CS220344B2 - Method of preparing new naphtyridine derivatives - Google Patents

Description

The present invention relates to a process for the preparation of novel naphthyridine derivatives in the form of racemates or optical isomers of the general formula I

in which

R 1 represents hydrogen atom, C 1 -C 4 alkyl, 2-oxo-propyl, 2-hydroxypropyl, 3-oxobutyl, 3-hydroxybutyl, cyclopropylmethyl, benzyl, halobenzyl, preferably fluorobenzyl or chlorobenzyl a group, acetyl, cyclliopropylcarbonyl, benzoyl or - (CH2) _n —R ', where n is 1 or 2 and R' is hydrogen, methoxycarbonyl, ethoxycarbonyl, or cyani,

R 2 represents a hydrogen atom, a halogen atom, a methyl group or a methoxy group;

R 6 represents a group of the formula -COR 7 wherein R 2 represents a hydroxyl group, a C 1 -C 4 alkoxy group, an amino group, a methylamino group, a dimethylamino group, or a cyclopropylamino group, as well as 1 pharmaceutically acceptable salts thereof.

The essence of the preparation of the novel naphthyridine derivatives by the process according to the invention is that the tryptamine derivative of the general formula II (II) in which

R represents a hydrogen atom, a (C1-C4) alkyl group, a cyclopropylmethyl group or a benzyl group; and

R 2, as defined above, is reacted with a succinic acid derivative of the formula III

ReOOC \

ch ₂

AND

CH — CHO /

ReOOC (III) wherein

R6 is C1-C4alkyl, and the obtained intermediate is reacted in a hydrochloric acid with an alcohol of formula R7 ' H in which R7 is C1-C4alkoxy to form a compound of formula IV

in which

R, R2 and R7 'are as defined above, and when R is hydrogen, the resulting compound of formula IV is optionally reacted with an aldehyde of ¹ Formula RGCH in acidic medium unbeaten with an acid of the formula R9COOH in the presence of sodium borohydride, wherein R9 in both formulas represents a hydrogen atom, a C1-C3 alkyl group, a cyclopropyl group, a phenyl group or a haloigenphenyl group, or a halide of the formula R1X in which R1 is as defined above except for hydrogen and X represents a halogen atom, in the presence of sodium carbonate ^, or a compound of ^one of the formula CH 2 = CH-R ', wherein R' is as defined above, or Ti halides acid of formula R 10 COX, wherein R10 is methyl, cyklopiropylovou or phenyl radical and X represents a halogen atom, and in the case where R is the same as R 1, the resulting compound of formula ¹ is formed IV is converted to an acid of formula I wherein:

R 7 is a hydroxyl group, or an acid, then an acid chloride, and finally an amide of formula I, wherein R 7 is an amino group, a methylamino group, a dimethylamino group, or a cyclopropylamino group, and the resulting compounds are optionally converted into salts.

The compounds of formula (I) and their salts are useful in both human and veterinary medicine.

All compounds produced by the process of the present invention can form two optical isomers, (+) and (-), since the carbon atom at the 3a position is asymmetric. In the following examples, racemates of the compounds are obtained.

Furthermore, ^one compound of formula I in which R is alkoxycarbonyl skuplpnou, appears also a cis / trans isomerism is due to the binding 3, 4th

The two isomers, cis and trans, can be separated by column chromatography.

The compounds according to the invention are prepared from tryptamine or a derivative thereof.

Tryptamine was not a derivative of the general formula

H in which

R is hydrogen, alkyl of 1 to 4 carbon atoms, cyclopropyl, benzyl, optionally halobenzyl, and

R 2 is as defined above, condensed with carbonyl-linked diacids or their aliphatic diesters, such as glutaric acid with a keto group in the α-position or succinic acid with an aldehyde group in the α-position, followed by cyclization to form indolo [3,2] , 1-de] [1,5] -naphthyridine nucleus and, finally, optionally, various reactions are carried out to introduce the desired substituents into the nucleus or convert existing substituents, or change the degree of saturation of the molecule.

The reaction schemes below illustrate the main routes for obtaining compounds of Formula I.

Scheme A: Ri = R, Re = COR7 ’

R & OOC

R _t

CHfCHi

NH J NHR

N

CH, H + ² /

CH-C

° ^C

N-R

H / CH

RfOOC-CH3COORs

R? H / HCl ·

BASE MODIFICATION

General scheme

DETAILED PROCEDURES (OPTIONS)

Scheme C

Scheme D

O

R <A NH N. _from CO ₃

O

Scheme Ε

Scheme J

The reduction is preferably carried out in a lower alcohol with an alkaline borohydride at room temperature.

Scheme K

The resulting two diastereoisomers are separated by chromatography.

Hydrolysis of the ester and conversion of the acid hydrochloride to the free acid is accomplished by conventional methods.

Scheme L

NH 2 or an amine corresponding amide

The acid chloride is preferably prepared with thtonyl chloride and the conversion to the amide is carried out in a conventional manner.

In the previous schemes, R 1, R 2, R 6, R 2, R 2 and n have the meanings given for Formula I,

R 6 denotes alkyl having 1 to 4 carbon atoms, in particular ethyl,

R 8 is hydrogen, C 1 -C 3 alkyl, cyclopropyl, phenyl or halo-phenyl,

R 10 is methyl, cyclopropyl or phenyl and

X represents a halogen atom, especially chlorine, thunder or iodine.

The following examples illustrate non-limiting embodiments of the invention and include details of the procedures set forth in Schemes A through L.

The procedure of Scheme A (first cyclization method) was performed essentially as described by Taborsky and McIsaes (j. Med. Chem. 1964, 7, 135) for related compounds.

IR and NMR spectra as well as analyzes confirm the structures of the compounds prepared.

Example 1

1,2,3,3a, 4,5-Hexahydro-3-methyl-6-oxo-6H-indolo [3,2,1-de] [1,5] naphthyridine-4-carboxylic acid methyl ester and its methanesulfonate (Method A) (R = _CH3, R - H, R ₆ = COOCH 3)

The cis and trans isomers

A solution of 48 g (0.23 mol) of N _b -methyltryptaminu in 2 liters of benzene was added 60 g (0.30 mol) of diethyl a-formyljantarové prepared according Payot and Grob (Helv. Chim. Acta 1954, 37, 1269 ) or Tocanny · aslselineau (Bull. Soc. Chim. Fr. 1965, 3346).

The resulting solution was stirred vigorously for one hour, then heated to reflux and refluxed for 4 hours while separating the resulting water using a Dean-Stark apparatus. After cooling, 1 liter of 3N hydrochloric acid was added to the solution, the mixture was stirred vigorously for a quarter of an hour, and then basified with dilute ammonia solution. The organic and aqueous phases are separated and the aqueous is extracted several times with ethyl acetate.

After combining, the organic phases are washed several times with water, then dried over sodium sulfate and the solvent is evaporated off under reduced pressure. This gives 70 g, i.e. 65-70% of the oil, which solidifies after scratching. The obtained material is a mixture of two isomers, cis and trans, as shown by thin layer chromatography and NMR spectrum. It is an intermediate diester, a derivative of 1,2,3,4-tetrahydro-3-methylpyrido [3,4-b] indole.

AND

CH 2 COOC

Vs ⁰

O

The product was used crude for the next reaction step. A sample purified for analysis by crystallization from petroleum ether melts at 92 ° C.

A solution of 6 g (0.016 mol) of the previous crude diester in 125 ml of methanol was charged to the pressure reaction apparatus. This solution was saturated at 0 ° C with hydrogen chloride gas and then heated in an autoclave at 120 ° C for 20 hours.

After cooling, the reaction mixture was poured into ammonia solution and then extracted several times with ethyl acetate. The extract was washed with water, dried over sodium sulfate and evaporated under reduced pressure. An oily residue is obtained, which is chromatographed on a silica gel column using dichloromethane containing 10-15% acetone.

The compound eluting first is an isomer of 3α, 4-H, H-cis. Yield 48-50; mp 205 ° C.

The second eluting compound is the 3a, 4-H, H-trans isomer. It is obtained in a yield of 20 to 25%. Mp 163 ° C.

One equivalent of a solution of methanesulfonic acid in ethyl acetate is added dropwise to a solution of the cis-isomer of the base in the same solvent.

After stirring for 30 minutes, the precipitate is filtered off with suction and recrystallized from ethanol. M.p.> 270 ° C. Yield 75-85%.

In the same manner, the methanesulfo220344 trans-isomer base is obtained, which melts at 257-258 ° C.

Example 2

1,2,3,3a, 4,5-Hexahydro-4-methyl ester

6-oxo-6H-indolo [3,2,1-de] - &lt; 1 & gt ^; [1,5] -naphthyridine-4-carboixyl (procedure A) (R 1 - R 2 = H, R 5 - COOCH 3) isomers of cis and trans.

1. Tryptamine (23 g; 0.14 mol) is dissolved hot in 100 ml of anhydrous methanol and, after cooling, a solution of 30 g (0.15 mol) of diethyl α-formylsuccinate in 50 ml is added dropwise with stirring. anhydrous methanol. Stirring is continued for one hour after the addition is complete, then the mixture is cooled to 0 ° C and 75 ml of concentrated sulfuric acid (d = 1.84) are added thereto while maintaining the temperature of the mixture at 0 ° C.

The reaction is terminated by heating the reaction mixture to 100 ° C for one hour. After cooling, the reaction mixture is poured into 1.5 liters of ice water, the pink flocculent precipitate is filtered off, the filtrate is neutralized with 150 ml of 28% ammonia pressure so that the internal temperature of the mixture does not exceed 10-15 ° C. The resulting precipitate was extracted with dichloromethane, the combined organic extracts were washed with water and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated and the gummy residue (39 g, 98% yield) was chromatographed on two kilograms of Merck silica gel (0.063-0.2) with dichloromethane / acetone 7: 3.

This gave 14 g (37% yield) of the first product, mp. 166 ° C, then eluting with acetone to give 14.6 g (38% yield) of the second product, mp. 195 ° C.

NMR spectra show that the two compounds are geometric isomers; an isomer of mp. 166 ° C has a trans structure, while an isomer of mp. 195 ° C has a cis structure.

These are the cis and trans isomers of the 1,2,3,3a, 4,5-hexahydro-6-oxo-6H-indolo [3,2,1-de] [1,5] naphthyridine-4-carboxylic acid methyl ester.

Example 3

1,2,3,3a, 4,5-Hexahydro-6H-indolo [3,2,1-de] [1,5] -naphthyridine-4-carboxamide (Procedure L) methyl-R, H; <])

To a suspension of 3 gl, 2,3,3a, 4,5-hexahydro-6-oxodndolo [3,2,1-de] [1,5] naphthyridine-carboxylic acid (cis isomer prepared according to Scheme K) in 100 ml of dichloroethane is added 0.011 mol of anhydrous pyridine (i.e.

0.9 ml) and the reaction flask is immersed in a cooling bath. After a few moments, 1 ml of thionyl chloride (0.011 mol) was added, the flask was removed from the ice bath and the contents stirred for 2 h. 30 min. at room temperature [with the chloro-calcium cap fitted).

Then 0.33 mol of cycloprioipylamine (about 2 ml) was added and stirred again for 2h. 30 min. Finally, after the addition of a solution of 100 ml of 0.5 N-NH 4 OH, it is again stirred, decanted, and the aqueous solution is extracted three times with 100 ml of dichloromethane. The organic solutions were combined and washed with water, dried over sodium sulfate and evaporated after filtration. 800 mg of N-cyclopropyl-1,2,3,3a, 4,5-hexahydro-6-oxo-6H-indolo [3,2,1-de], [1,5] naphthyridin-4- is obtained. carboxamide, mp 230 ° C.

Example 4

1,2,3,3a, 4,5-Hexahydro-6-oxo-10-fluoro-6H-indiollo [3,2,1-de] [1,5] naphthyridine-4-carbolxylic acid methyl ester (process

A) (R 1 = H, R ₂ = 10 F, Re = COOCH 3 - - 2 stereolsomers)

5-Fluorotryptamine is released in a decanter flask by shaking a suspension of 9.1 g (.0422 mol) of 5-fluorotryptamine hydrochloride in water and ether, in the presence of dilute ammonia. The phases are separated, the ether phase is washed with a wave and dried over sodium sulfate. The ether was evaporated in vacuo. Residual water is removed by evaporation with benzene under vacuum. The residual oil was dissolved in 150 ml of anhydrous diethyl ether and 4K molecular sieve (Merck, 10 g) was added followed by 9 g (0.044 mol) of α-formylsuccinic acid diethyl ester. The reaction mixture was allowed to stir at room temperature overnight. The screen is then filtered off. A stream of hydrogen chloride gas is introduced into the filtrate causing precipitation of a light brown resin which slowly turns into white crystals. It is allowed to stir for 30 minutes after the gas injection is complete and the ether is filtered off with suction. The precipitate was suspended in 50 mL of anhydrous methanol and concentrated sulfuric acid (25 mL) was added with stirring. The mixture was heated at 100 ° C for one hour. It is cooled by immersion in an ice bath and poured onto crushed ice. The pH is adjusted to alkaline by addition of the necessary amount of ammonia. It is then extracted with dichloromethane, washed with water, dried over sodium sulfate and evaporated. dry. A solid residue was obtained weighing 9.1 g (yield 70%). This was chromatographed on 600 g of Merck silica gel 60 0.063-0.2 with dichloromethane-acetone 7: 3.

The least polar product, Compound A, weighed 3.6 g (27% yield).

The most polar product, Compound B, weighed 2.8 g (21% yield).

Compounds A and B are crystallized separately from the smallest amount of thyl acetate required. A provides 2.8 g (22 percent yield) of the expected compound, mp 172 ° C Response isomer _H3 - Hi trans. B gives 1.9 g (15% yield) of rt. mp 214 ° C. Corresponds to the isomer H3 _and - H4 cis.

The compounds prepared according to the invention were subjected to a pharmacacoiigical assay.

Claims (6)

The lethal dose of 50 (LD 50 of the compounds was determined on CD1 mouse strains using a graphical method. Results. are given in Table II for a certain number of representative compounds. 2. Hypobaric anoxia CD1 mice were maintained in an oxygen-depleted atmosphere by reducing the pressure to 25.33 kPa, corresponding to 5.25% oxygen. Animal survival time was recorded. This time is prolonged after administration of agents capable of promoting tissue oxidation, particularly brain tissue. The test compounds are administered intraperltoneally in several doses, 10 minutes before the start of the experiment. Percentage prolongation of survival time was calculated relative to the values obtained with control animals. The median active dose, i.e. the one that increases the survival time by 100%, is determined graphically. The results are shown in Table II for a certain number of representative compounds. 2 20344 three id § O 00 in About CM t 1 CM O CO O CM in CM WHAT in th 10 tn WHAT Aeí tn CM rH CM r4 τ — 1 CM tH O O tn rH WHAT ΙΩ WHAT 05 / WHAT tF CM CM rH CM CM T • and tn Š tu C © N 'ideo ůi rt d rt rt rt rt and • ^ -4 O » $ 0 1 • w 0 1 • ř4 ς> ca +> 0) Ň rt ffi © - M 1 X. 05 / N t / 5 55 © - N X «§5 Φ ts rt sca with X 'a *what » X a x ” . «© i 'Honor d rt Λ . ja -si ΧΛ » and 1 X5 4 a-0 mQ d d • d < (B) ca honor honor what CD what what what * »/ Φ Λ rt ’S» E E AND Til cd co rt cd <C < cd £ AND X tn • i — I O x * rt a tH oá to X O to x x x x x o o x> <d H x X AND TF cď CO (3α, 4-H, H-trans) 268 C2H5H — COOCH3 D m. S-223 (3a, 4-H, H-cis) C2H5H — COOC2H5 D iq. S. 231 (3a, 4-H, H-cis) methanesulfonate II « c-2 £ 7> Λ 0) rt> o> o § and n— »C f * *“ < . o> t-i CO Λ CM what what CD · CO CO> 54 PU CM σ ». CO> ém n o tF rH CM TF TF compound - R1 R2 Re Method Base or salt Constant t. (° C) per number 0 O O CD rH O WHAT O rd 00 WHAT τ — 1 CD CD CD WHAT WHAT WHAT in 0 I> WHAT WHAT O) CD CD WHAT O CD CD CD rd CD tH rd rd CD i — l rd rd rd CD CD Λ (Ex. 4] (3a, 4-H, H-trans) 172 base (3a, 4-H, H-cis) 214 <0 three fr < what those honor ÉM í§ Honor i-t co • »M o Φ Φ what about and CĎ o co • rM O X co • rM CJ AND Q ΜΗ HM HM QJ HM _φ - N ~íd ~ N - td ~ S!. * ~ Q -3. _L. ^ _! - | xfi '' what CO »fM a I £ co • rM O I. ffi co CO £ Honor what about O o o honor what honor what honor what honor what ω S 2 s 4 s k Honor what honor honor what * q honor what T ΪΤ! ►Λ a) a> ht φ ^ω > -U Ň td t - N .'Cti 'Ctí -' Ctí £ C '2 £ 40 & £ 40 <rO T «honors what honors what honors what in o o at CD 2 2 it 2 0 here it 2 O F it 2 0 0 it 2 0 O it it 2 2 u o 0 0 it 2 O O O 2 2 0 0 00 0 at O 0 5 0 0 0 0 O .1 at 0 0 AND 1 J AND 1 1 0 , l i * o t0 to t0 t0 £ 2 £ 2 O O O O what τϊ <m • t Tt CD Ttl ffil o rd Pd to o to o o o OJ o N o 00 CD xp O ‘„ 2 AT I £ o o in fcO O o o o Cd f £ o rd CO O Í o ffi CD compound- R1 R1 R2 Method Base or salt Constants 1.1. (° C) per number CD O. ÍO O WHAT WHAT rH l ^ s Ή CM CM CM ca Φ n 'CD! Λ E. I ď What the E o O o o o rd ta it E O w and E W 'Cd · -'Cti cd what ce co CQ it E O o o o it E O o T-1 Cd cd ctf co 3. Influence on the duration of induced sleep Sodium 4-hydroxybutyrate This effect was determined by the action of: compounds on the duration of “sleep” induced by 4-hydroxybutyrate sodium (GHB) in treated rats. The animals used were male Charles River rats weighing 200 + 20 g. The animals were treated with alloferin at a dose of 1 mg / / kg by the intraperitoneal route and were subjected to artificial respiration using a mask attached to the muzzle (respiratory frequency: 50 / min; breath volume: 14 ml). Esophagus is performed prior to the experiment to prevent air from entering the stomach. The cortical frontal-parietal and occipiital electrodes allow recording of electrocorticographic activity using a Gnass model 79 P polygraph at a rate of 6 mim / s. The animal is prepared for local anesthesia (2% xylocaine) experiments. The rats are maintained at a constant temperature (37.5 ° C) throughout the experiment. Ten minutes after ¹ complete preparation, a 200 mg / kg dose of sodium 4-hydroxybutyrate is injected intravenously into the tail vein. Doses of 10 and 30 mg / kg of test compounds are administered to the animal intraperitoneally 3 minutes after administration of sodium 4-hydroxybutyrate. Recording is performed at 15 minute intervals 75 minutes after injection of “GHB”. During this analysis period, the total duration of sleep is determined. A series of 15 control animals allows the duration of “sleep after GBH” to be refined. Statistical analysis of the results was carried out by the "U" test by Mann-Whitney. The results are shown in Table III. A pharmacological study of the compounds of the invention shows that they are effective in the hypo -baric anoxia test in mice, are of low toxicity and have a significant exciting effect in the "sleep" test induced by sodium 4-hydroxybutyrate. The compounds according to the invention, which simultaneously have antianoxic and psychotnopian activity, can be used in therapy for the treatment of wakefulness disorders, in particular in combating the problems attributable to vascular brain disorders and cerebral sclerosis in geriatrics, as well as treating mental absences caused by cranial traumas. and treating depressive conditions. Pharmaceutical preparations containing the compounds produced by the process according to the invention and / or salts thereof as active ingredients in combination with all excipients suitable for their administration can be administered, in particular, by the oral or parenteral route. The daily dosage may range from 10 to 100 mg. Table II Compound Acute toxicity DLso (mg / kg) i. Hypobaric anoxia i. 30 (m. P.) 110 9 31 (m. Cis) 170 4 Table III Compound No. Toxicity mg / kg Activity Total duration Deviation i. v. i. p. number dose minutes in%  of animals mg / kg considering i. ke checks Control - - 15 Dec 54.12 + 2.07 - 1 47 185 3 40 32.01 + 2.59 —41 trans m. 49 - 600 6 30 38.51+ 3.12 —28 in. p 6 10 35.22 + 2.26 51 -. 760 6 30 37.51 + 2.12 —30 58 - 190 6 30 36.08 + 2.47 —33 isomer cis 58 - 170 6 30 31.12 + 2.18 —42 isomer trans 60 - 725 6 10 34.22 + 2.47 —37 isomer cis Subject A process for the preparation of novel naphthyridine derivatives of the general formula I wherein: R1 is hydrogen, C1-C4alkyl, 2-oxopropyl, 2-hydroxypropyl, 3-oxobutyl, 3-hydroxybutyl, cyclopropylmethyl, benzyl, halobenzyl, preferably fluorobenzyl or chlorobenzyl, acetylium, cyclopropylmethylcarbonyl, benzoyl or: - (CH2) n-R ', wherein n is 1 or 2 and R' is hydrogen, methoxycarbonyl, ethoxycarbonyl or cyano, R2 represents a hydrogen atom, a halogen atom, a methyl group or a methoxy group; R 6 represents a group of the formula --COR 7, wherein R 7 represents a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, an amino group, a methylamino group, a dimethylamino group or a cyclopropylamine group, as well as their pharmaceutically acceptable addition salts and / or optical isomers; characterized in that the tryptamine derivative of the general formula (II) in which: R is hydrogen, C 1 -C 4 alkyl, cyclopropylmethyl or benzyl; and R2 is as defined above, reacted with a succinic acid derivative of the formula III RsOOC CHz r CH — CHO OF RsOOC OF THE INVENTION in which R 6 is C 1 -C 4 alkyl, and the obtained intermediate is cyclized in hydrochloric acid by the liberation of an alcohol of formula R 7 'H wherein R 7 is C 1 -C 4 alkoxy to form a compound of formula IV wherein R 7 R 2 and R 6 are as defined above, and when R is hydrogen, the resulting compound of formula (IV) is optionally reacted with an aldehyde of formula RgCHO in an acidic medium or with an acid of formula RgCOOH in the presence of sodium hydride; R 8 in both formulas represents a hydrogen atom, a C 1 -C 3 alkyl group, a cyclopropyl group, a phenyl group or a haliogenphenyl group, or a haloogenide of the general formula R 1X in which R 1 is as defined outside hydrogen, in the presence of sodium carbonate, or with a compound of the formula CH 2 = CH-R ', wherein R' is as defined above, or an acid halide of formula R 10 COX in which R 10 is methyl, cyclopropyl or phenyl, and in the case where R is the same as R 1, the resulting compound of formula IV is converted to the acid of formula I in which R 7 is a hydroxyl group, or an acid, then an acid chloride, and finally an amide of the formula I, in which R 7 is an amino group, a methylamino group, a dimethylamino group or a cyclopropylamino group, and the racemic mixture formed is optionally separated into optical isomers and / or the resulting compounds are optionally converted into pharmaceutically acceptable salts. 2. A process according to claim 1 for the preparation of novel naphthyridine derivatives of the general formula (I). which R1 is hydrogen, alkyl of 1 to 4 carbon atoms, cyclopropylmethyl, benzyl, halobenzyl, acetyl, cyclopropylcarbonyl, benzyl or the group -CH2-CH2R ', wherein R' is methoxycarbonyl, ethoxycarbonyl a cyano group, Ra represents a hydrogen atom or a methyl group and R 6 is a group of the formula -COOR 7, wherein R 7 is a C 1 -C 4 alkyl group, and their editoral salts with pharmaceutically acceptable acids and / or optical isomers, characterized in that the tryptamine of formula II is condensed with an acid derivative of the amber of formula III, wherein R 6 is as defined above, the obtained intermediate is cyclized to form the indolo [3,2,1-de] [1,5] naphthyridine core, optionally introducing the aforementioned desired substituents into the resulting core or the substituents are modified within said substituents and / or the degree of saturation of the molecule within said substituents is modified, and the resulting compounds are optionally converted into salts and / or optical isomers. 