DE1913701C3 - Amine-substituted tricyclic compounds and their salts, processes for their preparation and pharmaceutical compositions containing them - Google Patents

Description

CH-A-CH ₂ -R

in the X

-CH ₂ -CH ₂ - -CH = CH-
or

CHj CHj
s ~ <

5. The method according to claim 2 for the preparation of the acid addition salts of the compounds according to Claim 1, in which Λ in formula (1) is a carbonyl group, characterized in that one for the isomerization of the acetylenic amino alcohol of the formula (2) to the formation the acid required for the desired acid addition salt is used.

6. Pharmaceutical compositions with antidepressant and anxiolytic activity, consisting of compounds according to claim 1 and customary additives.

The invention relates to amine-substituted tricyclic compounds of the formula

means A is a carbonyl or hydroxymethylene group (- CO - or - CHOH -) and R. is a mono- or dimethylamino radical, as well as theirs Acid deposition salts.

2. Process for the preparation of the amine-substituted tricyclic compounds and their salts according to claim 1, characterized in that the X is an acetylenic amino alcohol of formula

CH-A-CH ₁ -R

or

(2)

35 -CH ₂ -CH ₂ - -CH = CH-CH ₃ CHj

HO

C = C-CH ₁ -R

in which X and R have the meaning given in claim 1, or a salt of this amino alcohol isomerized with the aid of an acid, the reaction medium with an alkaline agent neutralized and the compound of the formula (!) thus obtained. jjeuebenentalls after reduction of the Carbonyl group A with hydrogen in a neutral medium in a low molecular weight alcohol Use of 5 to 20 percent by weight Raney nickel (based on the compound to be reduced) or with alkali borohydride to form a hydroxymethyl group. isolated and, if appropriate, the compounds of the formula for the preparation of the salts (1), optionally without isolating them from the reaction medium in which they occur, with organic ones or converts mineral acids.

3. The method according to claim 2, characterized in that the acetylenic amino alcohol of formula (2) or its salt with the aid of an aqueous or alcoholic solution isomerized by hydrochloric acid, sulfuric acid, phosphoric acid, formic acid or acetic acid.

4. The method according to claim 2, characterized in that sodium borohydride for the reduction used and in a low molecular weight alcohol at the boiling point of the reaction mixture is being worked on.

A denotes a carbonyl or hydroxyinethylene group (- CO - or - CHOH -) and R is a mono- or dimethylamino radical, as well as their acid addition salts.

These new amine-substituted tricyclic compounds are antidepressant and anxiolytic and thus very useful for human therapy.

These compounds are prepared in a suitable manner by using an acetylenic Amino alcohol of the formula

55

HO C = C-CH ₇ -R

in which X and R have the meanings already given, or a salt of this amino alcohol with the aid an acid isomerized, the reaction medium is neutralized with an alkaline agent and the resultant Compound of the formula (1), if appropriate after reduction of the carbonyl group A with hydrogen in a neutral medium in a low molecular weight alcohol using 5 to 20 percent by weight Raney-Niukel (based on the /.u reducing Compound) or with alkali borohydride to form a hydroxymethylene group.

The following implementation takes place schematically:

acid

CH-CO -CH, -R

+ Raney nickel
or borohydride

Ii

CH-CHOH-CH ₁ -R

It is preferred to give the acetylenic amino; ikühol or a salt thereof with organic or Vüneralsäuren to the aqueous or alcoholic, for example, methanolic or ethanolic) L dissolution of an organic or mineral acid, the mixture formed holds until completion of the reaction at a temperature betwe '; n room temperature and the boiling de ^r reaction mixture, then, for example, makes nt't sodium hydroxide solution alkaline and extracts or isolates the compound of formula (1) thus obtained, in which A is a carbonyl group, in a manner known per se. The above-mentioned organic or mineral acids are preferably hydrochloric acid, sulfuric acid, phosphoric acid, formic acid or acetic acid.

The reduction of the connection of the forms! (I). where A is a carbonyl group, with hydrogen in neutral medium in the presence of Raney nickel is preferably carried out with shaking or stirring in Hydrogen atmosphere at ambient pressure and temperature. Here, the compound to be reduced dissolved in a low molecular weight alcohol such as methanol or ethanol in which - based on the compound to be reduced - suspended from 5 to 20 percent by weight Raney nickel are. After the reduction is complete, the catalyst, e.g. B. by filtration, separated and the desired compound isolated from the filtrate in a manner known per se, for example by concentration.

