GB2209748A

GB2209748A - Imidazolinyl derivatives of dihydronapthalene and tetrahydronapthalene

Info

Publication number: GB2209748A
Application number: GB8721296A
Authority: GB
Inventors: Paolo Cozzi; Germano Carganico; Mario Varasi; Alessandro Rossi; Piero Melloni
Original assignee: Farmitalia Carlo Erba SRL; Carlo Erba SpA
Current assignee: Pfizer Italia SRL
Priority date: 1987-09-10
Filing date: 1987-09-10
Publication date: 1989-05-24
Anticipated expiration: 2007-09-10
Also published as: JPH01104054A; GB8721296D0; IT8821862A0; DE3830419A1; IT1230492B; GB2209748B

Description

1 r- 1 n 220 cl 7 L] U IlImidazolinyl derivatives of dihydronaphthalene

and tetrahydronaphthalenell The present invention relates to 2-imidazolin-2-yl derivatives of 1,2- dihydronaphthalene and 1,2,3,4-tetrahyd.ronaph- thalene, to a process for their preparation and to pharmaceutical compositions containing them.

The invention provides compounds having the following general formula (I):

X X N 2 N X;3: R R Z-1 R 1 wherein OH A is c CH -CH = or -CH 2 R is hydrogen, C 1_ c 6 alkyl or phenyl; R 1 is hydrogen, C 1-C 6 alkyl or phenyl-C l- c 4 alkyl; each of X19 X 2Y X 3 and X 49 which may be the same or different, is hydrogen, hydroxy, halogen, C I-C 6 alkyl, C 1-C 6 alkoxy or trihalo-C I- c 4 alkyl; or one of X19x 29 X 3 and X 4 is a substituent chosen from phenyl, phenylthio, phenoxy and benzyl in which each phenyl ring is unsubstituted or substituted by one, two or three substituents chosen independently from hydroxy, halogen, C 1_ c 4 alkyl and C 1_ c 4 alkoxy, the others 2_ being as defined above; and the pharmaceutically acceptabl salts thereof.

The present invention includes all the possible isomers of formula (1) and their mixtures, as well as the metabolites and the metabolic precursors of the compounds of formula OH The compounds of formula (I) in which A is - H - may be either in the cis - or in the trans-configuration. Both the single cis- and trans-isomers and their mixtures are included in the scope of the invention.

It has to be noticed that the compounds of formula (I) in which A is -C -, namely compounds of formula (Ia), may be represented by two other tautomeric structures, namely the enolstructure of formula (1b) and the enone-imi dazol i dine structure of formula (Ic):

N X 0 X 2 X IR 3 X nH X 2 L 1 NJ 1 k X 3 R Y 4 (Ib) Z i (Ia) H 1 X 1 0 N L U X 2 Oil."

N H X 3 R X 4 (IC) 1 A> wherein Xi. X 29 X 39 X49 R and R 1 are as define above.

In fact, when such compounds are in the free base form, they can exist and can be isolated in the structure (Ib) or in the structure (Ic), as proven by spectroscopic data.

Nevertheless such compounds are reported in the present specification as compounds of formula (Ia). The above compounds of formula (I), in which A represents when isolated in a salified form, e. g. as hydrochlorides, only exist in the keto-form of formula (Ia),as proven by spectroscopic data.

Pharmaceutically acceptable salts of the compounds of formula (I) include acid addition salts with inorganic acids,e.g. nitric, hydrochloric, hydrobromic, sulphuric, perchloric and phosphoric acid, or inorganic acids, e. g.

is acetic, propionic, glycolic, lactic, oxalic, malonic, malic, tartaric, citric, benzoic, cinnamic, mandelic and salicylic acids.

The alkyl and alkoxy groups may be branched or straight chain groups.

A halogen atom is preferably fluorine, chlorine or bromine, in particular fluorine or chlorine.

A C i-C 6 alkyl group is preferably a C i-C 4 alkyl group; in particular a C 1-C 4 alkyl group is methyl or ethyl.

A C i-C 6 alkoxy group is preferably a C i-C 4 alkoxy group; in particular a C i-C 4 alkoxy group is methoxy, ethoxy or iso propoxy.

A phenyl-C I-C 4 alkyl group is preferably benzyl or phenylethyl. A trihelo-C I-C 4 alkyl is for example trichloro-C I-C 4 alkyl, in particular trifluoromethyl.

When one of X.. X 29 X 3 and X 4 is a substituent chosen from phenyl, phenylthio, phenoxy and benzyl, which may be unsubstituted or substituted as defined above, each phenyl ring in such substituent is preferably unsubstituted or substituted by a substituent chosen from halogen and hydroxy.

As stated above the present invention also includes within its scope pharmaceutically acceptable bioprecursors and prodrugs of the compounds of formula (I), i.e. compounds which have a different formula to formula (I) above but which nevertheless upon administration to a human being are converted is directly or indirectly in vivo into a compound of formula (I).

Preferred compounds of the invention are the compounds of formula (I), wherein:

A is as defined above; R is hydrogen or C 1-C 4 alkyl; R 1 is hydr6gen, C 1-C 4 alkyl or benzyl; each of XV X 2 X 3 and X 49 which may be the same or different, is hydrogen, halogen, hydroxy or C I-C 4 alkoxy; or one of XV X 2 X 3 and X 4 is a substituent chosen from phenyl, phenylthio, phenoxy and benzyl and the others are as defined above; and the pharmaceutically acceptable salts thereof.

i 4 1 5- More preferred compounds of the invention are the compounds of formula (I), wherein A is as defined above; R and R 1 are hydrogen; each of XII X 29 X 3 and X 4 is independently hydrogen, hydroxy or C I- C 4 alkoxy; and the pharmaceutically acceptable salts thereof.

1 6 Examples of preferred compounds of the invention are the following:

3,4-dihydro-2-(2-imidazolin-2-yl)-1(2H)-naphthalenone; 3,4-dihydro-2-(2imidazolin-2-yl)-8-methoxy-1(2H)naphthalenone; 3) 3,4-dihydro-2-(2-imidazolin-2-yl)-7-methoxy-1(2H)naphthalenone; 3,4dihydro-2-(2-imidazolin-2yl)-6-methoxy-1(2H) naphthalenone; 5) 3,4-dihydro-2-(2-imidazolin-2-yl)-5-methoxy-1(2H)- naphthalenone; 6) 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-1-naphthalenol, in particular as trans-isomer; 7) 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-8-methoxy-lnaphthalenol, in particular as trans-isomer; 8) 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-7-methoxy-l- naphthalenol. in particular as trans-isomer; 9) 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-6-methoxy-l- naphthalenol, in particular as trans-isamer; 1,2,3,4-tetrahydro-2-(2imidazolin-2-yl)-5-methoxy-lnaphthalenol, in particular as trans-iscffer; 2-(3,4-dihydro-naphthalen-2-yl)-2-imidazoline; 2-(3,4-dihydro-8-methoxynaphthalen-2-yl)-2-imidazoline; 2-(3,4-dihydro-7-methoxy-naphthalen-2-yl)2-imidazoline; 2-(3,4-dihydro-6-methoxy-naphthalen-2-yl)-2-imidazoline; 2(3,4-dihydro-5-methoxy-naphthalen-2-yl)-2-imidazoline; 5,6-dihydro-7-(2imidazolin-2-yl)-1-naphthalenol: 5,6-dihydro-7-(2-imidazolin-2-yl)-2naphthalenol:

4) 10) 11) 12) 13) 25 14) 15) 16) 17) 1 1 1 1.

7 21) 23) 24) 25) 26) 27) 18) 7,8-dihydro-6-(2-imidazolin-2-yl)-2-naphthalenol; 19) 7,8-dihydro-6(2-imidazolin-2-yl)-1-naphthalencl; 20) 2-(3,4-dihydro-7,8-dimethoxynaphthalen-2-yl)-2imidazoline; 2-(3,4-dihydro-6,7-dimethoxy-naphthalen-2yl)-2imidazoline; 22) 2-(3,4-dihydro-5,6-dimethoxy-naphthalen-2-yl)2imidazoline; 5,6-dihydro-7-(2-imidazolin-2-yl)-1,2-naphthalenediol; 5,6-dihydro-7-(2-imidazolin-2-yl)-2,3-naphthalenediol; 7,8-dihydro-6-(2-imidazolin-2-yl)-1,2-naphthalenediol; 2-(1,2,3,4-tetrahydro-naphthalen-2-yl)-2-imidazoline 2-(1,2,3,4-tetrahydro-8-methoxy-naphthalen-2-yl)-2- imidazoline; 28) 2-(1,2,3,4-tetrahydro-7-methoxy-naphthalen-2-yl)-2- imidazoline; 29) 2-(1,2,3,4-tetrahydro-6-methoxy-naphthalen-2-yl)-2- imidazoline; 30) 2-(1,2,3,4-tetrahydro-5-methoxy-naphthalen-2-yl)-2- imidazoline; 31) 5,6,7,8.tetrahydro-7-(2-imidazolin-2-yl)-1-naphthalenol; 32) 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-2-naphthalenol; 33) 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-2-naphthalenol; 34) 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-1-naphthalenol; 35) 2-(1,2,3,4-tetrahydro-7,8-dimethoxy-naphthalen-2-yl)-2- imidazoline; i? 38) 36) 2-(1,2,3,4-tetrahydro-6,7-dimethoxy-naphthalen-2-yl)-2imidazoline; 2- (1,2,3,4-tetrahydro-5,6-dimethoxy-naphthalen-2-yl)-2imidazoline 5,6,7,8- tetrahydro-7-(2-imidazolin-2-yl)-1,2-naphthalenediol 39) 5,6,7,8tetrahydro-6-(2-imidazolin-2-yl)-2,3-naphthalenediol; 40) 5,6,7,8tetrahydro-6-(2-imidazolin-2-yl)-1,2-naphthalenediol, as well as the pharmaceutically acceptable salts thereof. The structured formulae of the above -numbered compounds,indicated according to their progressive number are reported in the following Table:

TABLE

ComDound X 1 X 2 X 3 X 4 R 1 R A 0 1 H H H H H H 2 OCH H H H H H 9 3 -C- Q 3 H OCH H H H H -C- 4 H H OCH 3 H H H -8 0 H H H OCH 3 H H -C- OH 6 H H H H H H -6H OH 7 OCH H H H H H -CH- f of 1.

Compound X 1 X 2 X 3 X 4 R 1 R A OH 8 H OCH 3 H H H H -CH 9H 9 H H OCH 3 H H H -CH OH H H H OCH H H -CH- 11 H H H H H H -CH= 12 OCH 3 H H H H H -CH= 13 H OCH 3 H H H H -CH= 14 H H OCH 3 H H H -CH= H H H OCH 3 H H -CH= 16 OH H H H H H -CH= 17 H OH H H H H -CH= is H H OH H H H -CH= 19 H H H OH H H -CH= OCH 3 OCH 3 H H H H -CH= is 21 H OCH 3 OCH 3 H H H -CH= 22 H H OCH 3 OCH 3 H H -CH= 23 OH OH H H H H -CH= 24 H OH OH H H H -CH= H H OH OH H H -CH= 26 H H H H H H -CH - 1 C> Compound X 1 X 2 X 3 X R R A 27 OCH 3 H H H H H -CH 2 28 H OCH 3 H H H H -CH 2 29 H H OCH 3 H H H -CH 2 30 H H H OCH 3 H H -CH 2- 31 OH H H H H H -CH 2 32 H OH H H H H -CH 2 33 H H OH H H H -CH 2 34 H H H OH H H. -CH 2 35 OCH 3 OCH 3 H H H H -CH 2- 36 H OCH 3 OCH 3 H H H -CH 2 37 H H OCH 3 OCH 3 H H -CH 2- 38 OH OH H H H H -CH 2 39 H OH OH H H H -CH 2 40 H H OH OH H H -CH 2- i j, 1 r 11 The compoundsof the invention and the salts thereof can b obtained by a process comprising:

a) reacting a compound of formula (II) X 0 NH 2 OR 2 X R 3 4 is HY (I1) wherein X19 X 29 X 3' X 4 and R are as defined above, R 2 is C 1_ c 4 alkyl and Y is halogen, with a compound of formula (III) H 2 N-CH 2 -CH 2 -NH-R 1 (111) wherein R 1 is as defined above, so as to obtain a compound of formula (I) wherein A is -91_; or b) submitting to B-elimination a compound of formula (IV) X OM X N R X (IV) wherein X 4 X19 X 29 X39 X 4'" R and R, are as defined above and M is hydrogen or the residue of an active derivative of an acid, so as to obtain a compound of formula (I) wherein A is -CH=; or 12- c) reducing a compound of formula (Ia), or a salt thereof, X 0 N X 'j 2 N X 3 R (Ia) wherein 4 X, X X39 X R and R are as defined above, so as to 29 49 1 9H obtain a compound of formula (1) in which A is -CH-; or d) reducing a compound of formula (V) X N- X 2 %,'!r71 N 1 X R R 1 X4 wherein xl? X 29 X 31 X 4, R and R, are as defined above, so as to obtain a compound of formula (I) wherein A is -CH 2_; and, if desired, converting a compound of formula (I) into another compound of formula (I), and/or, if desired, converting a compound of formula (I) into a pharmaceutically acceptable salt thereof, and/or, Is desired, obtaining a free compound of formula (I) from a salt thereof, and/or if desired separating a mixture of isomers into the singl isomers. When Y is halogen in a compound of formula (I1), it is for example, chlorine or bromine, preferably chlorine.

Q (V) z 13 13.

