title: Structure-activity relationship studies of CNS agents. Part 24: New analogs of N-tert.-butyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]-2-phenylpropanamide (WAY-100135).
abstract: A series of new N-substituted derivatives of 3-[4-(2-methoxyphenyl)-1-piperazinyl]-2-phenylpropanamide, 6-10, were synthesized and their 5-HT1A, 5-HT2A, and alpha 1 receptor affinities were determined. All the compounds were highly potent 5-HT1A ligands with a moderate or low 5-HT2A and alpha 1 affinity. It was shown that the 5-HT2A affinity of 1 and 6-10 depended crucially on the volume of amide substituents. None of the investigated racemic mixtures 1 and 6-8 antagonized the 8-OH-DPAT-induced lower lip retraction in rats, whereas (+/-)-7 behaved like a weak agonist of 5-HT1A receptors in the model used.
authors.affiliation: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
authors.forename: J
authors.initials: J
authors.lastname: Boksa
authors.forename: A
authors.initials: A
authors.lastname: Klodzińska
authors.forename: S
authors.initials: S
authors.lastname: Charakchieva-Minol
authors.forename: E
authors.initials: E
authors.lastname: Chojnacka-Wójcik
authors.forename: J L
authors.initials: JL
authors.lastname: Mokrosz
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin