Silyl Modification of Biologically Active Compounds. 10. Lipid Type Organosilicon Derivatives of 8-Hydroxyquinoline and N-(2-Hydroxyethyl)-1,2,3,4-tetrahydro(sila, iso)quinolines

Abstract

As a result of numerous investigations [1][2][3][4][5][6][7][8][9][10] it has been shown that silylation significantly increases the lipophilicity of biologically active compounds and therefore assists their transport within the organism. This is true not only in relation to reversibly silylated (hydrolytically unstable) compounds but also to compounds containing a triorganosilyl(oxy) group stable to hydrolysis under physiological conditions. According to literature data certain tetrahydro(iso)quinoline-containing ligands reveal affinity towards serotonin (5-HT 1A ) [11,12], dopamine [13], and N-methyl-D-aspartate (NMDA) [14] receptors, and certain opiate alkaloids contain hydrogenated residues of quinoline and isoquinoline [15]. In addition it was noted that on silylation of both aliphatic and heterocyclic amino alcohols, and also their salts, which are structural analogs of the neuromediators choline and colamine (2-aminoethanol), psychotropic activity is increased [16,17], and the acute toxicity of the synthesized compounds is reduced [18].With the aim of improving the pharmacological properties of biologically active molecules in vivo we propose to extend this principle to organosilicon derivatives of N-heterocyclic amino alcohols, simultaneously pursuing the aim of constructing lipid type bipolar compounds, consisting of derivatives of hydroxyquinoline or tetrahydroquinoline, tetrahydroisoquinoline, and tetrahydrosilaisoquinoline as hydrophilic "heads", and lipophilic trimethylsilylpropoxyethyl "tails".We have developed a method of obtaining 8-(3-trimethylsilylpropoxy)quinoline 1 by the interaction of 8-hydroxyquinoline with (3-chloropropyl)trimethylsilane under phase-transfer catalysis conditions [19].

Synthesis and characterization of nanoparticles with an iron oxide magnetic core and a biologically active trialkylsilylated aliphatic alkanolamine shell

“…To overcome the problem of colloid system stability the parent alkanolamine has been modified by introduction of organosilicon substituent and by preparing of salt of silyl modified substance. Introduction of organosilicon substituent into the molecule of alkanolamine is an attractive and original approach to the lipophilicity increase [12][13][14][15] interaction with lipophilic chains of the first coating. The transformation of the compounds into salts in many cases causes activity increase, but also changes (increases) the solubility of the compounds in water, that is very significant for preparing and stabilization of water bilayer colloid systems, used for biological purposes.…”

Unusual reaction of N-(2-methoxyethyl)-1,2,3,4-tetrahydroisoquinoline with ethyl acetate in the presence of silica gel

“…The separation of the products of the alkylation reaction of N-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline (1) on silica gel using ethyl acetate gave the N-(2-acetoxyethyl)-1,2,3,4-tetrahydroisoquinoline (3) [3].…”

“…The N-(2-hydroxyethyl)-1,2,3,4-tetrahydroquinoline (4) [3] is similarly acetylated to give the acetate 5. Unexpectedly, we found that the methyl ether of the N-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline 2 [4] was also converted to the acetate 3 in 25% yield.…”

“…The silicon-containing ethers of N-[2-(3'-dimethylheptylsilylpropoxy)ethyl]-1,2,3,4-tetrahydroisoquinoline (7) [3] and N-[2-(3'-dimethylheptylsilylpropoxy)ethyl]-1,2,3,4-tetrahydroquinoline (8) [3] also do not react with ethyl acetate.…”