THERAPEUTICALLY USEFUL TETRALIN DERIVATIVES III, PROCESSES FOR PREPARATION AND PHARMACEUTICAL PREPARATIONS FOR SUCH COMPOUNDS

Abstract: Compounds of the formula <IMAGE> wherein Y is OH, R<4>COO, (R<5>)2NCOO or R<6>O, whereby R<4> is an alkyl group having 1-5 carbon atoms or a possibly substituted phenyl group, R<5> is an alkyl group having 1-5 carbon atoms and R<6> is an allyl or benzyl group, R<1> is an alkyl group having 1-3 carbon atoms, R<2> is an alkyl group having 1-6 carbon atoms, and R<3> is an alkyl group having 1-3 carbon atoms, processes and intermediates for their preparation, pharmaceutical preparations and methods of treatment employing such compounds. The compounds are useful for therapeutic purposes, especially for treatment of disorders in the central nervous system.

Description: THERAPEUTICALLY USEFUL TETRALIN DERIVATIVES III, PROCESSES FOR PREPARATION AND PHARMACEUTICAL PREPARATIONS FOR SUCH COMPOUNDS. DESCRIPTION Technical Field The present invention is related to new 1 ,2,3 , -tetra-hydro-2- -naphtylamines, to processes for preparing such compounds, pharm¬ aceutical preparation of such compounds and the use of such com¬ pounds in therapy. An object of the invention is to provide compounds for therapeutic use, especially compounds having a therapeutic activity in the cen¬ tral nervous system. Background Art Compounds of the formula wherein Y M and R !V are H, Y ! is CH 0, R ! and R M are H or CH, and R'-' is either CH, or phenyl have been described in Chem. Pharm. Bull., 2_0_, 1321 (1972) and Chemical Abstracts 81 : 12G--417K, respectively Further, a compound wherein R , R 1 ' and R are H, Y and Y are CH,0 and R is phenyl has been described in Chem. Pharm. Bull.,_2J_, ^39 (1973). The above mentioned compounds possess analgesic activity. In J. Pharm. Sci., _6θ_, 201 (1971) and J. Med. Chem. k_, 60 (1971) com ¬ pounds wherein Y 1 is H or CH^O, Y 11 is H, R 1 and R N are H or CH3, R N i is CH, or benzyl and R is CH, have been described as compounds posse ing analgesic activity. W.H. Shelver (Thesis, 1962; Diss. Abstr. 25_, Ikkk (1965); CA 63 : 1^90 describes compounds of the formul_a wherein R I"f ' is C00H, C00CH > COCH,, COC^H CH 2 0H and CH j OCOCgHς. The •compounds have been tested for analgesic activity. German Patent 2,752,659 describes ϊ.a. compounds of the formula wherein Y 1 is 5"0H, 6-0H and 7-0H, R 1 is H, CH,, π-C,H-,, i-C,H-- or benzyl and R' ' Is H, CH, or C,H--. The compounds are stated to have stimulating effects on α- and β-adrenoreceptors as well as on dopamine receptors. In Biomed. Mass Spectrom., 8_, 90 (l98l) U. Hacksεl 1 et al. presents mass fragmentation analyses of several 2-aninotetral ins , i.a. a com¬ pound of the formula Disclosure of Invention According to the present invention it has been found that novel com ¬ pounds of the formula wherein Y is OH, R^COO, (R 5 ) 2 NC00 or R 6 0, whereby R^ is an alkyl group having 1-5 carbon atoms or a possibly substituted phenyl 5 . ~ 6 group, R is an alkyl group having 1-5 carbon atoms and R is an allyl or benzyl group, R is an alkyl group having 1-3 carbon 2 3 atoms, R is an alkyl group having 1-6 carbon atoms, and R is an alkyl group having 1 -3 carbon atoms, as bases and pharmaceutically acceptable acid addition salts thereof, possess unexpected pharm¬ acological properties rendering them useful in therapy and full- fill ing the objects stated above. Processes for preparation of such compounds, their pharmaceutical and medical use and pharmaceu¬ tical preparations and methods of treatment employing such compounds constitute further aspects of the invention. The alkyl groups may be straight alkyl groups or branched alkyl groups A possibly substituted phenyl group R may be a phenyl , 2,6-dϊmethyl- phenyl or 3~ or -^-hydroxyphenyl group or a 3~ or h-a1 kanoyloxypnenyl group with the formula wherein R is an alkyl group having 1-6 carbon atoms. Symbols for numbers, atoms or groups referred to belov.- have the broade meaning previously assigned unless specified otherwise. Both organic and inorganic acids can bε employed to form non-toxic pharmaceu ically acceptable acid addition salts of the compounds of th invention. Illustrative acids a re sulfuric, nitric, phosphoric, hydro ¬ chloric, citric, acetic, lactic, tartaric, pamoic, ethanedi sul fon ic, sulfamic, succinic, cyclohexy1 sul faπi c, fumaric, maleic and bεnzoic acid. These salts are readily prepared by methods known in the art. In a restricted embodiment the invention is related to compounds of th formula I above wherein Y is OH, is a possibly substituted phenyl group, R is CH, and R is an allyl 1 2 3 group, and R , R and R are as specified above. In a further restricte embodiment the invention is related to compounds of the formula I above k 6 k wherein Y is OH, R COO and R 0, whereby R is a possibly substituted 6 "" 1 9 * *? phenyl group and R is an allyl group, and R , R and R are as specifi above. In a still further restricted embodiment the -invention is relate k 5 to compounds of the formula I above wherein Y is OH, R COO, (R ) NC00 and R 60 wh ' ere"in R h is methyl, phenyl, or ***-alkanoyloxyphenyl wher in th alkyl group has 1- carbon atoms, R is methyl, R is ally], R is alky 2 3 having 1~3 carbon atoms, R is alkyl having 3~6 carbon atoms, and R js methyl or ethyl . Preferred among the compounds of the formula 1 wherein y represents R C aarree tthhoossee wwhheerreeiinn RR iiss aa group wherein the alkyl group (R ) has k-6 carbon atoms. According to a preferred embodiment the invention is related to compoun of the formula 1 wherein R is n-C,H 7 . Preferred compounds are those wherein R 1 is n-C,H 7 , R2 is an alkyl grou containing 3~6 carbon atoms and R 3 is CH or C ? H . Further preferred ar compounds wherein R 1 is n-C,H-., R2 is an alkyl group with 3~5 carbon at Examples of compounds of the formula I according to the invention ace g in the fol lowing Table. v/ D1 D *- α-> OH CH 3 n-C 3 H y CH 3 OH „-C 3 H 7 n- C 3 H 7 CH OH n-C 3 H_ i -C 3 H 7 CH OH