Synthesis and neurotropic activity of silyl propargyl alcohols and sulfides

New silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols were synthesized using phase-transfer catalytic and organometallic methods. These compounds were tested for acute toxicity and neurotropic activity in the pentylenetetrazole test, and for phenamine hypothermia, phenamine hyperactivity and passive avoidance response tests. We have found that the silyl propargyl alcohols and sulfides are low toxicity compounds, the LD₅₀ being 700-1300 mg kg^-1. In the PAR test, the synthesized compounds exerted some memory-improving activity. For di-1-(3-methyl-3-hydroxybutyn-1-yl)methyl(3-iodopropyl)silane (16) the effect was statistically significant and amounted to 250% of the control level. In the pentylenetetrazole test, all compounds possessed anticonvulsant activity, the most active compounds being 3-(benzoxazolylthio)-1-propynyl(trimethyl)silane (6) and di-[2- (1-hydroxycyclohexyl)ethynyl]methyl(3-iodopropyl)silane (17). The phenamine-induced hyperactivity was significantly elevated after treatment with (3-trimethylsilyl-2-propynyl)thiobenzene (1) or di-[1-(3-methyl-3-hydroxybutyn-1-yl)diphenylsilane (12). Our data show that these silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols possess certain memory improving and anticonvulsant activity that should be studied in detail to evaluate the receptor systems involved.