The reaction of a compound of formula (II) with a compound of formula (III) may be carried out in a suitable organic solvent, such as an alcohol, e.g. methanol, ethanol or isopropanol, in particular in ethanol at a temperature ranging from room temperature to about 1000C.

When M, in a compound of formula (IV), is the residue of an active derivative of an acid, it is in particular an acyl residue, e.g. a C 2_ C 4 alkanoyl group, preferably acetyl, or it is a sulfonyl group, e.g. a mesyl or tosyl group.

B-elimination in a compound of formula (IV) may be performed in a suitable solvent, e.g. glacial acetic acid, dimethylformamide or pyridine, in the presence of a suitable amount, even catalytic amount, of a strong acid, e.g. concentrated H 2 so 41 at temperatures ranging e.g. from room temperature to about 1500C.

In particular, when M in a compound of formula (IV) is hydrogen, the same reaction may be carried out by refluxing the compound of formula (IV) in concentrated mineral acids, e.g. a hydrohalic acid, preferably hydrochloric or hydrobromic acid, or by refluxing in pyridine in the presence of a suitable amount of SOC1 2' When M in a compound of formula (IV) is an acyl group, e. g. acetyl, the reaction may be performed by pyrolysis, at temperatures ranging from about 2000C to about 3000C.

Reduction of a compound of formula (Ia), or a salt thereof, to obtain a compound of formula (1) in which A is -CHOH- 1 L+ z may be performed preferably by catalytic hydrogenation of a salt thereof, e.g. the halide, in particular the chloride or bromide, in the presence of a suitable catalyst, e.g. Pd, Pt or PtO 2% in a suitable organic solvent, e.g. a lower aliphatic alcohol, in particular methanol or ethanol, or acetic acid, operating at a pressure varying from the atmospheric one to about 30 atm and at temperatures ranging from room temperature to about 1000C.

Reduction of a compound of formula (V) to obtain a compound of formula (I) in which A is -CH 2_ may be performed, for example, by catalytic hydrogenation in the presence of suitable catalyst, e.g. palladium, platinum, PtO 2' ruthenium or Raney-nickel in a suitable solvent, preferably chosen from an alkanol,e.g. methanol or ethanol, acetic acid, cyclohexane, n-hexane, ethyl acetate, benzene or toluene, operating at a pressure ranging from atmospheric pressure to about 30 atmospheres and at temperatures ranging from room temperature to about 1000C. A compound of formula (I) may be converted, if desired, into another compound of formula (I). These optional conversions may be carried out by methods known in themeselves. Thus, for example, a compound of formula (I) wherein one or more of X19 X 29 X 3 and X 4 is hydrogen may be converted into a compound of formula (I) wherein one or more of X19 X 2' X3 and X. is a halogen atom, e.g. chlorine or bromine, by reaction with chlorine or bromine in the presence of 1 Z; 1 4-_;- Friedel-Crafts catalyst, preferably A1C1 3p operating in suitable solvent, e.g. CH 2 cl 2 A compound of formula (I), wherein one or more of X19 X 21 X 3 and X 4 is hydrogen may be converted into a compound of formula (I), where one or more of X19 X 2 X 3 and X 4 is c I- c 6 alkyl, by alkylation through a Friedel-Crafts reaction, e.g. by reaction with a) a C 1_ c 6 alkylhalide, preferably chloride, bromide or iodide; or with b) a C 1_ c 6 alcohol in a suitable solvent, e.g. nitrobenzene or CH 2 cl 29 or CS 2 In both the cases a) and b), the reaction is performed in the presence of appropriate amounts of a FriedelCrafts catalyst, such as A1C1 39 ZnCl 29 or BF 3; and when a C I- c 6_ aliphatic alcohol is used, also in the presence of a strong mineral acid suchas HF, HC10 4 or, if desired, in concentrated H 2 so 4 or in concentrated H 3 PO 4 or in concentrated H 3 PO 4 without additional solvent, at temperatures ranging from the room temperature to 1000C. A compound of formula (I) wherein one or more of Xly X 29 X 3 and X 4 is a C 1_ c 6 alkoxy group may be converted into a compound of formula (1) wherein one or more of X,. X2 X 3 and X 4 is a hydroxy group by following conventional procedures well known in organic chemistry. For example by treatment with a strong mineral acid, i.e. HCl, HBr, HI, preferably HBr, at temperaturesranging from 300C to the reflux temperature, preferably at reflux temperature, or by treatment with a Lewis acid, for example A1C1 3 or 1 (6 - 16.

BF 3' in a suitable solvent, e.g. CH 2 cl 2 or nitrobenzene, at temperatures ranging from the room temperature to BOOC. Ihe optional salif ication of a compound of formula (I) as well as the conversion of a salt into the free compound and the separation of a mixture of isomers into the single isomers may be carried out by conventional methods. For example the separation of a mixture of geometric isomers, e.g. cis- and trans-isomers, may be carried out by fractional crystallization from a suitable solvent or by chromatography, either column chromatography or high pressure liquid chromatography. A compound of formula (II) may be obtained by reacting a compound of formula (VI) X 1 0 X 1 M 2 1 (VI) X 3 R 2 wherein 4 X19 X 21 X39 X 4 and R 2 are as defined above, with a suitable c 1_ c 4 alkanol in the presence of a gaseous hydrohalic acid, e.g. hydrochloric or hydrobromic acid, preferably hydrochloric acid, in a suitable solvent, such as a lower dialkyl ether, preferably diethylether, at a temperature ranging f-rom about OOC to about SOOC. A compound of formula (II) thus obtained may be reacted as a crude product with a compound of formula (III), according to process a), without being isolated from the reaction medium. Alternatively,if necessary,the obtained compound of formula (II) is separat- 1 -7 is 1 ed from the by-products and then reacted, in a purified form, with a compound of formula (II), according to process a). The compounds of formula (III) are known or may be obtained according to known methods. The compounds of formula (IV) in which M is hydrogen are compounds of formula (I) and may be obtained by reducing a compound of formula (V) or a salt thereof according to process c) described above. A compound of formula (IV), wherein M represents the residue of an active derivative of an acid, as defined above, may be obtained according to known methods, e. g. by reacting a compound of formula (IV) wherein M is hydrogen, with the suitable acyl or sulfonyl halide, preferably chloride, for example, with acetylchloride or with tosyl or mesyl chloride operating e.g. in anhydrous pyridine or in an inert solvent, e.g. anhydrous benzene, if desired in the presence of an equimolar amount of a base such as triethylamine, at temperatures ranging from room temperature to about 600C. The compoUnds of formula (Ia) are compounds of formula (I) in which A is -CO- and can be obtained by reacting a compound of formula (II) with a compound of formula (III) according to process a) described above. Also the compounds of formula Mare compounds of formula (1) in which A is -CH= and may be obtained from compounds of formula (IV) according to process b) above.

119 The Cyano derivatives of formula (VI) are known compounds and/or may be prepared by following methods well known in literature, e.g. J.A.C.S. 67, 1745 (1945). The compounds of the invention have been found active in regulating noradrenaline (NA) balance, as is proven by their affinity to c( 2-adrenergic receptors, e.g. in yohim- bine binding test, (T.M. Lavin, B.B. Hoffnan and R.J. Lefkowitz, Molecular Pharmacology, 20,28 (1981)) and also by the fact that thy are active in tests for potentiation or inhibition of clonidine-induced hypotermia in mice (Von Voigtlander P.F. et al., Neuropharmacology, 17, 37581, 1978). The compounds of the invention have been also found to be active in regulating serotonin (5-HT) balance, whether it be central or peripheral nervous system serotonin balance or blood constituent balance, as shown e.g. by the fact that they are sensitive in tests for potentiation on inhibition of 5-hydroxytryptophane-induced hypermotility in mice and rats, according for example to J. Buus Lassen, Europ. J. Pharmacol., 47, 351-358 (1978). Therefore.the compounds of the invention can be used in the alleviation, treatment or amelioration of any of numerous indications which are sensitive to changes in the noradrenaline and/or serotonine balance, for example migraine, thrombosis, diabetes, obesity, costipation, paralytic ileus, senile dementia, alcoholism, memory impairment, phobic anxiety; they can find also use in therapy as hypotensive- 4 1 antihypertensive agents and as antidepressants either alone or in complementary combination with an established antidepressant. The toxicity of the compounds of the invention is negligible, therefore they can be safely used in therapy. Nine hours food deprived mice and rats were treated orally with single administration of increasing doses, then housed and normally fed. The orientative acute toxicity (LD 50) was assessed on the seventh day after the treatment. The compounds of the invention can be administered in a variety of dosage forms, e.g., orally, in the form of tablets, capsules. sugar, or film coated tablets, liquid solutions or suspensions, rectally, in the form of suppositories, parenterally, e.g. intramuscularly, or by intravenous injection or infusion. In emergency situations the preferred one is intravenous. The suitable dosage depends, as usual, upon the route and purpose of administration, the form in which the compound is administered and the age, weight and conditions of the subject ipvolved. The compounds of the invention are preferably administered at the usual therapeutic doses of the known drugs having similar pharmacological activity; for instance the compounds of the invention can be administered for the treatment of depressive states in adult humans in a dosage ranging from about 5 to about 250 mg/day, preferably from about 10 to about 100 mg/day.

21 C) The invention includes pharmaceutical compositions comprising a compound of the invention in association with a pharmaceutically acceptable excipient (which can be a carrier or diluent). The pharmaceutical compositions containing the compounds of the invention are usually prepared following conventional methods and are administered in a pharmaceutically suitable form. For example, the solid oral forms may contains, together with the active compound, diluents, e.g. lactose, dextrose, saccharose, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and/or polyethylene glycols; binding agents, e.g. starches, arabic gums, gelatin, methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone; disaggregating agents, e.g. a starch, alginic acid, alginates or sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, such as lecithin, polysorbates, laurylsulphates; and, in general, non-toxic and pharmacologically inactive substances used in pharmiceutical formulations. Said pharmaceutical preparations may be manufactured in known manner, for example, by means of mixing, granulating, tabletting, sugar-coating, or film-coating processes. The liquid dispersions for oral administration may be e.g. syrups, emulsions, and suspensions. The syrups may contains as carrier, for example, saccharose or saccharose with glycerine and/or mannitol and/or sorbitol.

21 1 The suspensions and the emulsions may contain as carrier, for example, a natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymathylcellulose, or polyvinyl alcohol. The suspensions or solutions for intramuscular injections may contain together with the active compound a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g., propylene glycol, and if desired, a suitable amount of lidocaine hydrochloride. The solutions for intravenous injections or infusions may contain as carrier, for example, sterile water or preferably they may be in the form of sterile, aqueous, isotonic saline solutions. The suppositories may contain together with the active compound a pharmaceutically acceptable carrier, e.g. cocoabutter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin. The N.M.R. spectrum was measured preferably in solution of dimethyl sulphoxide-d 6 or of CDCl., using a 90 M-hertz Bruker HFX apparatus. The R f values were determined by thin layer chromatography on ready-to-use silica gel plates of 0.25 mm coating thickness. The following examples illustrate but do not limit th invention.

2Z Example 1

8.79 g (0.0513 mol) of 2-cyano-3,4-dihydro-1(2H)-naphtha- lenone, prepared according to the literature ZJACS, 67, 1745, (1945)_/, are dissolved in 100 ml of ether and 8 ml (0.15 mol) of absolute ethanol. HCl is bubbled through the solution for 2 hours. The solution is concentrated to half the volume and cooled. The precipitate is filtered, washed with ether and dried, giving 8.6 g of the imidate hydrochloride, m.p. 119-1200C, yeld 66%.

The crude imidate is dissolved in absolute ethanol (50 ml) and ethylenediamine (2.88 ml, 0.043 mol) is added. After refluxing for 3 hours the solution is cooled and the yellow precipitate filtered and washed with cold ethanol and with water. Drying under vacuum at 1000C in the pre;ence of P 2 0 5 is gives 5.77 g of 3,4-dihydro-2-(2-imidazolin-2-yl)-1 (2H)-naphthalenone, m.p. 256-2590C.

The compound, as already stated, does exist in the enolic form as proven by the obtained NMR data.

Elemental analysis:

Found: C 72.76; H 6.60; N 13.11; Calculated for C 13 H 14 N 2 0: C 72.73; H 6.58; N 13.07 T.L.C.: eluant CHCl 3:CH 3 OH = 180:20 R f = 0.52 N.M.R. (DMSO-d 6)J P.P.m.: 2.40-2.63 (4H, m, CH 2 CH 2 3.54 (4H, m, NCH 2 CH 2 N); 7.00-7.75 (4H, m, aromatics); 9.90 (1H, br s, OH enolic).

!b 2-31 Analogously the following compounds can be prepared; in the case of hydrochlorides, they can be obtained from the corresponding free bases as described in Example 6:

3,4-dihydro-2-(2-imidazolin-2-yl)-6-methoxy-1(2H)-naphthale- none hydrochloride, m.p. 228-232IC(C 2 H 5 OH) Elemental analysis Found: C 58.01; H 5.99; N 9.70; Cl 12.33; Calculated for C 14 H 17 Cl N 2 0 2: C 59.89; H 6.10; N 9.97; Cl 12.68 T.L.C.: eluant CHCl 3:CH 3 CH = 180:20 R f =0.47 N.M.R. (DMSO-d 6),6 p.p.m.: 2.40 (2H, m, CH 2CH2 CH); 3.05 (2H, m, CH 2 CH 2 CH); 3.83 (3H, s, OCH 3 3.88 (4H, s, NCH 2 CH 2 N); 4.18 (1H, dd, CH 2- CH 2-CH) 6.90-7.81 (3H, m, aromatics); 10.40 (2H, br, s, H) 3,4-dihydro-2-(2-imidazolin-2-yl)-7-methoxy-1(2H)-naphthalenone hydrochloride, m.p. 296-300'C Elemental analysis Found: C 59.58; H 6.17; N 9.85; Cl 12.54; Calculated or C 14 H 17 C1N 2 0 2 C 59.89; H 6.10; N 9.97; Cl 12.62 .L.C.: eluant CHCl 3:CH 3 OH 180:20 R f =0.51 N.M.R. (DMSO-d 6)6 p.p.m.: 2.40 (2H, m, CH 2CH2 CH); 3.00 (2H, m, CH 2 CH 2 CH); 3.80 (3H, s, OCH 3); 3.8B (4H, s, NCH 2 CH 2 N); 4.25 (1H, dd, CH 2 CH 22H-); 7.30 (3H, m, aromatics); 10.4 (2H, br s, H) d 2- Lt3,4-dihydro-2-(2-imidazolinyl-2-yl)-8-methoxy-1(2H)naphthalenone hydrochloride; and 3,4-dihydro-2-(2-imidazolinyl-2-yl)-5-methoxy-1(2H) naphthalenone hydrochloride, m.p. 3000C (dec.).

1 I 2 >- Example 2

A mixture of 3,4-dihydro-2-(2-imidazolin-2-yl)-1(2H)naphthalenone hydrochloride (1.7 g), 10% palladium on activated carbon and methanol (100 ml) is hydrogenated for 5 hours at room temperature in a Parr- Burgess low pressure apparatus at an initial pressure of 50 psi (3.42 atm. ).

At the end of this time 96% of the theoretical amount of hydrogen has been absorbed. The catalyst is filtered off and washed with methanol. The solution is evaporated under vacuum to small volume (20 ml) and treated with ether (50 ml). The white precipitate is filtered and dried, giving 1.42 g of trans-1,2,3,4- tetrahydro-2-(2-imidazolin-2yl)-1-naphthalenol hydrochloride, m.p. 207- 2100C.

Elemental analysis:

Found: C 61.66; H 6.79; N 11.05; Cl 14.07; Calculated for C 13 H 17 C1N 2 0: C 61.77; H 6.77; N 11.08; Cl 14.02; T.L.C.: eluant CHCl 3: CH 3 OH: CH 3 COOH = 15:35:0.5 N.M.R. (DM0-d 6):i p.p.m.: 2.07 (2H, m, CH 22-H2 CH); 2.90 (3H, m, CH 2 CH 2 CH, J=10H z); 3.84 (4H, s, NCH 2 CH p N); 4.93 (1H, m, CHOH,J=10H z); 5.80 (1H,br s, OH); 6.90-7.58 (4H, m, aromatics); 10.3 (2H, br, s, H) Analogously the following compounds can be prepared:

2 f, trans-1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-6-methoxyl-naphthalenol hydrochloride, m.p. 198-200OC; Elemental analysis Found: C 59.50; H 6.87; N 9.88; Cl 12.56; Calculated for C 14 H 19 C1N 2 0 2: C 59.46; H 6.77; N 9.90; Cl 12.53; T.L.C.: eluant CHCl 3: CH 3 COOH= 80:20:2 R f =0.375; N.M.R. (DMSO-d 6)S p.p.1n.: 2.02 (2H, m, CH 2CH2' CH); 2.80 (2H, m, CH 2 CH 2 CH); 2.90 (1H, m, CH 2 CH22t, J=10 H=): 3.72 (3H, s, OCH,,); 3.85 (4H, br s, N CHnCH N); 4.90 (1H, dd, CHOH, J=10Hz); 6.00 (1H, r_ 2 br s, OH); 6.65-7.41 (3H, m, aromatics); 10.45 (2H, br s, H) trans-1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-7-methoxy- l-naphthalenol hydrochloride, m.p. 225-230OC; Elemental analysis:

Found: C 59.15; H 6.75; N 9.79; Cl 12.45; Calculated for C H C1N 0: C 59.46; H 6.77; N 9.90; 14 19.2 21 Cl.12.53; T.L.C.: eluant CHCl 3:CH 3 DH; conc.NH 4 OH =50:50:1 R f =0.11; N.M.R. (DMSO-d 6)d p.p.m.: 2.03 (2H, m, CH 2 CH 2 CH); 2.77 (2H, m, CH 2 CH 2 CH); 2.9 (1H, m, CH 2 CH 2 CH, J=10 H z 3.75 (34, z, OCH 3); 3.86 (4H, br s, NCH 2 CH 2 N); 4.92 (IH, d, CHOH, J=10 H); 6.76-7.02 (3 H, m, z aromatics); ID.3 (2H, br, s, AH) A 1 2,-7 trans-1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-8-methoxyl-naphthalenol hydrochloride, trans-1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-5-methoxyl-naphthalenol hydrochloride, r.-i.p. 2250%r" (dec.), and trans-1,2,3,4-tetrahydro-7-hydroxy-2-(2-imidazolin-2-yl) l-naphthalenol hydrochloride, m.p.> 300OC; Elemental analysis Found: C 58.01; H 6.47; N 10.35; Cl 13.09; Calculated for C 13 H 17 C1N 2 0 2: C 58.10; H 6.37; N 10.42; Cl 13.19; T.L.C.: eluant CH 3 OH: conc.NH 4 OH 100:2 R f =0.14;N.M.R. (DMSO-d 6)2 P.P.m.: 1.80-2.20 (2H, m, CH 2 CH 2 CH); 2.60-3.00 (3H, m, CH 2 CH 2CH); 3.82 (4H, s, NCH 2 CH 2 N); 4.83 (IH, br d, CHOH, J 1- 2= 10 H z); 6.60-6.95 (3H, m, aromatics); 8.70-10.50 (3H, br, OH + H).

4 Z9 Example 3

A solution of trans-1,2,3,4-tetrahydro-2-(2-imidazolin-2yl)-6-methoxy-lnaphthalenol (6 g),glacial acetic acid (100 ml) and 96% sulphuric acid (10 ml) is stirred at room temperature for 3 hours. The solution is poured into ice-water (200 ml) and neutralized with conc. NH 4 OH. The precipitate is filtered, washed with water and dried under vacuum at 100OC; giving 4.8 g of 2-(3,4-dihydro-6-methoxy-naphthalen-2-yl)-2imidazoline, m.p. 114-1160C.

Elemental analysis:

Found: C 73.63; H 7.10; N 12.27; Calculated for C 14 H 16 N 2 0; C 73.65; H 7.06; N 12.27; T.L.C.: eluant CHCl CH OH: conc. NH OH = 70: 30: 1; R f =0. 37; is N.M.R. (DMSO-d 6) 3 3 k p.p.m.: 2.3-2.6 (4H, m, CH 2CH2-C=); 3.50 (4H, S, NCH 2 CH 2 N); 3.73 (3H, s, OCH 3); 6.75-7.07 (3H, m, aromatics); 6.97 (1H, br s, CH=-) Analogously the following compounds can be prepared; in the case of hydochlorides, they can be obtained from the cor responding free bases as described in Example 6:

2-(3,4-dihydro-naphthalen-2-yl)-2-imidazoline hydrochloride, M.P. 26226SOC; Elemental analysis Found: C 66.10; H 6.45; N 11.87; Cl 14.98; Calculated for C 13 H 15 C1N 2: C 66.52; H 6.44; N 11.93;C1 15.10 1 zc T.L.C.: eluant CHCl 3: CH 3 OH:conc. NH 4 OH 70:30:1 R f =0.53; N.M.R. (DMSO-d 6)6 p.p.m.: 2.60-2.90 (4H, m, CH 2 CH 2 C=); 3.90 (4H, s, NCH 2 CH 2 W; 7.30 (4H, s, aromatics); 7.77 (1H, br s, CH=C-); 10.3 (2H, br s, H); 1 2-(3,4-dihydro-7-methoxy-naphthalen-2-yl)-2-imidazoline hydrochloride, m.p. 268-270OC; Elemental analysis Found: C 63.14; H 6.37; N 10.41; Cl 13.27; Calculated for C 14 H 17 C1N 2 0: C 63.51; M 6.47; N 10.58; Cl 13.39; T.L.C.: eluant CHCl 3: CH 3 OH:conc. NH 4 OH = 70:30:1; R f =0.48; 1 N.M.R. (DMSO-d 6) p.p.m.: 2.80 (4H, m, CH 2CH2C=); 3.76 (3H, s, OCH 3); 3.92 (4H, s, NCH 2 CH 2 N); 6.84-7.20 (3H, m, aromatics); 7.72 (IH, br s, CH=C-); 10.40 (2H, br s, H) 5,6-dihydro77-(2-imidazolin-2-yl)-2-naphthaleno1 hydro- chloride, m.p. 295-297OC; Elemental analysis Found: C 62.02; H 6.03; N 10.06; Cl 14.24 Calculated for C 13 H is C1N 2 0: C 62.27; H 6.03; N 11.17; Cl 14.13 T.L. C.: eluant CH 3 OH conc. NH 4 OH = 100: 2 R f =0.29 N.M.R.(MSO-d 6) 5 p. p.:2. 3- 2. 9 (4H, M, CH 22-H2 CC._); Z z> 3.88 (4H, s, NCH 2 CH 2 N); 6.78-7.07 (3H, M, aromatics); 7.60 (IH, br s, CH=6_); 9.53 (IH, br s, OH); 10.14 (2H, br, H) 2-(3,4-dihydro-8-methoxy-naphthalen-2-yl)-2-imidazoline hydrochloride; 2-(3,4-dihydro-5-methoxy-naphthalen-2-yl)-2-imidazolin hydrochloride, m.p. 253-256OC; 5,6-dihydro-7-(2-imidazolin-2-yl)-1naphthalenol; 7,8-dihydro-6-(2-imidazolin-2-yl)-2-naphthalenol; 7,8-dihydro-6-(2-imidazolin-2-yl)-1-naphthalenol; 2-(3,4-dihydro-7,8-dimethoxy-naphthalen-2-yl)-2- imidazoline; 2-(3,4-dihydro-6,7-dimethoxy-naphthalen-2-yl)-2- imidazoline; 2-(3,4-dihydro-5,6-dimethoxy-naphthalen-2-yl)-2- imidazoline; 5,6-dihydro-7-(2-imidazolin-2-yl)-1,2-naphthalenediol; 5,6dihydro-7-(2-imidazolin-2-yl)-2,3-naphthalenedio1; and 7,8-dihydror6-(2-imidazolin-2-yl)-1,2-naphthalenediol.

X 31 Example 4

A mixture of 2-(3,4-dihydro-naphthalen-2-yl)-2-imidazoline hydrochloride (0.9 g), absolute ethanol (150 ml) and 10% pal ladium on activated carbon is hydrogenated following -the same procedure described in Example 2, giving, after usual work-up, 0.79 g of 2-(1,2,3,4-tetrahydro-naphthalen2-yl)-2-imidazoline hydrochloride.

The crude hydrochloride is dissolved in water and the solu tion is made alkaline with 20% NaOH and extracted with ethyl acetate (2 x 100 ml). The organic solution is dried over Na 2 so 4 and evaporated to dryness.

The crude free base is chromatographed on silica gel (eluant CHCl 3: CH 3 OH: conc. NH 3 OH=70:30:1), giving 0.63 g of 2 (1,2,3,4-tetrahydro-naphthalen-2-yl)-2-imidazoline, m.p.

71-720C.

Elemental analysis:

Found: C 77.69; H 8.04; N 13.77 Calculated for C 13 H 16 N 2: C 77.96; H 8.05; N 13.98; T.L.C.: eluant CHCl 3 /CH 3 OH: conc.NH 4 OH=70:30:1 R f =0.27 N.M.R. (DMS'O-d 6)S p.p.m.: 1.5-2.4 (2H, m, CH 21-H2 CH); 2.6-3.0 (5H, m, CH 2 CH 22-H-CH2); 3.39 (4H, s, NCH 2 CH 2 N); 7.04 (4H, s, aromatics) Analogously, the following compounds can be prepared:

2-(1,2,3,4-tetrahydro-6-methoxy-naphthalen-2-yl)-2-imidazoline, m.p. 106108OC; 32- Elemental analysis:

Found: C 72.82; H 7.85; N 12.06 Calculated for C 14 H 18 N 2 0 = C 73.01; H 7.88; N 12.16; T.L.C.: eluant CHCl CH OH conc.NH OH =70:30:1; 3 3 R f =0.31 N.M.R. (CDCI 3 P.P.m.: 1.6-2.4 (2H, m, CH 2CH2CH); 2.5-3.05 (SH, m, CH 2 CH 2CHCH2); 3.3 (IH, br s,NH); 3.6 (4H, br s, NCH 2 CH 2 N); 3.78 (3H, s, OCH 3 6.60-7.10 (3H, m, aromatics) 2-(1,2,3,4-tetrahydro-8-methoxy-naphthalen-2-yl)-2imidazoline; 2-(1,2,3,4tetrahydro-5-methoxy-na.Dhthalen-2-yl)-2imidazoline, m.p. 268T (dec.); 2(1,2,3,4-tetrahydro-7-methoxy-naphthalen-2-yl)-2imidazoline, m.p. 265267IC; 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-1-naphthalenol; 5,6,7,8tetrahydro-7-(2-imidazolin-2-yl)-2-naphthalenol; 5,6,7,8-tetrahydro-6-(2imidazolin-2-yl)-2-naphthalenol; 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)1-naphthalenol; 2-(1,2,3,41-tetrahydro-7,8-dimethoxy-naphthalen-2-yl)2imidazoli-e; 2- (1, 2, 3, 4-tetrahydro-6, 7-dimethoxy-naphthalen-2-yl) -2 imidazoline; 2-(1,2,3,4-tetrahydro-5,6-dimethoxy-naphthalen-2-yl)-2imidazoline; 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-1,2-naphthalenediol.; 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-2,3-naphthalene- diol; and 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-1,2-naphthalene- diol.