n-C 3 H -CH 2 CH (CH 3 ) 2 CH OH n-C 3 H n-C 3 H C 2 H 5 OH n-C 3 H 7 n-C 3 H " ; C 3 H 7 0CH 2 CH=CH 2 n-C 3 H_ 00CM(CH 3 ) 2 n-C3H mm r the heterocyclic ring moiety. The therapeutic properties of the com¬ pounds may to a greater or lesser degree be ascribed to either or bot of the two enantiomers occurring. Thus the pure enantio ers as well as mixtures thereof are within the scope of the invention. Preferred among the two pure enantiomeric forms is that form which ha the same absolute configuration (at the nitrogen - carrying 2-carbon atom) as the levorotameric (-)-5-hydroxy-2-mεthyl-2-(di-n-propylamino) tetral n. The invention takes into consideration that compounds which structurall deviates from the formula I, after administration to a living organis may be transformed to a compound of the formula I and in this structur form exert their effects. This consideration is a further aspect of th invention. Likewise, certain compounds of formula I may be metabolize into other compounds of formula I before exerting their effect. Compou of the invention wherein Y is R 4 C00, ( R 5 ) yAC00 or R 6 0 are thus believe to exert their main activity after metabolism to compounds wherein Y i Methods of Preparation The compounds of the invention may be obtained by one of the following methods constituting a further aspect of the invention. An ether or ester of the formula with RO in position 5 and wherein R represents a hydrocarbon or acyl residue, preferably an* alkyl group having 1-5 carbon atoms or a benzyl group, or an alkylcarbonyl grouo having 2-6 carbon atoms, and 1 1 22 33 RR ,, RR aanndd RR aarree aass ddeeffiinneedd aabboovvee,, mmaayy bbe cleaved to form a compound of formula I wherein Y is a hydroxy group When R is a hydrocarbon residue the cleavage may be carried out by treating the compound of formula II with an acidic nucleophilic reageni such as aqueous HBr, or HI, HBr/CH,00H, 33r,, A1C , pyridine-HCl or .(CH,), Si I, or with a basic nucleophilϊc reayent such as CH C.H, -S θ or C^Hς-S ^ . When R is a benzyl group the cleavage may also be carried out by reduction, preferably with hydrogen using Pd or PtO, as catalyst. When R is an acyl residue the cleavage may be carried out by hydrolysis in an aqueous acid or base or by reduction, preferably by LϊAlH, . The compound of formula II is obtainable by the following synthetic route 1 . RYCOC l , base 2. L ϊAl H,. Thus, a compound of formula I IA is methyl carboxyl ated by reaction wit methyl carbonate in the presence of NaH giving the keto-ester MB, whi is C-alkylated by R J X (X=Br, l) in the presence of a base such as NaO followed by hydrogenolysi s of the keto function and hydrolysis of the ester function giving the caboxylϊc acid I IC. Reaction of compound I IC with CICOOC ^ H-. in the presence of tr iethyl ami ne fo-1 lowed by convertion to an azide by NaN and Curtius-rearrangemeπt and acid hydrolysis to a a ino-containing compound II D, N-acylation by R C0C1 (wherein R is x 1 defined by the relation R -CH j -equa s R ) in the presence of a base, LiAlH.-reduction, once again N-acylation by R y C0Cl (wherein R y is defined by the relation R y -Cl- -equals R z ) in the presence of a base and finally tiA ii * -redaction give a compound of the formula II. A pure enantiomer of compound II may be prepared by first conversion of II E into the (-)-O-methylmandelic acid amide II F followed by chro atographic separation of the two diastereomers and cleavage by subsequent reaction with potassium tert-butoxide in tetrahydrofuran with traces of water and CH^Li , and then the desired of the two enan¬ tiomers (II E 'and E") is alkylated. A compound of formula 1 2 3 wherein R , R and R a re as defined above may be converted into a com- 5 6 pound of formula I wherein Y is R COO, (R )„NC00 or R 0 by treating the. first mentioned compound with an appropriate carboxyl ic acid hal ide R CO or anhydride (R Cθ)_0 or with an appropriate carbaπoyl hal ide (R COX in the presence of a base such as triethylamine or pyridine or an acid such as H„S0, or CF,C00H or with an appropriate allyl or benzyl hal ide R X in the presence of a base such as triethylamϊne , pyridine or potassi t-butoxide. X represents a halogen, preferably Cl or Br. h k Alternatively, when conversion of Y = OH into R COO is intended and R is R COOC^H, - a compound of formula I wherein Y is OH may first be con ¬ verted to a compound of formula I wherein Y is HOC,H, COO- which is then treated with an appropriate carboxyl ic acid hal ide R COX or anhydride (R CO O in the presence of a base or an acid. c) A compound of the formu l a wherei e as defined above, may be converted into a compound of formula 1 by alkyla ' tion of the nitroge atom with an appropriate alkylating agent. Thus, , the starting compound wherein R a is R may be treated with an alkyl halide or tosylate R X , wherein X represents C1 , Br, I or -0S0 2 -C^H^CH in an organic solvent such as acetonitrile or acetone and in the presence of a base such as Wmf-O or NaOH, or said starting compound may be treated with a carboxylic acid NaBH, complex R b C00H-NaBH, , wherein R is defined by the relation R b -CH equals R 2 . To the formation of a compound of formula 1 wherein at least one of R 2 and R is CH,, the alkylation reaction may be carried out by treatment of the compβund of formula IV with a formaldehyde - Na(CN)3H mixture, or with formaldehyde and formic acid. d) An amide of the formula wherein Y is OH or R 0, and R is as defined above, R C is an alkyl group defined by the relation R C -CH - equals either R or R and R is the other 1 2 of R and R , may be reduced, e.g. by treatment with a hydride reducing agent such as LϊAlH, in ether or tetrahydrofuran or BH_ in tetrahydro- furan, to the formation of a compound of formula I. e) A compound of the formula 1 2 wherein M and M are the same or different and each represents -CH,,-, H-Z 1 or or -Cξ? R z when M 1 and M 2 are -CH 2 ~ an in other s a group sensitive to hydrogenolys is su as hydroxy in benzyl ic position (M' or M ) or halogen, R is hydrogen, methyl or ethyl , Y is other than allyloxy and R , R and R 3 are as de above may be converted to a compound of formula I by reduction. Thus, keto function may be either directly converted to CH„ by treatment wit e.g. hydrazine under alkal ine conditions or by a stepwise reduction by using e.g. catalytic hydrogenatϊon which may involve an intermediary formation of an hydroxy group and,where possible,also an el imination t a double bond. Reduction of a group ^CH-Z' may be carried out by using a nucleophilic hydride reducing agent such as LϊAlH. , or catalytic hyd genat ion. f) An azir ormula 1 2 wherein Y is other than allyloxy and R and R are as defined above may be converted by reduction, preferably by catalytic hydrogenat ion , into a compound of the formula I wherein R is CH,. g) In a compound of the formula wherein X represents S0-.H, Cl or NH„ , a hydroxy group may be substitut for the group X to the formation of a compound of formula I wherein Y represents a hydroxy group. When X is SO H or Cl said reaction may be carried out by treatment with a strong alkal i under heating, suitably with an alkali melt such as KOH when X is S0,H, and with a strong aque alkali such as NaOH or KOH when X is Cl . When X is NH„ the reaction ma be carried out by treatment with aqueous nitrous acid to the formation of an intermediate diazoπϊum compound which is then subjected to hydro lysis in water. A racemic mixture or a mixture partly enriched on one of the enantiomers of a compound of formula may be subjected to enantiomeric separation to obtain a pure enantio er of compound I. This may be done by methods known in the art. These methods include recrystallization of diastereomeric saltswith pure enantiomers of acids such as tartaric acid, 0,0- -dibenzoyltartaric acid, mandelic acid and camphor-10-sulphonic acid. Free bases formed may subsequently be converted into their acid additio salts, and acid addition salts formed may subsequently be converted int the corresponding bases or other acid addition salts. Pharmaceutical Preparations Pharmaceutical preparations of the compounds of the invention constitut a further aspect of the invention. In clinical practice the compounds of the present invention will normal be administered orally, rectal ly, or by injection, in the form of pharm aceutical preparations comprising the active ingredient either as a fre base or as a pharmaceutically acceptable non-toxic, acid addition salt, e.g. the hydrochloride, lactate, acetate, sulfa ate, and the like, in ' association with a pharmaceutically acceptable carrier. Accordingly, terms relating to the novel compounds of this invention, whether geπerically or specifically, are intended to include both the free amlne base and the acid addition salts of the free base, unless the context in which such terms are used, e.g. in the specific examples, would be inconsistent with the broad concept. The carrier may be a solid semlsolid or liquid diluent or capsule. These pharmaceutical preparation constitute a further aspect of this invention. Usually the active sub¬ stance will constitute between 0.1 and 99% by weight of the preparation, more specifically between 0.5 and 20? by weight for preparation intended for injection and between 0.2 and 5% by weight for preparations sui tabl ' ^ ^- Pharmaceutical preparations containing a compound of the invention in a solid form of dosage units for oral appl ication may preferably contain between 2 and 95% by weight of the active substance, in such preparations the selected compound may be mixed with a solid fine grain carrier, e.g. lactose, saccharose, sorbitol, mannitol*, starches such as potato starch, corn starch or amylopect in, cellulose derivatives, or gelatin and a lubricant such as magnesium stearate, calcium stearate, polyethylene glycol waxes, and the like, and then compressed to form tablets. If coated tablets are required, the cores, prepared as described above, may be coated with a concentrated sugar solution which may contain, e.g. gum arabic, gelatin, talcum, titanium dioxide, and the like. Alternatively the tablet can be coated with a lacquer dissolved in a readily volatile organic sol¬ vent or mixture of organic solvents. Dyestuffs may be added to these coatin in order to readily distinguish between tablets containing different active substances or different amounts of the active compound. For the preparation of soft gelatin capsules (pearl-shaped closed capsules) consisting of gelatin and, for example, glycerol , or similar closed cap¬ sules, the active substance may be admixed with a vegetable oil. Hard gelatin capsules may contain granulates of the active substance in combination with solid, fine grain carriers such as lactose, saccharose, sorbitol, mannitol, starches (e.g. potato starch, corn starch or amylo- pectin), cellulose derivatives or gelatin. Liquid preparations for oral appl ication may be in the form of syrups or suspensions, for example, solutions containing from about 0.2% to about 20% by weight of the active substance herein described, the balance being sugar and a mixture of ethanol , water, glycerol and propylene- glycol. Optionally such liquid preparations may contain colouring agents, flavouring agents, saccharine and carboxymethyl eel 1ulose as a thickening agent. Solutions for parenteral appl ications by injection can be prepared in a aqueous solution of a water-soluble pharmaceutically acceptable salt of the active substance preferably in a concentration of from about 0.5% to about 10% by weight. These solutions may also contain stabil izing agents and/or buffering agents and may conveniently be provided in various dosage unit ampoules. In therapeutical treatment the suitable daily doses of the compounds of the invention are " 100-5000 mg for oral application, preferen ially 500-3000 mg, and 0.5-500 mg for parenteral appl icat ion , ' preferen 25-250 mg. Working examples The following examples will further illustrate the invention. f.utEi!I§!:l2D_2f_iD!:S-!