NZ211388A - Monosilylated aminophenylethylamines and growth promoting compositions - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £11 388 21 1388 Priority Date(s): .

Complete Specification Piled: U:2>:X5 c'oss: . .C.P^7/7.~?/f(P.} felKSt/.WS;.

A2Z&X/(<<>. fublicaiion Date: P.O. j0Ufri3.\ No: l-T>& ;ni V *J ^ u>*' ii^f N.Z.No.

NEW ZEALAND 11 MAR 1985 Patents Act 1953 ,o .it^' COMPLETE SPECIFICATION "MONOS IL YLATED AMINOPHENYLETHYLAMINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION, AND THEIR USE FOR PROMOTING GROWTH" We, BAYER AKTIENGESELLSCHAFT, a Company registered under the laws of the Federal Republic of Germany, of Leverkusen, Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement : - _ i _ (followed by 1A) The present invention relates to monosi ly I ated aminophenylethylamine derivatives, a process for their preparation, and their use in animal nutrition for increasing growth and for improving the flesh/fat ratio.

The use of feed additives for achieving greater increases in growth and improved feed utilisation is already a widespread practice in animal nutrition, particularly in the fattening of pigs, cattle and poultry.

The new monosiIy lated aminophenylethylamine derivatives of the general formula (I) (I) H»N~vO)~CHRi"CHjNR,Ra in which X and Y are identical or different and represent hydrogen or halogen, p / 4 -0-Si-R5 represents the radical ^^6 R2 denotes hydrogen or a s t r a i g h t-c h a i n , branched, saturated or unsaturated alkyl radical having up to 10 C atoms, R3 denotes hydrogen or a straight-chain, branched, saturated or unsaturated alkyl radical which can be substituted by halogen, preferably chlorine and/ or fluorine, or denotes a phenyl radical which can optionally be substituted by halogen, hydroxyl, alkyl, aryl, alkoxy, alkylthio, optionally substituted phenoxy or phenylthio, cyano or trifluoro-methyl or denotes a heterocyclic radical, or, together with (?2/ denotes a nitrogen-containing 2 © saturated heterocyclic radical, such as, for example, azabieyeLononane, substituted azabicyclo-nonane, az ab i c y c I ooc t an e and the like, and R4, R5 and R^ denote a straight-chain or branched 5 alkyl radical, and their physiologically tolerated salts have been found.

The substances possess excellent growth-promoting actions and furthermore improve the flesh/fat ratio in favour of flesh.

Preferred compounds are phenyIethyI amine deriva tives of the general formula (I), in which X and Y represent chlorine, R2 denotes a saturated or unsaturated, branched 15 or straight-chain alkyl radical having up to 6 C atoms, and Rj represents hydrogen, or compounds of the formula (I), in which X and Y denote chlorine, Rg denotes hydrogen and r3 denotes either a straight-chain or branched, saturated or unsaturated Cf-C^-alkyl radical which is substituted by one or more chlorine or fluorine 25 atoms, or a phenyl radical which can optionally be substituted by haLogen, hydroxyl, C-j-C^-a I ky I , Cf-C^-a Ikoxy, C^-C-jQ-aryl or C<|-C4-a Iky l-thio or by optionally substituted phenoxy or phenyl-t h i o, and their physiologically tolerated salts.

Particularly preferred compounds are phenylethyl-amine derivatives of the formula (I), in which X and Y represent chlorine, 35 R-j represents 0 S i ( C H3 ) 2 CH ( CH j) C H (C Hj) 2 R2 represents a saturated or unsaturated, branched or straiaht chain alkyl radical having up to 6 C atoms and Rg represents Hydrogen, and their physiologically tolerated salts.