The reduction with an alkali borohydride, such as sodium. Potassium or lithium borohydride is preferred by adding the borohydride fractionally to a solution of the compound to be reduced in a low molecular weight alcohol, such as methanol or ethanol, and add the reaction mixture then heated to boiling under reflux. After the reaction has ended, water is added and the reduced compound of formula (1) in a manner known per se, such as by extraction and concentration, isolated. Sodium borohydride is advantageously used as the alkali borohydride. When reducing with alkali borohydride One can also use a salt of the "carbonyl compound" (compound of the formula (I with A = - CO -; Reaction product of Isomeri sierunj, the acetylenic amino alcohol with acid go out.

The compounds of the general formula (i have a basic character, and according to the invention) their acid addition salts can be obtained by the action of the corresponding organic or mineral acids

ίο can be obtained on the compounds of formula (1) preferably working in a solvent, preferably anhydrous solvents, wii Benzene, ethyl ether, ethanol and acetone selected. Calze can be produced without the connec- tion fertilize the formula (1) from the reaction medium, ii to which they arise to isolate.

According to a variant of the preparation process according to the invention, the salts of the compound can be used fertilize the formula (1), in which A is a carbonyl group, obtained by the ent speaking acetylenic amino alcohol of the formula (2) with the sauna desired for salt formation treated and the salt obtained isolated directly.

The acetylenic used as starting material for the preparation of the compounds of the formula (1) Amino alcohols of the formula (2) can be obtained by reacting a substituted metal acetylide the formula

Me - C = C - CH ₂ - R

in which R has the meaning already given and Me an alkali metal, such as sodium or lithium, with a ketone of the formula

in which X corresponds to the definition given above and subsequent hydrolysis of the product formed obtained by adding water.

The addition takes place preferably in an anhydrous aromatic hydrocarbon and in the boiling point of the reaction mixture. After adding water, the alcohol formed becomes the Formula (2) isolated from the reaction mixture in a manner known per se.

The metal acetylides of the formula (3) can either be obtained by direct condensation of an acetylene derivative of the formula R - CH ₂ - C =C - H, in which R has the meaning already given, with a suitable alkaline agent, such as metallic sodium or sodium or lithium amide in liquid ammonia or indirectly in situ by reacting an ethylene derivative of the formula

H ₅ C = C-CH ₂ -R

Shark

in which R has the meaning given and Hai is a chlorine or bromine atom, with twice the stoichiometric Amount of sodium or lithium amide can be obtained in liquid ammonia.

I 913 701

The antidepressant and atutolyic properties the new tricyclics were specifically investigated on the following compounds and with the effect of the known Amitryptylins compared;

5- [3'-Dimethylaniinopropylidenone- (2 ')] - IO, i 1-

dihydru-SH-dibenzo-ia.dl-cyclohepten-hydro-

chiorid (hereinafter referred to as 2203-01),

9- [3'-dimethylaminopropylidenone- (2 ')] -10.10-

dimethyl ^ lO-dihydroanthracene hydrochloride

(hereinafter referred to as 2203-02),

5- (3'-dimethylarriino-2'-hydroxypropylidene) -

10.11 -dihydro-SH-dibenzo-Ca ^ i-cyclohepten-

hydrochloride (hereinafter referred to as 2203-03), 5- [3'-Methylaminpropylidenon- (2 ')] - 10, l 1-

dihydro-5H-dibenzo- [a, ri] -cyclohepten-

hydrochloride (2203-07),

5- (3'-methylamino-2'-hydroxypropylidene) -10, lldihydro-5H-dibenzo- [a, d] -cyclohepten-

hydrochloride (2203-08) and

5- [3'-dimethylaminopropylidenone- (2 ')] - 5H-

dibenzo [a, d] cycloheptene hydrochloride

(2203-09).

The following pharmacological results were achieved:

1. In the mouse, the counteraction was caused by the injection of 0.5 mg reserpine per kg Ptosis examined; the compounds to be tested and the reserpine were administered intraperitoneally at the same time administered. In the table below are the minimum effective doses of the Connections indicated.

2. It was found that the 6 mentioned connections when testing according to the method of Halliwell et al. (Brit. J. Pharmacol., 1964, 23, 332) from a dose of 20 mg / kg administered intraperitoneally to that in the rat by also intraperitoneally Administration of 5 mg reserpine antagonizes bradycardia induced. The connections 2203-02 and 2203-08 were found to be the most active.

3. In the mouse, the protective effect against electric shock was increased 30 minutes after intraperitoneal injection of connections examined. The table below shows the smallest effective doses of the individual compounds.

4. Further, the enhancing effect of the compounds on apomorphine after the test by Ther and Schramm (Arch, inter, phannacodyn ,, 1962, 138, 302) examined. The compounds were administered subcutaneously at the same time as one. Dose of 10 mg / kg apomorphine hydrochloride injected intraperitoneally. Then it became very clear An increase in the rodent activity of the animals was found to be a characteristic of an antidepressant effect

ίο Effectiveness according to Ther (Method in Drug Evaluation by Mantegazza and F. Piccini, North Holland Publishing Company Amsterdam, 1966, p. 201 and 202). The table shows the smallest effective doses of the compounds.

5. The intensification of the stereotype evoked in the rat by intraperitoneal injection of 5 mg / kg dexamphetamine was investigated by the method of Halliwell et al. (Brit. J. Pharmacol., 1964, 23, 330). The dexamphetamine was administered to the animals 1 hour after the compound to be tested. From those indicated in d ^"r Table doses of a very significant increase in stereotyped movements was observed.

6. In the mouse, the potentiating effect of the compounds on an infrahypnotic Do-iis of 25 mg / kg sodium mebubarbital were studied. The mebubarbital was injected intraperitoneally 30 minutes after the compounds to be tested administered. The table shows the effective threshold doses.

7. The 50% lethal doses (DL ₅₀ ) of the various compounds were determined in the mouse when administered intraperitoneally. The mortality was determined 48 hours after the administration and the DL ₅₀ value was calculated according to the Behrens and Karber method.

To test the parasympathicolytic effect of the products, groups of 10 mice each to be tested intraperitoneally with a dose of 20 mg

fender compound treated per kg. After 30 minutes, the animals were given 1,4-dipyrrolidino-2-butyne ("tremorin") injected intraperitoneally at a dose of 20 mg / kg and after a further 30 minutes the Animal behavior (absence or presence of

Muscle tremors) and noted the percentage of animals in which the tremor was completely suppressed was.

Examined products

2203-01 ....
2203-02 ....
2203-03 ....
2203-07 ....
2203-08 ....
2203-09 ....

Amitriptyline

Reserpine

> 5

20th

Electric shock

20th
20th
<20
20th
30th
30th

<20

effective doses (mg / kg) Dtxamphe! -
amine sodium
mebubarbital Tremor test DUn <10 <20 Ap.imorphine 20th 20th 0% ! mg kg) ₅ 20th 20th 0% 71 20th 10 <20 0% 163 10 10 <20 0% 49 > 20 10 > 20 0% 74 10 20th <20 &% 56 5 70-80% > 30 5 90

As you can see, the products according to the invention have a comparable antidepressant effect known ProduVi in that they are free from bothersome parasympathikolytisc hen side effects are. The compounds of the formula (1) and their acid addition salts are therefore

agents very useful, especially as antidepressant and anxiolytic agents. You can therefore Applied in the treatment of states of depression, character disorders and neurovegetative disorders will. The usual dose will depend on the compound administered, the patient being treated, the complaints and the method of administration. For example, it can be administered orally in humans 10 to 200 mg per day.

The new amine-substituted tricyclic compounds of the formula (1) used in the form of the bases or the addition salts formed with pharmaceutically acceptable acids will. Of the acid addition salts, preference is given to those which react with chlorine, bromine or hydriodic acid, nitric acid, sulfuric acid, succinic acid, tartaric acid, citric acid, benzoic acid, Alkanesulfonic acids, cyclohexylsulfamic acid and arylsulfonic acids are obtained.