3. A process according to item 1 for the preparation of ηιο naphthyridine derivatives of the general formula in which R 1 represents a hydrogen atom, a C 1 -C 4 alkyl group, a cyclopropylmethyl group, a 3-oxobutyl group, a 3-hydroxybutyl group or an ethoxycarbonylmethyl group, R2 represents a hydrogen atom or a methoxy group; R 6 represents a group of formula -COR 7 wherein R 7 represents a hydroxyl group, a C 1 -C 4 alkoxy group, an amino group, a methylamino group, a disinfethylamine group or a cyclopropylamine group, and their editorial salts with pharmaceutically acceptable acids and / or optically active isomers characterized in that a tryptamine of the formula II is condensed with a succinic acid derivative of formula III, the obtained intermediate is cyclized to form indoloí3,2,1 ^de-1] '] 1,5] naftyridinového core and resulting "core optionally introducing the aforementioned substituents or modifying existing substituents within said substituents, and optionally converting the resulting compounds into salts and / or optical isomers. 4. The process of item 1 for producing novel naphthyridine derivatives of the general formula R 1 represents a hydrogen atom, a C 1 -C 4 alkyl group, a cyclopropylmethyl group, a 3-oxobutyl group, a 3-hydroxybutyl group or an ethoxycarbonylmethyl group, R2 represents a halogen atom and R 6 is a group of formula -COR 7 wherein R 7 is hydroxyl, C 1 -C 4 alkoxy, amino, methylamino, dimethylamino or cyclopropylamino, and addition salts of these compounds with pharmaceutically acceptable acids and / or optically active isomers, characterized in that the appropriately substituted tryptamine or derivative thereof is condensed with a succinic acid derivative of the general formula III, the resulting intermediate is cyclized to form the indolo [3,2,1-de] itl, 5] naphthyridine core and optionally introduced the aforementioned desired substituents or existing substituents are modified within said or the degree of saturation of the molecule within said substituents is modified, and the resulting compounds are optionally converted into salts and / or! optically active isomers. 5. The process of item 1 for producing novel naphthyridine derivatives of the general formula wherein: R 1 represents a hydrogen atom, a C 1 -C 4 alkyl group, a cyclopropylmethyl group, a benzyl group, a halobenzyl group, an acetyl group, a cyclopropylcarbonyl group, a benzoyl group, a group of the general formula -CH 2 -CH 2 R 'wherein R' is hydrogen, methoxycarbonyl a group, an ethioxy220344 carboxyl group, or a cyani group, R 2 represents a halogen atom, a methyl or methoxy group and a R6 represents a group of the formula -COR7 in which R7 is a hydroxy, C1-C4alkoxy, amino, methylamino, dimethylamino or cyclopropylamino group, and their addition salts with pharmaceutically acceptable acids and / or optically active isomers, characterized in that tryptamine or a derivative thereof having the general formula ^Cf W'z NHR in which R represents a hydrogen atom, a C 1 -C 4 alkyl group, a C 3 -C 6 cycloalkyl group or a benzyl group optionally substituted by a halogen atom, and R2 is as hereinbefore defined, is induced with a succinic acid derivative of the general formula III, by cyclisation to form an indolo [3,2,1-de] [1,5] naphthyridine core and optionally introducing the above-mentioned desired substituents into the core, or the existing substituents or the degree of saturation of the molecule within the aforementioned substituents are modified, and the resulting compounds are optionally converted into salts and / or optical isomers. A process according to Hold 1 for the preparation of novel naphthyridine derivatives of the general formula wherein: R1 is 2-oxopropyl or 2-hydroxypropyl, R2 represents a hydrogen atom, a methyl group or a methoxy group; R6 represents a group of the formula -GOR7 in which R7 represents a hydroxyl group, a C1-C4 alkoxy group, an amino group, a methylamino group, a dimethylamino group or a cyclopropylamine group, and their addition salts with pharmaceutically acceptable acids and / or optical isomers, characterized in that tryptamine or a derivative thereof is condensed with a succinic acid derivative of the general formula III, the obtained intermediate is cyclized to a naphthyridine of the general formula wherein R2 and R6 are as defined above, which is then reacted with 2-oxopropylchloride; optionally reduced to the resulting compound and the resulting compounds are optionally converted into salts and / or optical isomers.