The new compounds of the formula (I) H,N-a )>-CHR,-CH,NR,R, (I) Y^ in wh i ch X and Y are identical or different and represent hydrogen or halogen. _ / 4 -0-Si-R5 represents the radical \ R6 Rg denotes hydrogen or a s t r a i g h t - c h a i n , branched, saturated or unsaturated alkyl radical having up to 10 C atoms, Rj denotes hydrogen or a straight-chain, branched, saturated or unsaturated alkyl radical which is substituted by halogen, preferably chlorine and/ or fluorine, or denotes a phenyl radical which can optionally be substituted by halogen, hydroxyl, alkyl, aryl, alkoxy, alkylthio, optionally substituted phenoxy or phenylthio, cyano or trifluoro-methyl, or denotes a heterocyclic radical or, together with R2, denotes a nitrogen-containing saturated heterocyclic radical, such as, for example, azabicycIon on ane, substituted azabicyclo-nonane, az abi c y c 100c t an e and the like, and R 4, R5 and R^ denote a s t r a i gh t-c h a in or branched alkyl radical, and their physiologically tolerated salts are obtained by a method in which compounds of the general formula (II) 7 <! ^ a (II) either as a racemate or as one of the enantiomeric forms, in which */ */ ^2 an^ ^3 have the meaning given above, 5 are reacted with suitable silylating agents of the formula (III) R4R5R6 Si-Z (III) in which Z denotes halogen, CN, -O-SO2-CF3, -0-SiR4R5R6 or -O-SC^-O-SiR^RjR^, and 4 5 6 R , R and R have the meaning given above.

The starting compounds of the formulae (II) and (III) are either known or can be prepared by known methods (see, for example, R.E. Lutz and Co-workers, J.Org.Chem. 15 12, 617-703 (1974)) .

The process according to the invention can be carried out in the presence of diluents. Suitable diluents are all inert organic solvents. These include, in particular, aliphatic and aromatic, optionally halogenated hydro 20 carbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, methyl ene chloride, ethylene chloride, chloroform, carbon tetrachloride, ch lorobenzene and o-dich Iorobenzene, ethers, such as diethyl ether and dibutyl ether, glycol dimethyl ether 25 and diglycol dimethyl eter, tetrahydrofuran and dioxane, ke tones, such as acetone, methyl ethyl ketone, methyl iso-propyl ketone and methyl isobutyl ketone, esters, such as methyl acetate and ethyl acetate, nitriles, such as, for example, acetonitrile and p rop i on i t r i I e, benzonitrile and 30 gLutarodinitri Ie, amides, such as, for example, dimethyl-formamide, dimethy I acetamide and N-methy I pyrr0 I idone, and dimethyl sulphoxide, tetramethylene sulphone and hexamethyl phosphoric acidtriamide.

The process according to the invention can be carried out in the presence of catalysts. Preferably used catalysts are: imidazole, triazole or diisopropyIethyI-5 amine.

The reaction temperature is kept between about 0°C and 130°C, preferably between about 20°C and 1oo°C. The process is preferably carried out under atmospheric pressure.

The starting compounds of the formulae II and III are employed in general in about an equimolar ratio. An excess of 10-2oo% of the compounds of the formula III is preferred.

Working-up after the reaction is complete is cai— 15 ried out in a manner which is known per se.

The following stock animals and pets may be mentioned as examples of animals for which the active compounds can be used for promoting and accelerating growth and for improving feed utilisation: warm-blooded animals, 20 such as cattle, pigs, horses, sheep, goats, cats, dogs, rabbits, fur-bearing animals, for example mink and chinchillas, poultry, for example chickens, geese, ducks, turkeys, pigeons, parrots and canaries, and cold-blooded animals, such as fish, for example carp, and reptiles, for ex-25 ample snakes.

The amounts of active compounds which are administered to the animals to achieve the desired effect can be varied substantially owing to the advantageous properties of the active compounds. It is preferably about 0.01 to 30 50, in particular 0.1 to 10, mg/kg of body weight daily. The period of administration can be from a few hours or days up to several years. The appropriate amount of active compound and the appropriate period of administration depend, in particular, on the species, age, sex, state of 35 health and nature of keeping and feeding of the animals, and can easily be determined by any expert.

