laboratorio de Química Farmacéutica, Facultad de Farmacia. Universidad de Santiago de Compostela, 15706-, Santiago de Compostela, Spain.
Raviña
E
E
Fontenla
J A
JA
Brea
J
J
Tristán
H
H
Loza
M I
MI
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002090:Butyrophenones / Q000737:chemistry*; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002831:Choroid Plexus / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D007555:Isoxazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
D014150:Antipsychotic Agents; D002090:Butyrophenones; D002227:Carbazoles; D007555:Isoxazoles; D010879:Piperazines; C409481:QF 2003B; C409482:QF 2004B; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists