title: [Lactones. 24. "Gamma-lactonized" neuroleptics--synthesis, stereochemistry and affinity at the D2 receptor].
abstract: Addition of piperidines 15a-d to methylene lactones 8,14a gives the "gamma-lactonized" diphenylbutylpiperidine-type neuroleptics 3a,b,d,4a-d. 8 can be produced by cyclization or--as well as 14--from the corresponding alpha-carboxylactone. 1H- and 13C-nmr data give evidence for the equatorial position of the aminomethyl group in all derivatives of 3 and 4 and bisequatorial-trans-configuration in 4a-d. 3H-spiroperidole displacement at the D2 receptor in rat brain by 3,4 and the "gamma-lactonized" butyrophenone neuroleptics 1,2a-c was investigated. Some compounds show moderate up to high (3b) activity.
authors.affiliation: Pharmazeutisches Institut, Universität Bonn.
authors.forename: J
authors.initials: J
authors.lastname: Lehmann
authors.forename: G
authors.initials: G
authors.lastname: Schulze
authors.forename: A
authors.initials: A
authors.lastname: Radwansky
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007783:Lactones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D007783:Lactones; D017448:Receptors, Dopamine D2; D013134:Spiperone
vernacular_title: Lactone, 24. Mitt. "gamma-Lactonisierte" Neuroleptika--Synthese, Stereochemie und Affinität am D2-Rezeptor.