title: Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazin-1-ylalkyl)-3-oxoisothiazolo[5,4-b] pyridines as CNS and antimycobacterial agents.
abstract: We have synthesized several new isothiazolopyridines possessing a side chain at the isothiazole ring typical, among others, for trazodone or NAN-195. Representatives of the novel isothiazolopyridines were examined for acute toxicity and in several commonly used CNS tests in mice and for arterial blood pressure in rats. Three of the five compounds tested showed significant analgesic activity. The most active compound (3b) exhibited analgesic action in the "writhing" test in a dose 1/1280 of LD50 (LD50 = 1135.5 mg/kg) after administration i.p. to mice. Additionally, the compounds described here and related isothiazolopyridines obtained previously were evaluated against Mycobacterium tuberculosis H37Rv at 12.5 micrograms/ml in in vitro assays. Seven of the nineteen compounds tested showed 100% inhibition of that mycobacterium.
authors.affiliation: Department of Chemistry of Drugs, Wrocław Medical University, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Malinka
authors.forename: M
authors.initials: M
authors.lastname: Sieklucka-Dziuba
authors.forename: G
authors.initials: G
authors.lastname: Rajtar
authors.forename: W
authors.initials: W
authors.lastname: Zgodziński
authors.forename: Z
authors.initials: Z
authors.lastname: Kleinrok
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D009043:Motor Activity / Q000187:drug effects; D009161:Mycobacterium / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D013055:Spectrophotometry, Infrared; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000700:Analgesics; D014151:Anti-Anxiety Agents; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D002491:Central Nervous System Agents; D011725:Pyridines; D013844:Thiazoles