The active compounds are administered to the animals by the customary methods. The nature of the administration depends, in particular, on the species, the behaviour and the state of health of the animals. Thus, administration can be effected orally or parenterally, once or several times daily at regular or irregular intervals.

The active compounds according to the invention are particularly suitable for parenteral use, and they are converted to a usable formulation with suitable, preferably non-aqueous tolerated solvents or diluents.

Suitable formulating agents are preferably physiological vegetable products, such as, for example, sesame oil, groundnut oil or maize germ oil. These oils or other synthetic triglycerides, such as, for example, Mi glycol" or My r i to I R can be thickened by suitable additives, such as, for example, hardened castor oil or Al monostea rate. By means of such combinations, the viscosity and hence the depot effect can be varied within wide limits.

Implants made of silicone or high molecular weight polyglycols or other physiologically tolerated polymers are also possible.

For reasons of expediency, oral administration, in particular in the rhythm of the intake of food and/or drink by the animals, is frequently to be preferred.

The active compounds can be administered as a mixture of pure substances or in the formulated form, that is to say mixed with non-toxic inert carriers of any kind, for example, with carriers and in formulations as are customary in the case of nutritive preparations.

The active compounds, optionally in the formulated form, can also be administered in a suitable form together with pharmaceutical active compounds, mineral salts, trace elements, vitamins, proteins, fats, colorants and/or flavouring agents.

Oral administration together with the feed and/or drinking water is recommended, the active compounds being added to the total amount or only portions of the feed and/ or drinking water as required.

In the case of oral administration, the compounds can be admixed to the feed and/or drinking water in 5 accordance with customary methods by simple mixing as pure substances, preferably in the finely divided form or in the formulated form mixed with edible nontoxic carriers, and optionally in the form of a premix or a feed concentrate.

The feed and/or drinking water can contain the ac tive compounds in a concentrations (w/w) of, for example, about 0.01 to 50 ppm, in particular 0.1 to 10 ppm. The optimum level of the concentration of the active compounds in the feed and/or drinking water depends, in particular, 15 on the amount of feed and/or drinking water taken in by the animals and can easily be determined by any expert.

In the case of parenteral administration, the optimum dose depends, in particular, on the frequency of administration, on the animal species and on the age and 20 weight of the animals.

The nature of the feed and its composition is irrelevant. All the customary or specific feed compositions, which preferably contain the customary equilibrium of energy substances and builder substances, including vita-25 mins and mineral substances, necessary for balanced nutrition, can be used. The feed can be composed, for example, of vegetable substances, for exampoLe, hay, beet, cereals and cereal by-products, animal substances, for example, meat, fats and bone meal, fish products, vitamins, 30 for example vitamin A, D complex and B complex, proteins, aminoacids, for example DL-methionine, and inorganic substances, for example lime and sodium chloride.

Feed concentrates contain the active compounds alongside edible substances, for example rye flour, maize 35 flour, soya bean flour or lime, optionally with further nutrients and builder substances, as well as proteins, ^W^STIL...

Ww - 8 - mineral salts and vitamins. They can be prepared by the customary mixing methods.

In premixes and feed concentrates, preferably, the active compounds can optionally also be protected from air, 5 light and/or moisture by suitable agents which coat its surface, for example with non-toxic waxes or gelatine.

The following is an example of the composition of a feed for rearing chicks, which contains an active compound according to the invention: 200 g of wheat, 340 g 10 of maize, 361 g of coarse soya bean meal, 60 g of beef /"> tallow, 15 g of dicalcium phosphate, 10 g of calcium car- O bonate, 4 g of iodinated sodium chloride, 7.5 g of a vitamin/mineral mixture and 2.5 g of an active compound pre-mix give, after careful mixing, 1 kg of feed. 15 One kg of feed mixture consists of: 600 I.U. of viatamin A, 100 I.U. of vitamin Dj, 10 mg of vitamin E, 1 mg of vitamin Kj, 3 mg of riboflavin, 2 mg of pyrid-oxine, 20 meg of vitamin B-jj/ 5 mg of calcium pantothenate, 30 mg of nicotinic acid, 200 mg of choline chloride, 20 200 mg of MnSO^ x ^0, 140 mg of ZnSO^ x 7^0, 100 mg of FeSO^ x 7^0 and 20 mg of CuSO^ x SHgO.

The active compound premix contains the active compounds in the desired amount, for example 10 mg, and also 1 g of Dt-methion ine as well as an amount of soya bean 25 flour such that 2.5 g of premix are formed.

The following is an example of the composition of a feed for rearing pigs, which contains the active compound according to the invention: 630 g of shredded cereal feed (composed of 200 g of maize, 150 g of shredded barley, 30 150 g of shredded oats and 130 g of shredded wheat), 80 g ^ of fish meal, 60 g of coarse soya bean meal, 60 g of tapioca meal, 38 g of brewers' yeast, 50 g of a vitamin/minera I mixture for pigs (composition, for example, as for the chick feed), 30 g of linseed cake meal, 30 g of maize glu-35 ten feed, 10 g of soya bean oil, 10 g of sugar cane molasses and 2 g of an active compound premix (composition, # - 9 - J f\ for example, as for the chick feed) give, after careful mixing, 1 kg of feed.

The feed mixtures indicated are intended preferably for rearing and fattening chicks or pigs respectively, but they can be used, in the same or a similar composition, on for rearing and fattening other animals.

Several investigations into feeding and metabolism were carried out with the active compounds according to the in ven t i on .

The foLlouing results were obtained: Example 1a a) Animal characteristics and feed a 1) Rats, female a 2) Number 15 a 3) Breed SPF Wistar, Hage- mann breed 150-200 g good a 4) Weight a 5) Condition a 6) Feed Raw nutrients * Rawprotein 19.0 Raw fat 4.0 Raw fibre 6.0 Ash 7.0 Wat er 13.5 N-free extract material 50.5 Convertible energy: Kcal/kg 3100 KJ/kg 13,000 Mineral substances * Calcium 0.9 Phosphorus 0.7 Magnesium 0.2 Sodi um 0.2 Vitamins ** Standard diet L 1 e, W o Vitamin A Vitamin D3 Vitamin E Vitamin Kj 5 Vitamin V^ Vitamin B2 Vitamin 84 Vitamin B^2 Nicotinic acid 10 Pantothenic acid Folic acid biot in choline Vitamin C 1 5 Amin oac i ds * lysine methionine + cystine phenylalanine + tyrosine a rg in in e 20 histidine t ryptophan threonine isoleucine leucine 25 valine Trace elements ** magn an ese i ron copper 30 zinc iodine fluorine * X in the diet (mean value) * * mg in 1 kg of diet (mean value) 3 5 b) Treatment of the animals The animals were accustomed for 2 days to the new ,000 I.U. 600 I.U, 75 mg 3 mg 18 mg 12 mg 9 mg 24 meg 36 mg 21 mg 2 mg 60 mg 600 mg 36 mg 0.9 0.6 1.4 1 .1 0.4 0.2 0.6 0.9 1 .3 0.9 75.0 135.0 13.0 70.0 0.9 9.0 1 5 I i J keeping conditions, the experimental feed being administered in general without added active compound. On the third day of the experiment, the animals were randomised, and the test groups were then formed so that both the mean values and the scatters in the body weights were the same from group to group. A preliminary period of 5 days was followed by a main period of 17 days, in which feed intake, additional growth and feed utilisation were determined.

The following treatments were tested: b 1) Negative control (n = 10) b 2) 25 ppm (active compound from Example 1) (n = 5) c) Result (feed intake, growth, feed utilisation) during the main period (17 days) Feed intake (g) 226 39.1 320 58.6 Add i t i on a I g rowt h (g) c 1) c 2) Negative control 25 ppm (active compound from Ex amp Ie 1) Example 1b) Feed ut i I i-s a t i on (9/9) 6.80 5.46 a) Animal characteristics and feed a 1) Rats, female a 2) Number a 3) Breed a 4) Weight a 5) Condition a 6) Feed b) Treatment of the animals SPF Wistar, Hage-mann breed 200-235 g good as in Example 1a The animals were accustomed for 2 days to the new keeping conditions, the experimental feed being administered in general without added active compound. On the third day of the experiment, the animals were randomised, 35 and the test groups were then formed so that both the mean values and the scatters in the body weights were the same o 1 5 *3 i w 88 from group to group. A preliminary period of 5 days was followed by a main period of 17 days, in which feed intake, additional growth and feed utilisation were determined.

The following treatments were tested: b 1) Negative control (n = 10) b 2) 0.2 ppm (active compound from Example 1) (n = 5) c) Result (feed intake, growth, feed utilisation) during the main period (17 days) Feed intake (9) 291 350 c 1) c 2) Add i t i on a I growth (g) 23.9 42.7 Feed utili-sat i on (g/g) 12.17 8.20 Negative c on t roI 0.25 ppm (active compound from Example 1) Preparation examples Example 1 N-C2-(4-Amino-3,5-dichloro-phenyl)-2-(1,2-dimethyl-propyl-dimethyl-silyloxy)-ethyl]-N-t-butylamine CI CI O-S CHjNHC(CH,), O-Si(CHj)aCH(CH,)CH(CH, )2 2.04 g (30 mmol) of imidazole are added to 2.77 g (10 mmol) of 1 -(4-amino-3,5-dich loro-phenyI)-2-(t-butyL-amino)-ethano I in 50 ml of absolute dimethylformamide, and 3.64 g (22 mmol) of dimethy I-isoamyl-siIyI chloride are 25 added dropwise to the stirred mixture. When the slightly exothermic reaction has died down, stirring is continued for a further hour at room temperature, after which the dimethylformamide is stripped off in vacuo, 50 ml of water is added to the syrupy residue, and the mixture is extrac-30 ted with 3 x 50 ml of toluene. The toluene extract is thoroughly washed 3 x with water, dried with magnesium sulphate and evaporated down in vacuo. The remaining pale • -n- 7 11 yellow syrup is then subjected to a high vacuum (0.01 mm Hg) for 2 hours. 4.02 g (99X of theory) of a pale yellow oil. The product is pure according to gas chromatography. Rf value: 0.76.

(TLC aluminium foil (Merck), silica gel 60 F254' mobile phase: 1:1 toluene/ethanoL) .

IR (CHCl3) cm"1 : 3495; 3403; 2961 (s); 2871 (m); 1620 (m); 1582; 1485 (s); 1414; 1399; 1366 (m); 1291; 1254 (s); 1226; 1091 (s); 10 975 (m); 925; 904; 874; 837 (s).

The following compounds were prepared as described above: Example 2 N-C2-(4-Amino-3,5-di ch loro-phenyl)-2-(1,2-dimethyl-propyl-15 dimethylsilyloxy)-ethyl3-N-isopropylamine CI O-Si(CH,)jCH(CHj)CH (CH,)2 H,N^CH-CH,NHCH (CH, ) , CI Yield: 70X of theory. Pale yellow oil. Pure according to gas chromatography.

Rf value: 0.68 20 (TLC aluminium foil (Merck), silica gel 60 F254* mobile phase: 1:1 to luene/ethan0 I).

IR (CHClj) cm"1 : 3501; 3401; 2963 (s); 2871 (s); 1620 (m); 1582 (m); 1487 (s); 1415; 1385; 1346; 1292; 1254 (s); 1177; 1081 (s); 25 971; 920; 875 (m); 837 (s).

Example 3 ^ N-C2-(4-amino-3,5-dichloro-phenyl)-2-(1,2-dimethyl-propyl- dimethylsilyloxy)-ethyl]-N-(2,2-dimethyl)-propyalmine C1 O-Si(CH,)1CH(CH,)CH(CH,)2 N I CH-CH2NHCHa-C(CH,), / CI Yield: 78X of theory. Pale yellow oil. Pure according to gas chromatography.

Rf value: 0.72 (TLC aluminium foil (Merck), silica gel 60 ^254' mobile phase: 3:1 toluene/ethanoL).

IR (CHCl3) cm"1 : 3498; 3403; 2960 (s); 2871; 2829; 2355; 1619 <m); 1585 (m); 1563; 1486 <s); 1413; 1367 Cm); 1291; 1254 (s); 1086 (a); 1010; 974; 928; 910 (m); 872; 837 (s); 728.

Exanple 4: N- (~2- (4-amino-3,5-dichloro-phenyl) — 2— (1,2-dinethyl-propyl-dimethyl-silyloxy) -ethyl] -N- (1,1 -dimethyl) -propylamin Yield: 86%t pale yellow oil, pure according to gas chromatography R^-value: 0,81 (TLC-aluminium foil (Merck) silicagel 60 ^254; mobile phase 1:1 toluene/ ethanol).

Example 5 N-C2-C4-amino-3,5-dichloro-phenyl)-2-(t-butyl-dimethyl-si lyloxy)-ethylD-N-t-butylamine C1 O-Si(CHi)2 C (CHj), CH-CHj NH-C(CH,), CI 4.16 g (15 mmol) of 1-(4-amino-3,5-dichloro-phenyI) ■ 2-butylamino)-ethanol are dissolved in 50 ml of absolute dimethylformamide, 3.06 g (45 mmol) of imidazole are added, and 4.97 g (33 mmol) of t-buty l-dimethyIsilyI chloride are added dropuise, while stirring. The mixture was stir red for 1 hour at room temperature, for 1 hour at 60°C and for 3 hours at 80°C. The solvent was then stripped off in vacuo, 50 ml of water were added to the residue, and the mixture was extracted 3 x with 50 ml of toluene. The toluene extract was once again washed 3 x with water, dried, and evaporated down in vacuo. The remaining syrup is chromatographed over 100 g of silica gel 60 (mobile phase: 1) toluene, 2) 30:1 t o I uen e / Et OH) . 5.3 g) 905! of theory) of a chromatographica I I y pure fraction are obtained in the form of a yellow oil.

Rf value: 0.65 (TLC aluminium foil (Merck), silica gel 60 F254; mobile phase: 3:1 toluene/ethano I).

Exanple 6: N- [2-(4-amino-3,5-dichloro-phenyl)—2—(1,2-dimethyl-propyl-dimethyl-silyloxy) -ethy^ -3-methyl-4- (4-trifluorrnethylmercapto-phenoxy) -anilin R^-value: 0,86; mobile phase toluene / aceticacidester 6:1 i _«. »y / . tp '16"

Claims (12)

WHAT WE CLAIM IS:

1) Monosily lated aminophenylethylamine derivatives of the general formula (I) CHRi-CHaNRjRj in which X and Y are identical or different and represent hydrogen or halogen, Rl represents the radical -O-Si-R,. R2 denotes hydrogen or a straight-cha in, branched, 1 \ saturated or unsaturated alkyl radical having up """ to 10 C atoms, Rj denotes hydrogen or a straight-cha in, branched, saturated or unsaturated alkyl radical which can be substituted by halogen, preferably chlorine and/ or fluorine, or denotes a phenyL radical which can optionally be substituted by halogen, hydroxyl, alkyl, aryl, alkoxy, alkylthio, optionally substituted phenoxy or phenylthio, cyano or trifluoro- methyl or denotes a heterocyclic radical, or, to-and the N atom to which they are attached gether with Rgl, denotes a nitrogen-containing saturated heterocyclic radical, and R4, R5 and R$ denote a straight-chain or branched alkyl radical, and their physiologically tolerated salts.