The present invention thus also includes the pharmaceutical compositions from one or more of the products according to formula (I) and / or their salts as active ingredients and customary Additives. These pharmaceutical compositions are prepared in such a way that they can be administered digestively or parenterally. They can be solid or liquid and in the in pharmaceutical forms commonly used in human medicine are present, such as, for example simple or sugar-coated tablets, capsules, granules. Solutions, suppositories or injectable preparations. They are manufactured using the usual methods. The active ingredient (s) can be used together with excipients commonly used in such pharmaceutical compositions are present, such as with talc, gum arabic, milk sugar. Strength. Magnesium stearate, cocoa butter, aqueous or non-aqueous carriers, various wetting agents. Dispersants or emulsifiers and preservatives.

example 1

Production of

5- [3'-dimethylaminopropylidenone- (2 ')] -

10.1 l-dihydro-5H-dibenzo- [a.d] -

cycloheptene hydrochloride

A mixture of 32.5 g (0.111 mol) 5- [V-dimethylaminopropin- (n-yr] -5-hydroxy-10.1-dihydro-5H-dibenzo- [a, d ~ J-cyc1ohepten] and 800 ml 6N sulfuric acid is heated with stirring for 30 minutes to 100 ° C. After cooling, 1 liter of water is added and the mixture is made alkaline with 40% sodium hydroxide solution a stream of dry hydrogen chloride is passed in. The mixture is left at ⁰ ° C. for 15 hours and the crystals formed are then filtered off with suction or centrifuged, which are recrystallized from a mixture of ethanol and ethyl ether, giving 31 g (85%) of 5- [3'- Dimethylaminopropylidenon- (2 ')] -10.11-dihydro-5H-dibenzo- [a.dl-cycloheptene hydrochloride in the form of cream-colored crystals with a melting point of 190 to 196 ⁰ C (observation under the hot stage microscope).

Molecular formula C ₂₀ H ₂₂ ClNO:

Example 2

Production of

9- [3'-Dimethylaminopropylidenone- (2 ')] - 10,10-dimethyl-9,10-dihydroanthracene hydrochloride

With the same procedure as described in Example 1, but starting from 6 g (0.0198 mol) of 9- [3'-dimethylaminopropine - (Γ) - yl] - 9 - hydroxy -10,10 - dimethyl-9,10-dihydroanthracene and 140 ml of 6 η sulfuric acid give 4.1 g (61%) of 9- [3'-dimethylaminopropylidenone - (2 ')] - 10.10 - dimethyl - 9.10 - dihydro anthracene hydrochloride with a melting point of 115 ° C (hot-stage microscope observation).

Molecular formula C ₂₁ H ₂₄ ClNO:

Calculated ... C 73.8, H 7.1, N 4.1%: found .... C 73.9, H 7.2, N 4.1%.

The 9- [3'-dimethylaminopropyn- (1 ') -yl] -9-hydroxy-10,10-dimethyl-9,10-dihydroanthracene used as starting material in Example 2 is obtained in the following manner: A solution of 32.8 g (0.2 mol) of 2-bromo-3-dimethylaminopropene in 20 ml of anhydrous ether is added dropwise to a mixture of 9.2 g (0.4 gram atom) of Nat. Given the suspension of sodium amide prepared in 300 ml of liquid ammonia. The ammonia is driven off with the addition of 301 ml of toluene and a solution of 22.2 g (0.1 mol) of IO.IO-dimethyl-9,10-dihydroanthrone- (a) in 100 ml of toluene is added. The mixture is refluxed for 6 hours while stirring, then allowed to cool and 200 ml of water are added dropwise. The precipitate formed is filtered off with suction or centrifuged, dried and recrystallized from 800 ml of methanol. Are thus obtained 17.8 g (58.5%) of 9- [3 'Dimethylaminopropin- (l') - yl] -9-hydroxy-10.l0-dimethyl-9.IO-dihydroanthracene having a melting point of 204-205 ^r C ( Hot stage microscope observation).

Molecular formula C ₂ , H ₂₃ NO H 7.6, N 4.6%: Calculated .. . C. 82.6. H 7.7. N 4.6%. found ... . C. 82.7.