7 -I 1 Example 5

A solution of 3,4-dihydro-2-(2-imidazolin-2-yl)-6-methoxy1(2H)naphthalenone (3 g) and conc. hydrobromic acid (90 ml) is heated at reflux for 8 hours. The solution is poured into lce/water and the pH is made alkaline with 2N NaOH solution. The solid precipitated is filtered, washed with water and dried. The crude product is recrystallized (EtOH) giving 2.62 g of 3,4-dihydro-6hydroxy-2-(2-imidazolin-2-yl)-1(2H)- naphthalenone, M.P.

282-2840C.

The compound, as already stated, does exist in the enoneimidazolidine form as proven by the NMR data.

Elemental analysis:

Found: C 66.90; H 6.12; N 12.09 Calculated for C 13 H 14 N 2 0 2: C 67.81; H 6.13; N 12.16 T.L.C.: eluant CHCl 3: CH 3 OH = 180: 20 R f =0.27 N.M.R. (DMSO-d 6)[, p.p.m.: 2.20-2.80 (4H, m, CH 2 CH 2 C=) 3.30-3.70 (4H, m, NCH 2 CH 2 N); 6.50-7.62 (3H, m, aromatics); 6.96 (IH, br s, NH transoid with C=O) 9.55 (1H, br s, NH cisoid with C=O) 9.75 (1H, br s, OH) Analogously, the following compounds can be prepared; in the case of hydrochlorides they can be obtained from the corresponding free bases as described in Example 6:

3 L4- 3,4-dihydro-7-hydroxy-2-(2-imidazolin-2-yl)-1(2H)-naphthalenone hydrochloride, m.p. 300IC; Elemental analysi Found: C 57.95; H 5.63; N 10.45; Cl 13.23 Calculated for C 13 H 15 C1N2 0 2: C 58.54; H 5.66; N 10.50; Cl 13.29 T.L.C.: eluant CHCl 3: CH 3 OH = 180: 20 R f = 0.43 N.M.R. (DMSO-d 6)G p.p.m.: 2.32 (2H, m, CH 2CH2 CH); 2.94 (2H, m, CH 2 CH 2 CH); 3.90 (4H, s, NCH 2 CH 2 N); 4.19 (1H, dd, CH 2 CH 2CH); 7.02-7.33 (3H, m, aromatics); 9.88 (1H, s, OW; 10.40 (2H, s, H) 3,4-dihydro-8-hydroxy-2-(2-imidazolin-2-yl)-1(2H)-naphthalene hydrochloride; and 3,4-dihydro-5-hydroxy-2-(2-imidazolin-2-yl)-1(2H)-naphthalene hydrochloride.

is 1 A >--5 - Example 6

4.8 g of 3,4-dihydro-6-hydroxy-2-(2-imidazolin-2-yl)-1 (2H)-naphthalenone are dissolved in methanol (400 ml) and gaseous HCl is bubbled through the solution while keeping the temperature below 200C. After evapora tion to small volume (50 ml), diethyl ether is added until the precipitation is complete. The product is fil tered, washed with ether and dried, giving 4.65 g of 3,4-dihydro-6-hydroxy-2-(2-imidazolin-2-yl)-1(2H)-naphthalenone hydrochloride, m.p. 296-3000C.

Elemental analysis Found: C 58.03; H 5.69; N 10.47; Cl 13.22 Calculated for C 13 H 15 C1N 2 0 2; C 58.54; H 5.66 Cl 13.29 N.M.R. (DMSO-d 6 p.p.m. : 2.32 (2H, m, CH 2 CH 2 CH); 2.92 (2H, m, CH 2 CH 2 CH); 3.90 (4H, s, NCH 2 CH 2 N); 4.11 (1H, dd, CH 2 CH 22-H); 6.71-7.82 (3H, m, aroma- tics); 10.36 (2H, s, H); 10.82 (1H, s, OH) By proceeding analogously and using the suitable hydrohalic acid the following compounds can be obtained: 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-2-nap,-,thalenol, m.p. 238-2401C (as hydrobrorLide); 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-1naphthalenol, m.p. 2600C (dec.), (as hydrochloride); 3,4-dihydro-5hydroxy-2-(2-imidazolin-2-yl)-1(2H)-nap,hthalene hydrobromide, m.p. 2901C (dec.).

N 10. 50; 3 j Example7

Tablets, each weighing 150 mg and containing 50 mg of th active substance can be manufactured as follows:

Compositions (for 10,000 tablets) trans-1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-1-naphtha lenol hydrochloride 500 g Lactose 710 g 237.5 g 37.5 g g Corn starch Talc powder Magnesium stearate T'rans-1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-1-naphthalenol hydrochloride, lactose and a half of the corn starch are mixed; the mixture is then forced through a sieve of 0.5 mm openings. Corn starch (18 g) is suspended in warm water (180 ml). The resulting paste is used to granulate the powder. The granules are dried, comminuted on a sieve of sieve size 1.4 mm, then the remaining quantity of starch, talc and magnesium is added, carefully mixed, and processed into tablets using punches of 8 mm diameter.

t 1-7

Claims

CLAIMS wherein 1. A compound of formula (I) X 1 N) X A 2 N 1 R X R X 4 OH

A is c CH -CH = or -CH 2- (I) R is hydrogen, C I- c 6 alkyl or phenyl; R 1 is hydrogen, C l- c 6 alkyl or phenyl-C 1- c 4 alkyl; e. ach of X 1 9 X 29 X 3 and X 41 which may be the same or different, is hydrogen, hydroxy, halogen, C 1- c 6 alkyl, C l- c 6 alkoxy or trihalo-C I- c 4 alkyl; or one of X19x 2' X 3 and X 4 is a substituent chosen from phenyl, phenylthio, phenoxy and benzyl in which each phenyl ring is unsubstituted or substituted by one, two o three substituents chosen independently from hydroxy, halogen, C 1- c 4 alkyl and C 1- c 4 alkoxy, the others being as defined above; and the pharmaceutically acceptable salts thereof.

-319 2. A compound of formula (1) according to claim 1 wherein A is as defined in claini 1; R is hydrogen or C 1-C 4 alkyl; R 1 is hydrogen, c 1-C 4 alkyl or benzyl; each of X19 X 23 X 3 and X,, which may be the same or different, Is hydrogen, halogen, hydroxy or CI-C 4 alkoxy; or one of Xl, X 29 X 3 and X 4 is a substituent chosen from phenyl, phenylthic, phenOXY and benzyl and the others are as defined In claim 1; and the pharmaceutically acceptable salts thereof.

