CS235991B2 - Method of acridanone derivatives production - Google Patents

Abstract

For the Contracting States BE CH DE FR GB IT LI LU NL SE 1. Acridanone derivatives of the general formula see diagramm : EP0110298,P20,F1 wherein the dotted line signifies an optional bond, R**1 signifies hydrogen, halogen or nitro, R**2 signifies hydrogen or lower alkyl, one of the symbols R**3 and R**4 signifies hydrogen or lower alkyl and the other together with R signifies an additional bond, A signifies lower alkylene, R**5 signifies a 5-membered, nitrogen-containig, optionally lower alkyl-substituted aromatic heterocycle, amino or a group see diagramm : EP0110298,P20,F2 or see diagramm : EP0110298,P20,F3 the symbol see diagramm : EP0110298,P20,F4 signifies a 5- or 6-membered, optionally lower-alkyl substituted saturated heterocycle which can contain as a ring member an oxygen or sulphur atom or the group >NH ou >N(B)n -A**1-R**6, B signifies the group -CO-, -COO- or -SO2 -, n signifies the number 0 or 1, A**1 signifies lower alkylene, R**6 signifies hydrogen, amino, lower alkylamino or di(lower alkyl)amino and R**7 signifies hydrogen or lower alkyl, and the residues denoted as lower contain 1 to 7 carbon atoms, and pharmaceutically acceptable acid addition salts thereof. For the Contracting State AT 1. A process for the manufacture of acridanone derivatives of the general formula see diagramm : EP0110298,P22,F1 wherein the dotted line signifies an optional bond, R**1 signifies hydrogen, halogen or nitro, R**2 signifies hydrogen or lower alkyl, one of the symbols R**3 and R**4 signifies hydrogen or lower alkyl and the other together with R signifies an additional bond, A signifies lower alkylene, R**5 signifies a 5-membered, nitrogen-containing, optionally lower alkyl-substituted aromatic heterocycle, amino or a group see diagramm : EP0110298,P23,F2 or see diagramm : EP0110298,P23,F3 the symbol see diagramm : EP0110298,P23,F4 signifies a 5- or 6-membered, optionally lower-alkyl substituted saturated heterocycle which can contain as a ring member an oxygen or sulphur atom or the group >NH ou >N(B)n -A**1-R**6, B signifies the group -CO-, -COO- or -SO2 -, n signifies the number 0 or 1, A**1 signifies lower alkylene, R**6 signifies hydrogen, amino, lower alkylamino or di(lower alkyl)amino and R**7 signifies hydrogen or lower alkyl, and the residues denoted as lower contains 1 to 7 carbon atoms, and pharmaceutically acceptable acid addition salts thereof, characterized by a) cyclizing a compound of the general formula see diagramm : EP0110298,P23,F5 wherein one of the symbols R**31 and R**41 signifies hydrogen or lower alkyl and the other signifies hydrogen, R**42 signifies hydrogen or lower alkyl, R**51 signifies a residue R**5, but does not contain a primary or secondary basic amino group, and X' signifies a leaving group, and R**1, R**2 and R**5 have the above significance, b) reacting a compound of the general formula see diagramm : EP0110298,P23,F6 wherein A, R**1, R**42 and R**51 have the above significance, with a compound of the general formula see diagramm : EP0110298,P23,F7 wherein X" signifies a leaving group and the dotted line and R**2 have the above significance, or c) reacting a compound of the general formula see diagramm : EP0110298,P23,F8 wherein Y(anion) signifies an anion and X signifies a leaving group, and A, R**1 and R**51 have the above significance, with a compound of the general formula see diagramm : EP0110298,P23,F9 wherein the dotted line, R, R**2, R**3 and R**4 have the above significance, or d) cleaving off the N-protecting group in a compound of the general formula see diagramm : EP0110298,P24,F10 wherein R**8 signifies a residue R**5 which contains a primary or secondary basic amino group blocked by a N-protecting group and the dotted line, R, R**1, R**2, R**3 and R**4 have the above significance, and e) if desired, converting a compound of formula I obtained into a pharmaceutically acceptable acid addition salt.

Description

The invention relates to a process for the preparation of novel acridanone derivatives of the general formula I

AND

A ^X R5 (I) in which the dotted line represents an optional bond is hydrogen, halogen or nitro;

R is hydrogen or alkyl having 1 to 7 carbon atoms,

And one of R and R is hydrogen or C 1 -C 7 alkyl, and the other is together with R an additional bond,

A is an alkylene group having 2 to 7 carbon atoms,

R represents a five-membered nitrogen-containing aromatic heterocyclic ring which is optionally substituted by an alkyl group having 1 to 7 carbon atoms, furthermore an amino group or a group of the formula

wherein the symbol - ^O represents a five- or six-membered, optionally C1-C7-alkyl, substituted heterocyclic ring optionally containing as the ring member a sulfur atom or a sulfur atom or a group or

LrN (B) _n -A ¹ H ⁶ ,

B is -CO-, -C00- or -SO2-, n is 0 or 1,

A ¹ means a ^{plurality of projections on} at TEAMMEMBERS SKU ^p yne with 2 to 7 C-11 ^^ znaroná hydrogen TPIN ^{of aminoalcohols,} and the ^{plurality of projections} 18minosku yne with ^p is ^{from 1 to 7} carbon atoms, or a di-to-alkyleminoskupinu having 1-7 carbon atoms in alkyl, and γ R ¹ is hydrogen or C 1 -C 7 alkyl, and its acid addition salts, which are pharmaceutically acceptable.

These novel compounds possess valuable pharmacological properties and can be used in the control of diseases or in the prevention of diseases.

It is an object of the present invention to provide novel acridanone derivatives of the above formula (I) and pharmaceutically acceptable salts thereof as pharmaceutically active substances.

The compounds of the formula I can exist, depending on the significance of the dotted line and R ³ and ^R \ ^f in riůzných teutomerních ormách. The present invention encompasses all possible tautomeric forms.

The term lower as used in the present description means that the compounds or residues so labeled contain up to 7, preferably up to 4, carbon atoms and can be straight or branched chain. The term lower alkyl refers to saturated hydrocarbon radicals such as metal, ethyl, propyl, isopropyl, n-butyl, n-pentyl, and the like. The term lower alkylene refers to divalent hydrocarbon groups such as methylene, dimethyl (L) trimethylene, 2-propylene, 1,4-butylene, 1,5-butylene or the like. The term halogen means fluorine, chlorine, bromine or iodine.

The term nitrogen-containing aromatic and aromatic heterocyclic ring refers to heterocycles having 1 to 2 heteroatoms, wherein, when 2 heteroatoms are present, one of them is optionally different from nitrogen and may, for example, be an oxygen atom or a sulfur atom. These heterocycles may be bonded to the group A via a carbon atom or optionally also via a nitrogen atom. Examples of suitable heterocyclic moieties which may be mentioned are 1-methyl-11-imidaaolyl, 2-pyrrolyl, 2-thiazolyl, 4-axazooyl, 1-pyraazlyl, 3-isoxazolyl.

The term Fppt.1 or šestičenný hehtrlcyOlický saturated ring which, as ring member, after the case ^{of PP} still contain a hydrogen atom or ^one SiO not a group ^b ^ ^^ ³ or denotes a saturated five or šestičeenné Ιο ο ^ ^ ^ ι ι which comprises either one heteroatom, namely a nitrogen atom, such as 1-pyrrolinyl and 1-piperiainyl, or containing two heteroatoms, i.e. 1 nitrogen atom and additionally 1 oxygen atom, sulfur atom or nitrogen atom such as 4-mono-amino, 3-hiazolinyl and 1-piperazin-1, wherein the latter may be substituted on the second nitrogen atom with a - (B 1 -A 1 -R ^{6) group} . As can be seen from the symbol -N 1, these heterocycles are bonded to the A group via a nitrogen atom.

^{R 1} substituent is, Poku ^d is other than hydrogen ^H above of ^d not in ^P oloze 1 2 1. Preferably, however, R 'is hydrogen. R is preferably hydrogen. Preferably, one of the substi. Pentium ^R 3 and ^{R 1} in the ^<to within a river basin and the other ni.c ^h with ^p olečně with ^R @ ^p r ^ID avnou neck at ^b. A is ^a group or preferably dimthylenovou ^^ methylene.

R znaemá preferably jminoskupiat _{pyrrolidiaylovct-1,} L-pi-penidlny nominal skupi7 11-Nu, L-moofolt ^ verifies the group, ^ J ^ ^ razt verifies ^P inu hundred or quick match -Ю? '- А ^1-R1 or group formula

^-ion-Ib-1 - ^A1- R ⁶¹ \ _V wherein A 'represents alkylsnovou group having 2-7 carbon atoms, в' is -00-, Zn ^and n ^represents the ^number 0 men Neto 1 ® ^R represents hydrogen and ^{the R} ? ^{zaamea, and} leads ^to no ^b of aloovou with oup ^{to 1} and ^{M 7} C uhHto. Zvváš options ^you preferred meanings of the substituents ^R are amino, dimethylaminostopina, dietУylamiacstopiaj, 1-pyrroIldiaylcvZ group, 1-piperidinyl, l-mettyl-l- ^p i ^p traziаllovZ and L-acetyl-1-piperazinyl.

Particularly preferred compounds of formula I are the following:

10- [2-d-Methyl-1-piperazinyl) ethyl] -9-α-triazine- (2-thiazazlyl) hydrazone,

10- [2- (1-Methyl-1-piperidinyl) ethyl] -9-pyridinazinyl- (2-thiazolinylilino) lydrazine,

10- [2- (l-acetyl-1-1 - ^^^ 21 ^ 1) ethyl] -9 ~ αkridjaon- (2-tУijzc idinyiiten)] _yl RDR azone,

10- [2- (dimethylamino) ethyl] -9-iodoanone- (2-thiazolidilyl-dtaa) -amide, m.p.

¹ 0- ^{[2- (di} lamiac et ^{yy) tУll} e] - ^{9 to} R -α jaon- ^{id (t 2-yl} αzc ^l -yl) hy ^d rαzcn,

10- (2- (1) п1У11] -9-atoidanone- (2-thiocyclo) yydrjzone,

0- (2-aminocttyУ.) - 9-jkridjaon- (tУijzc 2-yl) ^y ydrazcn,

10- [4- (dimethylamino) ethyl] -9-pyridinone- (2-thiaziazyl) acetic acid

10- (2- (1-acetyl-1-piperidin-1-yl) ethyl) -9-acridanone- (2-thiazol-yl) hydrazone,

10-4- (dimethyl amino-4-yl) -9-pyridinone- (2-trifluoromethyl) pyrrole;

10- [2- (dittУy-αmino) etyyL] -9-akridαaca- ^(2-i-d tУiαzc iayiiena)) yrdrazon,

Ю- PO pyrrrtidinyl tty ^ -j ^ ^{9 to} R ^d jnacn ^(2-α tУi ZC idinyliean ^l) and hydrαzca ^{1 -} - ^{(3- (di} ylaminc ^meth) prop ^-.] - ^ ² -t ¹ atoidanon- ^y ijzclidia ^l- i ^d tn Jtydrazone.

The other selected representatives of the group of substances, which is defined by the general formula I, are as follows. compounds:

¹ 0- ^{(2- (piperazinyl} ^ ^^^^ et KRM anon- ⁽² iazclidi -t ^{y] y i} i l ^e n) hydroxy ^azo-1 0- ^[2 - ^(di ylαmiao meth ^y) for y ^p ! J - ^ atoidanon- ^(jzclil -idenn ^{y)) y} d r ^ ^{and Zon,}

235991 4

10- [2- (1-piperidinyl) ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- [2- (2,6-Dimethyl-1-piperidinyl) ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- [2- (4-morpholinyl) ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- [2- (4-ethoxycarbonyl-1-piperazinyljethyl] -9-acridanone (2-thiazolidlnyllden) hydrazone _of

10- [2- (4-pivaloyl-1-piperazinyl) ethyl] -9-acridanone-2-thiazolidinylidene) hydrazone,

10- [2- [4- (methyleulfonyl) -1-piperazinyl] ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10 - [(1-ethyl-4-imidazolyl) ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- [2- [4- [2- (dimethylamino) acetyl] -1-piperazinyl] ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

1-chloro-10- [2- (diethylamino) ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- (2-aminoethyl) -9-acridanone- (2-thiazolidinylidene) -hydrazone,

10- [2- (methylsulfonyl) amino] ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- [4- (diethylamino) butyl] -9-acridanone- (2-thiazolidinylidene) hydrazone,

10- [5- (diethylamino) pentyl] -9-acridanone- (2-thiazolldinylidene) hydrazone,

10- [2- (diethylamino) ethyl] -9-acridanone-methyl- (2-thiazolin-2-yl) hydrazone,

10- [2- (diethylamino) ethyl-9-acridanone- (3-methyl-2-thiazolidinylidene) hydrazone,

10- [2- (diethylamino) ethyl] -9-acridinanomethyl- (2-thiazolyl) hydrazone,

10- [2- (4-morpholinyl) ethyl] -9-acridanone- (2-thiazolyl) hydraone,

AND

10- [2- (4-ethoxycarbonyl-1-piperazinyl) ethyl-9-acridanone- (2-thiazolyl) hydrazone,

10- [2- (4-pivaloyl-1-piperazinyl) ethyl] -9-acridanone- (2-thiazolyl) hydrazone,

10- [2- [4- (methylsulfonyl-1-piperazinyl) ethyl] -9-acridanone- (2-thiazolyl) hydrazone,

10- [2- [4- [2- (diethylamino) ethyl] -1-piperazinyl] ethyl] -9-acridanone- (2-thiazolyl) hydrazone; and

10- [2- (4-propyl-1-piperazinyl) ethyl] -9-acridanone- (2-thiazolyl) hydrazone.

The acridanone derivatives of the formula I as defined above and their acid addition salts which are pharmaceutically acceptable are prepared according to the invention by preparing a compound of the formula X (X)

in which anLont a

X stands for cleavable footprint,

A and ^R 'are as defined above and

5

R 'has the meaning of some of the radicals R' defined above, and sterile does not contain a primary or secondary amine base, and is a compound of formula XI

>

J (XI) wherein tečtovaná ěára, ^{R. r2, r3} and ^r4 to Mejia ^h ora defined above and the compound of formula I is optionally converted into an acid addition salt which is acceptable from a pharmaceutical standpoint.

According to the process of the invention, compounds of formula I may be prepared by treating a compound of formula X with a compound of formula * XI. The branched group represented by X in the compound of formula X is preferably a halogen atom, a lower alkanoyloxystopine or a lower alkoxystopine, in particular a chlorine atom, an acetyloxy group or a methoxy group. Some of the compounds of formula X are substances that are not particularly stable. These compounds are therefore conveniently prepared from the compound of formula XIV prior to reaction with the compound of formula XI

(XIV) in which

111

A, R and R 'are as previously described, and optionally without prior isolation, are further processed directly.

The compound of formula XI is conveniently used in the form of an acid addition salt, for example in the form of the hydrochloride or hydrobromide. The reaction can be carried out in the presence of an acid-binding agent, preferably using sodium carbonate and potassium carbonate and sodium hydrogen carbonate and sodium and potassium vinegar as acid binding agents. Suitable solvents for the above process variant are, for example, lower alcohols, such as methanol and ethanol, and other organic solvents which are inert under the reaction conditions, such as dimethylformamide, acetone, and the like. up to the boiling point of the reaction mixture.

The acridanone derivatives of the formula I as defined above can be converted according to the invention into pharmaceutically acceptable acid addition salts. The preparation of such acid addition salts is carried out by generally conventional methods. Both salts with pharmaceutically usable inorganic acids and salts with pharmaceutically acceptable organic acids, for example hydrohalides, hydroiroids, sulphates, citrates, acetates, succinates, methanol, phosphonates, β-toeoleateolphosates and the like are suitable.

Compounds of formula (X) which are used; as starting materials, they can be prepared from compounds of formula XIII.

2359916

151

The substituents A, R, R- and X are as defined above.

The compounds of formula (XII) belong to a group of compounds known per se.

Reaction scheme

AA \ ⁵¹ Xθ X _r5 1 (XIII) (XIV) X

Compounds of formula XIV may be prepared from compounds of formula ИП that - a compound of Formula XIII is alkylated in přítomiosti strong base such as sodium hydride with ^{odného n} e ^b under a., The reagent his mouth ^ ^ and ^p ^ oakytujícdího ztytek -AR . This action ^{will re p} rovádí the known - and for every expert conventional methods.

Those compounds of formula X in which X is a halogen atom can be prepared by treating a compound of formula XIV in an inert organic solvent with a halogenating agent. In a preferred embodiment, the halogenating agent used is oxalyl chloride or phosphorous phosphorus and as solvents of halogenated hydrocarbons such as methanol, chloroform, 1,2-dichloroethane or the like, acetone or the like. an excess of halogenating agent to give a compound of formula X wherein X is chloro. The reaction temperature is preferably in the range of about room temperature to the boiling point of the reaction mixture.

Compounds of formula X in which X represents a different leaving group from halogen may be prepared from the corresponding halogenated derivatives. The halogen atom in such a compound can be replaced, for example, by a group known in the art which is cleaved off, for example by lower alkoxy or lower alkalooyloxy groups.

The compounds of formula (X) are - at least ammonium salts, some of which, as previously mentioned, are not particularly stable. These compounds are suitably processed further immediately after yl ^{y b} vyrotony. The nature of the anion Szoa ^No. EO ^EL Y ^'3' and ⁿ ziávisí method for producing the corresponding compounds of formula X. P! ЧpraviUeeli example compounds - of formula X, wherein X is CHOR, etc. uuží ^ ^ v ^ ^ a kettle and if such halogenating agent sxalylcllsridu ^then zííká ^ o ^ compound X ^wherein znamerá cKtortoový anion PooHia · If a halogenating agent: phosphorus χtcllLoridu then yields the corresponding compound in which Y® means ^and the anion ^tp '

The acridsnone derivatives of the above formula (I) and their acid-addition salts which are pharmaceutically acceptable have valuable pharmacological properties. In particular, they have valuable astrosomicidal effects and can therefore be used to combat or prevent scosstomiasis.

The schistosomicidal effect of the compounds of the invention can be demonstrated by the following animal experiment:

White mice weighing 15 to 18 g are subcutaneously infected with 60 ± 5 cercariums of the Liberta intestine (Schistoooma mmnoos0) strain, 46 days after infection, the animals are treated with a single oral administration of the test substances. 5 to 10 animals are used per substance and dose: · 10 animals are used as a control. After 19 days, sections of the test animals are performed, whereby pairs of worms and individual worms in the orbital veins, gatehouse and liver are prepared and counted. The effect of the product is a reduction in the number of living parasites compared to the number of parasils in control animals. ’

For evaluation, the percentage reduction in parasites in treated animals compared to untreated control animals is calculated. The value of VD ^ q is determined by the probit method. The VD ₅₀ value is the dose that causes a 50% decrease in the number of worms.

The following table shows the results obtained with selected compounds prepared according to the invention. For each of these compounds, the VD ≥0 in mg / kg after oral administration is given, and for some of the compounds, the DL hodnota is expressed in m @ 2 / kg for a single oral administration.

Table

Compound of Formula I ™ ⁵⁰ (mg / kg po) ^DL50 (mg / kg po 10- [2- (diethylamino) ethyl] -9aalfluoro-2- (2-thiazolidinyl) -one 9.5 312 to 625 10- [3- ⁽ d ^^ h ^ eE ^ ¹ propyll-S-atoidanone-ketyl)] - [ič] L]] y ny ^])) ^ y a a a a] 4.7 125 to 250 10- [2 -. (4-.metthrl -piperazirny-1.) - ethyl] -9-acridanone - ^{(thiazol-2 and} d ^{0 nylieon)} У groove ⁱ⁾ 4.0 156 to 312 10- [2- (imidinoLaminocethyl) -9-acridanone- (2-lhiazylidylphlitone) 6.4 250 to 500 10- [2- (1 - ^p yrroliiioyl) ETB YRL] - □ Akli ridaočO- (2-thiazčlid0nyliton) Уidrazčn 6.2 156 to 312 10- [2- (4-acetyl-1-piperazinol) -ethyl] -9- -akriiaoono (2-liazazlid01yfliton) Уrazrazco - 3.4 1 250 to 2 500 10- [2- (Ethyl-tridolo) -ethyl] -4-acridanone-2-thiazyclyl) -firrazole x 2 HCl 3.3 > 5,000 .10- [1-Cdimethylaminolpropyl] -9-akrianian- 1- (4-thiazolyl) hydrazone x 2 HCl 3.5 312-625 10- [2- (1-piperidinoyl) ethyl] -acrylamide (2-thiazinyl) ydrazole x 2: 3 HCl 9.0 312-625 to- ^{[2- (4 -} ace ^t yl ^ l ^ TTYL piperazinyl] -9-akriianon- (2-thiazolyl) x 2 HC1 hyirazčn 2.6 312-625

). ^DL 50 (mg / kg po)

Compound of Formula I

VD (mg / kg p.o.)

10- (2-Aminoethyl) -9-acridanone- () -

hydrazone x 2 HCl 2.6 156 to 312 10- ^[2 - (dimethylamino ^t h ^{l ι} lcmino ETL ^hУL] -9-oidcoon- and ^the (2 x 2 thaazolyl repulsed MC1 4.9 312-625 10- ^[2 - ^{(4-MMT t} h ^y - ¹ - ^^ ^Razin) ethyl] -9-.a daooή- ^{bush (2} -t ^hi czolyl) У drczoo ^{d 2} x 5 ^H, C1 2.4 625 to 1 25—

The compounds produced by the process of the invention can be used as pharmaceuticals in the form of pharmaceutical preparations. The pharmaceutical preparations may be administered orally, for example in the form of tablets, coated tablets, dragees, hard and soft gelatin capsules, solutions, emulsions or suspensions.

In order to manufacture the pharma-ceutical preparations, the compounds produced by the process of the invention may be formulated with pharmaceutically inert, inorganic or organic carriers. As such carriers, for example, lactose, corn starch or derivatives thereof, maize, stearthe viburnum or salts thereof may be used for tablets, coated tablets, dragees and hard gelatine capsules. For soft gelatine capsules, suitable carriers are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. However, depending on the active ingredient, no carriers are required in the case of soft capsules. Suitable carriers for the production of solutions and syrups are, for example, water, polyols, sucrose, inverse sugar, glucose and the like.

The pharmaceutical compositions may additionally contain preservatives, co-solvents, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, colorants, salts for varying the osmotic pressure, buffers, coatings or a Oxidizing agents. These preparations may also contain other therapeutically valuable substances.

The present invention also relates to medicaments comprising acridanone derivative of formula (I) or an acid addition salt of such a compound which is pharmaceutically acceptable, and to a process for the preparation of such medicaments, comprising one or more compounds produced by the process of the invention. and optionally processing one or more other therapeutically valuable substances into a galenic dosage form.

As mentioned above, the compounds produced by the process of the invention may be used to combat disease or prevent cobbling. They are particularly suitable for combating or preventing the prevention. The dosage can vary within wide limits and can be varied. naturally adapt to each individual case in each individual case. Generally, a single dose for the treatment of sehistamine should be about 1- to about 50 mg / kg body weight, which dose may be administered in several divided doses divided into one day.

The following examples serve to illustrate the present invention in greater detail, but the scope thereof is by no means intended

Example 1

a) A mixture of 8.5 g of alpha acridanone 180 mL dime.thyioommamidu and 3.3 gh / lithium aluminiumhydride solution 'ae stirred for ^{0.5 h} ^ <^ d ^{LNY -} pitonise thereto ^Rida p ^p o l ^{t nn} ee ^h I0 ³ g of 2-fl - (4-m € t ^{h yl) pie} eocz ^and about ^yl] ethylchtarid d ⁱ hydoochloг ^the subtitled mixture ball ^{hook C} o for ³ days at t ^ lo ^ ⁸⁰ ° ^C at Otom The reaction mixture is extracted with water and extracted with methylene chloride. The teeth extract was washed with water, dried and sodium sulphate and evaporated, then the residue was recrystallized first from ether and then from ethyl acetate to give 10- [2- (4-methyl-1-p-piperidine)] ^. 156 DEG-157 DEG C .;

To a solution of 2.2 g of 10- [2- (4-methyl-1-piperazinyl) -ethiyl] -9ac] aridinion in 100 µL of dichloromethane is added portionwise at -5 ° C at 1.1 ° C. The mixture was stirred for 0.5 hour at room temperature and then evaporated. 2 g of 2-hydrazino-2-thiazolidine-lyrobroomide and 1.67 g of sodium acetate are added, the mixture is heated to reflux, cooled after 10 minutes and then washed with saturated carbonate solution. The organic extract was washed with water, dried over sodium sulfate and concentrated. (4-methyl-1-piperazinyl) ethyl] -9-arylamino- (2-thiazolidinyl) pyridine, m.p. 204-205 ° C;

The following compounds are obtained in an analogous manner:

b) From 9-acridamone and 3- (dimethylamino) propyl chloro - [beta] - [3-dioethylamino) propyl] -4-acaddimide is obtained, m.p. -9-acridanone-C2-thiazol-3-yl) hydrazone, m.p. 191-192 ° C;

c) -9- [2- (<diethylamino) ethyl] -9- (9-acridinyl) -ethyl- (2- (ethylethylamino) ethyl) ethyl-9-acridine is obtained from m.p. 2- (Уioethylloino) ethyl] ^-9-alα, 'iУanon- (2-ttiazolУdnyLΊУ · in) Уydrazon mp 153-115 ° C · <d) from 9-acridanone, and 2- (1-pyrroliУiiyl) etlylLcthlarУ-tyyr 143 DEG-145 DEG C., yielding 10- [2- (1-piperidin-1-yl) ethyl] 9-alginone, m.p. ttyl] -9-acranone- (2-thiazolУУi] yllУein) УyУrazone, m.p. 220 ° C (decomposition) ·

(e) From 9 acridanone and 2- (1-piperazinyl) ethyl-chloromethyl acetate, 10- [2- (1-piperidinyl) methyl] 9 _-a ] was obtained having a melting point of 165 °. From there, 10-β-β-piperidinyl) thiyl-9-acrananone (2-thiazazol-1-yl) llydaazone, m.p. 207 DEG C., is obtained.

f) 10- [2- (4-Morpholinyl) ethyl] -19-sulfonic acid, m.p. 196 ° C, was obtained from 9-acridanone and 2- (4-morpholinyl) ethyl ethyl-chloro-4-yl-acetyl. f2- (4-Morpholinyl) - ttll] -9-acrido-2- (2-thiazazol-1-yl) -yl (melting point 236 ° C) ·

Example 2

(a) A mixture of 4.5 g of 9-acridanone, 1.1 g of sodium hydride and 100 ml of dimethylformamide is stirred for 0.5 hours, after which 5.2 g of 2- (4-acetyl-1-pipealziilllethylether ^{) are} added. YitI ^y _J droctloaiУu mixture was. stirred for 15 hours at 70 ° C and then repel · to the residue was added water ,, oethylenchlorideo extracted, the extract was washed with water, dried over sodium sulfate and concentrated - with · Krystlizací from ethanol m.p. 341 DEG-243 DEG C., yields 10o [2- (4-acyl-1-piperazinyl) ethyl] 9-aryldi10i;

1.7 ml (20 momo) was added to a suspension of 3.5 g (10 mmol) of 10-L2- (4-methyl-1-piperealzilyl) piperazin-9,9l _and 100 ml of 100 ml. oxalylctloriУs, after half an hour the mixture was filtered and the filter residue (9-ctloa-10- [2- (4-acetyl-1-ρiperaziryL)) ttУLl] laaiУiinSшιctloaiУ) Fe 'postopně washed LCE ^t onihai · ether · EO and the mixture obtained substances · ^y 2 ^g (10 ^{2-hydroxy-2-Drazin} thlaoolin-УdrrobrooiУu, 2.5 g (30 mmol) of sodium acetate and 100 ol oothuolu was heated to reflux - Piot after 15 minutes ODPs * i, to the residue was added water, basified with sodium carbonate solution and extracted with methylene chloride, the extract was washed with water, dried and evaporated, and the residue was crystallized.

· After a methoiolu přefrystaLování from n-butanol gave 10- [2- (4-1-tcetyl pipertzinyl) ethyl] -9-tkridtnon- (2-thiazoLLidlцLiLie · n) Уdl ¹ tιzon mp 256 ° C.

The following compounds were obtained in an analogous manner:

b) From S-acridenoin and 2- (4-ethoxycyclohexyl-1-piperidinyl) thiyl chloride (4-fluorocyclohexyl) gave 10- (2- (4-ethoxycyclobutoyl-1-piperidinyl) ethyl) - 147 DEG C., from which 10o [2- (4- (thiocyclohexyl) PP-propynyl) ethh-9-aryridin-12-thiolidinidinidene) hydrazone, melting point 231 DEG C. (decomposition), is obtained.

c) 10- [2- (4-Trifluyl-1-piperidinyl) ethyl] -9-nitrocylmethyl] -9-nitrocyclone was obtained from m.p. 184 DEG-10 DEG C. and 10- [2- (4-pivloyl-1-piperazinyl) ethyl] -9-acetonitrile (2-thiazolinylidene) hddtazone, m.p. 208 DEG C., are obtained.

d) from 9-acre »d ^! ^ M and ^ nu, and 2- ^[4 - (R · ^r eChS8lUfon S) -1-pipertziiyl] ethyl] SfchloгUd-yUruchluriUu gave 10- [2- [4-.ζm · ehhiaslfooylL 1-plpertzlnyl] -9-ethyl tkгUtanon mp ^244-246 ° ^C aZN ^and J, was recovered ^á to- [2- [4- ^{(Detlhllulfoод yL} - ¹ - ^pip · RTZ ⁱ n ^yl] ethFl] 223 DEG-235 DEG C. (decomposition), 9-trifluoromethyl-2-thiazolinylidrazone.

Example - 3

(a) A mixture of 3.9 g of acridanone, 1.0 g of sodium hydride and 80 ml of dimethylformamide is stirred for 0.5 hour, after which 2.9 g of L-chloro-2 (mmetyl) aminomethylhydrochloride are added. After stirring for 18 hours at 60 DEG C., the mixture is evaporated and the residue is extracted with dichloromethane. The mixture is washed with water, dried over sodium sulphate and evaporated. Kystalizací from isopropyl ether gave to- [2- (UimethylarincUaeChrl] -9-a] α * Udвдun point is a temperature of 45 and ^{1 out of 146} ° C.

A solution of 3 g of 10- [2- (dimethylamino) ethyl] -9-acranione in 100 mL of dichloromethane and 1.93 ml of uXe-α-ethylurea is stirred for 0.5 hour. 25 g of 2-hydrazine-2-thiazolidine-boroboride and 3 g of sodium acetate are added and the mixture is stirred at ~ 100 rt. _rrehιшoUu> whereupon ee 10 minutes heated to reflux and again evaporated. To the residue, water was added, the mixture was basified with sodium carbonate solution and extracted with dichloromethane. The extract was washed with water, dried over sodium sulphate and evaporated. There was obtained 10- [2- (2-thiazolidinyl) ethyl] -9-trifluoromethyl- (2-thiazulidine) hydrazole, m.p. 192-194 ° C.

The following was obtained in an analogous manner:

b) From 10- (2- (ethyl) amino) propanol-4-yl chloride, 10- (2-

(9-Acrylonitrile) -9-α-crystalline with a melting point of 114 ° C and from it - [2- - (&lt; / RTI &gt; methylmethylamino) propyl-9-trifluoromethyl- (2-thiazolyl) yl] pyridine is obtained having a melting point of 152 ° C. ·

c) Starting from 9-acryl (mono and 2- (2,6-direttyl-1-piperidixyl)) - tlSlcCHloCHd-hydrochloride to give - [2- (2,6-trans-ethyl-1-piperidyl) ethyl] ethyl] - 9takiUtnlUi m.p. 146 ° C and it gave Ю- ^{[2- _(2>} 6 ^u irreC ^hS L1 - p ± p · L. ^{<u NSSL} l) e ^t h ^y l] -9-tkriάtiun> (2 -thiazul ^u d ⁱ l ^u ι ^yl DIN) Sůfrazui m.p. 161 - C ·

(d) From 9-acridinyl and (1-methyl- ^4- sulfazolyl) methyl chloro- ⁴ -trifluoromethylurea to give 10-β-a-methyl- ^4- imidazolyl) methyl] -9a acidil-1-yl having a melting point of 205-207 ° C; yielding 10 - [(1-methyl-4-methylsulphinylmethyl) -2-thiazolinyl] urea melting at -206 to 208 ° C.

e) From 9-acridanone and 2- [4- [2- (dimethylamino) acetyl] -1-piperazinyl] ethyl chloride hydrochloride to give 10- [2- [4- [2- (dimethylamino) acetyl] -1-piperidinyl] ethyl chloride -1 146-147 ° C and from there to give 10-3- 4- 2- (dimethylamino) -asyl-1-piperazinyl-ethyl-9-acridanone- (2-thiazolidinylidene) -piperazinyl] ethyl] -9-acridanone. hydrazone, m.p. 129-131 ° C.

f) From 1-chloro-9-acridanone and 2- (diethylamino) ethyl chloride hydrochloride to give 10-42- (dimethylamino) ethyl] -1-chloro-9-acridanone, m.p. 121 ° C, from which 10- . 42- (diethylamino) ethyl] -1-chloro-9-acridanone- (2-thiazolidinylidene) hydrazone, m.p. 181-183 ° C.

g) From 9-acridanone and 2- (4-propyl-1-piperazinyl) ethyl chloride dihydrochloride, 10- [2- (4-propyl-1-piperazinyl) ethyl] -9-acridanone is obtained and 10-? 2- (propyl-1-piperazinyl) ethyl] -9-acridanone- (2-thiazolidinylidene) hydrazone, m.p. 205-207 ° C (dec.).

