MXPA00001486A - 8-SUBSTITUTED-9H-1,3-DIOXOLO/4,5-h//2,3/BENZODIAZEPINE DERIVATIVES, AS AMPA/KAINATE RECEPTOR INHIBITORS - Google Patents

Abstract

The invention refers to novel 8-substituted-9H-1,3-dioxolo/4,5-h//2,3/benzodiazepine derivatives of formula (I), a process for preparing these compounds and to pharmaceutical compositions containing these active substances. Compounds (I) inhibit Ampa/Kainate receptors.

Description

DERIVATIVES OF 8 SUBSTITUTE-9H-1, 3-DIOXOLO [4, 5 h] [2,3] BENZODIAZEPINE AS AMPA / KAINATE RECEPTOR INHIBITORS The invention relates to novel derivatives of 8 substituted-9H-1, 3-dioxolo [4,5-h] [2, 3] enzodiazepine, with a pharmaceutical composition containing them, and with a process for the preparation of the ingredient active. More specifically, the invention relates to novel derivatives of 8 substituted-9H-1, 3-dioxolo [4,5-h] [2,3] enzodiazepine of the formula I wherein X represents a carbonyl group or a methylene group, and R 1 denotes a hydrogen atom, a hydroxy group, a C 1-4 alkoxy group, a C 1-4 alkanoyloxy group, a group (C 1-4 alkyl) sulfonyloxy or a group of the formula -NR4R5, wherein R4 and R5 signify, independently, a hydrogen atom, a C1-4 alkoxy group, a C1-4 alkanoyl group, or an C1-s alkyl group, the latter which is optionally substituted by a saturated or unsaturated heterocyclic group having 5 or 6 members and comprising 1 or 2 nitrogen atoms or a nitrogen atom and an oxygen atom as the heteroatom, and by a group N- [ phenyl- (C 1-4 alkyl)] -N- (Cj ^ Jamino alkyl, wherein the phenyl group is optionally substituted by 1 to 3 substituents, wherein the substituent consists of a C 1-4 alkoxy group, or R 4 and R5 form with the adjacent nitrogen atom and optionally with an additional nitrogen atom or an oxygen atom, a saturated or unsaturated heterocyclic group having 5 to 10 members, or X together with R1 forms a cyano group, a tetrazolyl group, a group of the formula -CHNOH, or a group of the formula -COR6, wherein R6 signifies a hydroxy group , a C1-4 alkoxy group, a phenoxy group, a naphthyloxy group or an amino group which is optionally substituted by a C1-4 alkyl group, R2 denotes a nitro group, an amino group or a group (alkanoyl) of C 1-4) amino, R 3 represents a hydrogen atom, a C 1-4 alkyl group, or a group of the formula -COR 7, wherein R 7 represents a hydrogen atom, a C 1-6 alkyl group, a group C 1-6 alkyl substituted by 1 to 3 halo atoms, a C 1-4 alkoxy group, a phenoxy group, a pyridyl group, a phenyl group or a naphthyl group these last two groups which are optionally substituted by 1 to 3 substituents or a group of the formula - (CH2) n-NR8R9, wherein R8 and R9 independently represent a hydrogen atom, a C1-4 alkyl group optionally substituted by a phenyl group or a saturated heterocyclic group having 5 or 6 members and containing a nitrogen group or a nitrogen group and an oxygen group , and the phenyl group is optionally substituted by 1 to 3 substituents wherein the substituents consist of a C1-4 alkoxy group, or R8 and R9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen atom, a saturated or unsaturated heterocyclic group that has or 6 members and which is optionally substituted by a phenyl group which is optionally substituted by 1 to 3 substituents, wherein the substituent consists of a halo atom or a C 1-4 alkoxy group, n has a value of 0.1. or 2, Y is a hydrogen atom, or a methyl group, or Y together with R3 form a valence bond between the carbon atom at position 8 and the nitrogen atom at position 7, with the proviso that: 1) if Y indicates a hydrogen atom or form together with R3 a valence bond and X represents a methylene group, then R1 is different from a hydrogen atom, and 2) if Y indicates a hydrogen atom or a methyl group and R3 represents an alkyl group of Cx_4, or a group of the formula -COR7, then X is different from a methylene group, and pharmaceutically suitable acid addition salts or quaternary ammonium derivatives thereof. A number of 2,3-benzodiazepine derivatives having biological activity are known. Tosifopam, i.e., 1- (3,4-dimethoxyphenyl) -5-ethyl-7-, 8-dimethoxy-4-methyl-5H-2,3-benzodiazepine having anxiolytic effect from HU-P No. 155 572 and GB-P No. 1 202 579, respectively. The known compound does not comprise the 1,3-dioxolo [4,5-h] [2,3] benzodiazepine ring system. Starting from HU-P No. 186,760, derivatives of 7,8-dihydro-8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine are known to have an effect on the central nervous system, among others. The known compounds are prepared by reducing the corresponding derivative of 8-methyl-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine. Several derivatives of substituted 8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine are known from HU-P No. 191 698 and the corresponding document GB-P- No. 2 162 162. The known compounds have anti-aggression and anxiolytic activities. A process for the preparation of partially new 8-methyl-l-9H-l, 3-dioxolo [4,5-h] [2, 3] benzodiazepine derivatives having antiaggressive activity is known from document HU-P No. 191 702. According to the novel process, suitably substituted 2-acetonyl-4, 5-methylenedioxybenzophenone is reacted with an excess of hydrazine hydrate. In addition, derivatives of 7,8-dihydro-8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine having antidepressant and antiparkinson activities are known, from document HU-P No. 206 719. A physical form of (R) -7-acetyl-5- (4-aminophenyl) -8,9-dihydro-8-methyl-7H-l, 3-dioxolo [4,5-h] [ 2,3] Benzodiazepine useful as an AMPA antagonist is described in EP No. 699 678.

Derivatives of 7-acyl-5- (4-aminophenyl) -8,9-dihydro-8-methyl-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine having anticonvulsant activity are known. and muscle relaxant, from EP No. 492 485. 5 The enantiomers of 7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine are described in WO 95/01357. The known enantiomers are useful as intermediates in the synthesis of therapeutically active compounds. In EP No. 699 677 a stereoselective process for producing known dihydro-2,3-benzodiazepine derivatives is described. The derivatives of 5- (4-substituted phenyl) -8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine are described in FR 2 566 15 774. The compounds have anti-aging activity . In J. Am. Chem. Soc. 117, 12358-9 (1995), the enantioselective synthesis for the preparation of 7-acetyl-5- (4-aminophenyl) -8-methyl-8,9-dihydro-7H- is described. 1, 3-dioxolo [4,5- h] [2, 3] benzodiazepine. 0 7-Acetyl-5- (4-aminophenyl) -8-alkyl-7H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine is described in DE-P No. 44 28 835 The known compounds inhibit AMPA receptors. An enantioselective synthesis is known for the preparation of derivatives of 7-acyl-5- (4-aminophenyl) -8-, 9-dihydro-8-methyl-7H-1, 3-dioxolo [4,5-h] [ 2,3] benzodiazepine from J. Chem. Soc. Perkin Trans I, 1995, 1423-1427. Some of the 2,3-benzodiazepine derivatives induce their effect through non-competitive inhibition of the AMPA / kainate (kainate) receptors [Donevan, S.D. et al., J. Pharmacol. Exp. Ther., 271, 25-29 (1994)]. From the literature, it is known that AMPA / kainate receptors play an important role in acute and chronic diseases of the central nervous system. By inhibiting these receptors, a muscle relaxant, a neuroprotective and spasm inhibiting effects can be obtained [Vizi, E.S. et al., CNS Drug Reviews, 2, 91-126 (1996); Lees, G.L., CNS Drugs, 5, 51-74 (1996)]. The object of the invention is to prepare novel 2,3-benzodiazepine derivatives which are more effective than the known 2,3-benzodiazepine derivatives. It has been found that the above objective is obtained by the novel derivatives 8 substituted-9H-1, 3-dioxolo [4, 5-h] [2, 3] benzodiazepine which they have - due to their non-competitive effect on AMPA / kainate - considerable muscle relaxing activities, neuroprotective and anticonvulsants. Therefore, novel compounds can be used for the treatment of any disease (such as epilepsy, diseases resulting in muscle spasms, various neurodegenerative diseases, attack) in which the inhibition of AMPA / kainate receptors is favorable. In the description and claims, in the definition of the substituents under a C ^ alkoxy group, in particular a methoxy, ethoxy, n-propoxy, isopropoxy or n-butoxy group, it is preferably meant a methoxy group. A C 1-4 alkyl group is a methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, therapeutically-butyl or isobutyl group. Preferably, a C 1-4 alkyl group is a methyl or an ethyl group. A C 1-6 alkyl group can be, in addition to the alkyl groups indicated above, for example, an n-pentyl, 2-methylbutyl, n-hexyl, 2,2-dimethylbutyl or 2,3-dimethylbutyl group, etc. A C 1-4 alkanoyl group is, primarily, a formyl, acetyl or n-propyl group. Preferably, a C 1-4 alkanoyl group is an acetyl group. Similarly, a C 1-4 alkanoyloxy group is primarily a formyloxy, acetyloxy or n-propionyloxy group. It is meant under a saturated or unsaturated heterocyclic group having 5 or 6 members and comprising 1 or 2 nitrogen atoms or a nitrogen atom and an oxygen atom such as the heteroatom, for example a pyrrolidinyl, piperidinyl, piperazinyl, imidazolyl or morpholino group. Suitably, the other nitrogen atom of the piperazinyl group is substituted. When the substituents R4 and R5 form with the adjacent nitrogen atom a saturated or unsaturated heterocyclic group having 5 to 10 members, the heterocyclic group containing 1 or 2 nitrogen atoms or a nitrogen atom and an oxygen atom such as the hetero atom , and that consists of a ring or two condensed rings. The heterocyclic ring (s) do not contain double bonds or one or more double bonds. The above heterocyclic group is, for example, a pyrrolidinyl, imidazolyl, piperidinyl, pyridyl, morpholino, piperazinyl or 1,5-diazabicyclo [4.3.0] non-5-enyl group. Suitably, one of the nitrogen atoms of the piperazinyl group is substituted. It is meant under a pharmaceutically acceptable acid addition salt an acid addition salt formed with a pharmaceutically acceptable inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, etc., or with a pharmaceutically suitable organic acid such such as formic acid, acetic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, succinic acid, citric acid, methanesulfonic acid, etc. A quaternary ammonium derivative is a derivative in which one of the nitrogen atoms of a compound of the formula I is present in a quaternized form.

The invention includes any isomer of the compounds of the formula I and mixtures thereof. Under the isomers of the compounds of the formula I - due to the presence of at least one chiral center in both enantiomers, and - because the isomers that exist in case of certain substitutions - are meant the E and Z isomers, diastereomers, tautomeric forms and mixtures thereof such as the racemate. A preferred subgroup of the compounds of formula I consists of the substituted 8-lH-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine derivatives and pharmaceutically suitable acid addition salts and quaternary ammonium derivatives of the same, wherein, in the formula I: X represents a carbonyl group or a methylene group, and R 1 denotes a hydrogen atom, a hydroxy group, a methoxy group, an acetoxy group, a methylsulfonyloxy group or a group of the formula -NR4RS, wherein R4 and R5 signify, independently, a hydrogen atom, a methoxy group, an acetyl group or a C1-4 alkyl group, the latter which is optionally substituted by a morpholino group or a dimethoxyphenylethyl-N group - (methyl) amino, or R4 and R5 form with the adjacent nitrogen atom and optionally with an additional nitrogen atom or an oxygen atom, a saturated or unsaturated heterocyclic group having 5 to 9 members, or X forms together with R1 a cyano group, a group you trazolyl, or a group of the formula -CHNOH, R2 denotes a nitro group, or an amino group, R3 represents a hydrogen atom, or an acetyl group, Y is a hydrogen atom, or Y together with R3 form a bond of valence between the carbon atom in position 8 and the nitrogen atom in position 7, with the proviso that: 1) if Y indicates a hydrogen atom or form together with R3 a valence bond and X represents a methylene group , then R1 is different from a hydrogen atom, and 2) if Y indicates a hydrogen atom or a methyl group and R3 represents a C1-4 alkyl group, or a group of the formula -COR7, then X is different from a methylene group. Within the above subgroup, the especially preferred compounds of the invention consist of the following 8 substituted-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine derivatives and their pharmaceutically suitable acid addition salts and quaternary ammonium derivatives thereof: amide 5- (4-aminophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid, 5- (4-aminophenyl) -8-cyano-9H-1,3-dioxolo [4,5-h] [2] , 3] benzodiazepine, 5- (4-aminophenyl) -8- (5-tetrazolyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine. A further preferred subgroup of the compounds of the invention consist of the substituted 8-lH-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine derivatives of the formula I, wherein R3 represents a hydrogen atom or a group of the formula -COR7, wherein R7 denotes a hydrogen atom, an alkyl group of C1-4, a C1-4 alkyl group substituted by 1 to 3 halo atoms, or a group of the formula - (CH2) n-NR8R9, wherein R8 and R9 signify, independently, a hydrogen atom, a group C 1-4 alkyl, optionally substituted by a phenyl group or a morpholino group, and the phenyl group is optionally substituted by 1 or 2 methoxy groups, or R 8 and R 9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen, a saturated or unsaturated heterocyclic group that has or 6 members and which is optionally substituted by a phenyl group which is optionally substituted by a halo atom or a methoxy group, n has a value of 0, 1 or 2, X forms together with R 1 a cyano group, or a group of the formula -COR6, wherein R6 represents a hydroxy group, or an amino group, Y denotes a methyl group, R2 is a nitro group, an amino group or a group (C1-4 alkanoyl) amino, and addition salts of pharmaceutically acceptable acids thereof. Within the above subgroup, suitable compounds of the invention consist of 8-substituted-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine derivatives of the formula I, wherein R3 represents a hydrogen or a group of the formula -COR7, wherein R7 denotes a hydrogen atom, a C1-4 alkyl group, a C1-2 alkyl group substituted by a chlorine atom, a trifluoromethyl group, a trichloromethyl group or a group of the formula - (CH2) n-NR8R9, wherein R8 and R9 independently represent a hydrogen atom, a C1-2 alkyl group, optionally substituted by a phenyl group or a morpholino group, and the phenyl group is optionally substituted by 2 methoxy groups, or R8 and R9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen atom, a pyridinyl, pyrrolidinyl, morpholino or piperazinyl group, wherein the piperazinyl group is substituted by a group fluorophenyl or methoxyphenyl, n has a value of 0, 1 or 2, X forms together with R 1 a cyano group, R 2 signifies an amino group or a group (C 1-4 alkanoyl) amino, Y denotes a methyl group, and pharmaceutically acceptable acid addition salts thereof. Especially preferred compounds of the invention consist of the derivatives of substituted 8-lH-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula I, wherein R 2 represents an acetylamino or propionylamino group, R1, R3, X and Y are as defined in the claim And pharmaceutically suitable acid addition salts thereof. The substituted 8-lH-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine derivatives of the invention are prepared by the following methods: a) for the preparation of 8-formyl-5- (4-) nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula II II being within the scope of the compounds of the formula I, 8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine is reacted with an agent oxidant; or b) for the preparation of 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid of formula III being within the scope of the compounds of the formula I, 8-formyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula II is react with an oxidizing agent; or c) for the preparation of compounds of formula I, wherein R 1 is an imidazolyl group, R 2 represents a nitro group, X denotes a carbonyl group and Y forms together with R 3 a valence bond, 5 - (4-nitrophenol) - 9H-1, 3-dioxolo [4, 5-h] [2,3] benzodiazepine-8-carboxylic acid of formula III is reacted with 1,1 '-carbonyldiimidazole; od) for the preparation of compounds of formula I, wherein R1 is a group of the formula -NR4RS, R2 represents a nitro group, X denotes a carbonyl group, and forms together with R3 a valence bond, R4 and Rs are as are defined in relation to formula I, 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid of formula III or a reactive derivative of the same of formula IV IV wherein Y1 is a leaving group, it is reacted with an amine of the formula V R "V wherein R4 and R5 are as stated above; oe) for the preparation of compounds of formula I, wherein R1 is a C1-4 alkoxy group, R2 represents a nitro group, X denotes a carbonyl group, and forms together with R3 a valence bond, 5- (4 -nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid of formula III which is esterified with a C 1-4 alkanol; of) for the preparation of compound of formula I, wherein R 1 is a group (C 1-4 alkyl) sulfonyloxy, R 2 represents a nitro group, X denotes a methylene group, and forms together with R 3 a valence bond, 8- formyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine of formula II which is reacted with a reducing agent and 8- (hydroxymethyl) - 5- (4-nitrophenyl) -9H-1,3-dioxolo [4, 5-h] [2,3] benzodiazepine obtained is reacted with a halide of (C 1-4 alkyl) sulfonyl; og) for the preparation of compounds of the formula I, wherein R 1 represents a C 1-4 alkoxy group, a C 1-4 alkanoyloxy group, or a group of the formula -NR 4 R 5, R 2 denotes a nitro group, and forms together with R3 a valence bond, R4 and R5 are as stated in relation to formula I, 8-formyl-5- (4-nitrofenyl) -9H-1,3-dioxolo [4, 5-h] [2 , 3] benzodiazepine of formula II which is reacted with a reducing agent, and 8- (hydroxymethyl) -5- (4-nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2, 3] benzodiazepine obtained or a reactive alkylating derivative thereof of formula VI wherein Q indicates a leaving group, it is reacted with a C 1-4 alkanol, a C 1-4 alkanoiccarboxylic acid, or a reactive acylating group thereof or an amine of the formula V, wherein R 4 and R 5 are as establish before; oh) for the preparation of a compound of the formula I, wherein X forms together with R1 a group of the formula -CHNOH, R2 represents a nitro group, and forms together with R3 a valence bond, 8-formyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula II which is reacted with hydroxylamine; oi) for the preparation of a compound of the formula I, wherein X forms together with R1 a cyano group, R2 represents a nitro group, and forms together with R3 a valence bond, 8- (hydroxyiminomethyl) -5- (4 -nitrophenyl) - 9H-1,3-dioxolo [4, 5-h] [2, 3] benzodiazepine which is reacted with a dehydrating agent; or j) for the preparation of a compound of the formula I, wherein X together with R1 forms a tetrazolyl group, R2 represents a nitro group, and forms together with R3 a valence bond, 8-cyano-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4 , 5-h] [2, 3] benzodiazepine which is reacted with an alkali metal acid; ok) for the preparation of 7,8-dihydro compounds of the formula VI, which have a narrower group of the compounds of the formula I, wherein X represents a carbonyl group or a methylene group, and R 1 is as defined in relation to formula I, a compound of formula VII wherein X and R are as indicated above, which is reacted with a reducing agent; or 1) for the preparation of 7,8-dihydro-7-acyl derivatives of the formula VIII, VIII which are a narrower group of the compounds of formula I, wherein X represents a carbonyl group or a methylene group, R1 is as stated in relation to formula I, R3 indicates a C1-4 alkanoyl group, a derivative 7,8-dihydro of the formula VI, wherein X and R1 are as defined above, and reacted with (1-4C) alkane carboxylic acid or a reactive acylating derivative thereof; om) for the preparation of compounds of the formula I, wherein R1 is a group of the formula -NR4R5, R2 represents a nitro group, X denotes a carbonyl group or a methylene group, one of R4 and R5 represents an alkanoyl group of C1_4, while the other is as defined in relation to formula I, Y means a hydrogen atom and in this case R3 indicates an alkanoyl group of C1-4, or Y forms together with R3 a valence bond, a compound of formula I, wherein R1 is a group of the formula -NR4R5, wherein one of R4 and R5 signifies a hydrogen atom, while the other is like defined above, X, R2, Y and R3 are as indicated above, and reacted with a (1-4C) alkane carboxylic acid or a reactive acylating derivative thereof, - n) for the preparation of compounds of the formula I, wherein Y represents a methyl group, -X-R1 denotes a cyano group, R3 is a hydrogen atom and R2 signifies a nitro group, the compound of formula IX it is reacted with hydrogen cyanide; oo) for the preparation of compounds of the formula I, wherein Y represents a methyl group, R3 denotes a hydrogen atom, R2 means a nitro group and -X-R1 represents a group of the formula -COR6, wherein R6 is as defined in relation to formula I, the compound of formula X it is hydrolyzed with a mineral acid, and the carboxylic acid which is obtained is optionally converted into an ester or a carboxylic amide; op) for the preparation of compounds of the formula I, wherein Y represents a methyl group, -X-R1 denotes a cyano group or a group of the formula -COR6, R2 means a nitro group, R3 is an alkyl group of C1 -4, and R6 is as defined in relation to formula I, a compound of formula I, wherein Y and R2 are as indicated above, R3 represents a hydrogen atom, is reacted with a halide (alkyl) from C1-4); or) for the preparation of compounds of the formula I, wherein Y represents a methyl group, -X-R1 denotes a cyano group or a group of the formula -COR6, R2 means a nitro group, R3 is a group of the formula -COR7, R7 represents a group of the formula - (CH2) n-NRβR9, R8, R9 and n are as defined in relation to formula I, a compound of formula XI wherein -X-R1, R2 and n are as indicated above, X1 is a leaving group, preferably a chlorine atom, and is reacted with an amine of the formula HNR8R9; and if desired, a compound obtained from the formula I, wherein R 2 represents a nitro group, R 1, R 3, X and Y are as defined in relation to the formula I, is transformed into a compound of the formula I, wherein R2 represents an amino group, by reduction; and if desired, a compound obtained from the formula I, wherein R 2 represents an amino group, R 1, R 3, X and Y are as stated in relation to the formula I, are reacted with a (C 1-4) alkane ) carboxylic or an acylating derivative thereof; and if desired, a base obtained from formula I is converted to a pharmaceutically acceptable acid addition salt or a liberated form of the acid addition salt; and if desired, a compound obtained from the formula I or a pharmaceutically acceptable acid addition salt thereof is converted to a quaternary ammonium derivative. In the process a) of the invention, the reaction is carried out in a manner known per se in the preparation of aldehydes [Houben-Weyl: Methoden der Organischen Chemie, Aldehyde, Band E3, Georg Thiem Verlag, Stuttgart, 1983]. A preferred oxidizing agent is selenium oxide (iv).