3. A compound of formula (I) according to claim 1 wherein A is as defined in claim 1; R and R 1 are hydrogen; each of Xl. X 21 X 3 and X 4 is independently hydrogen, hydroxy or C 1- c 4 alkoxy; and the pharmaceutically acceptable salts thereof.

f 4. A cwpound selected from the group consisting of:

3,4-dihydro-2-(2-imidazolin-2-yl)-1(2H)-naphthalenone; 3,4-dihydro-2-(2imidazolin-2-yl)-6-methoxy-1(2H)naphthalenone; 3,4-d4-hydro-2-(2imidazolin-2-yl)-7-methoxy-1(2H) naphthalenone; 3,4-dihydro-2-(2imidazolin-2-yl)-6-methoxy-1(2H) naphthalenone; 3,4-dihydro-2-(2imidazolin-2-yl)-5-methoxy-1(2H)naphthalenone; 1,2,3,4-tetrahydro-2-(2imidazolin-2-yl)-1-naphthalenol, as trans-isomer; 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-8-methoxy- inaphthalenol. as trans-isomer; 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)7-methoxy-lnaphthalenol; as trans-isomer; 1,2,3,.4-tetrahydro-2-(2-imidazolin-2-yl)-6-methoxy-lnaphthalenol, as trans-isomer; 1,2,3,4-tetrahydro-2-(2-imidazolin-2-yl)-5-methoxylnaphthalenol, as trans-isomer; 2-(3,4-dihydro-naphthalen-2-yl)-2imidazoline; 2-(3,4-dihydro-8-methoxy-naphthalen-2-yl)-2-imidazoline; 2(3,4-dihydro-7-methoxy-naphthalen-2-yl)-2-imidazoline 2-(3,4-dihydro-6methoxy-naphthalen-2-yl)-2-imidazoline; 2-(3,4-dihydro-5-methoxynaphthalen-2-yl)-2-imidazoline; 5,6-dihydro-7-(2-imidazolin-2-yl)-1naDhthalenol: 5,6-dihydro-7-(2-imidazolin-2-yl)-2-naphthalenol: 7,8dihydro-6-(2-imidazolin-2-yl)-2-naphthalenol; 7,8-dihydro-6-(2-iml. dazolin-2-yl)-1-naphthalenol; 2-(3,4-dihydro-7,8-dimethoxy-naphthalen-2yl)-2imidazoline; 2-(3,4-dihydro-6,7-dimethoxy-naphthalen-2-yl)2imidazoline; 2-(3,4-dihydro-5,6-dimethoxy-naphthalen-2-yl)-2imidazoline; 5,6-dihydro-7-(2-imidazolin-2-yl)-1,2-naphthalenediol; 5,6-dihydro-7-(2imidazolin-2-yl)-2,3-naphthalenediol; 7,8-dihydro-6-(2-imidazolin-2-yl)-1, 2-naphthalenediol; 2-(1,2,3,4-tetrahydro-naphthalen-2-yl)-2-imidazoline 2(1,2,3,4-tetrahydro-8-methoxy-naphthalen-2-yl)-2imidazoline; 2-(1,2,3,4tetrahydro-7-methoxy-naphthalen-2-yl)-2imidazoline; 2-(1,2,3,4-tetrahydro6-methoxy-naphthalen-2-yl)-2imidazoline; 4- c) 2-(1,2,3,4-tetra.hydro-5-methoxy-naphthalen-2-yl)-2imidazoline; 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-1-naphthalenol; 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-2-naphthalenol; 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-2-naphthalenol; 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-1-naphthalenol; 2-(1,2,3,4-tetrabydro-7,8-dimethoxy-naphthalen-2-yl)-2- -imidazoline; 2-(1,2,3,4-tetrahydro-6,7-dimethoxy-naphthalen-2-yl)-2- imidazoline; 2-(1,2,3,4-tetrahydro-5,6-dimethoxy-naphthalen-2-yl)-2- imidazoline; 5,6,7,8-tetrahydro-7-(2-imidazolin-2-yl)-1,2-naphthalene- diol; 5,6,7, 8-tetrahydro-6-(2-inidazolin-2-yl)-2, 3-naphthalene diol; 5,6,7,8-tetrahydro-6-(2-imidazolin-2-yl)-1,2-naphthalene- diol 9 and the pharmaceutically acceptable salts thereof.

5. A process for the preparation of a compound of formula (I) and the pharmaceutically acceptable salts thereof.

according to claim 1. the process comprising:

a) reacting a compound of formula (II) X 0 NH 2 OR X 3 R X 4 C HY 2 (11) 1 L. 1 wherein X X X 3 9 X an d R are as defined in claLT, 1, R i s CC 2 9 A 1 2 4 alkyl and Y is halogen, with a compound of formula (III) H 2 14-CH 2_ CH 2_ NH-R 1 (111) wherein R 1 is as defined in claim 1, so as to obtain a compound of formula (I) wherein A is -9.-; or b) submitting to B-elimination a compound of formula (IV) X 0 m N X N 3 C) (IV) X wherein 4 Xif X 29 X39 X 49 R and R 1 are as defined in claim 1 and M is hydrogen or the residue of an active derivative of an acid, so as to obtain a compound of formula (I) wherein A is -CH=; or reducing a compound of formula (Ia), or a salt thereof, X 0 N X 2 X R :1:: R 31 (1a) wherein 4 X19 X 2 X 39 X 4 ' R and R, am as defined in claim 1, so as to H obtain a compound of formula (I) in which A is -L; Or d) reducing a compound of formula (V) X N X 2 INN, X R 3 (V) wherein X4 X 1 1 X 2 X 3P X 4 R and R 1 are as defined in claim 1, so as to obtain a compound of formula (I) wherein A is -CH 2_; and, if desired, converting a compound of formula (1) into another compound of formula (I), and/or, if desired, converting a compound of formula (I) into a pharmaceutically acceptable salt thereof, and/or, is desired, obtaining a free compound of formula (I) from a salt thereof, and/or if desired separating a mixture of isomers into the single isomers.

6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and/or diluent and, as active substance, a compound of formula (1) or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4.

7. A compound of formula (1) as defined in claim 1 or a pharmaceutically acceptable salt thereof. for use in a method of treatment of the human or animal body by surgery or therapy or of diagnosis practised on the human or animal body.

n 1 8. A compound of formula (I) or salt thereof according to claim 7 for use in regulating noradrenaline balance.

9. A compound of formula (I) or salt thereof according to claim 7, for use in regulating serotonin balance.

10. A process for the preparation of a compound of formula (I) as defined in claim 1 or a pharmaceutically acceptable salt thereof, said process being substantially as hereinbefore described in any one of Examples 1 to 6.

11. A pharmaceutical composition substantially as hereinbefore described in Example 7.

1 Published 1988 at The Patent office. State House. 6671 High Holborn. London WC1R 4TP. Further copies may be obtained from The Patent OfRee, Sales Branch, St Mary Cray, Orpington, Kent. BR5 3RD- Printed by Multiplex techniques ltd, St Mary Cray, Kent. Con. 1,87.