title: Synthesis and evaluation of pharmacological properties of some new xanthone derivatives with piperazine moiety.
abstract: A series of new xanthone derivatives with piperazine moiety [1-7] was synthesized and evaluated for their pharmacological properties. They were subject to binding assays for α₁ and β₁ adrenergic as well as 5-HT₁A, 5-HT₆ and 5-HT₇b serotoninergic receptors. Five of the tested compounds were also evaluated for their anticonvulsant properties. The compound 3a 3-methoxy-5-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-9H-xanthen-9-one hydrochloride exhibited significantly higher affinity for serotoninergic 5-HT₁A receptors (Ki=24 nM) than other substances. In terms of anticonvulsant activity, 6-methoxy-2-{[4-(benzyl)piperazin-1-yl]methyl}-9H-xanthen-9-one (5) proved best properties. Its ED₅₀ determined in maximal electroshock (MES) seizure assay was 105 mg/kg b.w. (rats, p.o.). Combining of xanthone with piperazine moiety resulted in obtaining of compounds with increased bioavailability after oral administration.
authors.affiliation: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland. awaszkie@cm-uj.krakow.pl
authors.forename: A M
authors.initials: AM
authors.lastname: Waszkielewicz
authors.forename: A
authors.initials: A
authors.lastname: Gunia
authors.forename: N
authors.initials: N
authors.lastname: Szkaradek
authors.forename: K
authors.initials: K
authors.lastname: Pytka
authors.forename: A
authors.initials: A
authors.lastname: Siwek
authors.forename: G
authors.initials: G
authors.lastname: Satała
authors.forename: A J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: E
authors.initials: E
authors.lastname: Szneler
authors.forename: H
authors.initials: H
authors.lastname: Marona
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D006207:Half-Life; D007700:Kinetics; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D011485:Protein Binding; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy; D044004:Xanthones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: C585789:6-methoxy-2-((4-(benzyl)piperazin-1-yl)methyl)-9H-xanthen-9-one; D000927:Anticonvulsants; D010879:Piperazines; D011985:Receptors, Serotonin; D044004:Xanthones; C097216:serotonin 6 receptor; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; D000077489:Piperazine; C009689:xanthone