Synthesis and preliminary screening of derivatives of 2-(4-arylpiperazin-1-ylalkyl)-3-oxoisothiazolo[5,4-b]pyridines as CNS and antimycobacterial agents

We have synthesized several new isothiazolopyridines possessing a side chai n at the isothiazole ring typical, among others. for trazodone or NAN-195, Representatives of the novel isothiazolopyridines were examined for acute t oxicity and in several commonly used CNS tests in mice and for arterial blo od pressure in mts. Three of the live compounds tested showed significant a nalgesic 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) afte r administration i.p. to mice. Additionally, the compounds described here a nd related isothiazolopyridines obtained previously were evaluated against Mycobacterium tubericulosis H(37)Rv at 12.5 mu g/ml in in vitro assays. Sev en of the nineteen compounds tested showed 100% inhibition of that mycobact erium.