Example 3 Preparation of 5- (3'-dimethylamino-2'-hydroxypropylidene) -10.11 -dihydro-5H-dibenzo- [a.d] -cyclohepten-

hydrochloride

A solution of 5.8 g (0.02 mol) of 5- [3'-Di-nethylaminopropylidcnon- (2 ')] -10, ll-dihydro-5H-dibenzo- [a, d] -cyclohepten in 100 ml of ethanol with 1 g suspended Raney nickel is stirred or shaken in a hydrogen atmosphere at normal pressure at room temperature. After the theoretical amount of hydrogen has been absorbed, the catalyst is filtered off and dry hydrogen chloride is introduced into the filtrate. The ethyl alcohol is then driven off by concentration in vacuo and a solid residue is obtained which is recrystallized from a mixture of acetone and ether. 5.35 g (81% of 5 - (3 '- dimethylamine - 2' - hydroxypropylidene) -10.11 dihydro - 5H - dibenzo - [ad] - cycloheptene hydrochloride with a melting point of 206 ° C. (observation under the hot table microscope) are obtained ).
65

Molecular formula C ₂₀ H ₂₄ ClNO:

Calculated ... C 73.3. H 6.8. N 4.3. Cl 10.8%:
found .... C 73.1, H 6.8, N 4.1. Cl 10.6%.

Calculated ... C 72.8. H 7.3, N 4.3%: found .... C 72.6, H 7.5. N 4.3%.

■ JC9 611 3 /

Example 4

Production of

5- (3'-dimethylamino-2'-hydroxypropylidene) -

10,11-dihydro-SH-dibenzo- ^ a.dl-cyclohepten-

hydrochloride

3.8 g (0.1 mol) of sodium borohydride are added in portions to a solution of 6.6 g (0.02 mol) of 5- [3'-dimethylaminopropylidenone- (2 ')] -10.11 -dihydro-5H-di benzo - [a, d] - cycloheptene - hydrochloric! in 80 ml Added methanol with stirring. Stirring is continued for 1 hour at room temperature and then Boiling and refluxing for 1 hour. After cooling, add 100 ml of water and drive off the methanol in vacuo. The aqueous solution obtained is extracted several times with ether, and into the dried, combined ethereal extracts, dry hydrogen chloride is passed in. The ether is driven off by concentration and the residue is taken up again in 80 ml of acetone. When adding Ether to this solution one observes the formation of a precipitate, which consists of a mixture of Acetone and ether is recrystallized. 3 g (50%) of 5- (3'-dimethylamino-2'-hydroxypropylidene) -10.11 are obtained -dihydro-5H-dibenzo- [a, d] -cycloheptenhydrochlorid, which obtained according to Example 3 with Product is identical. Melting point: 205 to 206 ° C (hot stage microscope observation).

B e i s ρ i e 1 5 Manufacture of

5- [3'-methylaminopropylidenone- (2 ')] - 10.1 l-dihydro-5H-dibenzo- [a, d] -

cycloheptene hydrochloride

Using the same procedure as in Example 1 but using 11.1 g (0.04 mol) of 5- [3'-methylaminopropyn- (l ') -yl] -5-hydroxy-10.1 l-dihydro-5H-dibenzo- [a, d] -cycloheptene and 290 ml of 6N-sulfuric acid is obtained at the end after recrystallization from a mixture of ethanol and ethyl ether 8.8 g (70%) 5- [3 -methylaminopropylidenone- (2 ')] - 10.1 L-dihydro-SH-dibenzo-ia.dJ -cycloheptene hydrochloride in the form of creamy white crystals with a melting point of 215 to 217 "C (observation under a hot-stage microscope).

Molecular formula C ₁₉ H ₂₀ ClNO:

Calculated ... C 72.7, H 6.4.
found .... C 72.7, H 6.7,

Example 6 Production of

5- (3'-methylamino-2'-hydroxypropy'idene) -10.11 -dihydro-5H-dibenzo- [a, d] -cyclohepten-

hydrochloride

1.9 g (0.05 mol) of sodium borohydride are added in portions with stirring to a suspension of 3.1 g of 5- [3'-methylaminopropylidenone- (2 ') "! - 10, lldihydro - 5H - dibenzo - [a, d] - cycloheptene hydrochloride in 40 ml of methanol was added. It will be 1 hour stirred at room temperature for a further 1 hour and then under boiling and refluxing for 1 hour. After Cooling is added 50 ml of water and the methanol is driven off in vacuo. The obtained aqueous Solution is extracted several times with ether. In the combined and dried essential extracts dry hydrogen chloride is passed in. The formation of a precipitate is observed a mixture of acetone and ether is recrystallized. 2.4 g (76%) of 5- (3'-methylamino-2'-hydroxypropylidene) are obtained - 10.11 - dihydro · 5H - dibenzo [a, d] cycloheptene hydrochloride in the form of white crystals with a melting point of 171 to 174 ° C (hot-stage microscope observation).