In the process b) of the invention, the reaction is carried out in a manner known per se in the preparation of carboxylic acids from aldehydes [Houben-Weyl: Methoden der Organischen Chemie, Carbonsaure-Derivate, Band E5, Georg Thieme Verlag, Stuttgart, 1985; Saul Patai: The chemistry of acid derivatives, John Wiley ans Sons, New York]. In processes c), d) and e) of the invention, the reactions are carried out in a manner known per se in the carboxylic acid transformations [Houben-Weyl: Methoden der Organischen Chemie, Carbonsaure-Derivate, Band E5, Georg Thieme Verlag, Stuttgart, 1985]. In processes f) and g) of the invention, the reactions are carried out in a manner known per se in the conversion of oxo compounds to alcohols [Houben-Weyl: Methoden der Organischen Chemie, Alkohole, Band VI, Georg Thieme Verlag , Stuttgart, 1979]. The hydroxy compound that is formed is also reacted in a manner known per se with an alkylsulfonyl halide, preferably methylsulfonyl chloride in the case of process f); in the case of process g), the alkylsulfonyl ester of the hydroxy compound is reacted with an amine or the hydroxy compound is acylated, for example, with the corresponding alkanecarboxylic anhydride.

In processes h), i) and j) of the invention, the reactions are carried out in a manner known per se in the transformations of oxo compounds [Houben-Weyl: Methoden der Organischen Chemie, Carbonsaure und Carbonsaure-Derivate, Band E5, Georg Thieme Verlag, Stuttgart, 1985; Houben-Weyl: Methoden der Organischen Chemie, Heterane, Band III, Georg Thiem Verlag, Stuttgart, 1994]. In the process k) of the invention, the reduction is carried out in a manner known per se [Houben-Weyl: Methoden der Organischen Chemie, Reduction, Georg Thieme Verlag, Stuttgart, 1989]. In processes f), g) and k) of the invention, the reducing agent preferably is sodium tetrahydroborate. It should be noted that in the case of reducing a compound of the formula I, wherein X represents a carbonyl group, Y forms together with R3 a valence bond, R2 indicates a nitro group, using an equimolar amount of sodium tetrahydroborate, only the carbonyl group is reduced. In the presence of a large excess of sodium tetrahydroborate, in addition to the reduction of the carbonyl group, the double bond between the ring nitrogen in the 7-position and the ring carbon atom in the 8-position is also saturated. In processes 1) and m) of the invention, the acylation reactions are generally carried out using a reactive acylating derivative of (1-4C) alkane carboxylic acid such as acid halide, acid anhydride or an active ester , at a temperature of -20 to +150 ° C, preferably in the presence of an acid and / or pyridine binding agent, in the presence or absence of an organic solvent [Houben-Weyl: Methoden der Organischen Chemie, Carbonsaure und Carbonsaure- Derivate, Band E5, Georg Thiem Verlag, Stuttgart, 1985; S. Patai. : The chemistry of amides, Interscience Publishers, 1970]. In the process n) of the invention, the reaction of the compound of formula IX and hydrogen cyanide is carried out in a manner known from the literature [Houben-Weyl: Methoden der Organischen Chemie, Band VIII, Georg Thieme Verlag, Stuttgart]. The derivative 8-methyl-9H-1, 3-dioxolo [4, 5-h] [2, 3] benzodiazepine of the formula IX can be prepared by a method which is analogous to the process described in HU-P No. 191 702. In the process o) of the invention, the cyano group of the compound of the formula X can be hydrolyzed in a manner known per se, preferably in the presence of a mineral acid [S. Patai: The chemistry of the cyano group]. In the process p) of the invention, the nitrogen atom in the 8-position of the compound of the formula I can be acylated in a manner known per se, in general, with an acid chloride, an acid anhydride or an ester of chlorocarbonate, optionally in the presence of an acid-binding agent, in the presence or absence of a solvent, at a temperature from -20 to +150 ° C. For the preparation of carbamoyl derivatives, the acylated derivative which is obtained by using an active chlorocarbonate ester is reacted with an amino compound, or a compound of the formula I, wherein R represents a hydrogen atom, is reacted directly with the corresponding isocyanate. In the process r) of the invention, the compounds of the formula I, wherein the carbon atom is in the 8-position, are substituted by a group of the formula -CO- (CH2) n-NR4Rs, and can be prepared suitably by reacting the corresponding compound of the formula XI, wherein R1, R2 and n are as set forth in relation to the formula I, X denotes a leaving group, preferably a chlorine atom, with an amine of the formula HNR4R5, wherein R 4 and R 5 are as defined in relation to formula I. The compound of formula XI can be prepared by acylating a compound of formula I, wherein R means a hydrogen atom. The reactions indicated above are carried out in a manner known from the technique [Houben-Weyl: Methoden der Organischen Chemie, Band XI, G. Thieme Verlag, Stuttgart, 1957; S. Patai .: The chemistry of amino group, Interscience Publishers, 1968].

The nitro group of the compounds of the formula I can be converted to an amino group by reduction in a manner known per se. The reduction can be carried out, for example, with tin (II) chloride or in the presence of a catalyst using a hydrogen source. For example, the catalyst is Raney nickel, palladium oxide or platinum, the source of hydrogen consists, for example, of gaseous hydrogen, hydrazine, hydrazine hydrate, formic acid, trialkylammonium formate or an alkali metal formate. In the case of compounds of the formula I, wherein R 2 represents an amino group, the latter group can be acylated with a C 1-4 alkanecarboxylic acid in a manner known per se. The acylation reaction can be carried out by the method described in relation to process 1) and m). If desired, a base of the formula I is reacted with an inorganic or organic acid to transform it into a pharmaceutically suitable acid addition salt, or the base of the formula I is freed from the acid addition salt using a base stronger. The pharmacological effect of the novel compounds of the formula I is studied by in vitro and in vivo methods. 8 -me il -5- (4-aminophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine (compound: Ag) known from HUP No. 191,698 is used and GB-P No. 2 162 184, as the reference substance.

In vitro determination of AMPA antagonist effect QNTI test (inhibition of quisqualate neurotoxicity).

The method is based on the phenomenon that the neurological effect quiscualate [ie (S) -alpha-amino-3,5-dioxo-1,2,4-oxydiazolidin-2-propanoic acid, an agonist of AMPA / kainate ] in rat-primed telecephalic cell culture can be inhibited by AMPA / kainate antagonists. The test is performed as described in the literature [Kovács, AD, Egyed, A: Protection against non-NMDA receptor-mediated excitotoxicity by GYKI 52466 in mature telencephalic cultures of the rat, Neurobiology, 4, 59-72 (1996)] . Table I shows the IC50 values obtained.

PSI test (inhibition of population discharge).

Field potentials (population discharges) induced by electrical stimulation of the collateral Shaffer commissural pathway are measured in the CAI neurons of the rat hippocampus. Population discharges can be inhibited by AMPA / kainate antagonists. Table I shows the non-cumulative IC50 values. [Tarnawa, I., Molnár, P. Gaál, L. Andrási, F .: Inhibition of hippocampal field potentials by GYKY 52466 in vitro and in vivo, Acta Physiol. Hung. , 79. (2), 163-9 (1992)].

SD test (dispersion depression).

The method is based on the phenomenon of dispersion depression induced by kainate in the isolated retinal chicken preparation. Dispersion depression formation is inhibited (retarded) by AMPA / kainate antagonists [Sheardown MJ: The triggering of spreading depression in the chicken retina: a pharmacological study, Brain Res., 607 (1-2), 189-194 ( 1993)]. Table I shows the IC50 values obtained.

Table I IC50 values of the compounds examined in various in vitro AMPA antagonist tests "Inhibition of neurotoxicity by quisqualate in cortical culture primer. BInhibition of discharges in population c Dispersion depression test.

As shown in Table I, the inhibitory effects of the novel compounds are significantly higher than those of the reference compound.

In vivo assays Acute toxicity.

The study is carried out in NMRI mice of both sexes, weighing 20 to 25 g, with 6 animals in each dose group. The test compounds are applied at a volume of 20 mg / kg, and the maximum doses per os and ip. they are 500 mg / kg and 300 mg / kg, respectively. Accumulative mortality is recorded on day 7. Animals are kept under standard laboratory conditions. Table II shows the LD50 values that are found in Table II Acute toxicity Muscle relaxing effect.

The test is performed according to Hoppe in mice Male NMRI weighing 20 to 25 g, with 10 animals in each group [Hoppe, J.O., J. Pharmacol. Exp. Ther., 100, 333 (1950)].

After the ip treatment. of the animals, the number of mice showing muscle weakness is recorded every 10 minutes in the first hour and at intervals afterwards. Animals that fall off a 60 ° tilted mesh in the next 30 seconds are considered positive. The DES0 values of the given compounds are determined each time. The duration of the effect is defined as the time of the last reading when the effect is at least 30%. Table III summarizes the results obtained.

Table III Muscle relaxing effect determined at the time of maximum effect Although the toxicity and muscle relaxant activity of the novel compounds are similar to those of the reference compound ^ A ^, the duration of the muscle relaxant effect for example 73 is substantially longer, as shown in Table III.

Maximum electric shock test (MES) Male NMRI mice weighing 20 to 30 g are used for the method of Swinyard et al., [Swinyard, EA, Brown, WC, and Goodman, LS: Comparative assays of antiepileptic drugs in mice and rats, J. Pharmacol., 106 , 319 (1952)]. The animals - 10 in each group - are treated i. either with various doses of the test substance or with vehicle. After 30 minutes, a 40-mA 50 Hz electro-shock is applied for 0.4 h through electrodes in the cornea. The number of animals that developed tonic extensor convulsion of the hind limbs is recorded, the percent inhibition is calculated and the ED50 values are determined by the method of Litchfield and Wilcoxon [Litchfield, J.T. and Wilcoxon, F.A .: A simplified method of evaluating dose-effect experiments, J. Pharmacol. Exp. Ther., 96., 99 (1949)] and are summarized in Table IV.

Audiogenic attack test (AS) The experiments are carried out by the slightly modified method of De Sarro et al. [From Sarro, G.B. Croucher, M.J. and Medrum, B.S .: Anticonvulsant action of DS 103-282, Neuropharm. , 23., 525 (1984)]. Groups of 8 male mice of strain DBA / 2j weighing 7 to 14 g are treated ip. with the test substance in 10 ml / kg of volume. After 15 minutes, the animals are placed in a covered glass container (30 cm in diameter) and exposed to a 14 kHz tone of 120 dB for a maximum of 60 s. The attack response is determined using the following scale: 0 normal behavior, 1 = nonsense race, 2 = clone, 3 = tonic flexor attack, 4 = tonic extensor attack. The maximum response for 60 s is recorded for each animal. The mortality is also noted. The ED50 values are determined by the Litchfield and Wilcoxon method with respect to the inhibition of clonic seizures and tonic extensor seizures. Table IV summarizes the results.

Table IV Anticonvulsant effect after ip treatment Maximum electro-shock inhibition "Inhibition of sound-induced attacks.

The compound according to example 89 is significantly more effective for the inhibition of maximal electric shock and sound induced tonic convulsions compared to the reference compound i £ §, as shown in table IV.

Global ischemia induced by magnesium chloride The experiments are carried out as described by Berga et al., [Berga, P., Beckett, PR, Roberts, DJ, Full, J., Massingham, R.: Synergistic interactions between piracetam and dihydroergocristine in some animal models of cerebral hypoxia ans ischemia, Arzneim.- -Forsch., 3.6, 1314-1320 (1986)]. Groups of 10 male NMRI mice weighing 20 to 25 g, ip are treated. with the test substance in 10 mg / kg of volume. After 30 minutes, iv is applied. saturated aqueous solution of magnesium chloride (5 ml / kg) which results in immediate cardiac suppression. The time between the iv injection is measured. and the last gasp (panting time). The means of the treated groups is expressed as percent of the control. A statistical analysis is performed by analysis of variance followed by the DUNCAN test. The dose that results in a 50% decrease in panting time is calculated (ID50) by linear regression. Table V shows the results.

Table V Increased panting time in the global ischemia test induced by magnesium chloride in mice From table V it is evident that the values DIS0 of the novel compounds of the formula I are significantly lower than those of the reference compound.

It is clearly demonstrated that the same extent of neuroprotection can be obtained with significantly lower doses of the novel compounds compared to the reference compound.

Therefore, the novel derivatives of 8 substituted-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula I can be used as active ingredients of pharmaceutical compositions. Based on the above test results, the novel compounds of the invention - due to their competitive AMPA / kainate antagonist property - have considerable effects of muscle relaxant, neuroprotective and anticonvulsant. Accordingly, novel compounds can be used for the treatment of any disease such as epilepsy, diseases resulting in muscle spasm, neurodegenerative diseases, post-stroke conditions, migraine and vomiting, wherein the inhibition of AMPA / kainate receptors can have a favorable effect. In addition, the acute toxicity of the compounds of the formula I is substantially less than that of most of the known 2, 3-benzodiazepines of AMPA / kainate antagonists known to be more efficient. This property generates a significant therapeutic advantage, in contrast to the known compounds, in the treatment of clinical conditions included above. The pharmaceutical compositions of the invention contain a therapeutically active amount of the compound of the formula I or a pharmaceutically suitable acid addition salt or a quaternary ammonium derivative thereof and one or more conventional carriers.

The pharmaceutical compositions of the invention are suitable for peroral, parenteral, or rectal administration or for local treatment, and can be solid or liquid. The solid pharmaceutical compositions suitable for peroral administration may be powders, capsules, tablets, film-coated tablets, microcapsules, etc., and may comprise binding agents such as gelatin, sorbitol, poly (vinylpyrrolidone), etc.; presentation agents such as lactose, glucose, starch, calcium phosphate, etc .; auxiliary substances for tableting such as magnesium stearate, talc, poly (ethylene glycol), silica, etc .; wetting agents such as sodium lauryl sulfate, etc., as the carrier. Liquid pharmaceutical compositions suitable for peroral administration may be solutions, suspensions, or emulsions and may comprise, for example, suspension-improving agents such as gelatin, carboxymethylcellulose, etc.; emulsifiers such as sorbitan monooleate, etc .; solvents such as water, oils, glycerol, propylene glycol, ethanol, etc .; preservatives such as methyl p-hydroxybenzoate, etc., as the carrier. Pharmaceutical compositions suitable for parenteral administration consist of sterile solutions of the active ingredient, in general.

The dosage forms included above as well as other dosage forms are well known per se, see, for example, Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing Co. , Easton, United States of America (1990). The pharmaceutical compositions of the invention generally contain 0.1 to 95.0 mass percent of a compound of formula I or a pharmaceutically suitable acid addition salt or quaternary ammonium derivative thereof. A typical dose for adult patients constitutes 0. 1 to 20 mg of the compound of the formula I or a pharmaceutically acceptable acid addition salt or a quaternary ammonium derivative thereof, daily. The previous dose can be administered in one or more portions. The actual dosage depends on many factors and is determined by the doctor. The pharmaceutical compositions of the invention are prepared by mixing a compound of the formula I or a pharmaceutically acceptable acid addition salt or a quaternary ammonium derivative thereof to one or more carriers, and converting the obtained mixture to a pharmaceutical composition of a known way per se. Useful methods are known from the literature, for example Remington's Pharmaceutical Sciences. A preferred subgroup of the pharmaceutical compositions of the invention contains a derivative of substituted 8-lH-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine or a pharmaceutically acceptable acid addition salt or a derivative of quaternary ammonium thereof, wherein X represents a carbonyl group or a methylene group, and R1 denotes a hydrogen atom, a hydroxy group, a methoxy group, an acetoxy group, a methylsulfonyloxy group or a group of the formula -NRR5, in where R4 and R5 signify, independently, a hydrogen atom, a methoxy group, an acetyl group or an alkyl group of Ci.4, the latter which is optionally substituted by a morpholino group or a N- (dimethoxyphenylethyl) -N group - (methyl) amino, or R4 and Rs form with the adjacent nitrogen atom and optionally with an additional nitrogen atom or an oxygen atom, a saturated or unsaturated heterocyclic group having 5 to 9 members, or X forms together with R1 a cyano group, a group tetrazolyl, or a group of the formula -CHNOH, R2 denotes a nitro group, or an amino group, R3 represents a hydrogen atom, or an acetyl group, Y is a hydrogen atom, or Y together with R3 form a bond of valence between the carbon atom in position 8 and the nitrogen atom in position 7, as the active ingredient. Within the above preferred subgroup of the invention, suitable pharmaceutical compositions contain one of the following compounds: 5- (4-aminophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine- amide 8-carboxylic acid, 5- (4-aminophenyl) -8-cyano-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine, 5- (4-aminophenyl) -8- (5- tetrazolyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine, or an acid addition salt or a pharmaceutically acceptable quaternary ammonium derivative thereof, as the active ingredient. A further preferred subgroup of the pharmaceutical compositions of the invention contains a compound of formula I, wherein R3 represents a hydrogen atom or a group of the formula -COR7, wherein R7 denotes a hydrogen atom, a C1- alkyl group 4, a C 1-4 alkyl group substituted by 1 to 3 halo atoms, or a group of the formula - (CH 2) n-NR 8 R 9, wherein R 8 and R 9 signify, independently, a hydrogen atom, an alkyl group of C1-4, optionally substituted by a phenyl group or a morpholino group, and the phenyl group is optionally substituted by 1 or 2 methoxy groups, or R8 and R9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen atom or oxygen, a saturated or unsaturated heterocyclic group having 5 or 6 members and which is optionally substituted by a phenyl group which is optionally substituted by a halo atom or a methoxy group, n has a value of 0, 1 or 2, X forms together with R1 a cyano group, or a group of the formula -COR6, wherein R6 represents a hydroxy group, or an amino group, and Y denotes a methyl group, R2 is a nitro group, an amino group or a (C 1-4 alkanoyl) amino group, or a pharmaceutically acceptable acid addition salt thereof as the active ingredient. Within this latter subgroup, the especially preferred pharmaceutical compositions of the invention contain a compound of formula I, wherein: R3 represents a hydrogen atom or a group of the formula -COR7, wherein R7 denotes a hydrogen atom, a group C1-4 alkyl, a C1-2 alkyl group substituted by a chlorine atom, a trifluoromethyl group, a trichloromethyl group or a group of the formula - (CH2) n-NR8R9, wherein R8 and R9 independently represent a hydrogen atom, a C1-2 alkyl group, optionally substituted by a phenyl group or a morpholino group, and the phenyl group is optionally substituted by 2 methoxy groups, or R8 and R9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen atom, a pyridinyl, pyrrolidinyl, morpholino or piperazinyl group, wherein the piperazinyl group is substituted by a fluorophenyl or methoxyphenyl group, n has a value of 0, 1 or 2, X forms together with R 1 a cyano group, R 2 signifies an amino group or a group (C 1-4 alkanoyl) amino, and denotes a methyl group, or a pharmaceutically acceptable acid addition salt thereof as the active ingredient. Furthermore, the invention relates to a pharmaceutical treatment method which comprises administering a non-toxic and therapeutically effective amount of an 8-substituted-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine derivative of the formula I or a pharmaceutically suitable acid addition salt or a quaternary ammonium derivative thereof, to a patient suffering from especially epilepsy, or a neurodegenerative disease or in a post-attack state. The invention further includes a process for the preparation of a pharmaceutical composition suitable for the treatment of especially epilepsy or a neurodegenerative disease or a state after attack, in which the substituted 8-9H-l, 3-dioxolo derivative [4, 5 -h] [2,3] benzodiazepine of the formula I or a pharmaceutically suitable acid addition salt or a quaternary ammonium derivative thereof is converted to a pharmaceutical composition using one or more carriers commonly used in the manufacture of medicaments. The invention is further elucidated in detail by means of the following examples.

Example 1 8-formyl-5- (4-nitrophenyl) -9H-1,3-dioxolo- [4,5-h] [2,3] -benzodiazepine A mixture of 3.23 g (10.0 mmol) of 8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo- [4,5-h] [2,3] benzodiazepine, 1.66 g (10.5 moles) of selenium oxide (IV) and 100 cm3 of dioxane is stirred on an oil bath of 80 ° C for 3 hours. The hot solution obtained is filtered through a bed of charcoal which is washed with 50 cm 3 of hot dioxane and the solution is evaporated under reduced pressure. The resulting crude product is recrystallized from 100 cm 3 of acetonitrile. Therefore, 2.50 g (74%) of the title compound are obtained. P.f .: 244-248 ° C. XH-R N [(CD3) 2S0]: d 9.48 (1H; s), 8.33 (2H, d, J = 8.8 Hz), 7.90 (2H, d, J = 8.8 Hz), 7.04 (1H, s), 6.83 (1H, s), 6.15 (1H, s), 6.09 (1H, s), 4.03 (1H, d, J = 13.1 Hz), 2.78 (1H, d, J = 13.1 Hz).

Example 2 - (4-nitrofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid A solution of 1.60 g (40.0 mmoles) of sodium hydroxide in 25 cm3 of water is added in a stirred solution of 3.40 g (20.0 mmoles) of silver nitrate (I) in 25 cm3 of water. The reaction mixture is stirred for an additional 10 minutes, then diluted with 50 cm.sup.3 of tetrahydrofuran. To the resulting solution, 3.37 g (10.0 mmol) of the aldehyde obtained in Example 1 are added under ice-water cooling. The reaction mixture is stirred at room temperature for 5 hours, then filtered through a bed of charcoal which is washed with cold water. The pH of the solution obtained is adjusted to a value of 2 with a solution of hydrochloric acid 6 N. After cooling, the precipitate is filtered and washed with 10 cm 3 of cold water. The resulting crude product is recrystallized from 30 cm 3 of dimethylformamide. In this manner, 2.30 g (65%) of the title compound are obtained. P.f. 198-203 ° C. XH-R N [(CD3) 2S0]: 6 8.33 (2H, d, J = 8.8 Hz), 7.89 (2H, d, J = 8.8 Hz), 7.07 (1H, s), 6.85 (1H, s), 6.18 (1H, s), 6. 12 (1H, s), 4.10 (1H, d, J = 12.8 Hz), 2.80 (1H, d, 12.8 Hz).

Example 3 Imidazolide 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 3.53 g (10.0 mmol) of the carboxylic acid described in Example 2 are suspended in 75 cm 3 of anhydrous dimethylformamide at room temperature, and 1.95 g (12.0 mmol) of 1,1'-carbonyldiimidazole are added to the suspension in one portion. The reaction mixture is stirred at room temperature for 5 hours, and subsequently, after cooling with ice-water, the precipitated product is filtered and washed with 50 cm 3 of diethyl ether.

In this way 3.15 g (78%) of the title compound are obtained. P.f .: 216-220 ° C. ? -NRM [(CD3) 2S0]: d 8.33 (2H, d, J = 8.8 Hz), 7.88 (2H, d, J = 8.8 Hz), 7.86 (1H, s), 7.11 (2H, s), 7.04 (1H, s), 6.82 (1H, s), 6.16 (1H, s), 6.10 (1H, s), 6.10 (1H, s), 4.10 (1H, d, J = 12.6 Hz), 2.60 (1H, s), d, J = 12.6 Hz).

Example 4 Amide 5- (4-nitrofenyl) -9H-1,2-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 75 cm 3 of dimethylformamide, 25 cm 3 of a 25% aqueous ammonia solution are added to the suspension obtained, and the reaction mixture is added at room temperature. sealed is stirred for 6 hours. The solvent is evaporated at a pressure of 55 Pa, the residue is suspended in 100 cm 3 of water, stirred for 1 hour and then filtered, and washed with 50 cm 3 of water. The crude product is dried, then boiled in 100 cm 3 of acetonitrile for 1 hour, cooled, filtered and washed with 50 cm 3 of diethyl ether. In this way 2.96 g (84%) of the title compound are obtained. P.f .: 287-290 ° C.

? -RMN [(CD3) 2S0 + CDC13]: d8.33 (2H, d, J = 8.9 Hz), 7.92 (2H, d, J = 8.9 Hz), 7.70 (1H, broad s), 7.50 (1H, s broad), 6.98 (1H, s), 6.75 (1H, s), 6.16 (1H, s), 6.11 (1H, s), 4.30 (1H, d, J = 12.3 Hz), 2.67 (1H, d, J = 12.3 Hz).

Example 5 (N-methylamide) of 5- (4-nitrofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 100 cm3 of dichloromethane, 20 cm3 of 33% methylamine in ethanol are added at room temperature to the suspension. The reaction mixture is sealed and stirred for 8 hours, and subsequently, after ice-water cooling, the separated product is filtered and washed with 50 cm 3 of diethyl ether. In this manner, 3.15 g (86%) of the title compound are obtained. P.f .: 284-287 ° C. XH-NMR [(CD3) 2 SO]: 6 8.36 (2H, d, J = 8.9 Hz), 8.26 (1H, m), 7.93 (2H, d, J = 8.9 Hz), 7.03 (1H, s), 6.82 (1H, s), 6.19 (1H, s), 6.13 (1H, s), 4.30 (1H, s), d, J = 12.5 Hz), 2.77 (3H, d, J = 4.8 Hz), 2.76 (1H, d, J = 12.5 Hz).

Example 6 (N-ethylamide) 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid To 100 cm 3 of anhydrous dimethylformamide, 1.63 g (20.0 mmoles) of ethylamine hydrochloride and 2.76 g (20.0 mmoles) of potassium carbonate are added at room temperature and, after stirring for 10 minutes, 4.03 g (10.0 mmoles) are added. of the imidazolide derivative described in Example 3. The reaction mixture is stirred for 6 hours, and then the solvent is evaporated at a pressure of 55 Pa. The residue is suspended in 100 cm3 of water, stirred for half an hour, filtered, washed with 50 cm3 of water and dried. The crude product is boiled in 75 cm 3 of acetone, cooled, filtered and washed with 50 cm 3 of diethyl ether. In this way, 2.74 g (72%) of the title compound are obtained. P.f .: 272-274 ° C. ? -RMN [(CD3) 2SO]: 6 8.49 (1H, t, J = 5.8 Hz), 8.33 (2H, d, J = 8.8 Hz), 7.86 (2H, d, J = 8.8 Hz), 7.01 (1H , s), 6.80 (1H, s), 6.15 (1H, s), 6.0) (1H, s), 4.22 (1H, d, J = 12.8 Hz), 3.17 (2H, m), 2.69 (1H, d) , J = 12.8 Hz), 1.04 (3H, t, J = 7: 2 Hz).

Example 7 (N-butylamide) of 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 100 cm3 of dichloromethane. To the suspension, 1.47 g (1.99 cm 3, 20.0 mmoles) of butylamine are added at room temperature. The reaction mixture is stirred at room temperature for 12 hours, then washed twice with 30 cm3 of water each time, and once with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue is crystallized from 75 cm 3 of acetonitrile and the crystals are washed with 15 cm 3 of diethyl ether. Therefore, 2.82 g (69%) of the title compound are obtained. P.f. 241-245 ° C? -RMN t (CD3) 2S0]: 6 8.36 (1H, t, J = 5.8 Hz), 8.33 (2H, d, J = 9.0 Hz), 7.86 (2H, d, J = 9.0 Hz) ), 7.02 (1H, s), 6. 81 (1H, s), 6.15 (1H, s), 6.10 (1H, s), 4.22 (lh, d, J = 12.4 Hz), 3.10 (2H, m), 2.70 (1H, d, J = 12.4 Hz), 1.30 (4H, m), 1. 04 (3H, t, J = 7.3 Hz).

Example 8 (N, N-dimethylamide) of 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5] [2,3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 100 cm3 of dichloromethane. To the suspension, 20 cm 3 of a 33% dimethylamine aqueous solution are added at room temperature. The reaction mixture is stirred at room temperature for 5 hours, then washed twice with 30 cm 3 of water each time, once with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue is crystallized from 85 cm 3 of acetonitrile and the crystals are washed with 30 cm 3 of diethyl ether. In this way 2.85 g (75%) of the title compound are obtained. P.f. : 259-264 ° C. 'H-NMR (CDC13): d 8.29 (2H, d, J = 9.0 Hz), 7.89 (2H, d, J = 9.0 Hz), 6.96 (1H, s), 6.64 (1H, s), 6.08 (1H , s), 6.00 (1H, s), 3.96 (1H, d, J = 12.5 Hz), 3.24 (3H, s), 3.05 (3H, s), 2.89 (1H, d, J = 12.5 Hz).

Example 9 N- (4-morpholinoethyl) amide of 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 75 cm 3 of anhydrous dimethylformamide. To the suspension, 2.86 g (2.86 cm 3, 22.0 mmoles) of 4-morpholinoethylamine are added at room temperature. The reaction mixture is stirred at room temperature for 10 hours, and then cooled with ice-water, the precipitated product is filtered and washed with 50 cm.sup.3 of diethyl ether. In this way 3.96 g (85%) of the title compound are obtained. P.f. : 248-252 ° C. Analysis: for C23H23N506 (465.47) Calculated: C 59.35%, H 4.98%, N 15.05%; found: C 59.78%, H 5.05%, N 14.92%. XH-NMR [(CD3) 2S0]: d 8.29 (2H, d, J = 9.0 Hz), 8.02 (1H, t, J = 5.7 Hz), 7.87 (2H, d, J = 9.0 Hz), 6.96 (1H, s), 6.75 (1H, s), 6.12 (1H, s), 6.06 (1H, s) , 4.23 (1H, d, J = 12.6 Hz), 3.55 (4H, m), 3.30 (2H, m), 2.70 (1H, d, J = 12.6 Hz), 2.43 (2H, t, J = 6.7 Hz) , 2.38 (4H, m).

Example 10 N- [N1 - (3,4-dimethoxyphenylethyl) - (N '-methyl) aminopropyl] amide of 5- (4-nitrofenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 100 cm3 of dichloromethane. To the suspension are added at room temperature 2.76 g (11.0 mmoles) of N- (3,4-dimethoxyphenylethyl) - (N-methyl) aminopropylamine. The reaction mixture is stirred at room temperature for 24 hours, then washed twice using 30 cm3 of water each time, and once with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue is crystallized from 50 cm 3 of ethanol, the crystals are washed with 10 cm 3 of diethyl ether. In this way 3.58 g (61%) of the title compound are obtained. P.f. : 140-145.5 ° C Analysis: for C31H33N507 (587.64) Calculated: C 63.36%, H 5.66%, N 11.92%; found: C 62.85%, H 5.68%, N 12.17%. XH-NMR [(CD3) 2SO]: d 8.58 (1H, t, J = 5.7 Hz), 8.32 (2H, d, J = 8.8 Hz), 7.86 (2H, d, J = 8.8 Hz), 7.00 (1H , s), 6.70 (1H, s), 6.15 (1H, s), 6.07 (1H, s), 4.23 (1H, d, J = 12.6 Hz), 3.71 (3H, s), 3.69 (3H, s) , 3.17 (2H, m), 2.69 (1H, d, J = 12.6 Hz), 2.55 (4H, m), 2.34 (2H, m), 2.17 (3H, s), 2.34 (2H, m).

Example 11 Morpholide of 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are suspended in 100 cm3 of dichloromethane. To the suspension, 1.74 g (1.74 cm3, 20 mmol) of morpholine are added at room temperature. The reaction mixture is stirred at room temperature for 10 hours, then washed twice with 30 cm3 of water each time, and once with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The residue is crystallized from 80 cm 3 of ethanol, and the crystals are washed with 30 cm 3 of diethyl ether. In this way 2.96 g (70%) of the title compound are obtained. Mp: 239-244 ° C XH-NMR [(CD3) 2S0]: d 8.31 (2H, d, J = 8.0 Hz), 7.87 (2H, d, J = 8.0 Hz), 7.12 (1H, s), 6.81 (1H, s), 6.15 (1H, s), 6.11 (1H, s), 3.82 (1H, d, J = 12.8 Hz), 3.50 (8H, m), 2.97 (1H, d, J = 12.8 Hz) .

Example 12 (N-methoxyamide) 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 1.67 g (20.0 mmoles) of methoxyamine hydrochloride and 2.76 g (20.0 mmoles) of potassium carbonate are added to 100 cm3 of anhydrous dimethylformamide at room temperature, and the mixture is stirred for 10 minutes. 4.03 g (10.0 mmol) of the imidazolide derivative described in Example 3 are added to the above mixture and the obtained reaction mixture is stirred for 6 hours. Subsequently, the solvent is distilled off at a pressure of 55 Pa. The residue is suspended in 100 cm 3 of water, stirred for half an hour, filtered, washed with 50 cm 3 of water and dried. The crude product is recrystallized from 85 cm 3 of acetonitrile and washed with 20 cm 3 of diethyl ether. In this manner, 2.30 g (60%) of the title compound are obtained. P.f. : 247-252 ° C. XH-NMR [(CD3) 2SO]: d 11.89 (1H, s), 8.33 (2H, d, J = 8.4 Hz), 7.87 (2H, d, J = 8.4 Hz), 7.06 (1H, s), 6.82. (1H, s), 6.17 (1H, s), 6.12 (1H, s), 4.16 (1H, d, J = 12.6 Hz), 3.63 (3H, s), 2.77 (1H, d, J = 12.6 Hz) .

Example 13 Amide (±) -7,8-dihydro-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 1.76 g (5.0 mmol) of the carboxylic amide derivative described in Example 4 are suspended in a mixture of 75 cm 3 of ethanol and 75 cm 3 of dichloromethane, and to the ice-water cooled suspension are added in one portion 0.19 g (5.0 mmoles). ) of sodium tetrahydroborate and 0.55 g (5.0 mmol) of calcium chloride in 25 cm3 of ethanol are added dropwise. The reaction mixture is stirred at room temperature for 24 hours and then evaporated under reduced pressure. The residue is boiled in 100 cm3 water for half an hour and filtered while still hot. The crude product obtained is boiled in 50 cm 3 of acetonitrile for half an hour, cooled with ice-water, filtered and washed with 20 cm 3 of diethyl ether. In this way 1.40 g (79%) of the title compound are obtained. P.f. : 269-272 ° C.

XH-NMR [(CD3) 2SO]: d 8.19 (2H, d, J = 9.0 Hz), 7.80 (1H, d, J = 5.3 Hz), 7.64 (2H, d, J = 9.0 Hz), 7.20 (1H , s), 7.16 (1H, s), 6.82 (1H, s), 6.48 (1H, s), 6.03 (1H, s), 6.02 (1H, s), 4.30 (1H, m), 3.00 (2H, s), m).

Example 14 (N-methylamide) of (±) -7,8-dihydro-5- (4-nitrofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8- acid carboxylic 1.83 g (5.0 moles) of the carboxylic amide derivative described in Example 5 are suspended in a mixture of 75 cm 3 of ethanol and 75 cm 3 of dichloromethane, and to the ice-water cooled suspension, 0.19 g (5.0 g) are added in one portion. mmoles) of sodium tetrahydroborate and 0.55 g (5.0 mmol) of calcium chloride in 25 cm 3 of ethanol are added dropwise. The reaction mixture is stirred at room temperature 24 hours, then evaporated under reduced pressure. The residue is boiled in 100 cm3 of water for half an hour and filtered while still hot. The resulting crude product is crystallized from 75 cm 3 of ethanol and the crystals are washed with 15 cm 3 of diethyl ether. In this way, 1.25 g (68%) of the title compound are obtained. P.f. : 201-202 ° C.

XH-NMR [(CD3) 2SO]: 6 8.20 (2H, d, J = 9.0 Hz), 7.69 (2H, d, J = 9.0 Hz), 6.76 (1H, s), 6.62 (1H, m), 6.45 (1H, s), 6. 12 (1H, d, J = 6.7 Hz), 6.00 (2H, s), 4.66 (1H, m), 3.17 (1H, dd, J = 14.0 and 4.7 Hz), 3.05 (1H, dd, J = 14.0 and 3.9 Hz), 2.68 (3H, d, J = 5.0 Hz).

Example 15 [N- (4-morpholinoethyl) amide] of (+) - 7,8-dihydro-5- (4-10 nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine-8-carboxylic acid 3.64 g (7.8 mmol) of the carboxylic amide derivative described in Example 9 are suspended in a mixture of 75 cm3 of ethanol and 125 cm3 of dichloromethane, and to the ice-water cooled suspension, 0.30 g (7.8 mmol) of sodium tetrahydroborate is added in one portion, and 0.87 g (7.8 mmol) of calcium chloride is added in 50 g. cm3 of ethanol drop by drop. The reaction mixture is stirred at room temperature for 24 hours and then evaporated under reduced pressure. The residue is boiled in 100 cm3 of water for half an hour, and filtered while still hot. The crude product obtained is crystallized from 150 cm 3 of acetonitrile and the crystals are washed with 30 cm 3 of diethyl ether.

In this way 2.56 g (70%) of the title compound are obtained. P.f. : 192-195 ° C. XH-NMR [(CD3) 2S0]: d 8.19 (2H, d, J = 9.0 Hz), 7.94 (1H, d, J = 6.0 Hz), 7.65 (2H, d, J = 9.0 Hz), 7.46 (1H , t, J = 5.8 Hz), 6.74 (1H, s), 6.45 (1H, s), 6.00 (2H, s), 4.41 (1H, m), 3.50 (4H, m), 3.10 (2H, m) , 2.94 (2H, m), 2.22 (4H, m), 2.07 (1H, m), 1.94 (1H, m).

Example 16 Amide of (±) -7-acetyl-7,8-dihydro-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid 3.54 g (10.0 mmol) of the dihydrocarboxylic amide derivative described in Example 13 are suspended in 50 cm 3 of acetic anhydride and the suspension is stirred at room temperature for 48 hours. The reaction mixture is cooled with ice-water, the precipitated product is filtered, recrystallized from 100 cm 3 of acetonitrile and washed with 20 cm 3 of diethyl ether. Therefore, 3.13 g (79%) of the title compound are obtained. P.f. : 164-165 ° C.

? -RMN [(CD3) 2SO]: d 8.35 (2H, d, J = 9.0 Hz), 7.82 (2H, d, J = 9.0 Hz), 7.35 (1H, s), 7.05 (1H, s), 6.92 (1H, s), 6. 54 (1H, s), 6.12 (1H, s), 6.10 (1H, s), 5.53 (1H, dd, J = 7.7 and 2.7 Hz), 3.31 (1H, dd, J = 14.5 and 7.7 Hz), 3.16 (1H, dd, J = 14.5 and 2.7 Hz), 3.39 (3H, s).

Example 17 (N-methylamide) of (±) -7-acetyl-7,8-dihydro-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine - 8 -carboxylic 3.68 g (10.0 mmol) of the dihydrocarboxylic amide derivative described in Example 14 are suspended in 25 cm 3 of acetic anhydride and stirred at room temperature for 48 hours. The reaction mixture is poured into a mixture of 200 cm3 of water and 100 cm3 of dichloromethane, the resulting mixture is stirred for 1 hour, and then the pH is adjusted to a value of 8 by adding sodium carbonate in portions. The phases are separated, the aqueous phase is extracted twice using 100 cm 3 of dichloromethane each time, the combined organic phases are washed with 50 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The resulting crude product is recrystallized from 150 cm 3 of ethanol, the crystals are washed with 25 cm 3 of diethyl ether.

In this way 3.08 g (75%) of the title compound are obtained. P.f. : 148-151 ° C. ? -RMN [(CD3) 2S0]: d 8.27 (2H, d, J = 8.9 Hz), 7.79 (2H, d, J = 8.9 Hz), 6.83 (1H, s), 6.45 (1H, s), 6.07 (1H, m), 6. 03 (2H, s), 5.64 (1H, dd, J = 9.2 and 3.9 Hz), 3.31 (1H, dd, J = 14.4 and 9.2 Hz), 3.16 (1H, dd, J = 14.5 and 3.9 Hz), 2.68 (3H, d, J = 4.8 Hz), 2.35 (3H, s).