*I?S-5il-;S s Example- 11 (±)-5~Methoxy-2-methyl-2-(di-n-propylamϊπo) tetral in 5-Hethoxy-2-methyl tetral ϊn-2-carboxyl ic acid A solution of methyl 5~methoxy-l-oxotetral in-2-carboxylate (25 g» 100 πmol) in dry EtOH (125 mL) was slowly added to a freshly prepared mixture of 80% NaH (3-3 g, 110 mmol), dry benzene (125 L) , and dry EtOH (125 mL) . The resulting slurry was refluxed for 20 h under After cooling, three 10 mL portions of methyl iodide (68.4 g, 5 mmol) was added. The reaction mixture was refluxed for 1 h, whereafter It was neutralized with acetic acid. The volatiles were evaporated in vacuo and the residue was first passed through a short alumina column wi h ether as eluant and then chromatographed on a silica column with ether- — light petroleum (1:2) as eluant affording 2k g of methyl 5-methoxy- -2-methyl-1-σ"xotetral ϊn-2-carboxylate as an oil. The oil was dissolved in acetic acid (500 L) , perchloric acid (l L) was added and the result¬ ing solution was hydrogenated at atmospheric pressure over Pd/C (5 g) . After 2 h the reaction was complete, the catalyst was filtered (Celite) and CHC1, (1000 L) was added. Washing the organic layer several times with 100 L portions of H_0 followed by evaporation of the CHCl, in vacuo gave on oil which was refluxed for k h with HeOH (100 mL) , H 2 0 (125 L) and KOH pellets (50 g) - The HeOH was evaporated in vacuo, and the product was precipitated by addition of ice-cold 10% HCl to the resulting solution. Two recrystal 1 isations from EtOH-H-O gave 9-6 g {hk%) of pure 5-methoxy- -2-methyl tetral ϊn-2-carboxyl ic acid , mp 138-149 C. (-)-2-Aπrino-5-methoxy-2-nethyltetral n This compound was prepared from 5-methoxy-2-methyl tetra1 In-2-carboxyl ic acid (8.75 g > 38 mmol) according to the method used by Nichols et al . (J. Med. Chem. 2Λ_, 395 (1978) for the preparation of 2,3-dimethoxy-9~ amIno-9, 10-dϊhydrophenantrene from 2,3-dimethoxy-9. 10-dfhydrophenantrene- -9~carboxyl ic acid. The a iπe was converted to the hydrochloride and recrystal 1 ized twice from EtOH-ether. Yield 5-8 g (76%), mp 249.5 - 251-5 (decomp.) ( ±)-5-Methoxy-2-.τιethy1 -2- (τι-rpropyl ami no) tetral i n Propionyl chloride (4.6 g, 9 mmol) in dry ether (60 mL) was added to a solution of 2-amino-5~methoxy-2-rnethyl tetral in (6.3 g, 33 mmol) and triethylamine (4.9 g, 9 mmol) in dry ether (750 L) . After 30 min at room temperature the reaction mixture was filtered and the ether -was evaporated. The resulting crude amide was passed through an alumina column eluted with- ether. The purified amide dissolved in dry THF (100 L) was added to a suspension of LiAlH, (7-2 g, 187 mmol) in dry THF (200 mL) under N«. After stirring under reflux for 3 h, the reaction mixture was hydrolyzed, the precipitate was filtered off and the solvent was evapor¬ ated. The oily residue was chromatographed on an alumina column with ether-light petroleum (1:1) as eluant yielding 6.4 g (83%) of pure 5-methoxy-2-methyl-2~ * (n-propylamino)tetral in. The base was converted to its hydrochloride, mp 239 - 239-5 C (decomp.) (from EtOH-ether). (±)-5-Methoxy-2-methyl-2-(d?-n-propylamino) tetral in A mixture of 5~methoxy-2-methyl-2-(n-propylamino) tetral in (4.5 g, 19 mmol), propionyl chloride (2.7 g, 29 mmol), triethylamine (2.9 g, 29 mmol), and benzene (150 mL) was stirred at room temperature for 10 h. The precipitate was filtered off,the solvent was evaporated In vacuo, and the resulting crystal Is were rinsed with ether. The resulting pure amide (3.8 g) was heated with LiAlH, (1.5 g, 39 mmol) and dioxane (100 mL) at 80 C until TLC indicated that the reaction was complete (19 h) . Destruction of the reaction mixture followed by addition of water and 15% NaOH, filtration of the precipitate, and evaporation of the volatiles gave an oil. This was passed through an alumina column eluted with ether affording 3-6 g (68%) of pure 5-mεthoxy-2-methyl-2-(di-n-propylamino) etral in The base was converted into the hydrochlorIde, mp 1 5 _ 1 5-5 C (from EtOH-ether) . Example I 2 (+)- and (-) -5-Methoxy-2-methyl -2(di-n-propylamino) tetral in (+)-5-Methoxy-2-methy1-2-(d?-n-propyIamino) tetral in. R-(-)-0-Methylmandel ic acid chloride (6,0 g, 0.033 mol), prepared from R-(-) -O-methylmandel ic acid by treatment with thionyl chloride at 20 C for 10 hours, dissolved in CH_C1„ (5 ml) was added at room temperature to a stirred mixture of (-) -5 _ methoxy-2-methyl -2-(n-proρylamino) tetral in (7-0 g, 0.026 mol), CH 2 C1 2 (50 ml), H £ 0 (50 ml) and 5% aqueous NaOH (80 ml). After stirring for 15 h the phases were separated and the organic phase was washed once with.water then dried (Na„S0, ) , filtered and evaporated. Ether/light petroleum (1:3) (15 ml) was added to the residue. The mixtur was cooled to about -70 C and one of the diastereomeric amide ' s precipita (0.9 g) . The filtrate was evaporated and the oily residue was chro ato- graphed on a S10. (40.63 um) column with ether/light petroleum (1:3) as eluant. The diastereomer which was first eluated (0.7 g) showed to be the opposite to the diastereomeric amide which first came out as crystal from the mixture. The diastereomer which was secondly eluated (0.5 g) showed to be the same as the diastereomeric amide which first crystalliz The crystals (see above) and the diastereomer which was secondly eluated (0.9 + 0.5 g;totally: 1.4 g) were stereochemical ly pure according to HPLC. This diastereomeric a ide (1.4 g, 0.0037 mol) was dissolved in THF (50 ml) and kept at -15 C. Potassium tert-butoxide (4.0 g) was added and the mixture was kept at this temperature and under stirring for 5 hours. Ehter and H„0 were added and the phases were separated. The ether phase was extracted with 10% HCl, dried (Na„S0,) and evaporated giving an oil which was dissolved in day THF (20 ml) and stirred with 1.6 M solution of CH Li in ether (5 ml) for 30 minutes at -15 C and then extracted with 10% HCl. The aqueous phase was combined with the 10% HCl-extract of above, alkalized with Na CO , extracted with ether. The ether phase was treated with HCl in ether, yielding a precipitate which was recrystal 1 ized from ethanol/ether giving colorless crystals of (+) _ 5 _ methoxy-2-(n-propylamino) tetral in hydrochloride (0.75 g,2,8mmol) , mp 218-222 °C,[«3 21 = + 19.6° (c 0.2 ,MeOH) . Propionylchloride (θ,20g , 2.1 mmol) in CH„C1 2 (10 ml) was slowly added to a solution of (÷)-5~methoxy-2-mεthyl-2-(n-proρylamfno) tetral in (0,25g,l,1 mmol) in CH_C1_ (10 ml) and triethylamine (2 ml).The mixture was stirred at room temperature for 1 h , ater was added and the organic layer was separated,dried (Na.SO.) and the solvent was evaporated.The residue (0,25 g) in ether (25 ml) was added to a stirred suspension of LiAlHi (0,25 g) in ether (25 ml) and the mixture was refluxed for 1 h. Usual workup afforded the base as an oil,which was converted to the hydrochloride with ethereal HCl,giving (+)-5-methoxy-2-methyl-2- (n-propylamino) tetral in hydrochloride (0,20 g) . (-) -5-Methoxy-2-methy 1 -2- ( i -n-propyl am i no) et ra l i n The first fractions from the separation of the diastereomeric R-(-)-Q-metylmandelamϊdes on SiO with ether/light petroleum (1:3) as eluant (see above) containing the other diastereomeric amide, were combined and evaporated.The oily residue (0,7 g,1.8 mmol) was treated with potassium tert-butoxϊde (2,0 g) in THF (20 ml) at -15 °C and then with CH,Li (2,5 ml of a solution being 1 ,6 H in ether)as described above,to give (-) -5-methoxy-2-methyl-2-(n-propylamiπo) tetral in hydrochloride (0.30 g, 1 ,1 mmol),mp 215-219 °C, {jxζj ^' = -21,0 °(c o,2 ,«eOH) Th.ϊ.έ product (0,30 g,1,1 mmol) was acylated with propionylchloride (0,21 g,2,2 mmol) In CH CL (10 ml) and triethylamine (1.5 ml) , yielding an amide which was reduced with LiAlH, (0,25 g) in ether (see above) giving (-)-5-methoxy-2-methyl-2-(dϊ-n-propylamino) tetral in hydrochloride (0,20 g) . _Pre_p_a_ra_t_i_on_*of_ejτ_d_cc * m ojnjds Example El. (±)~5 _ Hydroxy-2-meth 1-2-(di-n-propyla ino) tetral in (±)-5-Methoxy-2-methyl -2-(di-n-propyla ino) etral in hydrochlo ide (0,75 g, 2,4 mmol) was heated in 48 % aqueous HBr for 2 h at 120°C N_.The volatiles were removed under reduced pressure and the residue was recrystal 1 ized from EtOH/ether giving 0,40 g (58%) of (t)-5-hydroxy- 2-methyl-2-(di-n-propylamino) tetral in hydrobromide,mp 217"2l8 C. Example E2. (+)-5~Hydroxy-2-methyl-2-(di-n-propylamino) tetral in (+)-5 _ Methoxy-2-methy1-2-(di-n-propylamino) tetral in hydrochloride (0.20 g,0.65 mmol) in CH CL (5 ml) was treated with BBr.. (2 ml) at - 70 C for 5 mlπ and then at room temperature for 30 in.The mixture was extracted with 10% Na„C0,,the organic layer was dried (Na_S0,) and the solvent was evaporated.The oily residue was chromatographed on a SiO_ (40-63 urn) column with MeOH as eluant.Treatment with ethereal HCl afforded crystals which were recrysta11 ized from HeOH/ether, yielding (+)-5-hydroxy-2-methyl -2-(dϊ-n-propylamino) tetral in hydrochJLqrita , (80 mg), mp 212-215 °C ,[θJ Example E3. (-)-5-Hydroxy-2-methyl-2-(di-n-propylamino) tetral in (-)-5-Hethoxy-2-methyl-2-(di-π-peopylamiπo) tetral in hydrochloride (0,20g,0,65 mmol) in CH 2 C1 2 (5 ml) was treated with-BBr (2 ml) as described above in Example E2 to give (-)-5-hydroxy-2-methyl-2-(df- n-propyla ino) tetral in hydrochloride (100 mg) , mp 211-217 °C , 21- 0 = - 21.3 °(c 0.1 ,HeOH) D Example E4. (i) -5-Acetoxy-2-methyl-2-(dϊ-n-propy1amino) tetral in (-)-5-Hydroxy-2-methyl-2-(di-n-propylamino) tetral in was dissolved in acetic anhydride (10 ml) .Triethylamine (0.5 ml) was added and the solution was refluxed for 1,5 h.EtOH ("25 ' ml) was added and the solvents were evaporated giving an oil.The oil was made alkaline with diluted NaOH to pH 10 during external cooling and then extracted with ether. The organ ' ic phase was dried and evaporated giving the desired compound as an oil.Ethereal HCl gave the hydrochloride of the desired compound, mp C , Example E5. (-)-5-Benzoyloxy-2-methyl-2-(dϊ-n-propylamTno) tetral in (±)-5-Hydroxy-2-mathyl-2-(di-n-propylamϊno) tetral in ( 0 -20 g,6,0 mmol) was dissolved in CH„C1 ? (10 ml) and pyridine (l ml).Benzoyl chloride (0.98 g ,7,0 mόl) was added and the mixture was stirred at room te erature for h. ater (15 ml) was added,the organic layer was •separated,dried (Na_S0^) and evaporated giving an oil,which was convert to its hy rochloride with ethereal HCl, mp - C. According to the methods of the Examples above the following compounds were prepared and. recrystal 1 ized as acid addition salts from ethanol/ ether or isolated as the bases. End Compounds Compound/ Y Salt/ Method Mel ing point Yield Example Base (Ref.to (°C) or other % No. Ex. No.) date 1 OH CH- n-C H CH 2/E1 OH n-C H n-C H CH 3 HBr a 217 • - 218 58 (- -2/E2 OH n-C H n-C 3 H ? CH 3 HCl a 212 - ■ 215 (-J-2/E3 OH n-C H 7 n-C 3 H 7 CH HCl a 211 - ■ 217 3 OH n-C H n-C 3 H y C 2 H 5 4 OH n-C-H- n-C H -C 3 H ? Pharmaceutical Preparations The following examples illustrate how the compounds of the present invention may be included into pharmaceutical preparations. Example P 1. Preparation of soft gelatine capsules 500 g of active substance are mixed with 500 g of corn oil, whereupon the mixture is filled in soft gelatine capsules, each capsule contain¬ ing 100 mg of the mixture (i.e. 50 mg of active substance). Example P 2. Preparation of tablets 0.5 kg of active substance are mixed with 0.2 kg of silicic acid of the trade mark Aerosil. 