Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents.
A series of novel tetracyclic tetrahydrofuran derivatives was prepared and evaluated for its potential psychotropic properties. In vitro affinities for multiple dopaminergic, serotonergic, alpha-adrenergic, and histamine receptors and for the norepinephrine transporter as well as the ED(50) values obtained in some in vivo assays for antipsychotic, anxiolytic, and antidepressant potential are reported. Compounds (-)-1, (-)-8d, and (+)-8d have been identified as potential broad-spectrum psychotropic agents.
Fernández
Javier
J
Johnson & Johnson Pharmaceutical Research & Development, Drug Discovery CNS; Jarama 75, 45007 Toledo, Spain. jfernan0@prdes.jnj.com
Alonso
José M
JM
Andrés
José I
JI
Cid
José M
JM
Díaz
Adolfo
A
Iturrino
Laura
L
Gil
Pilar
P
Megens
Anton
A
Sipido
Victor K
VK
Trabanco
Andrés A
AA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D011619:Psychotropic Drugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D005663:Furans; D006576:Heterocyclic Compounds, 4 or More Rings; D011619:Psychotropic Drugs