Example 18 [(N-morpholinoethyl) amide] of (±) -7-acetyl-7,8-dihydro-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] ] -benzodiazepine-8-carboxylic acid 2.60 g (5.6 mmoles) of the dihydrocarboxylic amide derivative described in Example 15 are suspended in 15 cm3 of acetic anhydride and stirred at room temperature for 48 hours. The reaction mixture is poured into a mixture of 150 cm3 of water and 75 cm3 of dichloromethane, the resulting mixture is stirred for 1 hour, and then the pH is adjusted to a value of 8 by adding sodium carbonate in several portions. . The phases are separated, the aqueous phase is extracted twice using 75 cm 3 of dichloromethane each time, the combined organic phases are washed with 25 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The resulting crude product is recrystallized from 100 cm 3 of acetonitrile, the crystals are washed with 20 cm 3 of diethyl ether. In this way 1.73 g (68%) of the title compound are obtained. P.f. : 212-217 ° C. XH-NMR [CDC13 + (CD3) 2SO]: d 8.19 (2H, d, J = 8.8 Hz), 7. 74 (2H, d, J = 8.8 Hz), 7.06 (1H, m), 6.76 (1H, s), 6.39 (1H, s), 5.97 (1H, s), 5.95 (1H, s), 5.45 (1H , dd, J = 7.9 and 3.1 Hz), 3.55 (4H, m), 3.23 (1H, dd, J = 14.6 and 7.9 Hz), 3.06 (3H, m), 2.33 (3H, s), 2.28 (4H, m), 2.17 (1H, m ), 2.12 (1H, m).

Example 19 8 -. 8-hydroxy iminomethyl -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 3.37 g (10.0 mmol) of the aldehyde obtained in Example 1, 0.83 g (12.0 mmol) of hydroxylamine hydrochloride and 1.09 g (13.0 mmol) of anhydrous sodium acetate, in 100 cm3 of ethanol, are subjected to boiling for 10 hours. . The reaction mixture is evaporated under reduced pressure, the residue is suspended in 150 cm 3 of water, stirred at room temperature for half an hour, filtered and washed with 25 cm 3 of water. The resulting crude product is dried, and then boiled in 30 cm 3 of acetone, cooled with ice-water, filtered and washed with 30 cm 3 of diethyl ether. In this way 2.85 g (81%) of the title compound are obtained. P.f. : 262-265 ° C.

Example 20 8-cyano-5- (4-nitrofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 2.00 g (5.7 mmol) of the oxime obtained in Example 19 are suspended in 100 cm3 of dichloromethane. To the suspension that is obtained, they are added, drop by drop, under cooling with ice-water, 1.37 g (1.90 cm3, 13.6 mmol) of triethylamine and then 0.78 g (0.53 cm3, 6.8 mmol) of methanesulfonyl chloride in 10 cm3 of dichloromethane. The reaction mixture is stirred at room temperature for 4 hours, and then washed twice with 30 cm 3 of water each time, once with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is recrystallized from 75 cm 3 of acetonitrile, the crystals are washed with 20 cm 3 of diethyl ether.

In this way, 1.27 g (67%) of the title compound are obtained. P.f. : 230-234 ° C. ? -RMN [CDC13 + (CD3) 2SO]: d 8.30 (2H, d, J = 8.6 Hz), 7.89 (2H, d, J = 8.6 Hz), 6.92 (1H, s), 6.72 (1H, s) , 6.15 (1H, s), 6.13 (1H, s), 3.67 (1H, d, J = 13.8 Hz), 3.17 (1H, d, J = 13.8 Hz).

Example 21 8- (5-Tetrazolyl) -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 4.06 g (12.2 mmol) of the nitrile obtained in Example 20, 0.65 g (12.2 mmol) of ammonium chloride and 7.90 g (121.5 mmol) of sodium azide in 100 cm3 of anhydrous dimethylformamide are stirred in an oil bath. of 80 ° C for 6 hours. The solvent is evaporated at a pressure of 50 Pa, the residue is treated in 75 cm 3 of water and the pH of the solution is adjusted to a value of 3 with 6 N hydrochloric acid. The product that precipitates is cooled with ice-water, it is filtered and washed with 15 cm3 of cold water. The resulting crude product is boiled in cm 3 of acetone for half an hour, cooled with ice-water, filtered and washed with 20 cm 3 of diethyl ether.

In this way 3.25 g (71%) of the title compound are obtained. P.f. : 228-232 ° C. ? -NMR t (CD3) 2SO]: 6 8.32 (2H, d, J = 8.8 Hz), 7.92 (2H, d, J = 8.8 Hz), 7.04 (1H, s), 6.79 (1H, s), 6.11 (1H, s), 6.02 (1H, s), 4.52 (1H, d, J = 12.4 Hz), 3.06 (1H, d, J = 12.4 Hz).

Example 22 8 -. 8 -. 8-methanesulfonyloxymethyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine 3.37 g (10.0 mmol) of the aldehyde obtained in Example 1 are dissolved in a mixture of 100 cm 3 of dichloromethane and 10 cm 3 of methanol. To the obtained solution, 0.10 g (2.5 mmoles) of sodium tetrahydroborate is added in one portion under ice-water cooling. The reaction mixture is stirred for half an hour, filtered, washed twice with 30 cm3 of water each time, once with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is taken up in 75 cm 3 of anhydrous dichloromethane and to the obtained solution are added, dropwise, under cooling with ice-water, 1.11 g (11.0 mmoles) of triethylamine, then 1.26 g (0.85 cm 3, 11.0 mmoles) of chloride of methanesulfonyl in 5 cm 3 of anhydrous dichloromethane. The reaction mixture is stirred at 0 ° C for 1.5 hours, the precipitated product is filtered, washed with 25 cm 3 of diethyl ether. In this way 2.67 g (64%) of the title compound are obtained. P.f. : 190-192 ° C. XH-NMR [(CD3) 2SO]: d 8.28 (2H, d, J = 8.8 hz), 7.86 (2H, d, J = 8.8 Hz), 7.07 (1H, s), 6.76 (1H, s), 6.13 (1H, s), 6.10 (1H, s), 4.98 (1H, d, J = 13.8 Hz) , 4.93 (1H, d, J = 13.8 Hz), 3.63 (1H, d, J = 13.1 Hz), 3.23 (3H, s), 2.88 (1H, d, J = 13.1 Hz).

Example 23 8 - (4-morpholinomethyl) -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine 2.08 g (5.0 mmol) of the mesylate obtained in Example 22 are suspended in 75 cm 3 of dichloromethane, to the obtained suspension 2.18 g (2.18 cm 3, 25.0 mmol) of morpholine are added and the reaction mixture is stirred at room temperature during a day. The clear solution obtained is washed twice with 30 cm3 of water each time, once with 30 cm3 of saturated saline, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is stirred in 35 cm3 of acetone for half an hour, cooled with ice-water, filtered and washed with 20 cm3 of diethyl ether. In this way 1.61 g (79%) of the title compound are obtained. P.f. : 235-237 ° C. XH-NMR (CDC13): d 8.27 (2H, d, J = 9.0 Hz), 7.87 (2H, d, J = 9.0 Hz), 6.85 (1H, s), 6.65 (1H, s), 6.07 (1H, s), 6.02 (1H, s), 3.72 (1H, d, J = 12.1 Hz), 3.67 (4H, m), 3.23 (2H, m), 2.86 (1H, d, J = 12.1 Hz), 2.45 ( 2H, m), 2.32 (2H, m).

Example 24 8-methylaminomethyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 2.08 g (5.0 mmol) of the mesylate obtained in Example 22 are suspended in 75 cm 3 of dichloromethane. 25 cm 3 of a 25% aqueous ammonia solution are added and the reaction mixture is stirred at room temperature for one day. The phases of the reaction mixture are separatedThe organic phase is washed twice with 30 cm3 of water each time, then with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is stirred in 20 cm3 of acetone for half an hour, cooled with ice-water, filtered and washed with 15 cm3 of diethyl ether. In this way 1.32 g (75%) of the title compound are obtained. P.f. : 214-215 ° C. XH-NMR (CDC13): d 8.27 (2H, d, J = 9.0 Hz), 7.87 (2H, d, J = 9.0 Hz), 6.79 (1H, s), 6.66 (1H, s), 6.09 (1H, d, J = 1. 3 Hz), 6.03 (1H, d, J = 1.3 Hz), 3.61 (1H, d, J = 15.9 Hz), 3.48 (1H, d, J = 12.5 Hz), 3.47 (1H, d, J = 15.9 Hz ), 2.87 (1H, d, J = 12.5 Hz), 2.39 (3H, s), 1.25 (1H, broad s).

Example 25 8 -. 8 -dimeti laminomethyl -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine 2.08 g (5.0 mmol) of the mesylate obtained in Example 22 are suspended in 75 cm 3 of dichloromethane, 25 cm 3 of an aqueous 40% dimethylamine solution are added and the reaction mixture is stirred at room temperature for one day, the phases are separated, the organic phase is washed twice with 30 cm of water each time, then with 30 cm of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is stirred in 25 cm 3 of acetone for half an hour, then cooled with ice-water, filtered and washed with 15 cm 3 of diethyl ether. In this way 1.17 g (64%) of the title compound are obtained. P.f .: 182-185 ° C. ? -NRM (CDC13): d 8.26 (2H, d, J = 9.0 Hz), 7.88 (2H, d, J = 9.0 Hz), 6.84 (1H, s), 6.66 (1H, s), 6.08 (1H, d, J = 1. 3 Hz), 6.04 (1H, d, J = 1.3 Hz), 3.74 (1H, d, J = 12.3 Hz), 3.21 (1H, d, J = 13.5 Hz), 3.07 (1H, d, J = 13.5 Hz ), 2.80 (1H, d, J = 12.3 Hz), 2.25 (6H, s).

Example 26 8- (N-Acetyl-N-methylaminomethyl) -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 3.52 g (10.0 mmol) of the benzodiazepine derivative obtained in Example 24 are stirred in 25 cm3 of acetic anhydride at room temperature for 24 hours. The reaction mixture is poured into a mixture of 150 cm3 of water and 75 cm3 of dichloromethane, the resulting mixture is stirred for 1 hour and the pH is adjusted to a value of 8 by adding several portions of sodium carbonate. The phases are separated, the aqueous phase is extracted twice using 75 cm 3 of dichloromethane each time, the combined organic phases are washed with 25 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The resulting crude product is recrystallized from 75 cm 3 of acetonitrile, the crystals are washed with 20 cm 3 of diethyl ether. In this way 3.11 g (79%) of the title compound are obtained. P.f .: 224-228 ° C. 7H-NMR (CDC13): d 8.26 (2H, d, J = 8.9 Hz), 7.86 (2H, d, J = 8.9 Hz), 6.80 (1H, s), 6.66 (1H, s), 6.07 (1H, d, J = 1. 2 Hz), 6.04 (1H, d, J = 1.2 Hz), 4.42 (1H, d, J = 14.4 Hz), 4. 23 (1H, d, J = 14.4 Hz), 3.52 (1H, d, J = 12.5 Hz), 2.86 (3H, s), 2.79 (1H, d, J = 12.5 Hz), 2.18 (3H, s).

Example 27 - (4-Nitrophenyl) -9H-1,3-dioxo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid methyl ester In 3.53 g (10.0 mmol) of the carboxylic acid described in Example 2 are suspended in 150 cm3 of methanol, 0.2 cm3 of concentrated sulfuric acid are added and the reaction mixture is boiled for 10 hours. After cooling, the pH is adjusted to a value of 8 by means of triethylamine, the mixture is cooled with ice-water and the product is filtered. The resulting crude product is recrystallized from 100 cm 3 of acetonitrile, the crystals are washed with 25 cm 3 of diethyl ether. In this manner 3.2 g (85%) of the title compound are obtained. P.f .: 237-240 ° C. XH-NMR (CDC13): d 8.29 (2H, d, J = 9.0 Hz), 7.90 (2H, d, J = 9.0 Hz), 6.90 (1H, s), 6.68 (1H, s), 6.09 (1H, d, J = 1.3 Hz), 4.19 (1H, d, J = 12.8 Hz), 3.90 (3H, s), 2.83 (1H, d, J = 12.8 Hz).

Example 28 (±) -7-acetyl-8- (acetyl-N-methylaminomethyl) -7,8-dihydro-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3 ] -benzodiazepine Dissolve 1.76 g (5.0 mmol) of the amino derivative described in Example 24, in a mixture of 100 cm 3 of methanol and 100 cm 3 of ethyl acetate, to the solution obtained, add it in small portions at room temperature 7.3 cm 3 of concentrated hydrochloric acid and then 2.20 g (58.2 mmol) of sodium tetrahydroborate. The reaction mixture is stirred for half an hour, and then it is evaporated and the residue is taken up in a mixture of 100 cm 3 of dichloromethane and 100 cm 3 of water. The pH of the solution is adjusted to a value of 8 by adding a 10 N sodium hydroxide solution. The layers are separatedThe aqueous phase is extracted twice using 50 cm 3 of dichloromethane each time, the combined organic phases are washed with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated. The resulting residue is stirred in 15 cm of acetic anhydride for 10 hours, and then diluted with a mixture of 100 cm 3 of water and 100 cm 3 of dichloromethane. The mixture is stirred for 1 hour and the pH of the aqueous phase is adjusted to a value of 8 by adding sodium carbonate. The phases are separated, the aqueous phase is extracted twice using 50 cm 3 of dichloromethane each time, the combined organic phases are washed with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is recrystallized from 50 cm 3 of diethyl ether. In this manner, 1.49 g (68%) of the title compound are obtained. P.f .: 115-117 ° C. XH-NMR [(CD3) 2S0, 140 ° C]: d 8.38 (2H, d, J = 8.4 Hz), 7.94 (2H, d, J = 8.4 Hz), 7.12 (1H, s), 6.67 (1H, s), 6.17 (2H, s), 5.61 (1H, m), 3.39 (2H, m), 3.03 (3H, s), 3.01 (2H, m), 2.23 (3H, s), 2.04 (3H, s) ).

Example 29 8-acetoxymethyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 3.37 g (10.0 mmol) of the aldehyde obtained in Example 1 are dissolved in a mixture of 100 cm 3 of dichloromethane and 10 cm 3 of methanol and to the resulting solution, 0.10 g (2.5 mmol) of sodium tetrahydroborate is added to the solution. one portion under cooling with ice-water. The reaction mixture is stirred for half an hour, filtered, washed twice with 30 cm3 of water each time, and then with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is stirred in 25 cm 3 of acetic anhydride for 10 hours, then diluted with a mixture of 100 cm 3 of water and 100 cm 3 of dichloromethane, the resulting mixture is stirred for 1 hour and the pH of the aqueous phase is adjusted to a value of 8 when adding sodium carbonate. The phases are separated, the aqueous phase is extracted twice using 50 cm 3 of dichloromethane each time, the combined organic phases are washed with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is recrystallized from 50 cm 3 of acetonitrile. Therefore, 2.74 g (72%) of the title compound is obtained.

P.f. : 189-193 ° C. XH-NMR [CDC13 + (CD3) 2S0]: d 8.18 (2H, d, J = 9.0 Hz), 7. 82 (2H, d, J = 9.0 Hz), 6.81 (1H, s), 6.60 (1H, s), 6.02 (1H, s), 5.98 (1H, s), 4.81 (1H, d, J = 13.9 Hz ), 4.69 (1H, d, J = 13.9 Hz), 3.47 (1H, d, J = 12.9 Hz), 2.81 (1H, d, J = 12.9 Hz), 2. 07 (3H, s).

Example 30 (±) -7-acetyl-8-acetoxymethyl-7,8-dihydro-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 3.37 g (10.0 mmoles) of the aldehyde obtained in Example 1 are dissolved in a mixture of 100 cm 3 of dichloromethane and 10 cm 3 of methanol and, to the resulting solution, 0.38 g (10.0 mmoles) are added in one portion. ) of sodium tetrahydroborate in one portion under ice-water cooling. The reaction mixture is stirred for half an hour, filtered, washed twice with 30 cm3 of water each time, and then with 30 cm3 of saturated brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue is stirred in 25 cm3 of acetic anhydride for 24 hours, and then diluted with a mixture of 100 cm3 of water and 100 cm3 of dichloromethane. The resulting mixture is stirred for 1 hour, and then the pH of the aqueous phase is adjusted to a value of 8 by adding sodium carbonate. The phases are separated, the aqueous phase is extracted twice with 50 cm 3 of dichloromethane each time, the combined organic phases are washed with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is boiled in 50 cm3 of diethyl ether for 1 hour and then cooled with ice-water and filtered. In this way 3.19 g (75%) of the title compound are obtained. P.f .: 114-115 ° C. ^ -RMN (CDC13): 6 8.28 (2H, d, J = 9.0 Hz), 7.72 (2H, d, J = 9.0 Hz), 6.75 (1H, s), 6.48 (1H, s), 6.03 (2H, s), 5.60 (1H, m), 3.88 (2H, m), 3.05 (2H, m), 2.34 (3H, s), 2.03 (3H, s).

Example 31 8- (1, 5-diazabicyclo [4.3.0] non-5-enio-5-yl-methyl) -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] methanesulfonate [2,3] -benzodiazepine 2.08 g (5.0 mmol) of the mesylate obtained in Example 22 and 0.68 g (0.66 cm 3, 5.5 mmol) of 1,5-diazabicyclo [4.3.0] non-5-ene in 50 cm 3 of tetrahydrofuran are boiled. Anhydrous for 4 hours, then cooled with ice-water, the precipitated product is filtered and washed with 25 cm3 of diethyl ether. In this manner, 2.33 g (86%) of the title compound are obtained. P.f .: 205-207 ° C. ? -NRM (CDC13): d 8.27 (2H, d, J = 8.6 Hz), 7.85 (2H, d, J - 8.6 Hz), 7.01 (1. s), 6.66 (1H, s), 6.11 (1H, s), 6.09 (1H, s), 4.84 (1H, d, J = 19.2 Hz), 4.53 (1H, d, J = 19.2 Hz), 3.81 (2H, m), 3.57 (1H, d, J = 13.0 Hz), 3.53 (2H, m), 3.35 (2H, m), 3.12 (2H, m), 2.94 (1H, d, J = 13.0 Hz), 2.85 (2H, m), 2.75 (3H, s), 2.18 (4H, m).

Examples 32 to 56 A general method for reducing the nitro group of the compounds described in Example 1 to 31 by catalytic hydrogenation .0 mmol of nitro compound are dissolved in a mixture of 100 cm3 of dichloromethane and 100 cm3 of methanol, and the solution is hydrogenated in the presence of 0.10 g of 10% palladium / carbon catalyst at room temperature and a pressure of 5.065 x 105 Pa. After hydrogenation, the catalyst is filtered, the solvent is evaporated under reduced pressure and the crude product is recrystallized.

Example 32 Amide 5- (4-aminofenyl) -9H-1,3-dioxol or [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: dimethylformamide and ethanol. P.f. : 276-280 ° C. Yield: 68% Analysis: for C17H14N403 (322.33) Calculated: C 63.35%, H 4.38%, N 17.38%; found: C 63.93%, H 4.31%, N 17.24%. XH-NMR [(CD3) 2SO]: 6 7.80 (1H, s), 7.50 (1H, s), 7.38 (2H, d, J = 8.6 Hz), 6.97 (1H, s), 6.80 (1H, s) , 6.66 (2H, d, J = 8.6 Hz), 6.17 (1H, s), 6.11 (1H, s), 5.73 (2H, s), 4.18 (1H, d, J = 12.3 Hz), 2.65 (1H, d, J = 12.3 Hz).

Example 33 (N-methylamide) 5- (4-aminofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: ethanol. P.f. : 149-152 ° C Yield: 72% Analysis: for C18H16N403 (336.35) Calculated: C 64.28%, H 4.79%, N 16.66%; found: C 64.88%, H 4.85%, N 16.33%. ? -RMN [(CD3) 2S0]: d 7.95 (1H, m), 7.39 (2H, d, J = 8.7 Hz), 6.82 (1H, s), 6.73 (1H, s), 6.66 (2H, d, J = 8.7 Hz), 6.04 (1H, d, J = 1.0 Hz), 5.98 (1H, d, J = 1.0 Hz), 5.05 (2H, s), 4.22 (1H, d, J = 12.4 Hz), 2.78 (3H, d, J = 5.0 Hz), 2.67 (1H, d, J = 12.4 Hz).

Example 34 (5- (4-aminofenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid N-ethylamide Solvent for crystallization: ethanol. P.f. : 137-140 ° C Yield: 76% Analysis: for C19HlgN403 (350.38) Calculated: C 65.13%, H 5.18%, N 15.99%; found: C 64.92%, H 5.18%, N 15.44%. XH-NMR [(CD3) 2S0]: d 8.40 (1H, t, J = 5.9 Hz), 7.32 (2H, d, J = 8.6 Hz), 6.92 (1H, s), 6.75 (1H, s), 6.62 (2H, d, J = 8.6 Hz), 6.12 (1H, d, J = 1.0 Hz), 6.07 (1H, d, J = 0.7 Hz), 5.65 (2H, broad s), 4.14 (1H, d, J = 12.5 Hz), 3.16 (2H, m), 2.63 (1H, d, J = 12.5 Hz), 1.03 (3H, t, J = 7.1 Hz).

Example 35 (N-butylamide) 5- (4-aminofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: acetonitrile. P.f. : 215-216 ° C. Yield: 70% Analysis: for C21H22N403 (378.43) Calculated: C 66.65%, H 5.86%, N 14.80%; found: C 66.44%, H 5.97%, N 14.45%. -NRM [(CD3) 2SO]: d 8.37 (1H, t, J = 6.0 Hz), 7.33 (2H, d, J = 8.4 Hz), 6.91 (1H, s), 6.75 (1H, s), 6.61 (2H, d, J = 8.4 Hz), 6.12 (1H, s), 6.07 (1H, s), 5.67 (2H, broad s), 4. 13 (1H, d, J = 12.4 Hz), 3.09 (2H, m), 2.63 (1H, d, J = 12.4 Hz), 1.40 (2H, m), 1.25 (2H, m), 1.03 (3H, t , J = 7.1 Hz).

Example 36 (N, N-dimethylamide) of 5- (4-aminofenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: ethanol. P.f. : 257-262 ° C. Yield: 69% Analysis: for C19H18N403 (350.38) Calculated: C 65.13%, H 5.18%, N 15.99%; found: C 65.54%, H 5.22%, N 15.53%. XH-NMR [(CD3) 2S0]: d 7.31 (2H, d, J = 8.4 Hz), 7.01 (1H, s), 6.76 (1H, s), 6.60 (2H, d, J = 8.4 Hz), 6.12 (1H, s), 6.09 (1H, s), 5.63 (2H, broad s), 3.68 (1H, d, J = 12.8 Hz), 2.90 (3H, s), 2.88 (3H, s), 2.87 (1H , d, J = 12.8 Hz).

Example 37 [N- (4-morpholinoethyl) amide] 5- (4-aminophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: ethanol. P.f. : 254-255 ° C. Yield: 70% Analysis: for C21H20N403 (392.42) Calculated: C 63.44%, H 5.79%, N 16.08%; found: C 63.85%, H 5.76%, N 15.91%. ^ -RMN (CDC13): d 7.52 (2H, d, J = 8.7 Hz), 6.87 (1H, s), 6.70 (1H, s), 6.69 (2H, d, J = 8.7 Hz), 6.02 (1H, d, J = 1.2 Hz), 5.95 (1H, s), 4.58 (1H, d, J = 12.4 Hz), 4.02 (2H, broad s), 3.69 (4H, m), 3.48 (1H, m), 3.36 (1H, m), 2.75 (1H, d, J = 12.4 Hz), 2.48 (2H, m), 2.42 (4H, m).

Example 38 [N- [(N1 - (3,4-dimethoxyphenylethyl) - (N '-methyl) amino-propyl] amide] 5- (4-aminofenyl) -9H-1,3-dioxolo acid [4, 5] h] [2, 3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: toluene. P.f. : 123-126 ° C. Yield: 63% Analysis: for C31H3SN505 (557.66) Calculated: C 66.77%, H 6.33%, N 12.56%; found: C 65.61%, H 6.31%, N 12.25%. XH-NMR (CDC13): d 7.67 (1H, t, J = 8.6 Hz), 7.58 (2H, d, J = 8.6 Hz), 6.98 (2H, d, J = 8.6 Hz), 6.85 (1H, s) , 6.75 (3H, m), 6.70 (1H, s), 5.99 (1H, d, J = 0.8 Hz), 5.91 (1H, d, J = 1.0 Hz), 4.28 (1H, d, J = 12.6 Hz), 3.83 (6H, s), 3.35 (2H, m), 2.65 (1H, d, J = 12.6 Hz), 2.60 (6H, m) , 2.29 (3H, s), 1.74 (2H, t, 6.6 Hz).

Example 39 - (4-aminophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid morpholide Solvent for crystallization: ethanol. P.f. : 254-255 ° C. Yield: 83% Analysis: for C21H20N404 (392.42) Calculated: C 64.28%, H 5.14%, N 14.28%; found: C 63.48%, H 5.18%, N 14.08%. XH-NMR (CDC13): d 7.50 (2H, d, J = 8.7 Hz), 6.90 (1H, s), 6.76 (1H, s), 7.50 (2H, d, J = 8.7 Hz), 6.02 (1H, d, J = 1.2 Hz), 5.95 (1H, d, J = 1.2 Hz), 3.95 (2H, m), 3.85 (1H, d, J = 12.4 Hz), 3.66 (8H, m), 2.95 (1H, d, J = 12.4 Hz).

Example 40 (N-methoxyamide) 5- (4-aminofenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: acetonitrile. P.f. : 159-162 ° C Yield: 74% Analysis: for C18H16N404 (352.35) Calculated: C 61.36%, H 4.58%, N 15.90%; found: C 59.26%, H 4.51%, N 15.50%. ? -NRM [(CD3) 2S0]: d 11.76 (1H, s), 7.32 (2H, d, J = 8.6 Hz), 6.95 (1H, s), 6.76 (1H, s), 6.61 (1H, d, J = 8.6 Hz), 6.13 (1H, s), 6.08 (1H, s), 5.68 (2H, s ampliio), 4.05 (1H, d, J = 12.6 Hz), 3.60 (3H, s), 2.69 (1H , d, J = 12.6 Hz).

Example 41 Amide (±) - 5 - (4-aminophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: acetonitrile. P.f. : 256-258 ° C. Performance: 69%. Analysis: for C17H1SN403 (324.34) Calculated: C 62.95%, H 4.97%, N 17.27% found: C 62.74%, H 4.87%, N 17.38% XH-NMR [(CD3) 2S0]: d 7.20 (1H, broad s ), 7.15 (2H, d, J = 8.6 Hz), 7.00 (1H, broad s), 6.81 (1H, s), 6.51 (2H, d, J = 8.6 Hz), 6.50 (1H, broad s), 6.48 (1H, s), 6.04 (1H, s), 6.03 (1H, s), 5.37 (2H, broad s), 4.15 (1H, c, J = 1.05 and 5.9 Hz), 2.78 (2H, m).

Example 42 (N-methylamide) of (±) -5- (4-aminofenyl) -7,8-dihydro-9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8- acid carboxylic Solvent for crystallization: acetonitrile. P.f. : 231-234 ° C. Yield: 71% Analysis: for C18H18N403 (338.37) Calculated: C 63.89%, H 5.36%, N 16.56%; found: C 63.90%, H 5.48%, N 16.30%. XH-NMR [(CD3) 2S0]: d 7.47 (1H, m), 7.17 (2H, d, J = 8.4 Hz), 6.77 (1H, S), 6.53 (2H, d, J = 8.4 Hz), 6.49 (1H, s), 6.04 (1H, s), 6.02 (1H, s), 5.37 (2H, broad s), 4.22 (1H, m), 2.79 (2H, d, J = 5.4 Hz), 2.54 (3H , d, J = 4.6 Hz).

Example 43 Solvent for crystallization: acetonitrile. P.f. : 231-234 ° C. Yield: 71% Analysis: for C18H18N403 (338.37) Calculated: C 63.89%, H 5.36%, N 16.56%; found: C 63.90%, H 5.48%, N 16.30%.

XH-NMR [(CD3) 2SO]: 6 7.47 (1H, m), 7.17 (2H, d, J = 8.4 Hz), 6.77 (1H, s), 6.53 (2H, d, J = 8.4 Hz), 6.49 (1H, s), 6.04 (1H, s), 6.02 (1H, s), 5.37 (2H, broad s), 4.22 (1H, m), 2.79 (2H, d, J = 5.4 Hz), 2.54 (3H , d, J = 4.6 Hz).

Example 43 [N- (4-morpholinoethyl) amide] of (±) -5- (4-aminofenyl) -7,8-dihydro-9H-l, 3-dioxolo [4,5-h] [2,3 ] -benzodiazepine-8-carboxylic acid Solvent for crystallization: ethanol. P.f. : 184-186 ° C Yield: 50% Analysis: for C23H27N504 (437.50) Calculated: C 63.14%, H 6.22%, N 16.01%; found: C 62.44%, H 6.18%, N 15.81%. ? -RMN [CDC13 + (CD3) 2SO]: Ó 7.31 (2H, d, J = 8.7 Hz), 7.30 (1H, broad s), 6.70 (1H, s), 6.62 (2H, d, J = 8.7 Hz ), 6.58 (1H, s), 5.97 (2H, s), 5.83 (1H, broad s), 4.50 (2H, broad s), 4.45 (1H, m), 3.55 (4H, m), 3.32 (1H, m), 3.13 (1H, m), 2.96 (1H, dd, J = 13.8 and 6.0 Hz), 2.88 (1H, dd, J = 13.8 and 3.87 Hz), 2.25 (6H, m).

Example 44 Amide (±) -7-acetyl-5- (4-aminophenyl) -7,8-dihydro-9H-l, 3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: ethanol. P.f. : 214-242 ° C. Yield: 74% Analysis: for C19H18N404 (366.38) Calculated: C 62.29%, H 4.95%, N 15.29%; found: C 61.78%, H 4.88%, N 15.38%. XH-NMR [(CD3) 2SO]: d 7.34 (2H, d), J = 8.6 Hz), 7.11 (2H, broad s), 6.99 (1H, s), 6.61 (1H, s), 6.60 (2H, d, J = 8.6 Hz), 6.10 (1H, s), 6.07 (1H, s), 5.76 (2H, broad s), 5.23 (1H, dd, J = 12.2 and 4.8 Hz), 3.04 (1H, dd, J = 13.6 and 4.8 Hz), 2.75 (1H, t, J = 12.6 Hz), 2.00 (3H, s).

Example 45 (N-methylamide) of (±) -7-acetyl-5- (4-aminophenyl) -9H-1, 3-dioxolo [4, 5-h] [2,3] -benzodiazepine-8-carboxylic acid.

Solvent for crystallization: acetonitrile. P.f. : 164-167 ° C. Yield: 63% Analysis: for C20H20N4O4 (380.41) Calculated: C 63.15%, H 5.30%, N 14.73%; found: C 63.04%, H 5.30%, N 14.46%. XH-NMR (CDC13): d 7.53 (2H, d, J = 8.6 Hz), 6.81 (1H, s), 6.69 (2H, d, J = 8.6 Hz), 6.61 (1H, m), 6.60 (1H, s), 6.03 (1H, s), 6.02 (1H, s), 5.56 (1H, dd, J = 11.8 and 7.0 Hz), 4.16 (2H, broad s), 3.05 (2H, m), 2.79 (3H, d, J = 4.8 Hz), 2.05 (3H, s).

Example 46 [N- (4-morpholinoethyl) amide] of (±) -7-acetyl-5- (4-aminophenyl) -7,8-dihydro-9H-l, 3-dioxolo [4,5-h] [2] , 3] -benzodiazepine-8-carboxylic acid Solvent for crystallization: acetonitrile. P.f. : 200-202 ° C. Yield: 75% Analysis: for C25H29N505 (479.54) Calculated: C 62.62%, H 6.10%, N 14.60%; found: 61.27%, h 6.22%, n 14.32%. XH-NMR [(CD3) 2S0]: d 7.50 (1H, t, J = 5.2 Hz), 7.35 (2H, d, J = 8.8 Hz), 7.00 (1H, s), 6.62 (1H, s), 6.61 (2H, d, J = 8.8 Hz), 6.09 (1H, s), 6.06 (1H, s), 5.76 (2H, broad s), 5.24 (1H, dd, J = 12.0 and 4.8 Hz), 3.56 (4H, m), 3.15 (2H, m), .02 (1H, dd, J = 8.8 and 6.4 Hz), 2.75 (1H, t, J = 12.8 Hz), .35 (4H, m), 2.01 (3H, s).

Example 47 - (4-aminophenyl) -8-cyano-9H-l, 3-dioxolo [4, 5] [2, 3] benzodiazepine Solvent for crystallization: acetonitrile. P.f. : 245-248 ° C. Yield: 59%. Analysis: for C17H12N402 (304.31) Calculated: C 67.10%, H 3.97%, N 18.41%; found: C 65.65%, H 4.07%, N 18.06%. XH-NMR [(CD3) 2SO_: d 7.32 (2H, d, J = 8.6 Hz), 7.19 (1H, s), 6.82 (1H, s), 6.60 (2H, d, J = 8.6 Hz), 6.17 (1H, s), .12 (1H, s), 5.82 (2H, broad s), 3.75 ( 1H, d, J = 13.9 Hz), .12 (1H, d, J = 13.9 Hz).

Example 48 - (4-aminophenyl) -8- (5-tetrazolyl) -9H-1,3-dioxolo [4, 5] [2, 3] enzodiazepine Solvent for crystallization: acetonitrile.

P.f. : 244-246 ° C. Performance: 67%. Analysis: for C17H13N702 (347.34) Calculated: C 58.79%, H 3.77%, N 28.23%; found: C 58.62%, H 3.79%, N 28.23%. ? -NRM (CDC13: d 9.00 (3H, broad s), 7.39 (2H, d, J = 8.6 Hz), 7.05 (1H, s), 6.81 (1H, s), 6.65 (2H, d, J = 8.6 Hz), 6.14 (1H, s), 6.05 (1H, s), 4.30 (1H, d, J = 13.2 Hz), 3.22 (1H, d, J = 13.2 Hz).

Example 49 - . 5- (4-Amino-phenyl) -8- (4-morphine-methyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine Solvent for crystallization: ethanol. P.f. : 208-212 ° C. Performance: 63%. Analysis: for C21H22N403 (378.43) Calculated: C 66.65%, H 5.86%, N 14.80%; found: C 65.06%, H 5.83%, N 14.35%. XH-NMR [(CD3) 2 SO]: d 7.26 (2H, d, J = 8.8 Hz), 6.98 (1H, s), 6.69 (1H, s), 6.58 (2H, d, J = 8.8 Hz), 6.09 (1H, d, J = 0.4 Hz), 6.04 (1H, d, J = 0.8 Hz), 5.51 (2H, broad s), 3.55 (1H, d, J = 12.0 Hz), 3.52 (4H, m), 3.15 (1H, d, J = 12.9 Hz), 3.02 (1H, d, J = 12.9 Hz), 2.68 (1H, d, J = 12.0 Hz), 2.30 (2H, m), 2.10 (2H, m).

Example 50 - (4-Amino-phenyl) -8-dimethyl-ami-nome-t-yl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine Solvent for crystallization: ethanol. P.f. : 185-189 ° C. Yield: 61%. Analysis: for C19H20N4O2 (336.40) Calculated: C 65.13%, H 5.18%, N 15.99%; found: C 65.54%, H 5.22%, N 15.53%. XH-NMR (CDC13: d 7.48 (2H, d, J = 8.4 Hz), 6.78 (1H, s), 6.75 (1H, s), 6.65 (2H, d, J = 8.4 Hz), 6.00 (1H, s), , J = 1.2 Hz), 5.96 (1H, d, J = 1.2 Hz), 3.93 (2H, broad s), 3.60 (1H, d, J = 12.4 Hz), 3.18 (1H, d, J = 13.2 Hz) , 3.00 (1H, d, J = 13.2 Hz), 2.85 (1H, d, J = 12.4 Hz), 2.22 (6H, s).

Example 51 8- (N-acetyl-N-methyl amin orne) -5- (4-aminophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine Solvent for crystallization: acetonitrile. P.f .: 129-133 ° C. Performance: 69%. Analysis: for C20H20N4O3 (364.41) Calculated: C 65.92%, H 5.53%, N 15.37%; found: C 65.81%, H 5.45%, N 15.04%. 1 H-NMR [(CD 3) 2 SO]: (the product is a mixture of two conformers): d 7.27 (2H, d, J = 8.4 Hz), 6.99 (1H, s), 6.73 (1H, s), 6.59 ( 2H, d, J = 8.4 Hz), 6.10 (2H, m), 5.54 (2H, broad s), 4.30 (1H, d, J = 18 Hz), 4.14 (1H, d, J = 18 Hz), 3.30 (1H, d, J = 12.4 Hz), 2.75 (1H, d, J = 12.4 Hz), 2.65 (3H, s), 1. 75 (3H, s). d 7.27 (2H, d, J = 8.4 Hz), 6.83 (1H, s), 6.72 (1H, s), 6.59 (2H, d, J = 8.4 Hz), 6.10 (2H, m), 5.54 (2H, s broad), 4.16 (2H, m), 3.30 (1H, d, J - 12.4 Hz), 2.66 (1H, d, J = 12.4 Hz), 2.71 (3H, s), 2.04 (3H, s).

Example 52 - (4-Amino-phenyl) -9H-1,3-methyl-dioxo [4,5-h] [2,3] benzodiazepine-8-carboxylate Solvent for crystallization: ethanol. P.f. : 206-209 ° C.

Yield: 56%. Analysis: for C19H17N304 (351.37) Calculated: C 64.09%, H 4.48%, N 12.46%; found: C 64.32%, H 4.48%, N 12.54%. XH-NMR [(CD3) 2S0]: d 7.30 (2H, d, J = 8.4 Hz), 6.94 (1H, s), 6.75 (1H, s), 6.59 (2H, d, J = 8.4 Hz), 6.10 (1H, s), 6.04 (1H, s), 5.67 (2H, broad s), 3.93 (1H , d, J = 13.0 Hz), 3.74 (3H, s), 2.74 (1H, d, J = 13.0 Hz).

Example 53 (±) -7-acetyl-8- (acetyl-N-methylaminomethyl) -5- (4-aminophenyl) -7,8-dihydro-9H-l, 3-dioxolo [4,5-h] [2, 3] benzodiazepine Solvent for crystallization: acetonitrile. P.f. : 184-188 ° C. Performance: 73%. Analysis: for C22H24N404 (408.46) Calculated: C 64.69%, H 5.92%, N 13.72%; found: C 64.42%, H 5.99%, N 13.43%. XH-NMR (CDC13): (the product is a mixture of two conformers): d 7.53 (2H, m), 6.78 (1H, s), 6.68 (2H, m), 6.60 (1H, s), 5.98 (2H , m), 5.38 (1H, m), 4.11 (2H, broad s), 3.96 (1H, dd, J = 13.2 and 5.6 Hz), 3.72 (1H, dd, J = 14.4 and 6.8 Hz), 3.02 (3H , s), 2.74 (2H, m), 2.22 (3H, s), 1.95 (3H, s). d 7.53 (2H, m), 6.75 (1H, s), 6.68 (2H, m), 6.57 (1H, s), 5.98 (2H, m), 5.35 (1H, m), 4.11 (2H, broad s) , 3.31 (1H, dd, J = 13.6 and 6.0 Hz), 3.13 (3H, s), 2.74 (3H, m), 2.07 (3H, s), 1.97 (3H, s).

Example 54 8-acetoxymethyl-5- (4-aminophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine Solvent for crystallization: ethanol. P.f. : 206-209 ° C. Performance: 64%. Analysis: for C19H17N304 (351.37). Calculated: C 64.95%, H 4.88%, N 11.96%; found: C 64.59%, H 4.98%, N 11.70%. XH-NMR [(CD3) 2SO]: d 7.28 (2H, d, J = 8.4 Hz), 7.01 (1H, s), 6.71 (1H, s), 6.59 (2H, d, J = 8.4 Hz), 6.10 (1H, s), 6. 08 (1H, s), 5.54 (2H, broad s), 4.76 (1H, d, J = 14.0 Hz), 4. 64 (1H, d, J = 14.0 Hz), 3.44 (1H, d, J = 12.8 Hz), 2.74 (1H, d, J = 12.8 Hz), 2.07 (3H, s).

Example 55 (±) -7-acetyl-8-acetoxymethyl-5- (4-aminophenyl) -7,8-dihydro-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine Solvent for crystallization: ethanol. P.f. : 199-205 ° C. Yield: 66%. Analysis: for C21H21N305 (395.42). Calculated: C 63.79%, H 5.35%, N 10.63%; found: C 63.34%, H 5.34%, N 10.36%. XH-NMR (CDC13): d 7.51 (2H, d, J = 8.4 Hz), 6.78 (1H, s), 6.65 (2H, d, J = 8.4 Hz), 6.59 (1H, s), 6.01 (1H, d, J = 1.4 Hz), 5.97 (1H, d, J = 1.4 Hz), 5.42 (1H, m), 4.35 (1H, dd, J = 11.2 and 6.4 Hz), 4.12 (3H, m), 2.74 ( 2H, m), 2.04 (3H, s), 2.01 (3H, s).

Example 56 - (4-Amino-phenyl) -8- (1,5-diazabicyclo [4.3.0] -non-5-enio-5-ylmethyl) -9H-1,3-dioxolo [4,5-h] methanesulfonate 2,3] benzodiazepine Solvent for crystallization: acetonitrile. P.f. : 178-182 ° C. Yield: 66%.

Analysis: for C25H29N505S (511.60) Calculated: C 58.69%, H 5.71%, N 13.69%, S 6.27%; found: C 56.90%, H 5.94%, N 13.73%, S 6.01%. XH-NMR [(CD3) 2SO]: d 7.28 (2H, d, J = 8.5 Hz), 7.13 (1H, s), 6.75 (1H, s), 6.61 (2H, d, J = 8.5 Hz), 6.13 (1H, s), 6.11 (1H, s), 5.65 (2H, broad s), 4.59 (1H, d, J = 17.5 Hz), 4.36 (1H, d, J = 17.5 Hz), 3.69 (2H, t , J = 6.5 Hz), 3.42 (1H, d, J = 12.7 Hz), 3.35 (2H, m), 3.28 (1H, m), 3.15 (1H, m), 2.90 (1H, m), 2.81 (1H , d, J = 12.7 Hz), 2.60 (1H, m), 2.33 (3H, s), 1.98 (4H, m).