0.45 kg of potato starch and 0.5 kg of lactose are mixed therewith and the mixture is moistened with a starch paste prepared from 50 g of potato starch and distilled water, whereupon the mixture is granulated through a sieves. The granulate is dried and sieved, whereupon 20 g of magnesium stearate are mixed into it. Finally the mixture is pressed into tablets each weighing 172 mg. Example P 3. Preparation of a syrup 100 g of active substance are dissolved in 300 g of 95% ethanol , whereup 300 g of glycerol, aroma and colouring agents (q.s.) and 1000 ml of wate are mixed therein. A syrup is obtained. Example P 4. "Preparation of an Injection solution Active substance (hybrobromide) (1 g) , sodiumchloride (0.8 g) and ascorbi acid (0.1 g) are dissolved in sufficient amount of distilled water to giv 100 ml of solution. This solution, which contains 10 rng of active substan per ml, is used in filling ampoules, which are sterilized by heating at 120°C for 20 minutes. Pharmacological evaluation Drugs affecting neurohumoral transmission are of considerable interest in the treatment of a variety of disease states of central and peripheral origin. For example, compounds having specific effects on the monoamin- ergic systems are of great value in the therapy of e.g. parkinsoni s , schizophrenia, mental depression, senile mental and motor disturbances, hypo- and hypertensive states etc. While searching for new dopamine (DA)-receptor active agents we sur¬ prisingly found that a group of compounds of the formula 1 were able to significantly alter the central serotonin (5"HT) and DA synthesis, turn¬ over and metabolism while exhibiting a unique pharmacological profile with regard to behavioural effects. In order to evaluate the actions of compounds of the formula 1 the following biochemical and behavioural investigations were undertaken. §§ §yΪ2 !I§I_§0^_biochem2ca _actJ_vj_tγ_j_n_ra s . a) Antagonism of the reserpine-induced "neuroleptic syndrome" In the rat (gross behaviour) . Depletion of the monoa ine stores with reserpine brings about a "neuro¬ leptic syndrome" characterized by akinesia, catalepsy, muscle rigidity, hunch-backed posture as well as a number of other central and peripheral signs of monoamine depletion. The reserpine-induced syndrome has been frequently' used as an animal model mimicking Parkinson's disease as well as mental depression. The whole or parts of this syndrome can be reversed by the administration of drugs that stimulate DA or 5-HT receptors directly or indirectly. ■*•>) Determination of tyrosine and tryptophan hydroxylation rates of the rat brain in vivo (biochemical evidence of DA- and 5 _ HT receptor activity). The compounds under evaluation were tested biochemically for central DA- aπd 5"HT-receptor (pre- and/or postsynapt ic) stimulating activity. The concept of this biochemical screening method is that a DA- or 5-HT-receptor agonist will stimulate the receptor and through regulatory feedback systems effect a decline in tyrosine or tryptophan hydroxylat ing act ivi y, respect- ively, and a subsequent reduction in the synthesis rate for DA and 5-HT in the presynaptic neuron. Dopa and 5~HTP formation, as determined after ϊn-vivo inhibition of the aromatic L-aπrino acid decarboxylase with NSD 1015 (3-hydroxybenzylhydraz?ne hydrochloride), are taken as ϊndi rect " measures of DA- and 5-HT-synthesϊs rates, respectively. Analogous conditions exist also for central NA-neurons. Effects on the dopa formation in the NA-predomina ed hemϊspheral parts (mainly cortex) may thus be considered to reflect NA-recεptor-mediated changes. c) Experimental procedures. Male Sprague-Dawley rats (200-300 g) , non-pretreated or reserpine-pretreate (5 mg/kg, 18 h before), were given the compounds under evaluation. Gross behavioural observations (changes in motility, body posture, stereotypies etc.) and locomotor activity recordings (electronic motility meters; Motron Products) were made. Body temperature was measured by means of a rectal pro (Yellow Springs Instr.). Subsequent administration of NSD 1015, decapitatio brain dissection (corpora striata, the limbic forebrain, cortex, diencephal brain stem), homogeniza ion, centrϊfugation, ion-exchange chromatography and spectro luorimetric measurements (all as described in detail by Wikstrδ et al., J. Med. Chem., _21_, 864-867, 1978 and references cited therein) gave the actual dopa and 5~HTP levels. In one experiment the test drug was given without any other treatment and the brain levels of the moπoarnines, their precursors and metabol ites were determined by means of high performance liqu chromatography (HPLC) with electrochemical detection. d ) Results Compound 2 markedly antagonized the reserpine-induced akinesia (Table l). However, there was no complete reversal of the "neuroleptϊc syndrome". The animals remained in a hunch-backed posture while exhibiting forward locomotion. Moreover, they frequently exhibited whole body shakes ("wei- -dog shakes"). Since the motor stimulation induced by compound 2_ was not prevented by pretreat ent with reserpϊne (10 mg/kg I.p.,6 h before) plus the tyrosine hydroxylase inhibitor α-methyl-para-tyrosiπe (250 mg/kg i.p., { _ C.-.7I 1 h before) it can be concluded that it is not mediated via catechol- amine release (data not shown). In addition, in contrast to the DA-re- " receptor stimulants 5-hydroxy-2-(di-n-propylamino) tetral in and apo- morphlne, the locomotor activity elicited by compound 2_ was never accompanied by any signs of stereotypies typical of DA-receptor stim¬ ulation (licking, sniffing, gnawing etc.) and was totally resistant to pretreatment with haloperidol, given in a dose producing an efficient blockade of the DA receptors (Table 1). The ethoxy-analogue of com¬ pound _2_, 5 _ methoxy-2-methyl -2-(di-n-propylamino) tetral in (20 mg/kg s.c. was unable to antagonize the reserpine-induced akinesia. Concomitant measurements of the monoamine synthesis rates following compound 2_ a1 so revealed significant alterations. Thus, the 5-HT-synthe rate in all brain regions investigated was increased 20-30% above con¬ trol values following compound 2_. The increase was observed both In the absence and presence of reserpine-pretreatment (Table I II) . In addition the tyrosine and tryptophan levels were consistently elevated following compound J2. A slight, though significant, increase of the DA-synthesis rate was also noted in the brain stem (Table I I). These biochemical changes were, at least in non-reserpinized rats, accompanied by a