2) Monosi I yI ated aminophenylethylamine derivatives according to Claim 1, in which X and Y represent chlorine, R? denotes a saturated or unsaturated, branchfjd. l) c or st r a i gh t-c h a i n alkyl radical having u|> '6 Co^ o\ r ~ »ORJS •A C atoms, and R3 represents hydrogen, ' and their physiologically tolerated salts.

3) HonosilyI ated aminophenylethylamine derivatives according to Claim 1, in which X and Y denote chlorine, Rj denotes hydrogen and R3 denotes either a straight-chain or branched, saturated or unsaturated C-j-C^~alkyl radical which is substituted by one or more chlorine or fluorine atoms, or a phenyl radical which can optionally be substituted by halogen, hydroxyl, C^-C^-alkyl, C1 -C^-a I koxy, C6-C-jg-aryl or C-j-C^-alkyl-thio or by optionally substituted phenoxy or phenyl-t h i 0, and their physiologically tolerated salts.

4) Monosilylated aminophenylethylamine derivatives according to Claim 1, in which X and Y represent chLorine, Rg represents hydrogen and R3 represents a phenoxyphenyI or phenyIthiophenyL group which is substituted by one or more CF3S, CF3SO2/ C^-C^-alkyl, halogen or phenyl radicals, and their physiologically tolerated salts.

5) Process for the preparation of monosi I yI ated aminophenylethylamine derivatives of the formula (I) X HjN -OH -CHR,-CHjNRIRJ (I) in which X and Y are identical or different and represent •J ' < ' - 13 - vU" " hydrogen or halogen, i R4 Ri represents the radical ^ *6 5 R2 denotes hydrogen or a straight-chain, branched, saturated or unsaturated alkyl radical having up to 10 C atoms, Rj denotes hydrogen or a straight-cha 1n, branched, saturated or unsaturated alkyl radical which can 10 be substituted by halogen, preferably chlorine and/ or fluorine, or denotes a phenyl radical which can \yi **7 optionally be substituted by halogen, hydroxyl, alkyl, aryl, alkoxy, alkylthio, optionally substituted phenoxy or phenylthio, cyano or trifluoro-15 methyl or denotes a heterocyclic radical, or, to gether with R gP ^fen 0^ s* a1 rn f Fog^Vn"- cV?r?a^f^i ,^|tached saturated heterocyclic radical, and R^, Rj and denote a straight-chain or branched alkyl radical, 20 characterised in that compounds of the formula (II) x V-^ ?H OH (II) CH^-NR R_ 2 2 3 in which X, Y and R2 and R3 have the meaning given above, either as a racemate or in one of the enantiomeric forms, 25 are reacted with suitable silylating agents of the formula (III) R4R5r6 si~z (III) in which Z denotes halogen, CN, -0-S02~CF3, -O-SiR^RjR^ 30 or -0-S02~0-SiR^RjR^, and R^, R^ and R^ have the meaning given above. Sp/

6) Use of monosilylated aminophenylethylamine deriva- 1 >.o Jfr tives of the formula I according to Claim 1 and their phy siologically tolerated salts as growth promoters for animals.

7) Use of monosilylated aminophenylethylamine deriva tives of the general formula (I) according to Claim 1, in amounts of 0.01 to 50 mg per kg of body weight, as growth promoters for animals. one or more

8) Animal feed containing|monosilylated aminophenylethylamine derivative of the general formula (I) according to Claim 1. i one or more

9) Growth-promoting agent for animals containing! monosilylated aminophenylethylamine derivative of the general formula (I) according to Claim 1.

10) Process for the preparation of growth-promoting animal feed, characterised in that j~m'oneo§^ l"5^fted amin o-phenylethylamine derivative of the general formula (I) according to Claim 1 are added to the animal feed.

11) A compound according to claim 1 substantially as herein described or exemplified.

12) A process according to claim 5 substantially as herein described or exemplified. BAYER AKTIENGESELLSCHAFT By Their Attorneys HENRY HUGHES,LIMITED