Example 57 - (4-aminophenyl) -8-hydroxymethyl-9H-l, 3-dioxolo [4,5-h] [2, 3] benzodiazepine 2.63 g (7.5 mmol) of the acetoxy compound obtained in Example 54 are dissolved in 50 cm 3 of tetrahydrofuran. To the solution obtained, first with 50 cm3 of water, and then under cooling with ice-water, 9 cm3 (9.0 mmol) of a 1 N sodium hydroxide solution are added dropwise. The reaction mixture it is stirred at room temperature for 1.5 hours and then extracted three times using 50 m3 of ethyl acetate each time. The combined organic phases are washed with 30 cm 3 of saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The resulting crude product is recrystallized from 30 cm 3 of acetonitrile. In this manner, 1.79 g (77%) of the title compound are obtained. P.f .: 250 ° C (decomposition). Analysis: for C17H15N303 (309.33) Calculated: C 66.01%, H 4.89%, N 13.58%; found: C 65.52%, H 4.95%, N 13.18%. ? -RMN [(CD3) 2S0]: d 7.28 (2H, d, J = 8.5 Hz), 6.96 (1H, s), 6.70 (1H, s), 6.60 (2H, d, J = 8.5 Hz), 6.10 (1H, s), 6. 05 (1H, s), 5.51 (2H, broad s), 5.20 (1H, t, J = 6.0 Hz), 4. 07 (2H, m), 3.56 (1H, d, J = 12.4 Hz), 2.64 (1H, d, J = 12.3 Hz).

Example 58 (+) -8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine They are introduced into 36.0 g (111.4 mmol) of 8-methyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine and 180 cm3 of glacial acetic acid in an acid-resistant steel pump tube of 400 cm3 capacity. To this suspension, 21.75 g (334.1 mmol) of potassium cyanide are added at a temperature of 20 to 26 ° C under cooling with ice-water for 20 minutes. The pump tube is sealed and stirred at 70 ° C for 22 hours. After cooling, the reaction mixture is stirred with 600 cm 3 of dichloromethane and 600 cm 3 of water, the phases are separated, the aqueous layer is further extracted twice using 300 cm 3 of dichloromethane each time, the combined organic phases are washed three times with 300 cm3 of water each time, dry over anhydrous magnesium sulfate and evaporate. The residue is crystallized from 250 cm3 of ether, the crystals are filtered and washed three times using 60 cm3 of ether each time. In this manner, 33.6 g (86.0%) of the title compound are obtained. P.f .: 162-164 ° C. Analysis: for C18H14N404 (350.34) Calculated: C 15.99%; found: C 15.62%. XH-NMR (CDC13): d 8.23 (2H, d, J = 8.9 Hz), 7.78 (2H, d, J = 8.9 Hz), 6.84 (1H, s), 6.52 (1H, s), 6.05 (1H, d, J = 1.3 Hz), 6.03 (1H, d, J = 1.3 Hz), 5.58 (1H, s), 3.12 (1H, d, J = 14.1 Hz), 2.83 (1H, d, J = 14.1 Hz) , 1.68 (3H, s).

Example 59 (±) -7, 8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxamide 10.0 g are added (28.5 mmoles) of the compound prepared according to Example 58 to 90 cm 3 of concentrated hydrochloric acid at a temperature of -10 to -20 ° C in 15 minutes, then allow the solution to warm to 25 ° C. The yellow solution is stirred at 25 ° C for 18 hours. During this time, the crystals precipitate. The mixture is evaporated under reduced pressure, 50 cm 3 of ethanol are added to the residue, the resulting mixture evaporates and this process is repeated once more. The evaporation residue is dissolved in 55 cm 3 of ethanol, 80 cm 3 of ether are added to the resulting solution. The yellow crystals that precipitate are filtered and washed three times using 10 cm3 of ether each time. In this manner, 10.0 g (86.3%) of the hydrochloride of the title compound are obtained. P.f .: 182-184 ° C. The hydrochloride is suspended in 80 cm3 of water, and the pH is adjusted with 10% sodium hydroxide to a value of 10, from 5 to 10 ° C. After 10 minutes of stirring, the crystals are filtered, washed with ether and dried. In this way 6.6 g (62.7%) of the title compound are obtained. P.f .: 209-210 ° C. Analysis: for C18H16N405 (368.35) Calculated: C 58.69%, H 4.38%, N 15.21%; found: C 58.75%, H 4.32%, N 15.11%. XH-NMR (CDC13): d 8.22 (2H, d, J = 8.9 Hz), 7.69 (2H, d, J = 8.9 Hz), 6.77 (1H, s), 6.67 (1H, broad s), 6.45 (1H , s), 6.00 (1H, d, J = 1.2 Hz), 5.98 (1H, d, J = 1.2 Hz), 5.72 (1H, s broad), 5.24 (1H, broad s), 3.12 (1H, d, J = 13.6 Hz), 2.83 (1H, d, J = 13.6 Hz), 1.65 (3H, s).

Example 60 Acid (±) -7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4, 5-h] [2,3] benzodiazepine-8-carboxylic acid .0 g (85.6 mmoles) of the compound prepared according to Example 58 are added to 450 cm 3 of concentrated hydrochloric acid at -10 ° C in 10 minutes, and the solution is stirred at 25 ° C for 18 days. The reaction mixture is evaporated under reduced pressure, 200 cm 3 of ethanol are added to the evaporation residue and the evaporation process is repeated. The evaporation residue is boiled in 180 cm 3 of ethanol for 5 minutes, then 200 cm 3 of ether are added under cooling with ice-water. The mixture is stirred at 10 ° C for 60 minutes, the crystals which precipitate are filtered and washed three times using 30 cm3 of ether each time. 17.6 g of the hydrochloride obtained are transferred to 70 cm 3 of water, and the suspension becomes alkaline by the addition of 55 cm 3 of a 10% sodium hydroxide solution. The resulting solution is extracted with 50 cm 3 of dichloromethane, the pH of the aqueous solution is adjusted with 10% hydrochloric acid to a value of 5, and the solution is extracted twice with 200 cm 3 of dichloromethane each time. The organic phase is dried, evaporated under reduced pressure, the evaporation residue is crystallized with 30 cm3 of ether. The crystals are filtered, washed twice using 5 cm3 of ether each time. In this way, 6.7 g (21.1%) of the title compound are obtained. P.f .: 230-232 ° C. Analysis: for C18H15N306 (369.32) Calculated: C 58.53%, H 4.09%, N 11.38%; found: C 57.78%, H 4.12%, N 11.13%. -NRM (DMSO-d: d 12.72 (1H,? Broad), 8.21 (2H, d, J = 8.9 Hz), 7.68 (2H, d, J = 8.9 Hz), 7.50 (1H, broad s), 6.96 ( 1H, s), 6.50 (1H, s), 6.05 (2H, s), 3.02 (1H, d, J = 13.8 Hz9, 2.85 (1H, d, J = 13.8 Hz), 1.39 (3H, s).

Example 61 (+) -7-acetyl-8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine .51 g (30 mmol) of the compound prepared according to Example 58 are added to 44 cm 3 of acetyl chloride, and the reaction mixture is stirred at 10 ° C for one hour. The reaction mixture is allowed to warm to room temperature and is stirred at 25 ° C for an additional 3 days, then evaporated under reduced pressure. To the evaporation residue, 250 cm3 of water are added and the mixture is stirred for half an hour under cooling with ice-water. The crystals obtained are filtered, washed three times using 20 cm3 of cold water each time, and dried under a lamp that emits infrared radiation. 11.2 g (95.1%) of the crude product obtained are suspended in 20 cm3 of ethanol, stirred for half an hour, and then filtered. The crystals are washed twice with 10 cm3 of ethanol each time, and once with 25 cm3 of ether. After drying, 9.5 g (80.7%) of the title compound are obtained, m.p .: 289-292 ° C. Analysis: for C20H16N405 (392.37) Calculated: C 61.22%, H 4.11%, N 14.28%; found: C 60.85%, H 4.18%, N 13.98%. XH-NMR (CDC13): d 8.29 (2H, d, J = 9.0 Hz), 7.83 (2H, d, J = 9.0 Hz), 6.99 (1H, s), 6.51 (1H, s), 6.10 (1H, d, J = 1.2 Hz), 6.07 (1H, d, J = 1.2 Hz), 3.11 (2H, m), 2.30 (3H, s), 1.84 (3H, s).

Example 62 (±) -7-acetyl-7,8-dihydro-8-methyl-5 - (4-n-phenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine- 8 - carboxamide 9.8 g (24.98 mmol) of the compound prepared according to Example 61 are added to 130 cm 3 of concentrated hydrochloric acid. The reaction mixture is stirred at 5 to 10 ° C, for 2 hours, and then at 25 ° C for 1 hour, and evaporated under reduced pressure. To the evaporation residue, 120 cm 3 of ethanol are added and the solution evaporated again.

To the evaporation residue 150 cm3 of water are added.

After 30 minutes of stirring, the crystals are filtered, washed three times with 10 cm3 of water each time, twice with diisopropyl ether and dried under a lamp emitting infrared radiation. Transfer 9.4 g (91.7%) of the crude product obtained to a column of silica gel eluting with ethyl acetate. The appropriate fraction is evaporated, the evaporation residue is rubbed with ether, the crystals obtained are filtered and washed with ether. In this manner, 4.5 g (43.9%) of the title compound are obtained. P.f .: 183-184.5 ° C. Analysis: for C20H18N4O6 (410.39) Calculated: C 58.53%, H 4.42%, N 13.65%; found: C 58.70%, H 4.52%, N 13.21%. XH-NMR (DMSO-d6): d 8.30 (2H, d, J = 8.8 Hz), 7.79 (2H, d, J = 8.8 Hz), 7.03 (1H, s), 6.89 (2H, broad s), 6.56 (1H, s), 6.11 (1H, s), 3.09 (1H, d, J = 14.2 Hz), 2.83 (1H, d, J = 14.2 Hz), 2.27 (3H, s), 11.43 (3H, s) .

Example 63 (±) -8-cyano-7,8-dihydro-8-methyl-5- (4-nitrofenyl) -7-trichloroacetyl-9H-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine 3.5 g (10 mmol) of the compound prepared according to Example 58 are transferred to 20 cm3 of chloroform.

To the cooled suspension with ice-water, 2.46 cm3 is added (22 mmol) of trichloroacetyl chloride, dropwise, for 5 minutes and then add 1.53 cm3 (11 mmol) of triethylamine, dropwise, over 10 minutes. The reaction mixture is stirred at 5 to 10 ° C for 2 hours, then at 25 ° C for 19 hours, then poured into 150 cm 3 of ice-water.

After stirring for 60 minutes, the layers are separated, the product is extracted with chloroform, the organic phase is dried over anhydrous magnesium sulfate and evaporated. The evaporation residue is crystallized from ether, the crystals are stirred for half an hour and filtered. 3.0 g (60.6%) of the crude product obtained is recrystallized from 25 cm 3 of ethanol, filtered, washed with ethanol and ether. In this way, 2.6 g (52.5%) of the title compound are obtained. P.f .: 254-255 ° C. Analysis: for C20H13C13N405 (495.70) Calculated: C 48.46%, H 2.64%, N 11.30%; found: C 48.57%, H 2.65%, N 11.10%.

? -NRM (CDCI3): d 8.32 (2H, d, J = 8.6 Hz), 7.98 (2H, d, J = 8.6 Hz), 7.06 (1H, s), 6.50 (1H, s), 6.13 (1H, s), 6.09 (1H, s), 3.13 (2H, m), 1.93 (3H, s).

Example 64 (±) -8-cyano-7, 8-dihydro-8-methyl-5- (4-nitrophenyl) -7-trifluoroacetyl-9H-1, 3-dioxolo [4, 5-h] [2, 3] benzodiazepine 8.76 g (25 mmol) of the compound prepared according to Example 58 are dissolved in 60 cm3 of chloroform. To the solution is added 6.5 cm3 (46 mmol) of trifluoroacetic anhydride, dropwise, under ice-water cooling of 5 to 10 ° C, in 10 minutes. The mixture is stirred at 10 ° C for 2 hours, at 25 ° C for 25 hours, then poured into 300 cm 3 of ice-water. The layers are separated, the aqueous phase is extracted twice using 100 cm3 of chloroform each time. The organic phase is dried, and then evaporated. The evaporation residue is crystallized from 70 cm3 of ether. After 60 minutes of stirring, the crystals are filtered and washed three times using 100 cm3 of ether each time. In this way 8.6 g (77.1%) of the title compound are obtained. P.f .: 231-234 ° C. Analysis: for C20H13F3N4O5 (446.33) Calculated: C 53.82%, H 2.94%, N 12.55%; found: C 54.09%, H 2.94%; N 12.32%. XH-NMR (DMSO-d6): d 8.38 (2H, d, J = 8.6 Hz), 7.86 (2H, d, J = 8.6 Hz), 7.28 (1H, s), 6.76 (1H, s), 6.19 ( 2H), 3.44 (2H, m), 1.89 (3H, s).

Example 65 Acid (±) -7, 8-dihydro-8-methyl-5- (4-nitrophenyl) -7-trifluoroacetyl-9H-l, 3-dioxolo [4, 5-h] [2,3] benzodiazepine- 8- carboxylic .6 g (15.2 mmol) of the compound prepared according to Example 60 are suspended in chloroform 5. To the suspension 4.0 cm3 (28.3 mmol) of trifluoroacetic anhydride are added dropwise under ice-water cooling at 10 ° C. in 10 minutes. The mixture is stirred at 10 ° C for 2 hours, at 25 ° C for 20 hours and then poured into 130 g of crushed ice. After 60 minutes of stirring, the crystals are filtered, washed three times with 30 cm3 of chloroform each time and once with 50 cm3 of ether. In this way 3.76 g (53.3%) of the title compound are obtained. P.f .: 160-162 ° C. Analysis: for C20H14F3N307 (465.33) Calculated: C 51.62%, H 3.03%, N 9.03%; found: C 51.69%, H 3.05%, N 8.91%.

XH-NMR (DMSO-d6): 8.39 (2H, d, J = 8.6 Hz), 7.67 (2H, broad s), 7.25 (1H, s), 6.39 (1H, s), 6.17 (2H), 3.64 ( 1H, d, J = 17.4 Hz), 3.50 (1H, d, J = 17.4 Hz), 1.67 (3H, s).

Example 66 (±) -8-cyano-7,8-dihydro-7-formyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine .0 g (14.27 mmol) of the compound prepared according to Example 58 are added to 40.0 cm3 (539.6 mmol) of a mixed anhydride of formic acid and acetic acid at 5 ° C, in 5 minutes. The reaction mixture is stirred at 5 to 10 ° C for one hour, at 25 ° C for 17 hours and then poured into 100 g of ice. After stirring for one hour, the crystals are filtered, washed three times with 20 cm3 of water each time, once with 20 cm3 of ether and dried under a lamp emitting infrared radiation. In this way 4.0 g (74.1%) of the title compound are obtained. P.f .: 230.7-232.5 ° C. Analysis: for C19H14N405 (378.35) Calculated: C 60.32%, H 3.73%, N 14.81%; found: C 59.85%, H 3.80%, N 14.88%. XH-NMR (CDC13): d 8.65 (1H, s), 8.28 (2H, d, J = 8.8 Hz), 7.83 (2H, d, J = 8.8 Hz), 6.96 (1H, s), 6.51 (1H, s), 6.10 (1H, d, J = 1.3 Hz), 6.08 (1H, d, J = 1.3 Hz), 3.26 (1H, d, J = 14.4 Hz), 3.16 (1H, d, J = 14.4 Hz) , 1.87 (3H, s).

Example 67 (±) -8-cyano-7, 8-dihydro-8-methyl-5- (4-nitrophenyl) -7-propionyl-9H-1,3-dioxolo [4,5-h] [2, 3] - benzodiazepine .0 g (14.27 mmol) of the compound prepared according to Example 58 are added to 15 cm3 of propionyl chloride of 5 to 10 ° C in 10 minutes. The reaction mixture is stirred at 5 to 10 ° C for half an hour, at 25 ° C for 23 hours and then evaporated. To the evaporation residue 30 cm3 of ether are added and the suspension is stirred for 30 minutes. The crystals are filtered, washed three times using 10 cm3 of ether each time, and dried under a lamp that emits infrared radiation. In this way 5.1 g (88.0%) of the title compound are obtained. P.f .: 216-218 ° C. XH-NMR (CDC13): d 8.30 (2H, d, J = 9.0 Hz), 7.83 (2H, d, J = 9.0 Hz), 6.99 (1H, s), 6.51 (1H, s), 6.10 (1H, d, J = 1.3 Hz), 6.06 (1H, d, J = 1.3 Hz), 3.12 (1H, d, J = 14.4 Hz), 3.08 (1H, d, J = 14.4 Hz), 2.75-2.43 (2H, m), 1.84 (3H, s), 1.17 (3H, t, J = 7.4 Hz).

Example 68 (±) -7-butyryl-8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] - benzodiazepine .0 g (14.27 mmoles) of the compound prepared according to Example 58 are added to 15 cm3 of butyric chloride at 5 to 10 ° C, in 20 minutes. The reaction mixture is stirred at 5 to 10 ° C for 2 hours, then at 25 ° C for 2 weeks. The suspension is filtered, the crystals are washed three times using 20 cm3 of ether each time, and dried under a lamp that emits infrared radiation. In this way 4.6 g (76.8%) of the title compound are obtained. P.f .: 248-250 ° C? -RMN: d 8.30 (2H, d, J = 8.9 Hz), 7.83 (2H, d, j = 8. 9 Hz), 6.99 (1H, s), 6.51 (1H, s), 6.09 (1H, d, J = 1.3 Hz), 6.06 (1H, d, J = 1.3 Hz), 3.13 (1H, d, J = 14.5 Hz), 3.07 (1H, d, J = 14.5 Hz), 2.56-1.69 (4H, m), 1.84 (3H, s), 0.99 (3H, t, J = 7.4 Hz).

Example 69 (+) - 8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -7- (pyridine-3-carbonyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 5.0 g (14.27 mmol) of the compound prepared according to Example 58 are dissolved in a mixture of 50 cm 3 of pyridine and 25.2 cm 3 (181.8 mmol) of triethylamine. To the resulting solution, 12.7 g (71.3 mmoles) of nicotinic acid chloride hydrochloride are added at 0 to 2 ° C, in 20 minutes, and the mixture is stirred at 25 ° C for 2 days. Then, 15 cm3 of pyridine is added to the solution which has been cooled to 5 ° C and an additional 10.2 g (57.3 mmoles) of nicotinic acid chloride are added and the mixture is stirred at 25 ° C for an additional 7 days. Then, 200 cm3 of water are added to the mixture, drop by drop, from 5 to 10 ° C, the crystals are filtered, washed three times with 50 cm3 of water each time, and dried under a lamp that emits infrared radiation. . 6.4 g (98.5%) of the obtained crude product is transferred to a column of silica gel which is eluted with a mixture of cyclohexane and ethyl acetate in a ratio of 1: 1. The appropriate fraction is evaporated, the evaporation residue is crystallized from ether. The crystals are filtered and washed with ether. In this way 1.7 g (26.2%) of the title compound are obtained. P.f .: 246-248 ° C Analysis: for C24H17N505 (455.43) Calculated: C 63.30%, H 3.76%, N 15.38%; found: C 63.32%, H 3.74, N 14.96%. XH-NMR (CDC13 + DMSO-d6): d 8.68 (1H, dd, J = 4.9 and 1.7 Hz), 8.54 (1H, d, J = 2.0 Hz), 8.12 (2H, d, J = 8.9 Hz), 7.75 (1H, dt, J = 7.9 and 1.9 Hz), 7.46-7.38 (1H, m), 7.40 (2H, d, J = 8.9 Hz), 7.15 (1H, s), 6.67 (1H, s), 6.12 (1H, s), 6.11 (1H, s), 3.27 (1H, d, J = 14.4 Hz), 3.20 (1H, d, J = 14.4 Hz), 1.91 (3H, s).

Example 70 (Dimethylamide) of (±) -8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] acid [2,3] -benzodiazepine-7-carboxylic acid .5 g (30 mmol) of the compound prepared according to Example 58 are dissolved in 100 cm 3 of absolute pyridine. To the obtained solution, 15.6 g (100 mmol) of phenyl chloroformate are added, dropwise, at 0 ° C in 20 minutes. The reaction mixture is stirred at 0 ° C for 120 minutes, at 10 ° C for 90 minutes, at 25 ° C for 20 hours and evaporated under reduced pressure. To the evaporation residue is added 100 cm3 of benzene, the precipitated crystals are filtered and washed three times using 40 cm3 of benzene each time. The filtrate is evaporated under reduced pressure to obtain 13.0 g of the residue. 7.8 g of the evaporation residue obtained as described above, 80 cm 3 of ethanol, 8.11 g (99.5 mmoles) of dimethylamine hydrochloride and 10.06 g (99.5 mmoles) of triethylamine are transferred in a sealed pump tube, and the contents are stirred at 90 ° C for 18 hours. The mixture is cooled, and concentrated to half its volume under reduced pressure. The suspension is stirred at 5 to 10 CC for 30 minutes. The crystals are filtered, washed three times with 20 cm3 of ether each time, three times with 10 cm3 of water each time, and again three times with 20 cm3 of ether each time. Once, and dried under a lamp that emits infrared radiation. In this way 3.3 g (39.0%) of the product of the title are obtained. P.f .: 214-217 ° C.

