Silyl Modification of Biologically Active Compounds. 8. Trimethylsilyl Ethers of Hydroxyl-containing Thiazole Derivatives

Trimethylsilyl ethers of various hydroxyl-containing thiazole derivatives have been synthesized. The psychotropic activity (in vivo) and the cytotoxicity (in vitro on tumor cell lines HT-1080 and MG-22A) of these ethers and of their unsilylated precursors have been studied. It was discovered that the obtained compounds possess a sedative action. A moderate cytotoxic effect was detected for piperidine-containing thiazoles, displayed most strongly in relation to MG-22A cells.     

Silyl modification of biologically active compounds. 11. Synthesis,physico‐chemical and biological evaluation of N‐(trialkoxysilylalkyl)tetrahydro(iso,silaiso) quinoline derivatives

N‐(trialkoxysilylalkyl) derivatives of 1,2,3,4‐tetrahydroquinoline, 1,2,3,4‐tetrahydroisoquinoline and 4,4‐dimethyl‐4‐sila‐1,2,3,4‐tetrahydroisoquinoline were prepared and characterized by elemental analysis, ¹H, ¹³C and ²⁹Si NMR spectroscopy. In vivo psychotropic properties and in vitro cytotoxic effects of 3‐[N‐(1,2,3,4‐tetrahydroisoquinolyl)]propyltriethoxysilane methiodide and 3‐[N‐(1,2,3,4‐tetrahydroisoquinolyl)]propylsilatrane are reported. Comparative study of ²⁹Si shifts in newly synthesized compounds suggested donor–acceptor interaction between nitrogen and silicon atom, which increased electron density at Si nuclei, revealing a stronger increment of N → Si transannular bond in comparison with N → Si α‐effect. The molecular structure of 3‐[N‐(1,2,3,4‐tetrahydroisoquinolyl)]propylsilatrane features a penta‐coordinate silicon atom having CSiO₃ pattern and Si…N intramolecular interaction. Copyright © 2005 John Wiley & Sons, Ltd.     

Silyl Modification of Biologically Active Compounds. 7. Synthesis, Structure, Physicochemical and Biological Properties of Some Silicon-containing “3+1” Oxorhenium(V) Complexes

With the aim of studying the structure-physicochemical properties-biological activity relation, we have synthesized a series of organosilicon neutral oxorhenium(V) complexes with mixed ligands and we have determined their lipophilicity. X-ray diffraction has been used to establish the molecular structure of (3-triphenylsiloxypropanethiolato)(3-thiapentane-1,5-dithiolato)oxorhenium(V), (2-trimethylsiloxy- and 2-hydroxyethanethiolato)[3-(N-methyl)azapentane-1,5-dithiolato]oxorhenium(V). We have studied the neurotropic properties and acute toxicity of the synthesized complexes in vivo and their dependence on the nature of the monodentate and tridentate ligands. We have established that all the studied compounds have pronounced sedative action (they prolong the life of mice under hypoxia conditions, they are phenamine antagonists, they exhibit anticonvulsive action and prevent retrograde amnesia).     

Silyl Modification of Biologically Active Compounds. 9. Synthesis and Biological Activity of Novel 1,3-Disilabenzo[5,6]cyclohexene Derivatives

We have synthesized a series of 1,3-disilabenzo[5,6]cyclohexene derivatives starting from (o-bromomethylphenyl)dimethylchlorosilane. Based on NMR data, we have concluded that there is a transannular N Si interaction in the 3',3'-5-trimethyl-2,8-dioxa-5-aza-1-silacyclooctane-1-spiro-1'-(1',3'-disilabenzo[4',5']cyclohexene) obtained. We have studied the psychotropic activity of this compound and its iodomethylate and also 3-(3-chloropropyl)-1,1,3-trimethyl-1,3-disilabenzo[5,6]cyclohexene, and we have shown that they have a sedative effect.     

Silyl modification of biologically active compounds. 13. Synthesis,cytotoxicity and antibacterial action of N‐methyl‐N‐(2‐triorganylsiloxyethyl)‐1,2,3,4‐tetrahydro(iso)quinolinium iodides

A series of N‐methyl‐N‐(2‐triorganylsiloxyethyl)‐1,2,3,4‐tetrahydro(iso)quinolinium iodides has been synthesized via dehydrocondensation reaction of N‐(2‐hydroxyethyl)‐1,2,3,4‐tetrahydroisoquinoline, N‐(2‐hydroxyethyl)‐1,2,3,4‐tetrahydroquinoline and 4,4‐dimethyl‐N‐(2‐hydroxyethyl)‐4‐sila‐1,2,3,4‐tetrahydroisoquinoline with trialkyl(aryl)hydrosilanes and subsequent alkylation, and characterized by ¹H, ¹³C and ²⁹Si NMR and mass spectroscopy. The biological activity data exhibited a marked enhancement of inhibitory activity against tumour cell lines and almost all the test bacterial/fungal strains in comparison with their 2‐hydroxyethyl precursors. Cytotoxicity in the microgram range against HT‐1080 (human fibrosarcoma) and MG‐22A (mouse hepatoma) cancer cell lines was observed for most of compounds. Copyright © 2012 John Wiley & Sons, Ltd.