Example 4

A solution of 4.94 g (16.8 mmol) of 10- [2- (diethylamino) ethyl] -9-acridanone in 300 mL of dichloromethane was stirred with 2.85 mL (33.6 mmol) of oxalyl chloride for 1 hour. The resulting (9-chloro-10- [2- (diethylamino) ethyl] acridinium chloride) salt was filtered off and 100 ml of methanol, 2.82 g (16.8 mmol) of 2- (3-methyl) thiazolidinylidene hydrazine were added. hydrochloride and 4.1 g (50 mmol) of sodium acetate. The mixture was heated at reflux for 10 minutes, then evaporated, water was added to the residue, the solution was basified with sodium carbonate solution and then extracted with dichloromethane. The extract was washed with water, dried and evaporated. Crystallization from ethanol gave 10- [2- (diethylamino) ethyl] -9-acridanone- (3-methyl-2-thiazolidinylidene) hydrazone, m.p. 123-125 ° C.

Example 5

a) A mixture of 3 g (9.33 mmol) of 10- [2- (4-methyl-1-piperazinyl) ethyl] -9-acridanone, 100 ml of dichloromethane and 1.6 ml (18.66 mmol) of oxalyl chloride was stirred for 0 hours. The mixture was concentrated to half its original volume and the salt (9-chloro-10- {2- (4-methyl-1-piperazinyl) ethyl] rakridinium chloride) precipitated by addition of 100 ml ethyl acetate. The salt is filtered off, washed with petroleum ether.

With ether and dried. The red-brown powder was heated to reflux with 1.42 g (9.33 mmol) of 2-thiazolylhydrazine hydrochloride, 2.3 g (28 mmol) of sodium acetate and 100 ml of methanol for 5 minutes, then the reaction mixture was refluxed. Evaporate to the residue with 50 ml of water, basify with sodium carbonate solution and extract with dichloromethane. The extract was washed with 10% sodium chloride solution, dried and evaporated. The residue is taken up in 100 ml of methanol, acidified with ethanolic hydrogen chloride, the precipitated product is filtered off and washed successively with a small amount of cold ethanol and petroleum ether. 10- 2- (4-methyl-1-piperazinyl) ethyl] -9-acridanone- (2-thiazolyl) hydrazone x 2.5 HCl is obtained, m.p. 230 ° C (dec.).

The following compounds were prepared in an analogous manner:

b) From 10- [2- (dimethylamino) ethyl] -9-acridanone and 2-thiazolylhydrazine hydrochloride, 10- [2- (dimethylamino) ethyl] -9-acridanone- (2-thiazolyl) hydrazone dihydrochloride is obtained Melting point> 200 ° C (decomposition).

c) 10- [2- (4-ethoxycarbonyl-1-piperazinyl) ethyl] -9 is obtained from 10- [2- (4-ethoxycarbonyl-1-piperazinyl) ethyl] -9-acridanone and 2-thiazolylhydrazine hydrochloride. -acridanone- (2-thiazolyl) hydrazone dihydrochloride, m.p. 185 ° C (dec.).

235991 12

d) From 10- [2- [4- (aethylsulfonyl-1-piperazinyl] -ethyl] -9-ecridanone and 2-thiazolylhydraain hydrochloride, 10- [2- [4- (aethylaulfonyl) -1-piperazinyl] ethyl] -9-acridanone-2 (2-thlazolyl) hydrazone dihydrochloride, m.p. 200 ° C.

e) From 10-2- (4-propyl-1-piperazinyl) ethyl-9-acridanone and 2-thiazolylhydrazine hydrochloride, 10- [2- (4-propyl-1-piperazinyl) ethyl] -9-acridanone is obtained. (2-thiazolyl) hydrazone x 2.5 HCl, m.p. 220 ° C (dec.).

Example 6

a) A mixture of 9.75 g (50 mmol) of 9-acridanone, 200 ml of dimethylformamide and 4.8 g (200 mmol) of sodium hydride is stirred for 0.5 hour, then 17.6 g (50 mmol) are added in portions. 2- (4- [2- (diethylamino) ethyl] -1-piperazinyl] ethyl chloride trihydrochloride, stirred at 70 ° C for 18 hours, then heated at reflux for 8 hours and evaporated. 100 ml of water are added to the residue, extraction is performed with dichloromethane, the extract is washed with water, dried and evaporated. The product was twice crystallized from petroleum ether to give 0- £ 1 £ 2 £ 4- 2- (diethylamino) ethyl] -1-piperazinyl ethyl] -9-acridanone, mp 106-108 C. ^Q

To a suspension of 4.06 g (10 mmol) of this material in 100 mL of absolute acetonitrile was added portionwise with stirring 1.7 mL (20 mmol) of oxalyl chloride, then the mixture was evaporated, acetonitrile was added to the residue, the product was filtered off and gradually Wash with ether and petroleum ether and then dry. The brown powder (9-chloro-10- [2- [4- [2- (diethylamino) ethyl] -1-piperazinyl] ethyl] acridinium chloride) was taken up in 100 mL of methanol, and 1.52 g (10 mmol) of 2- of thiazolylhydrazine hydrochloride and 2.46 g (30 mmol) of sodium acetate, and the reaction mixture was heated to reflux for 10 minutes. After evaporation, 100 ml of water are added to the residue, the mixture is basified with 2N sodium hydroxide solution to phenolphthalein, and the precipitated product is taken up in 100 ml. dichloromethane, the resulting solution was washed with water until neutral, dried and evaporated. The residue is dissolved in 100 ml of methanol, then acidified with ethereal hydrogen chloride. The precipitated salt is filtered off and washed successively with methanol, ether and petroleum ether. 10 - (2 -? - 4 -? - 2- (diethylamino) ethyl] -1-piperazinyl] ethyl] -9-acridanone- (2-thiazolyl) hydrazone x 3.5 HCl are obtained, m.p. 235 ° C (dec.) ).

