Azepinoindole derivatives with high affinity for brain dopamine and serotonin receptors.
We synthesized 20 and 21 as conformationally constrained analogues of the dopamine receptor antagonist SKF-83742, as well as analogues 6-9, 16, and 18-22. Although 20 and 21 were inactive, 7, 9, and 19 showed strong binding to D-1, D-2, S-2, and alpha-1 receptors, as well as antipsychotic activity in vivo.
Maryanoff
B E
BE
R. W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477, USA.
McComsey
D F
DF
Martin
G E
GE
Shank
R P
RP
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001552:Benzazepines / Q000737:chemistry*; D001921:Brain / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015195:Drug Design; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D001381:Azepines; D001552:Benzazepines; D018492:Dopamine Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; C035674:SK&F 83742