title: Synthesis and anorectic activity of 2H-4,6-dimethyl-2-[(4- phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5,4-b]pyridin e.
abstract: The synthesis of 2H-4,6-dimethyl-2-[(4- phenylpiperazin-1-yl)methyl]-3-oxo-2,3-dihydroisothiazolo[5, 4-b]pyridine. (3) and its biological properties are described. Compound 3 pharmacologically evaluated in vivo by use of behavioral tests showed to have a profile of activity characteristic of stimulation of the central serotoninergic system, mostly 5-HT52A receptors (anorectic action: 2 mg/kg i.p., 8.5 mg/kg po) However, receptor activity of isothiazolopyridine 3 was not confirmed in vitro using 5-HT2A and 5-HT1A receptor binding technique. Molecular modeling studies demonstrated that it is difficult to predict bioactive conformation of title molecule 3.
authors.affiliation: Department of Chemistry of Drugs, Wrocław University of Medicine, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Malinka
authors.forename: M
authors.initials: M
authors.lastname: Rutkowska
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D018360:Crystallography, X-Ray; D004347:Drug Interactions; D005247:Feeding Behavior / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008958:Models, Molecular; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior
chemical_list: C111395:2H-4,6-dimethyl-2-((4-phenylpiperazin-1-yl)methyl)-3-oxo-2,3-dihydroisothiazolo(5,4-b)pyridine; D018712:Analgesics, Non-Narcotic; D001067:Appetite Depressants; D010879:Piperazines; D011725:Pyridines; D006916:5-Hydroxytryptophan