The following compounds are obtained in an analogous manner:

b) From 10- [2- [4- [2- (diethylamino) ethyl] -1-piperazinyl] ethyl] -9-acridanone and 2-hydrazino-2-thiazoline hydrobromide, ξθ- [2- [4- [2- (diethylamino) ethyl] -1-piperazinyl] ethyl] -9-acridanone- (2-thiezolidinylidene) hydrazone, m.p. 144-146 ° C (dec.).

Example 7

a) A mixture of 4.94 g (16.8 mmol) of 10- [2- (diethylamino) ethyl] -9-acridanone, 300 ml of dichloromethane and 2.85 ml (33.6 mmol) of oxalyl chloride is stirred for 20 minutes, the crystals obtained (9-chloro + 10 * p - (diethylamino) ethyl] pyridinium chloride) was filtered off and washed with ether. Dissolve the substance in 100 mL of methanol, add 2.8 g (16.8 mmol) of N-methyl-N- (2-thiazolyl) hydrazine-hydrochloride and 4.1 g (50 mmol) of sodium acetate to the solution, the reaction mixture The mixture was heated at reflux for 15 minutes and then evaporated. The residue was basified with sodium carbonate solution, extracted with dichloromethane, washed with water, dried and evaporated. Crystallization of the residue from isopropyl ether gave 10- 2- (diethylamino) ethyl-9-acridanomethyl- (2-thiazolyl) hydrazone, m.p. 103-104 ° C.

b) In an analogous manner, 10- [2- (diethylamino) ethyl] - is obtained from 10- [2- (diethylamino) ethyl] -9-acridanone and N-methyl-N- (2-thiazolin-2-yl) hydrazone. 9-acridanone-methyl- (2-thiazolin-2-yl) hydrazone, m.p. 109-110 ° C.

Example 8

To a suspension of 2 g (30 mmol) of ^[ 2- (9-oxo-10 (9H-) - acridinyl) ethyl] kebbic acid benzyl ester in 100 l of glacial acetic acid is added 20 g of glacial acetic acid containing about 30% hydrogen bromide and the reaction mixture was stirred for 1 hour. The product is filtered off and pMO 2 is glacial acetic acid and ether. Give the 10- (2-aoinoe thh.l-9-al-ddanion chloride-hydrate, a teptetě ^th it is higher than ²⁵⁰ ° C. The free ^b Aze in ^{Y and} Z of the SR vodnéto solution přWánío hh solution ^{(ddolennhtlčitailu} sodium filtered and ^ is with water and acetone. from the free ^bá zíslsaný anatyzovaný tydrocJU.or and ^t ^ ^e and ^d at teptete to ²⁵⁰ ° C.

6.11 g (27 m @ 2 H of the above free base) are suspended in 100 l of pyridine, and 2.33 l of 30 ml of methanol are added to the obtained suspension. The solution is concentrated to 300 l, 500 l of water are added and concentrated again to 300 l in vacuo. The product is filtered off, washed with water and recrystallized from ethanol. N- [2- (9-oxo-10-akrídanyl) e ^thyl] rnethansulfonao te ^ o ^p ture t.ání ²²⁶ and ²² 7 ° C.

950 g (3 hours) of this material is suspended in 10 l of meetth-β-β-chloride, then 0.8 l (9 n oo oo) of β-β-tor is added and the reaction mixture is evaporated after 1 hour.

100 ol ^ βίοη ^^^ and add. The product was filtered off, washed with ether and dissolved in a saline salt and stirred (97: 3). The solution was basified. roztokern hydrogenuhhičitamu solution, extracted ocethrlenchlorideo dried sírarneo sodnýrn and evaporated. After the srněěi meettУenihtorifu, oethaiolu · petroleum ether to give N- [2- ^{[9- (2-thiazol 2-yl i} n ^{t) fy} h bzlinq ] 110bl ^{to fb} r i rlj ^h) '1 ^] ^ oe.ttonsulfonao m.p. ²⁰⁶ and ²⁰⁷ ° ^C (dec.

Example 9

(a) 9.75 g (50% by weight) of 9-allyidanone are added to a suspension of 1.44 g (60 onol) of sodium hydride in 100 µl of dimethyltrroaoif over 10 minutes, and the mixture is maintained at ⁵⁰ ° C for 2 hours. businesses temperature of ²⁰ ° C ^for PA ^{9.5 g} (53 rn ^ ^{o) 4,} 4- ^F iethc> ut χ ^{Yb y} lc ^tl ORIF. After 16 hours, the mixture was cooled, poured into water, extracted with dichloromethane, dried over sodium sulfate and evaporated. Odpíarek hexanes solution and extracted twice crystallized from Exan ^{h. From} IS ^{Ka 1} 0- ^{(4, 4} - ^fi ettox ^yb ut ^yl) -9-alУ ^'f -O dínιln tepldě friction and ^{73 F 74.5} ° C.

8.5 g (25 RNNO.) Of this solid was rozpuutí ol in 20 l ^^ ^ diets, to which is added 15 ol tyseli mE ^ ^ ^ ⁱ i ^{bee, and} from Soeste l ^gro IV ^and after a ^{d b} u todn ²⁰ to ¹⁰⁰ ° C, ^cooled, treated with water and dilute hydrochloric acid and the aqueous solution is for ^ ETHEREA. Sodium hydroxide was added to the aqueous solution and extracted with methylene chloride. The extract was dried over sodium sulphate and evaporated. ^Z byte ^k crystallizes from. toxan. ^From IS ^{Ka 1} 0- [4- ^(f IE ^TTYL Aoin) uS ^{b y L} l -9 "bk'idbnln a melting-point of 66.5 to 68.7 ° C. Melting point: 126.8 to 128.3 ° C.

К solution of 3.0 g (9.3 rnrnol) of the above free base in 200 ш1 dichlornethanu at 0 ° C for 3 tohern oinut dropwise ^2.4 RNL (2 ^7,9 rn ^ ^o.) Oxalylch.ori.d . Soeste the OIC ^hook at ^one Tochni oíítumsi then ofppb ^{of zb y} Tek (9 ctllr-10- ^[4 -deeth aminl ^{yb) Butyl]} bllrifinisochllrif to about 300 vyjoe acetoidtrilu added 1.57 g of I- it 10.2) 2-hydrazlno- -2-ttiazllin-lhrfylctllУifu, Soeste heated for 0.5 hours to boiling under zpětnýto chladičeo, Oichi still Todini 1.5 ^s at room temperature and cooled to 0 ° C. Sell is filtered off, washed with diethyl ether and ether and washed with water. The solution is made alkaline with sodium carbide, extracted with ethylene chloride, and the solution is dried with sodium sulphate and evaporated. Kyytabizbcí srněěi dchlo of methane and petroleum ether of ⁱ with ^k and ¹ 0- ^[4 - ^(FI et LEmiil ^t h ^{l) b utyi]} -9-b ^{to f} bion- yl (2-t ^I bzllf ^d iy ^y l ^f eilth ^d lrazln with temperature ten!