signϊf icant rise in body temperature (Table I I ). Compound 2. induced a pronounced increase of the locomotor activity and "wet-dog shakes" also in otherwise non-treated rats (Table I I I). Sub¬ sequent analysis of the brain monoamines, their precursors and metabolit showed that, in the brain regions Investigated, the noradrenal ine (NA) and 5~HT levels remained unaltered whereas the homovanillic acid (HVA) levels were significantly increased as compared to controls. Further¬ more, the 5-hydoxyϊndoleacet ic acid (5-H1AA) level was slight, though significantly increased in the l imbic forebrain and the DA and 3,4-di- -hydroxypheπy1acetic acid (DOPAC) levels significantly decreased in striatum. As in previous experiments there was a rise in tryptophan and tyrosine levels although statistical significance was reached only for tryptophan. All the results obtained for compound 2_ as described above was also obtained for the pure 1 evorotameric enantiomer { - ) -2_ ,but not for the dextrorotameric (+)-_2_. / "' U £^ O ?j CONCLUSION The pharmacological data demonst ate " hat compounds of the present in¬ vention have pronounced pharmacodynamic actions. The concomitant behav¬ ioural and biochemical alterations Induced by the compounds under con¬ sideration constitute a unique pharmacological profile, not previously described. Said compounds are of great clinical interest in the therapy of pathological states referred to in the Introduction, for example Parkinson's disease, mental depression and senile disturbances in the nervous system. Table I : Compound 2: Antagonism of the reserpine-induced akinesia; a comparison with some dopamlnergic -stimulants Drug treatment Motor act ivi ty,counts 0-30 min P < A. Reserpine (R) + Vehicle 3. 5 - 0.5 4 B. R + Haloperidol (H) 4.0 ± 1 .5 4 NS s, C. R + Compound 2 121 - 14 4 D. R + H + Compound 2_ 130 - 14 4 NS s, E. R + 5-0H-2-(dl-n-propy1amino)tetra1in (5-0H-DPAT ■ ))222266 i i 1166 4 F. R + H + 5-OH-DPAT 5.0 - 1 .7 4 0.001 vs, G. R + Apomorphine 299 t 4 H. R + H + Apomorphine 14 i 3.3 4 0.001 vs, Reserplne-pretreated (5 mg/kg i.p., 18 h before) rats were given haloperidol (0.5 mg/kg i.p.) and compound 2_ (20 mg/kg s.c) , 5-0H-DPAT (0.1 mg/kg s.c) or apomorphine (0.1 mg/kg s.c) at 30 and 0 minutes, respectively, Table I I . Compound 2} Effects on the rat rectal temperature and the DA- and 5- -synthesis rates of . he rat brain in vivo. Reserpine n=4 TYROSINE TRYPTOPHAN DOPA 5-HTP 4.98 - 0.16 Limbic Contr. 1715 i 1.2 703 ^ 36 152 i 4 foreb ,ra .in C p omp. 2 22 < .5 ^~^0.72 5.79 ± 0.13 767 42 192 - 2 < 0.01 ns (> .05) < 0.00 Striatum Contr 17.8 i 0.69 5.22 ± 0.15 1455 107 89.8 - 0 Comp. 2 21.7 i 0.76 6.25 i 0.14 1464 62 118 - 8 P < 0.01. < 0.005 ns (> .05) < 0.02 Contr Cortex 18.9 ± 1-2 4.96 * 0.12 129 4.2 99.0 - Comp. 2 22.1 - 0.61 5.86 - 0.12 140 4.6 118 - P ns (> 0.05) < 0.005 ns (> .05) < 0.02 Dien¬ Contr 17.8 - 0.85 4.52 - 0.05 315 - 18.2 217 i cephalon Comp. 2 20.4 - 0.60 5.46 - 0.13 351 - 17.5 277 - P < 0.05 < 0.001 ns (> 0.05) < 0.01 Brain Contr, 15.8 - 0.55 4.70 ± 0.07 213 i 12.1 263 - stem Comp. 2 18.9 i 0.37 5.87 - 0.24 278 i 14.7 338 i P < 0.005 < 0.005 < 0.025 < 0.00 No reserpine n=5 Contr. 24.2 - 0.92 Li bic 4.74 - 0.17 355 ± 8.4 118 - forebrain Comp. 2 29.5 - 1.49 6.62 - 0.16 422 + - 20 154 - P < 0.025 < 0.001 < 0.025 < 0.00 Striatum Contr. 20.2 - 0.53 4.22 - 0.10 488 + - 13.6 59.4 - Comp. 2 23-4 - 0.77 5.71 i 0.18 522 + - 12.5 66.6 - P < 0.01 <-0.001 ns (> 0.05) ns (> 0.05 Contr. Cortex 20.1 - 0.35 3.98 - 0.08 63.8 ± 5.7 63.4 - Comp. 2 25.2 - 0.50 5.42 - 0.10 78.4 ± 1.4 77.6 - P < 0.001 < 0.001 < 0.05 < 0.00 lo reserpine Basel ine After 30 rnin Change P ι=5 Contr. 38.7 - 0.08 39.0 - 0.07 0.36 i 0.11 < 0.02 RECTAL TEMP. Comp. 2 38.8 - 0.09 40.0 - 0.05 1.2 - o.n < 0.00 P < 0.001 Reserpinized (5 mg/kg i.p., 18 h before) or non-pretreated rats were given comp (20 mg/kg s.c.) 60 rnin before death. Controls received vehicle. All animals rec NSD 1015 (lOO mg/kg i.p.) 30 rnin before death. The rats were killed by decapita the brains dissected and taken for determination of Dopa, 5 _ HTP. tyrosine and t phan levels in the different brain parts. Body temperatures were measured by me a rectal probe. Shown are the means * s.e.m. Statistics: Student's t-test. P de significance level, πs=not significant (p > 0.05). Table III. Compound ^: Effects on locomotor activity and brain levels of monoamines, their metabolites and precurso in the rat. Brain area DA NA 5-HT HVA DOPAC 5-HIAA Tyrosine Trypt (μg/g) (ng/g) (yg/g) (ng/g) (ng/g) (ng/g) (μg/g) (μg n=5 .. .. Contr. 1.65 0\07 673 i 26 0.99 ϊ 0.02 imblc 159 i 6.3 284 - 16 t 17 - 5.53 forebrain Comp. ! 1.54 * 0.03 695 ± 47 1.08 t 0.05 180 ± 3.9 296 i 5.5 519 * 13 7.22 P ns ns ns < 0.05 ns < 0.05 < 0 Contr. 5.67 ± 0.09 105 * 2.3 0.521 * 0.043 591 ± 8.7 887 i 18 539 * 48 15.3 * 0.69 5-32 Striatum Comp. 2 5.10 - 0.05 110 - 5-3 0.462 - 0.0Ϊ9 671 z 18 809 - 20 506 - 30 17.3 - O.97 6.54 < 0.001 ns ns < 0.005 < 0.025 ns ns < 0 Contr, 16 - 1.4 137 ± 6.1 15-3 ± 0.80 3-82 Cortex 0.039 Z 0.007 232 - 6.5 0.191 - 0.004 21 - 0.84 Comp, 0.034 * 0.005 213 - 12 0.189 - 0, 005 26 - 1.3 17 ± 0.60 152 * 3.3 16.5 i i - 10 4.84 P ns ns ns < 0.01 ns ns ns < 0 n-=5 Counts 0-60 min Contr. 180 * 15 Locomotor act ivi ty Comp. 2_ 457 ± 40 P < 0.001 Rats were given compound 2 ^ (20 mg/kg s.c) or vehicle, placed individually into motility meters (Motron) and the locom activity was followed and recorded during the subsequent 60 min. Immediately thereafter the animals were decapitated, brains dissected and taken for determination of the levels of DA, NA, 5"HT, HVA, DOPAC, 5"HIAA, tyrosine and tryptopha not significant ( p > 0.05 Best mode of carrying out the invention The compound 5-hydroxy-2-methyl-2-(di-n-propylamino) tetral-in and its salts, processes for preparing said compound and methods of employing said compound in therapy, particularly in the therapy of mental de¬ pression, represent the best mode of carrying out the invention known to us at present.