Example 71 (±) -8-cyano-7,8-dihydro-8-methyl-7- (morpholin-4-carbonyl) -5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine .5 g (30 mmol) of the compound prepared according to Example 58 are obtained in 100 cm 3 of absolute pyridine and, to the resulting solution, 15.6 g (100 mmol) of phenyl chloroformate are added, drop by drop, to 1 ° C in 20 minutes. The reaction mixture is stirred at 0 ° C for 120 minutes, at 10 ° C for 90 minutes, at 25 ° C for 20 hours and evaporated under reduced pressure. To the evaporation residue is added 100 cm3 of benzene, the precipitated crystals are filtered and washed three times using 40 cm3 of benzene each time. The filtrate is evaporated under reduced pressure, the evaporation residue constitutes up to 13.0 g. The evaporation residue obtained as described above is dissolved in 100 cm 3 of ethanol, and 7.2 cm 3 (83 mmoles) of morpholine are added to the solution. The mixture is boiled for 23 hours, and then cooled with ice-water and stirred at 5 to 10 ° C for half an hour. The crystals obtained are filtered and washed three times using 40 cm3 of ether each time. In this way 6.3 g (45.4%) of the title compound are obtained. Mp: 234-236 ° C XH-NMR (CDC13): d 8.29 (2H, d, J = 8.8 Hz), 7.91 (2H, d, J = 8.8 Hz), 6.94 (1H, s), 6.54 (1H, s), 6.10 (2H, s), 3.60 (4H, m), 3.31 (2H, m), 3.22 (2H, m), 3.17 (1H, d, J = 14.4 Hz), 2.85 (1H, d, J = 14.4 Hz), 1.79 (3H, s).

Example 72 (±) -8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -7- (pyrrolidin-1-carbonyl) -9H-1,3-dioxolo [4,5-h] [2, 3] -benzodiazepine .5 g (30 mmol) of the compound prepared according to Example 58 are dissolved in 100 cm 3 of absolute pyridine and, to the resulting solution, 15.6 g (100 mmol) of phenyl chloroformate are added, dropwise to 1 g. ° C in 20 minutes. The reaction mixture is stirred at 0 ° C for 120 minutes, at 10 ° C for 90 minutes, at 25 ° C for 20 hours and evaporated under reduced pressure. To the evaporation residue is added 100 cm3 of benzene, the precipitated crystals are filtered and washed three times using 40 cm3 of benzene each time. The filtrate is evaporated under reduced pressure, the evaporation residue constitutes up to 13.0 g. 13.0 g of the evaporation residue obtained as described above are transferred to a pump tube, and then 55 cm3 of ethanol and 13.8 cm3 (166.9 mmoles) of pyrrolidine are added. The pump tube is sealed and the contents are stirred at 110 ° C for 8.5 hours, and then at 25 ° C for 16 hours. The crystals obtained are filtered and washed three times using 100 cm3 of ether each time. In this manner 8.4 g (62.6%) of the title compound are obtained. P.f .: 270-272 ° C. Analysis: for C23H21Ns05 (447.45) Calculated: C 61.74%, H, 4.73%, N 15.65%; found: C 63.01%, H 4.81%, N 15.23%. XH-NMR (CDC13): d 8.28 (2H, d, J = 7.8 Hz), 7.95 (2H, d, J = 7.8 Hz), 6.96 (1H, s), 6.57 (1H, s), 6.10 (2H, s), 3.20 (4H, m), 3.13 (1H, d, J = 13.8 Hz), 2.82 (1H, d, J = 13.8 Hz), 1.84 (7H, m).

Example 73 (±) -8-cyano-7, 8-dihydro-7-chloroacetyl-8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2, 3] - benzodiazepine .6 g (44.5 mmol) of the compound prepared according to Example 58 are added to 60 cm3 (752.8 mmol) of chloroacetyl chloride under stirring at 5 to 10 ° C in 10 minutes. The mixture is stirred at 5 to 10 ° C for 1 hour, at 25 ° C for 47 hours, and then poured into 500 cm 3 of ice-water. The mixture obtained is extracted three times using 100 cm 3 of dichloromethane each time, the organic phase is dried over anhydrous magnesium sulfate and evaporated. The evaporation residue is crystallized from ether, after stirring for half an hour, the crystals are filtered, and then dissolved in 380 cm.sup.3 of hot acetone, precipitated with hot petroleum ether and filtered. In this way 6.1 g (32.1%) of the title compound are obtained. P.f .: 231-233 ° C Analysis: for C20H15ClN4O5 (426.82) Calculated: C 56.28%, H 3.54%, Cl 8.31%, N 13.13%; found: C 55.54%, H 3.67%, Cl 8.10%, N 12.73%. XH-NMR (CDC13): d 8.30 (2H, d, J = 8.9 Hz), 7.81 (2H, d, J = 8.9 Hz), 6.99 (1H, s), 6.50 (1H, s), 6.11 (1H, d, J = 1.3 Hz), 6.08 (1H, d, J = 1.3 Hz), 4.43 (1H, d, J = 13.7 Hz), 4.36 (1H, d, J = 13.7 Hz), 3.18 (1H, d, J = 14.5 Hz), 3.11 (1H, d, J = 14.5 Hz), 1.87 (3H, s).

Example 74 (±) -8-cyano-7,8-dihydro-8-methyl-7-morpholino-acetyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3 ] -benzodiazepine To 5.0 g (11.7 mmol) of the compound which is prepared according to Example 73, 70 cm3 of acetonitrile and 2.18 g (25 mmol) of morpholine are added. The reaction mixture is boiled for 4 hours, cooled, the crystals are filtered and washed with ether. The filtrate is evaporated under reduced pressure, 50 cm3 of water are added to the evaporation residue. After stirring for 1 hour, the crystals are filtered and washed three times using 15 cm3 of water each time. In this manner 5.2 g (93.0%) of the title compound are obtained. P.f .: 121-123 ° C. XH-NMR (CDC13): d 8.31 (2H, d, J = 9.0 Hz), 7.82 (2H, d, J = 9.0 Hz), 7.01 (1H, s), 6.53 (1H, s), 6.11 (1H, d, J = 1.1 Hz), 6.08 (1H, d, J = 1.1 Hz), 4.00-3.25 (2H, m), 3.73 (4H, t, J = 4.6 Hz), 3.62 (1H, d, J = 16.7 Hz), 3.35 (1H, d, J = 16.7 Hz), 2.64 (4H, m), 1.87 (3H, m).

Example 75 (±) -8-cyano-7, 8-dihydro-7- [2- [2- (3,4-dimethoxyphenyl) -N-methyl-amino] -acetyl] -8-methyl-5- (4-nitrophenyl) ) - 9H- 1, 3-dioxolo [4, 5-h] [2, 3] -benzodiazepine To 11.35 g (26.6 mmol) of the compound prepared according to Example 73, 130 cm 3 of acetonitrile and 10.4 g (53.3 mmol) of 2- (3,4-dimethoxyphenyl) -N-methylethylamine are added. The reaction mixture is boiled for 5.5 hours, and then evaporated. The residue is stirred in 100 cm3 of water, at 25 ° C for 3 hours, then the crystals are filtered and washed with water. In this manner, 15.2 g (97.6%) of the title compound are obtained. Mp: 138-140 ° C XH-NMR (CDC13): d 8.28 (2H, d, J = 8.9 Hz), 7.79 (2H, d, J = 8.9 Hz), 6.99 (1H, s), 6.74 (3H, m), 6.48 (1H, s), 6.09 (1H, d, J = 1.1 Hz), 6.05 (1H, d, J = 1.1 Hz), 3.86 (3H, s), 3. 83 (3H, s), 3.77 (1H, d, J = 17.1 Hz), 3.55 (1H, d, j = 17.1 Hz), 3.09 (2H, s), 2.8 (4H, m), 2.54 (3H, s ), 1.86 (3H, s).

Example 76 (±) -8-cyano-7, 8-dihydro-8-methyl-5- (4-nitrophenyl) -7- (3-chloropropionyl) -9H-1, 3-dioxolo [4,5-h] [2 , 3] -benzodiazepine 15.6 g (44.5 mmol) of the compound prepared according to Example 58 are added to 60 cm3 (616 mmol) of 3-chloropropionyl chloride under stirring at 5 to 10 ° C, in 15 minutes. The mixture is stirred at 5 to 10 ° C for 1 hour, at 25 ° C for 6 days and then poured into 300 cm 3 of crushed ice. The mixture is stirred for 100 minutes, then extracted three times using 300 cm3 of dichloromethane each time.

The organic phase is washed with 100 cm.sup.3 of an aqueous solution of 5% sodium hydroxide and 100 cm.sup.3 of water, dried over anhydrous magnesium sulfate and evaporated. The evaporation residue is boiled with 150 cm 3 of methanol, cooled and the crystals that form are filtered. In this manner, 10.7 g (54.6%) of the title compound are obtained. P.f .: 216-218 ° C. Analysis: for C21H17C1N405 (440.85) Calculated: C 57.22%, H 3.89%, Cl 8.04%, N 12.71%; found: C 57.10%, H 4.10%, Cl 8.02%, N 12.41%. XH-NMR (DMS0-d6): d 8.34 (2H, d, J = 8.8 Hz), 7.87 (2H, d, J = 8.8 Hz), 7.21 (1H, s), 6.69 (1H, s), 6.16 ( 1H, s), 6.15 (1H, s), 3.83 (2H, m), 3.50-2.90 (4H, m), 1.75 (3H, s).

Example 77 (±) -8-cyano-7, 8-dihydro-8-methyl-7 - [3 - [4 - (2-methoxyphenyl) piperazinyl] propionyl] -5- (4-nitrophenyl) -9H-1, 3- dioxolo [4, 5-h] [2, 3] -benzodiazepine To 5.95 g (13.5 mmol) of the compound prepared according to Example 76, 100 cm 3 of acetonitrile and 5.1 g (26.5 mmol) of (2-methoxyphenyl) piperazine are added. The reaction mixture is boiled for 3 hours, cooled, filtered and the solids washed with water and ether. The crude product is boiled in 80 cm 3 of ethanol, cooled and filtered. In this way 4.8 g (59.6%) of the title compound are obtained. P.f .: 222-223.5 ° C. Analysis: for C32H32N606 (596.65) Calculated: C 64.42%, H 5.41%, N 14.09%; found: C 64.78, H 5.45%, N 14.08%. XH-NMR (CDC13): d 8.29 (2H, d, J = 9.0 Hz), 7.86 (2H, d, J = 9.0 Hz), 7.10-6.80 (5H, m), 6.51 (1H, s), 6.09 ( 1H, d, J = 1.2 Hz), 6.05 (1H, d, J = 1.2 Hz), 3.86 (3H, s), 3.30-2.60 (14H, m), 1.85 (3H, s).

Example 78 (±) -8-cyano-7,8-dihydro-7- [3- [2- (3,4-dimethoxy phenyl) -N-methylethylamino] propionyl] -8-methyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4, 5-h] [2, 3] -benzodiazepine To 6.17 g (14 mmol) of the compound prepared according to Example 76, 70 cm 3 of acetonitrile and 5.48 g (28 mmol) of 2- (3,4-dimethoxyphenyl) -N-methylethylamine are added. The reaction mixture is boiled for 5.5 hours and then evaporated. The residue is stirred in 50 cm3 of water at 25 ° C for 60 minutes, the crystals are filtered, the crude product filtered is heated in 100 cm3 of water to boiling, then cooled, the crystals are filtered, washed with water and Petroleum ether. In this way 7.1 g (81.6%) of the title compound are obtained. P.f .: 96-98 ° C. Analysis: for C32H33N507 (599.65) Calculated: N 11.68%; found: N 11.22%. XH-NMR (CDC13): 6 8.27 (2H, d, J = 8.8 Hz), 7.8 5 (2H, d, J = 8.8 Hz), 6.99 (1H, s), 7.85-7.65 (3H, m), 6.50 (1H, s), 6.08 (1H, s), 6.05 (1H, s), 3.86 (3H, s), 3.85 (3H, s), 3.20-2.60 (10H, m), 2.41 (3H, s), 1.83 (3H, s).

Example 79 (±) -7- [3- (N-Benzyl-2-morpholinoethylamino) -propionyl] -8-cyano-7,8-dihydro-8-methyl-5- (4-nitrophenyl) -9H-1, 3 - dioxolo [4,5-h] [2, 3] -benzodiazepine To 20 g (45.3 mmol) of the compound prepared according to Example 76, 500 cm 3 of acetonitrile and 25.66 g (113 mmoles) of N-benzyl-2-morpholinoethylamine are added. The reaction mixture is boiled for 6 hours, and then allowed to stand at 25 ° C for 12 hours. The precipitated N-benzyl-2-morpholinoethylamine hydrochloride is filtered and the filtrate is evaporated. The evaporation residue is stirred at 300 cm3 of water at 25 ° C for 18 hours, and the crystals are filtered and washed with water. The crude product is transferred to a column of silica gel which is eluted with a mixture of hexane, acetone and methanol in a proportion of 1: 3: 0.1. The appropriate fraction is evaporated, the residue is suspended in water and filtered. In this way 15.5 g (54.8%) of the title compound are obtained. P.f .: 78-79 ° C. Analysis: for C34H36N606 (624.70): Calculated: N 13.45%; found: N 12.93%.

'H-NMR (CDCl 3): d 8.26 (2H, d, J = 8.9 Hz), 7.75 (2H, d, j = 8.9 Hz), 7.35-7.15 (5H, m), 6.99 (1H, s), 6.40 (1H, s), 6. 10 (1H, d, J = 1.2 Hz), 6.06 (1H, d, J = 1.2 Hz), 3.70-3.59 (6H, m), 3.08 (2H, m), 2.95-2.60 (6H, m), 2.55-2.30 (6H, m), 1.83 (3H, s).

Example 80 (±) -8-cyano-7,8-dihydro-7- [3 - [4- (2-fluoro-phenyl) piperazinyl] propionyl] -8-methyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4, 5-h] [2,3] -benzodiazepine To 5.5 g (12.48 mmol) of the compound prepared according to Example 76, 75 cm 3 of acetonitrile and 4.0 g (22.19 mmoles) of 2-fluorophenyl-piperazine are added. The reaction mixture is boiled for 7.5 hours and then allowed to sit for 12 hours. The precipitated crystals are filtered, washed with water and ether. The crude product is dissolved in 250 cm 3 of toluene, and precipitated with 150 cm 3 of petroleum ether, the crystals are filtered. In this way 3.96 g (54.3%) of the title compound are obtained. P.f .: 191-192 ° C. Analysis: for C31H29FN60s (584.61) Calculated: N 14.38%; found: N 14.11%.

'H-NMR (CDCI3): d 8.29 (2H, d, J = 8.8 Hz), 7.86 (2H, d, J = 8.8 Hz), 7.20-6.80 (5H, m), 6.51 (1H, s), 6.09 (1H, d, J = 1.2 Hz), 6.05 (1H, d, j = 1.2 Hz), 3.30-3.05 (6H, m), 3.05-2.60 (8H, m), 1.85 (3H, s).

Example 81 (±) -7-acetyl-5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 18.3 g (46.6 mmol) of the compound prepared according to Example 61 are suspended in a mixture of 370 cm 3 of ethanol and 90 cm 3 of water. To the suspension is added 3.7 g of palladium 10% catalyst / carbon and then 46.7 cm3 (941.7 mmoles) of hydrazine hydrate 98% are added in 20 minutes, while the temperature of the reaction mixture reaches 40 ° C and the Initial compound dissolves. The mixture is stirred for 2.5 hours at room temperature. During this time, the reaction mixture is cooled to 25 ° C and the product precipitates. The catalyst is filtered, washed twice with 200 cm3 of ethanol each time, and then three times using 500 cm3 of chloroform each time. The filtrate is under reduced pressure and 300 cm3 of water are added to the crystalline residue. After one hour of stirring, the crystals are filtered, washed three times using 70 cm3 of water each time, and twice using 50 cm3 of ether each time. 14.0 g are recrystallized (82.8%) of the crude product from 420 cm3 of ethyl acetate, the crystals are filtered, washed three times with 30 cm3 of ether each time, and dried under a lamp emitting infrared radiation. In this manner, 10.5 g (62.1%) of the title compound are obtained. P.f .: 162-164 ° C. Analysis: for C20H18N403 (362.39) Calculated: C 66.28%, H 5.01%, N 15.46%; found: C 66.88%, H 5.12%, N 14.78%. 'H-NMR (CDC13): d 7.46 (2H, d, J = 8.7 Hz), 6.96 (1H, s), 6.67 (2H, d, j = 8.7 Hz), 6.65 (1H, s), 6.05 (1H , d, J = 1. 2 Hz), 6.01 (1H, d, J = 1.2 Hz), 4.15 (2H, broad s), 3.05 (1H, d, J = 13.9 Hz), 2.92 (1H, d, J = 13.9 Hz), 2.16 (3H, s), 1.81 (3H, s).

Example 82 Hydrochloride of (±) -7-acetyl-5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-9H-l, 3-dioxolo [4, 5-h] [2 , 3] -benzodiazepine At 0.95 g (2.6 mmol) of the compound prepared according to Example 81, 15 cm3 of diethyl ether and 3.0 cm3 of 17.3% hydrogen chloride in ether are added. The suspension is stirred at 25 ° C for 90 minutes, the yellow crystals are filtered and washed with diethyl ether. In this way 0.75 of the title compound is obtained. P.f .: 241-243 ° C. 'H-NMR (DMSO-d6) d 8.10 (3H, broad s), 7.67 (2H, d, J = 8.7 Hz), 7.33 (2H, d, J = 8.7 Hz), 7.19 (1H, s), 6.70 (1H, s), 6.17 (1H, s), 6.16 (1H, s), 3.20 (1H, s), d, J = 14.3 Hz), 3.11 (1H, d, J = 14.3 Hz), 2.17 (3H, s), 1.72 (3H, s).

Example 83 (±) -5- (4-Amino-phenyl) -8-cyano-7,8-dihydro-8-methyl-7- (pyrrolidin-1-carbonyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine .5 g (12.3 mmol) of the compound prepared according to Example 72 are transferred to a mixture of 330 cm 3 of methanol and 55 cm 3 of water. 3.3 g of 10% palladium / carbon catalyst are added to the mixture and then 11.0 cm3 (226 mmoles) of hydrazine hydrate 98% are added in 15 minutes. The reaction mixture is stirred at room temperature for 5 hours. The catalyst is filtered and washed three times using 100 cm3 of methanol each time. The filtrate is evaporated under reduced pressure and 100 cm 3 of water are added to the residue. After stirring for one hour, the crystals are filtered and washed three times with 15 cm3 of water each time. 4.0 g (78.0%) of the crude product obtained is transferred to a column of silica gel eluting with chloroform. The appropriate fraction is evaporated under reduced pressure, the residue is stirred in diisopropyl ether, the crystals are filtered, washed three times using 10 cm3 of diisopropyl ether each time and dried under a lamp emitting infrared radiation. In this manner, 2.8 g (54.6%) of the title compound are obtained. P.f .: 188-190 ° C Analysis: for C23H23N503 (417.47) Calculated: C 66.17%, H, 5.55%, N 16.78%; found: C 65.96%, H 5.58, N 16.54%. 'H-NMR (CDC13): d 7.54 (2H, d, J = 8.6 Hz), 6.91 (1H, s), 6.66 (2H, d, J = 8.6 Hz), 6.66 (1H, s), 6.05 (1H , d, J = 1.3 Hz), 6.04 (1H, d, J = 1.3 Hz), 4.21 (2H, broad s), 3.2 (4H, b), 3.04 (1H, d, J = 13.8 Hz), 2.79 ( 1H, d, J = 13.8 Hz), 1.81 (3H, s), 1.74 (4H, b).