105.6 - 107.2 ° C.

b) In an analogous manner, 10- (5,5-diethoxy-pententyl) -9-acridonone having a melting point of 82-83 ° C is obtained from 9-acrimonone and 5,5-diethoxy-pentyl chloride, from which 10- [5- (diethylanilino) is obtained. -pentyl] -9-acridinone, m.p. 59-61.2 ° C, yielding 10- [5- (diethylamino) phenyl] -9-a] l] dianone (2-thiazolidiryrlienn) hyrdrazone, m.p. 128.5-130.1 ° C.

Example A

Production of tablets of the following composition:

mm / tablet active ingredient milk sugar bulletMeat Starch povidone mothers magnesium salt of stearic acid

100 ·

100 mg tablets 300 mg

The active ingredient is mixed with milk sugar and corn starch, moistened with an aqueous solution of povidone and granulated. The grinnuate is dried at 40 ° C and sieved. The screened mixture is crosslinked with talc and magnesium stearic acid and the tablets are compressed.

They can be processed as active ingredients in the manner described above. the following compounds of formula I:

10- [2- (4-οο) 1 ') of 1- piperazinyl PethylI 1-S-acridanone (2-thiazooyl) hydrazone [2- ^(4-ethyl -оп ^ - ^^ piperazinyl) eth ^yl] - 9-a ^to r ^id aoon- ^{(2 t} h ⁱ azo ^l id ^of llinon r ^{l)) l} drazoo,

10- [2- (4-acetyl-1-piperazinyl) beta] -9-pyridino-4- (2-thaazolinolinyl) lydrazoo,

10- [2- (dimethylamino) ethyl-5-acridanone- (2-thiazolidiryllieone) hydrazone,

10- [2- (1 (piperidin) ethyl)] -9-krx ^, idlolo- (2-thiazolesP (-idogazoo),

10- [2- (diethyl) pyrrolidin-11-yl] -9-amino-o- (2-thiazolyl) -yl azole,

10- (2-Amino-4-yl) -9-arylamino- (2-thiazolyl)) -drazoo,

10- [2- (dimethylamino) ethyl] -S-acridanone-N-thiazol-4-yl-drazone,

10- [2- (4-acetyl-1-piperazinyl) ethyl] -9-acridanone- (2-thiazolyl) hydrazone,

10- [3- (dimethylamino) proppyl-acridanone- (2-thiazolyl) hydrazone,

10- (4- (diethylthmino) nyl) -9-acrnianooo (2-thiazolniiollidno) hydrazone,

10- [2- (1-pyrrolidinyl) thienyl] -9-bromoimido- (2-thaazoninolyl) -lydrazoo, and

10- (3- (dioo) thiopheno) ppooyl-99akkiddaoo- (2-thiazolidinidin) yrdrazoo.

Claims (8)

SUBJECT OF THE INVENTION A process for the preparation of acridanone derivatives of the general formula I wherein: A (I) dotted line means an optional bond, R ¹ is hydrogen, halogen or nitro R; represents hydrogen or an alkyl group having 1 to 7 carbon atoms, R @ 4 is one of R @ 1 and R @ 1 is hydrogen or (C1 -C7) alkyl and the other is, together with R, an additional bond, A represents a C 2 -C 7 alkylene group, a nitrogen-containing five-membered aromatic heterocyclic ring which is optionally substituted with a C 1 -C 7 alkyl group, furthermore an amino group or a group of formula. (B) _n -A-R ⁶ -N wherein the symbol -10 denotes a saturated heterocyclic ring optionally containing a oxygen or sulfur atom as a ring member or a 3ΖΣΝΗ or T ^NCBA -A --- group with a 5- or 6-membered, optionally C 1 -C 7 alkyl group, R 6 is -CO-, -COO- or -SO 8 -, or is 0 or 1, A ^ represents a (C až-C alX) alkylene group, R £ is hydrogen, amino, (Clam-C alky) alkylamino or (C až-C dial) dialkylamino group, and R ⁷ is hydrogen or C 1 -C 7 alkyl, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula (X): Y® stands for anion, (X) X is a leaving group, A and ^R1 are as defined above and R &lt; ^{1 &gt;} has the meaning of any of the radicals R &lt; ⁵ &gt; defined above but which does not contain a primary or secondary, &gt; basic amino group; (XI) in which: The dotted line, R, R, R and Г are as defined above, and the compound of formula I obtained is optionally converted into a pharmaceutically acceptable acid addition salt, ♦ 2. A process according to claim 1, wherein the corresponding compounds of formula X and XI are used as starting materials to form compounds of formula I wherein R1 is in the 1-position and is hydrogen, halogen or nitro. and R, R ² , R ³ , _and д _{have the} meaning given in point 1. 3. A process according to claim 1, characterized in that the corresponding compounds of the formulas X and XI are used as starting materials to give compounds of the formula I in which: 45 R is hydrogen and R, R, R, R, R and A are as defined in 1. 4. A process according to claim 1, characterized in that the corresponding compounds of the general formulas (X) and (S1) are used as starting materials to give compounds of the general formula (I) in which: 2 13 45 R is hydrogen and R, R, R, R, R and A are as defined in point 1. 5 · The process according to claim 1, characterized in that starting from the corresponding compound of formula X а XI to give compounds of formula I wherein one of R ³ and R 'is hydrogen and the other together with R means an additional bond 125 and R, R, R and A have the meaning given in point 1. 6. A method according to claim 1, characterized in that starting from the corresponding compound of formula X а XI to give compounds of formula I wherein A represents a dimethylene or trimethylene group and R, ^R \ R ^2, R ³ , R ^, R ^ have the meaning given in point 1. 7. A process according to claim 1, wherein the compounds of formula (X) and (XI) are used as starting materials to form compounds of formula (I) wherein R * is amino, 1-pyrrolidinyl, 1-piperidinyl, 1-morpholinyl, 1-piperazinyl or a group of the formula -NR 4 -A 4 -R 4, or a group of the formula -NN- (B 4) _n -A 4 -R 4A ¹ represents an alkylene group of 2 to 7 atoms carbon, N is 0 or 1, R is hydrogen and R 'is hydrogen or alkyl of 1 to 7 carbon atoms and R, R, R, R, R * and A have the meaning given in point 1 «* 8. A method according to claim 7, characterized in that starting from the corresponding compound of formula X obecnáho а XI to give compounds of formula I v.méaž is amino, dimethylamino, diethylamino, 1-pyrrolidinyl Groups should _t pin, 1-piperidinyl, 4-methyl-1-piperazinyl or 4-acetyl-1-piperazinyl and R 1, R ² , R ² , R ³ , R 6 and A are as defined in point 1.