Claims: C l a i ms 1. A compound of the formula wherein Y is OH, R^COO, (R 5 ) NC00 or R 6 0, whereby ^ is an alkyl group having 1-5 carbon atoms or a possibly substituted phenyl group, 5 6 R is an alkyl group having 1-5 carbon atoms and R is an allyl or 1 2 . benzyl group, R is an alkyl group having 1-3 carbon atoms, R is an alkyl group having 1-6 carbon atoms, and R is an alkyl group having 1-3 carbon atoms, as the base and pharmaceutically acceptable acid addition salt thereof. Lc 2. A compound according to claim 1 wherein R is a possibly substi_ tuted phenyl group, R is a methyl group, and R is an allyl group, 1 2 3 and R , R and R have the meaning specified in claim 1. 4 6 3. A compound according to claim 1 wherein Y is OH, R COO or R 0, 4 6 whereby R is a possibly substituted phenyl group and R is an allyl group, and R 1 , R2 and R3 have the meaning specified in claim 1. 4. A compound according to clain 1 wherein R is methyl, phenyl or 4-alkanoyloxyphenyl wherein the alkyl group has 1-4 carbon atoms, R 6 1 2 is methyl, R is allyl, R is alkyl having 1-3 carbon atoms, R is alkyl having 3"6 carbon atoms, and R is methyl or ethyl. 5. A compound according to claim 1 wherein Y is R COO, and wherein R is a 4-alkanoyloxyphenyl group wherein the alkyl grcjp has 4-6 1 2 3 carbon atoms, and R , R and R have the meaning specified in claim 1. 6. A compound according to anyone of claims 1-5 wherein R is n-propyl 2 7. A compound according to claim 6 wherein R is an al yl group having 3-6 carbon atoms and R 8. A compound according to anyone of claims 1-7 wherein R is methyl. 9. A compound according to anyone _of claims 1-4 and 6-8 wherein Y is O 10. A compound according to anyone of claims 1-9 in its pure enantiomeri form having the same absolute configuration as the levorota eric (-)-5-hydroxy-2-methyl-2-(di-n-propylamino) tetral In. 11. A compound according to one or more of the preceding claims char- k acterized in that R Is an alkyl group having 1-5 carbon atoms, a phenyl, 2,6-dϊmethylphenyl or 3" or 4-hydroxyphenyl group or a 3" or 4-alkanoyloxyphenyl group with the formula wherein R is an alkyl group having 1-6 carbon atoms. 12. The compound 5~hydroxy-2-methyl-2-(di-n-propylaminσ)tetral in. 13-» A process for preparation of a compound of the formula • wherein Y is OH, R COO, (R 5 ) NCOG or R 0, whereby R is an alkyl group having 1-5 carbon atoms or a possibly substituted phenyl group, is an alkyl group having 1-5 carbon atoms and R Is an allyl or benzyl 1 2 group, R is an alkyl group having 1-3 carbon atoms, R Is an alkyl group having 1-6 carbon atoms, and R is an alkyl group having 1-3 carbon atoms, as the base and pharmaceutically acceptable acid addi¬ tion salt thereof, characterized in that a) an ehter or ester of the forrr.- la MO -^ul 1 2 wherein R represents a hydrocarbon or acyl residue and R , R and R are as defined above is cleaved, to form a compound of formula I wherein Y is a hydroxy group, or b) a compound of formula 1 2 3 wherein R , R and R are as defined above is converted into a com¬ pound of formula I wherein Y is R COO, (R ) NC00 or R 0 by treating 1 h, the first mentioned compound with a carboxylic acid halide R COX or 4 5 anhydride (R C0) 9 0 or with a carbamoyl halide (R )_NC0X in the presenc of a base or an acid, or with an allyl or benzyl halide R X in the presence of a base, wherein X represents halogen, or c) a wherei d Y are as defined abo is converted Into a compound of formula I by alkylation of the nitrogen atom with an alkylating agent, or d) an amide of the formula , herein Y is OH or R 0, and R is a defined above, R is an alkyl group c 1 2 d defined by the relation R -CH - equals either R or R and R is the 1 2 other of R and R , Is reduced with a reducing agent to the formation of a compound of formula I, or e) a compound of t he formu l a 1 2 wherein M and M are the same or different and each represents -CH -, when M 1 and M 2 are -CH - and group sensitive to hydrogenolysis, 7 1 2 R*- Is hydrogen, methyl or ethyl, Y is other than allyloxy and R , R and R are as defined above is converted to a compound of formula I by reduction, or f) an formula ■ wherei s defined above is converted by reduction into a compound of the formula 1 wherein R 3 is CH or g) in a compound of the formula wherein X represents SO H, Cl or NH , a hydroxy group is substituted for the group X to the formation of a compound of formula 1 wherein Y represents a hydroxy group,or h) a racemic mixture or a mixture partly enriched on one of the enanti of the formula is subjected to enantiomeric separation to obtain a pure enantio .er of compound 1 ;whereupon optionally an isomeric mixture obtained is separat to a pure ϊsomer. H. A process according to claim 13 characterized in that Y, R , 2 R and R are as defined In anyone of claims 1- 12. 15- .A pharmaceutical preparation comprising as an active ingredient a compound according to one or more of claims 1 to 12, in conjunction with a pharmaceutically acceptable carr i er . 16. The use of a compound according to anyone of claims 1-12 as active ingredient in the preparation of pharmaceu ical preparations for treat¬ ment of disorders in the central nervous system. -]7 # A compound according to anyone of claims 1-12 for use in the treat¬ ment of disorders in the central nervous system.

Inventors: ARVIDSSON FOLKE LARS ERIK, CARLSSON PER ARVID EMIL, HACKSELL ULI ALF, HJORTH JOHN STEPHAN MIKAEL, JOHANSSON ANETTE MARGARETA, LINDBERG PER LENNART, NILSSON JOHN LARS GUNNAR, SANCHEZ DOMINGO, WIKSTROEM HAKAN VILHELM
Applicants: ARVIDSSON FOLKE LARS ERIK, CARLSSON PER ARVID EMIL, HACKSELL ULI A, HJORTH JOHN STEPHAN MIKAEL, JOHANSSON ANETTE MARGARETA, LINDBERG PER LENNART, NILSSON JOHN LARS GUNNAR, SANCHEZ DOMINGO, WIKSTROEM HAOKAN VILHELM, HACKSELL ULI ALF, WIKSTROEM HAKAN VILHELM
Application year: 1982
Main classification: C07C93
IPC codes: A61K31, C07C67, C07C213, C07C215, C07C217, C07C219, C07C239, C07C271