Patent GB-1123846-A (GB)
Title: Organosilicon compounds
Inventor: BELSKY IGAL
IPC: C07F7/08
Filed: 1967-05-22
Abstract: The invention comprises (i) pharmacologically active compounds of the general formula <FORM:1123846/C3/1> where (a) the phenyl group is substituted ortho-, meta- or paraby the (R1R2R3Si) group where R1, R2, R3 (same or different) are alkyl or aryl groups of 1-10 C atoms; (b) R4 and R5 (same or different) are H, saturated or unsaturated straight-chain or branched aliphatic hydrocarbon or substituted aliphatic hydrocarbon groups, or aryl or substituted aryl, or aralkyl or substituted aralkyl groups, all said hydrocarbon groups having up to 15 C atoms, or cyclohexyl, cyclopentyl or cyclohexyl groups; or R4 and R5 together with the adjoining C atom form part of a cyclohexyl, cyclopentyl or cycloheptyl group; and (c) R6 is OH, or a residue of an alcohol, ester-linked, and containing a tertiary amino group and having an alkyl, cycloalkyl, heterocyclic or condensed biheterocyclic skeleton; or a residue of ammonia, hydroxylamine, hydrazine or an N-alkyl or aryl-substituted hydrazine, or a substituted or unsubstitituted, alipathic, aromatic, or heterocyclic primary or secondary amine, or urea, thiourea, or guanidine or their substituted derivatives, all said residues being connected by C-N bonds; and (ii) intermediates in their preparation having the general formula <FORM:1123846/C3/2> where R1, R2, R3, R4 and R5 are as above, X is halogen or OH and Y is acetyl, trifluoroacetyl or benzoyl.  In the examples sodium p-trimethylsilylphenyl acetate, prepared from the acid and sodium metal (Example 1), may be treated with isopropyl chloride/Mg and acetone to yield b ,b -dimethyl-p-trimethylsilyltropic acid (Example 3).  The latter was treated with acetyl chloride to acetylate the free -OH group (Example 10) and then reacted with SOCl2 to convert it to an acid-chloride. This was treated with ammonia and the O-acetyl group removed by alkaline-hydrolysis to yield a -(p-trimethyl-silyl) - phenyl - b  - hydroxy - b ,b  - dimethyl propionamide (Example 11).  A water-soluble salt, the b -dimethylamino ethyl ester of a (p-trimethylsilyl) - phenyl - b  - hydroxy - b ,b  - dimethylpropionic acid hydrochloride, may be prepared by reacting b -dimethylaminoethyl chloride with the required acid (from Example 3). Amide derivatives incorporating allylamine, phenylethylamine, piperidine morpholine and amino-acid esters are preferred. Water-soluble salts of the aminoesters may be prepared by treatment with organic or inorganic acids such as acetic, citric, malic, lactic, hydrochloric or sulphuric aicd.ALSO:The invention comprises pharmacologically active trialkyl or triaryl silyl tropic acids and their derivatives (see Div. C3). Combinations of the novel compounds and pyridine-2-aldoxime methane sulphonate were treated for antidotal action against organo-phosphate poisoning in mice.  The specific compounds tested include b -diethylaminoethyl ester of a -(p-trimethylsilyl) phenyl-b -hydroxy-b , b -dimethylpropionic acid hydrochloride, b -diethylaminoethyl ester of a -(p-trimethylsilyl)-phenyl-b -hydroxypropionic acid hydrochloride and b -dimethylaminoethyl ester of a -(p-trimethylsilyl)-phenyl-a -1-cyclohexanolacetic acid hydrochloride.