Molecular formula C ₁₉ H ₂₂ ClNO:

Calculated
found .

C 72.3,
C 72.0,

H 7.0%; H 7.0%.

Example 7

Production of

5- [3'-Dimethylaminopropylidenone- (2 ')] -5H-dibenzo- [a, d] -cycloheptene-hydrochloricl Using the same procedure as described in Example 1, but using 5.8 g (0.02 mol) 5- [3'-Dimethylaminopropyn- (1 ') - yr] -5-hydroxy-i> H -dibenzo- [a, d] -cycloheptene and 145 ml of 6 n-sulfuric acid are finally obtained after two consecutive steps Recrystallization from a mixture of acetone, ethanol and ether 4.7 g (72 "») 5 - [3 '- dimethylaminopropylidenone - (2')] - 511 dibenzo- [a, d] -cyclohcptene hydrochloride in the form of creamy crystals with a. Melting point 180 to 183 "C (hot-stage microscope observation).

Molecular formula

Calculated ..
found ...

C ₂₀ H ₂₀ ClNO:

C 73.7, H 6.2, Cl 10.9%; , C 73.3, H 6.6, Cl 10.2%.

Cl 11.3%; Cl 11.3%.

The 5- | used as starting material. ^: Dim'-thylaminopropin - (Γ) - yl] - 5 - hydroxy - 5! i dibcnzo- [a, d] -cyclohepten is obtained in the following VVV: 29.9 g (0.25 mol) of 2-chloro-3-dimethylamine: propene become one starting from 11 (0.5 gram atom) sodium in 500 ml of liquid Ann ¹ niak suspension prepared from sodium.> ■ mid dropped. The reaction mixture is stirred for 1 hour and then a solution of 50 g (0.242 mol) of 5H-dibenzo- [a, d] -cycloheptenone in 200 ml of anhydrous xylene is added dropwise. It is because stirred until the complete disappearance <■ '- excess ammonia and dropwise 200; Water added. The precipitate formed ν is sucked off or spun off and dried. M receives 36.5 g (52%) 5- [3'-dimethylaminopropynyl] -5-hydroxy-5H-dibenzo- [a, d] -cycloheptene in Fo of white crystals with a melting point v 176 to 178 ° C (hot-stage microscope observation ) after recrystallization from a mixture of benzene and petroleum ether.

Molecular formula C ₂₀ H ₁₉ NO:

Calculated
found .

C 83.0, H 6.6, C 83.3, H 6.7,

N 4.8%; N 4.9%.

Example 8 Tablets are produced with the following formulation

5- [3-dimethylaminopropylidenone (2)] - 10, H -dihydro-SH-dibenzo- [a, d] -cycloheptene hydrochloride. 20 mg

Excipient q.s.p 200 mg

(Excipient in detail:

Lactose, starch, talc, magnesium stearate).

3903

Example 9 Tablets are produced with the following formulation:

9- [3-Dimethylaminopropylidenone- (2)] -10, 10-dimethyl-10-dihydroanthracine hydrochloride .. 20 mg

Excipient q.a.p 200 mg

(Excipient in detail:

Lactose, starch, talc, magnesium stearate).

Example 10 Tablets were produced with the following formulation:

- (3 - dimethylamino - 2 - hydroxy propylidene) -10.11 -dihydro-5H-dibenzo - [a, d] - cycloheptene -

hydrochloride 20 mg

Excipient q.s.p 200 mg

(Excipient in detail:

Lactose, starch, talc, magnesium stearate).

3 701

Example 11 Tablets were made with the following recipe:

5- [3-dimethylaminopropylidenone- (2)] -5H- dibenzo - [a, d] - cyclo -

heptene hydrochloride 20 mg

Excipient q.s.p 200 mg

(Excipient in detail:

Milk sugar, starch, talc, ίο magnesium stearate).

'5

Example 12

An injectable solution is made up with the following formulation:,

5- [3-Dimethylaminopropylidenone- (2)] -10,11-dihydro-5H-dibcnzo- [a.dj-cycloheptene hydrochloride.

In aqueous solution too

20 mg 2 ml

3903

Claims (1)

I 913 claims: 1. Amine-substituted tricyclic compounds of the formula (D IO