Example 84 (±) -5- (4-Amino-phenyl) -8-cyano-7,8-dihydro-8-methyl-7- (morpholine-4-carbonyl) -9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 2.5 g (5.4 mmol) of the compound prepared according to Example 71 are transferred to a mixture of 80 cm 3 of ethanol and 20 cm 3 of water. 0.5 g of 10% palladium / carbon catalyst is added to the mixture and then 5.0 cm3 is added (100.8 mmol) of hydrazine hydrate in 15 minutes. The reaction mixture is stirred at room temperature for 24 hours, the catalyst is filtered and washed three times using 50 cm3 of methanol each time. The filtrate is evaporated under reduced pressure and 100 cm 3 of water are added to the residue. After 1 hour of stirring, the crystals are filtered and washed three times with 20 cm3 of water each time. 1.1 g (47.0%) of the crude product obtained is transferred to a column of silica gel eluting with a mixture of chloroform and methanol in a ratio of 9 to 1. The appropriate fraction is evaporated under reduced pressure, and then stirred in 20 cm3 of diisopropyl ether, the crystals obtained are filtered, washed three times using cm3 of diisopropyl ether each time, and dried under a lamp that emits infrared radiation. In this way, 0.4 g (17.1%) of the title compound is obtained. P.f .: 236-238 ° C Analysis: for C23H23Ns04 (433.47) Calculated: C 63.73%, H 5.35%, N, 16.16%; found: C 63.03%, H 5.48%, N 15.84%. 'H-NMR (CDC13): d 7.53 (2H, d, J = 8.7 Hz), 6.89 (1H, s), 6.67 (2H, d, J = 8.7 Hz), 6.63 (1H, s), 6.07 (2H , s), 4.16 (2H, broad s), 3.60 (4H, t, J = 4.7 Hz), 3.24 (4H, m), 3.13 (1H, d, J = 13.9 Hz), 2.79 (1H, d, J = 13.9 Hz), 1.77 (3H, s).

Example 85 Dihydrate of (±) -5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-7- (pyridine-3-carbonyl) -9H-1,3-dioxolo [4, 5] h] [2,3] -benzodiazepine 7.5 g (16.46 mmoles) of the compound prepared according to Example 69 are reduced using the method of Example 84. 2.0 g (26.3%) of the title compound are obtained. P.f. : 244-245 ° C. Analysis: for C24H19N503 (461.46) Calculated: C 62.47%, H 5.02%, N 15.18%; found: C 63.36%, H 4.73%, N 14.80%. 'H-NMR (CDC13): d 8.65 (1H, dd, J = 4.9 and 1.7 Hz), 8.57 (1H, d, J = 1.4 Hz), 7.75 (1H, dt, J = 7.9 and 1.9 Hz), 7.367 .28 (1H, m), 7.09 (2H, d, J = 8.7 Hz), 7.03 (1H, s), 6.75 (1H, s), 6.53 (2H, d, J = 8.7 Hz), 6.10 (1H, d, J = 1.3 Hz), 6.06 (1H, d, J = 1.3 Hz), 4.15 (2H, broad s), 3.08 (2H, broad s), 1.95 (3H, s).

Example 86 (±) -5- (4-Amino-phenyl) -8-cyano-7,8-dihydro-8-methyl-7-propionyl-9H-1,3-dioxolo [4,5-h] [2,3] - benzodiazepine 4.5 g (11.1 mmol) of the compound prepared according to Example 67 are transferred in a mixture of 360 cm 3 of ethanol and 90 cm 3 of water. To the mixture is added 2.7 g of 10% palladium / carbon catalyst and then, in 25 minutes, 18.0 cm3 (363 mmoles) of 98% hydrazine hydrate are added at 15 to 20 ° C. The mixture is stirred at room temperature for 5 days. Subsequently, the catalyst is filtered, washed three times using 100 cm 3 of ethanol each time, three times with 300 cm 3 of chloroform each time. The filtrate is evaporated under reduced pressure and, for the crystalline residue, 150 cm3 of water are added. After stirring for 1 hour, the crystals are filtered and washed three times using 30 cm3 of water each time. 3.2 g are transferred (76.8%) of the crude product to a column of silica gel eluting with a mixture of chloroform and methanol in a ratio of 9: 1. The appropriate fraction is evaporated and the residue is crystallized from 30 cm3 of ether. The crystals obtained are filtered and washed with a large amount of ether. In this manner, 1.28 g (30.7%) of the title compound are obtained. P.f .: 212-214 ° C. Analysis: for C21H20N4O3 (376.42) Calculated: N 14.88%; found: N 14.69%. 'H-NMR (DMSO-d6): d 7.35 (2H, d, J = 8.8 Hz), 7.11 (1H, s), 6.87 (1H, s), 6.61 (2H, d, J = 8.8 Hz), 6.13 (1H, s), 6.12 (1H, s), 6.12 (1H, s), 5.8 (2H, broad s), 3.08 (1H, d, J = 14.4 Hz), 2.95 (1H, d, J = 14.4 Hz ), 2.6-2.2 (2H, m), 1.68 (3H, s), 0.96 (3H, t, J = 7.2 Hz).

Example 87 (±) -5- (4-aminophenyl) -7-butyryl-8-cyano-7,8-dihydro-8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] - benzodiazepine 4.1 g (9.75 mmol) of the compound prepared according to Example 68 are transferred to a mixture of 330 cm 3 of ethanol and 80 cm 3 of water. To the mixture is added 2.5 g of 10% palladium / carbon catalyst, and then, in 15 minutes, 16.4 cm3 (330 mmoles) of hydrazine hydrate 98% are added from 20 to 30 ° C. The mixture is stirred at room temperature for 4 hours. The catalyst is then filtered and washed three times using 80 cm3 of methanol each time. The filtrate is evaporated under reduced pressure and 200 cm 3 of water are added to the crystalline residue. After stirring for 1 hour, the crystals are filtered and washed three times with 30 cm3 of water each time. The crude product is transferred to a column of silica gel which is eluted with a chloroform and methanol mixture in a ratio of 15: 1. The appropriate fraction is evaporated and the residue is crystallized from 25 cm 3 of diisopropyl ether.

The crystals obtained are filtered and washed with diisopropyl ether. In this way 2.3 g (60.5%) of the title compound are obtained. P.f .: 152-154 ° C. 'H-NMR (DMS0-d6): d 7.49 (2H, d, J = 8.8 Hz), 6.96 (1H,, s), 6.68 (2H, d, J = 8. (Hz), 6.64 (1H, s), 6.06 (1H, d, J = 1.2 Hz), 6.01 (1H, d, J = 1.2 Hz ), 4.18 (2H, broad s), 3.04 (1H, d, J = 14.1 Hz), 2.90 (1H, d, J = 14.1 Hz), 2.43 (2H, m), 1.81 (3H, s), 1.61 ( 2H, m), 0.93 (3H, t, J = 7.4 Hz).

Example 88 (±) -5- (4-aminophenyl) -8-cyano-7,8-dihydro-7- [2- [2- (3,4-dimethoxyphenyl) -N-methyl-ethylamino] acetyl] -8-methyl -5- (4-nitrophenyl) -9H-1, 3-dioxolo [4, 5-h] [2, 3] -benzodiazepine 2.14 g (3.65 mmol) of the compound prepared according to Example 75 are transferred into 60 cm3 of ethanol, 3.31 g (14.7 mmol) of crystalline tin (II) chloride (SnCl2.2H20) are added, and the mixture is mixed. Boil for 1.5 hours. After cooling, the reaction mixture is evaporated. To the residue 50 cm3 of water and 100 cm3 of dichloromethane are added, the phases are separated, the aqueous phase becomes alkaline when a 10% sodium hydroxide solution is added (it is adjusted to pH 11), and the mixture is extracted three times using 100 cm3 of dichloromethane each time. The combined dichloromethane phases are dried and evaporated under reduced pressure. To the evaporation residue, 30 cm 3 of diisopropyl ether are added and, after 30 minutes of stirring, the crystals are filtered and washed with diisopropyl ether. The crude product is transferred to a column of silica gel which is eluted with a mixture of chloroform and methanol in a ratio of 9: 1. The appropriate fraction is evaporated and the residue is stirred in 30 cm3 of diisopropyl ether for half an hour. The crystals that are obtained are filtered. In this manner, 0.35 g (17.3%) of the title compound is obtained. P.f .: 112-114 ° C. Analysis: for C31H33N505 (555.64) Calculated: N 12.60%; found: N 12.41%. 'H-NMR (CDC13): d 7.45 (2H, d, J = 8.7 Hz), 6.95 (1H, s), 6.80-6.68 (3H, m), 6.66 (2H, d, J = 8.7 Hz), 6.59 (1H, s), 6.05 (1H, d, J = 1.3 Hz), 5.99 (1H, d, J = 1.3 Hz), 4.08 (2H, broad s), 3.85 (3H, s), 3.83 (3H, s ), 3.75-3.60 (1H, m), 3.25-3.45 (1H, m), 3.02 (1H, d, J = 13.8 Hz), 2.95-2.60 (5H, m), 2.45 (3H, s), 1.82 ( 3H, s).

Example 89 (±) -5- (4-Aminophenyl) -8-cyano-7,8-dihydro-8-methyl-7- [3- (2-morpholinoethyl) amino) -propionyl] -9H-1,3-dioxolo [4 , 5-h] [2,3] -benzodiazepine 8.5 g (13.6 mmol) of the compound prepared according to Example 79 are transferred into a mixture of 300 cm 3 of ethanol and 60 cm 3 of water, 3.0 g of palladium / 10% carbon catalyst are added to the mixture, and then 15 minutes 10.0 cm3 (190 mmoles) of hydrazine hydrate 98% are added. The reaction mixture is stirred at room temperature for 24 hours. The catalyst is filtered, and washed three times using 50 cm3 of ethanol each time. The filtrate is evaporated under reduced pressure and 200 cm 3 of water are added to the residue. After 2 hours of stirring, the crystals are filtered, the resulting crude product is transferred to a column of silica gel eluting with methanol. The appropriate fraction is evaporated under reduced pressure, the residue is dissolved in dichloromethane, filtered through a filter paper and the filtrate is evaporated. The obtained crystals are suspended in 25 cm3 of ether, stirred for a short time and washed three times using 10 cm3 of ether each time. In this way 1.45 g (21.1%) of the title compound are obtained. P.f .: 141-143 ° C.

Analysis: for C27H32N604 (504.59) Calculated: N 16.66%; found: N 16.44%. 'H-NMR (CDC13): d 7.47 (2H, d, J = 8.8 Hz), 6.96 (1H, s), 6.66 (2H, d, J = 8.8 Hz), 6.63 (1H, s), 6.06 (1H , d, j = 1.2 Hz), 6.02 (1H, d, J = 1.2 Hz), 4.25 (2H, broad s), 3.71-3.65 (2H, m), 3.10-2.00 (17H, m), 1.81 (3H , s).

Example 90 (±) -5- (4-aminophenyl) -8-cyano-7,8-dihydro-7- [3- [2- (3,4-dimethoxyphenyl) -N-methyl-ethylamino] propionyl-8-methyl- 9H-1, 3-dioxolo [4,5-h] [2,3] -benzodiazepine .0 g (16.6 mmol) of the compound prepared according to Example 78 are transferred into a mixture of 350 cm 3 of methanol and 60 cm 3 of water. To the mixture is added 5.0 g of 10% palladium / carbon catalyst and then, in 20 minutes, 30.0 cm3 (605 mmoles) of 98% hydrazine hydrate are added at 15 to 20 ° C. The mixture is stirred at room temperature for 6.5 hours, the catalyst is filtered and washed three times using 100 cm3 of methanol each time. The filtrate is evaporated under reduced pressure and 100 cm 3 of water are added to the residue. After stirring for 1 hour, the crystals are filtered, and washed three times with 30 cm3 of water each time. The crude product is transferred to a column of silica gel eluting with a mixture of chloroform and methanol in a ratio of 4: 1. The appropriate fraction is evaporated and the residue is stirred in 30 cm3 of ether for half an hour. The crystals obtained are filtered and washed with ether. In this way 3.5 g (33.7%) of the title compound are obtained. P.f .: 148-150 ° C. Analysis: for C32H35N50B (569.64) Calculated: N 12.29%; found: N 11.89%. 'H-NMR (CDC13): d 7.48 (2H, d, J = 8.6 Hz), 6.96 (1H, s), 6.92-6.64 (3H, m), 6.62 (2H, d, J = 8.6 Hz), 6.62 (1H, s), 6. 05 (1H, d, J = 1.3 Hz), 5.98 (1H, d, J = 1.3 Hz), 4.15 (2H, s broad), 3.85 (6H, s), 3.04 (1H, d, J = 14.1 Hz) , 2.92 (1H, d, J = 14.1 Hz), 2.88-2.54 (8H, m), 2.32 (3H, s), 1.80 (3H, s).

Example 91 (±) - 5 - (4-aminophenyl) -8-cyano-7,8-dihydro-7- [3- [4- (2-fluorophenyl) piperazinyl] -propionyl-8-methyl-9H-1, 3 - dioxolo [4,5-h] [2, 3] -benzodiazepine 16.4 g (27.5 mmol) of the compound prepared according to Example 80 are transferred into 180 cm3 of ethanol. To the mixture is added 7.26 g (32.2 mmol) of crystalline tin (II) chloride (SnCl2.2H20) and the reaction mixture is boiled for 3.5 hours. After cooling, the reaction mixture is evaporated under reduced pressure. To the residue 180 cm3 of water are added. The mixture is made alkaline by the addition of 135 cm 3 of a 40% aqueous solution of sodium hydroxide, and extracted three times using 400 cm 3 of dichloromethane each time. The dichloromethane phase is dried and evaporated under reduced pressure. To the evaporation residue is added 50 cm.sup.3 of ether, the mixture is stirred for 30 minutes, the crystals are filtered and washed with ether. The resulting crude product is transferred to a column of silica gel eluting with a mixture of chloroform and methanol in a ratio of 9: 1. The appropriate fraction is evaporated and the residue is crystallized from 10 cm3 of ether. The crystals are filtered and washed with ether. In this way 1.85 g (34.9%) of the title compound are obtained. P.f .: 159-161 ° C. Analysis: for C31H31FN603 (554.63) Calculated: C 67.13%, H 5.63%, N 15.15%; found: C 66.50%, H 5.50%, N 15.11%. 'H-NMR (CDC13): d 7.50 (2H, d, J = 8.8 Hz), 7.15-6.8 (4H, m), 6.96 (1H, s), 6.67 (2H, d, J = 8.8 Hz), 6.65 (1H, s), 6. 05 (1H, d, J = 1.3 Hz), 5.98 (1H, d, J = 1.3 Hz), 4.19 (2H, broad s), 3.09 (4H, t, J = 4.8 Hz), 3.05-2.68 (6H, m), 2.65 (4H, t, J = 4.8 Hz), 1.81 (3H, s).

Example 92 (±) -5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-7-morpholinoacetyl-9H-l, 3-dioxolo [4,5-h] [2,3] - benzodiazepine 2.0 g (4.19 mmol) of the compound prepared according to Example 74 are transferred in 70 cm 3 of ethanol. To the mixture is added 3.8 g (16.8 mmol) of tin chloride (II) crystalline (SnCl2.2H20) and the reaction mixture is boiled for 3 hours. After cooling, the reaction mixture is evaporated under reduced pressure. To the residue is added 50 cm3 of water and 100 cm3 of dichloromethane. After stirring for 1 hour, the phases are separated, the pH of the aqueous phase is adjusted to 11 by the addition of an aqueous solution of 10% sodium hydroxide, and the mixture is extracted three times using 150 cm 3 of dichloromethane each time. The combined dichloromethane phases are dried, and evaporated under reduced pressure. To the evaporation residue is added 30 cm.sup.3 of ether and, after 30 minutes of stirring, the crystals are filtered and washed with ether. 0.6 g (32%) of the obtained crude product is transferred to a column of silica gel which is eluted with a mixture of chloroform and methanol in a ratio of 15: 1. The appropriate fraction is evaporated and the residue is crystallized from 20 cm3 of ether, the crystals are filtered and washed with ether.

In this way 0.53 g (28.6%) of the title compound is obtained. P.f .: 171-172 ° C. 'H-NMR (CDC13): d 7.45 (2H, d, J = 8.6 Hz), 7.00 (1H, s), 6.68 (2H, d, J = 8.6 Hz), 6.65 (1H, s), 6.07 (1H , d, J = 1.3 Hz), 6.03 (1H, d, J = 1.3 Hz), 4.10 (2H, broad s), 3.71 (4H, t, J = 4.7 Hz), 3.54 (1H, d, J = 14.0 Hz), 3.19 (1H, d, J = 14.3 Hz), 3.04 (1H, d, J = 14.0 Hz), 2.92 (1H, d, J = 14.3 Hz), 2.65-2.50 (4H, m), 1.83 ( 3H, s).

Example 93 Acid (±) -5- (4-aminophenyl) -7,8-dihydro-8-methyl-7-trifluoroacetyl-9H-l, 3-dioxolo [4,5-h] [2,3] -benzodiazepine- 8-carboxylic acid. 2.0 g (4.3 mmol) of the compound prepared according to Example 65 are dissolved in 40 cm3 of methanol. To the solutis added 1.0 g of 10% palladium catalyst / carbon suspended in 10 cm3 of methanol, and the mixture is stirred vigorously at room temperature under a hydrogen atmosphere. The reductends in 7 hours. The catalyst is then filtered, washed three times using 50 cm3 of methanol each time and the filtrate is evaporated under reduced pressure. To the residue is added 20 cm.sup.3 of ether, and the mixture is stirred for one hour. The crystals obtained are filtered, washed three times with 10 cm3 of ether each time and dried under a lamp emitting infrared radiat In this way 125 g (53.8%) of the title compound are obtained. P.f .: C20H16F3N30S (435.36) Analysis: for C 55.18%, H 3.70%, N 9.65%; Calculated: C 55.18%, H 3.70%, N 9.65%; found: C 54.58%, H 3.89%, N 9.35%. 'H-NMR (CDC13): d 7.18 (2H, broad s), 6.88 (1H, s), 6.67 (2H, d, J = 7.8 Hz), 6.55 (1H, s), 6.08 (1H, s), 6.04 (1H, s), 4.15 (2H, broad s), 3.70 (1H, d, J = 16.7 Hz), 3.35 (1H, d, J = 16.7 Hz), 1.78 (3H, s).

Example 94 (Dimethylamide) of (±) -5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-9H-l, 3-dioxolo [4,5-h] [2,3] -benzodiazepine- 7 -carboxylic 2.5 g (5.93 mmol) of the compound prepared according to Example 70 are dissolved in 90 cm3 of methanol. To the solutis added 0.5 g of 10% palladium / carbon catalyst suspended in 10 cm3 of methanol, and the mixture is stirred vigorously at room temperature under a nitrogen atmosphere. The reductis completed in 25 hours. The catalyst is filtered, washed three times using 40 cm3 of methanol and the filtrate is evaporated under reduced pressure. To the residue is added 30 cm3 of ether and the mixture is stirred for one hour. The crystals obtained are filtered, washed three times with 10 cm3 of ether each time and dried under a lamp emitting infrared radiat 1.6 g (68.9%) of the crude product is transferred to a column of silica gel eluting with a mixture of chloroform and methanol in a ratio of 9: 1. The appropriate fractis evaporated under reduced pressure, the residue is crystallized from 20 cm3 of ether, the crystals are filtered, washed with ether and dried in a drying gun at 120 ° C. In this manner 1.17 g (50.4%) of the title compound are obtained. P.f .: 248-250 ° C. 'H-NMR (CDC13): d 7.36 (2H, d, J = 8.6 Hz), 7.13 (1H, s), 6.70 (1H, s), 6.65 (2H, d, J = 8.6 Hz), 6.12 (2H , s), 5.84 (2H, s), 2.94 (2H, broad s), 2.65 (6H, broad s), 1.59 (3H, s).

Example 95 (±) -5- (4-Aminophenyl) -7,8-dihydro-8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine-8-carboxamide 3.2 g (8.69 mmol) of the compound prepared according to Example 59 are transferred into 80 cm3 of ethanol, 7.84 g (34.75 mmol) of crystalline tin (II) chloride (SnCl2.2H20) are added and the mixture is subjected to at boiling for 90 minutes. After cooling, the reactmixture is evaporated under reduced pressure. To the residue is added 150 cm3 of water and the mixture is extracted three times using 100 cm3 of dichloromethane each time. The organic phase contains only by-products. The aqueous phase is made alkaline by the additof 120 cm.sup.3 of a 10% sodium hydroxide solut(pH = 11) and extracted three times using 200 cm.sup.3 of dichloromethane each time. The dichloromethane phase is dried and evaporated under reduced pressure. To the evaporatresidue is added 40 cm3 of diisopropyletherThe mixture is stirred for 30 minutes, the crystals are filtered and washed three times with 10 cm3 of diisopropyl ether each time. 1.1 g (37.4%) of the crude product are obtained and boiled in 25 cm 3 of ethanol, cooled, stirred and washed with a large amount of ether. In this manner, 0.6 g (20.4%) of the title compound is obtained. Mp: 248-249 ° C 'H-NMR (CDC13): 6 7.21 (2H, d, J = 8.6 Hz), 7.08 (2H, m), 6.78 (1H, s), 6.54 (2H, d, J = 8.6 Hz), 6.49 (1H, s), 6.06 (1H, s), 6.03 (1H, d, J = 1.1 Hz), 6.01 (1H, d, J = 1.1 Hz), . 28 (2H, broad s), 2.77 (1H, d, J = 13.6 Hz), 2.56 (1H, d, J = 13.6 Hz), 1.29 (3H, s).

Example 96 (±) -5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-7-trifluoroacetyl-9H-l, 3-dioxolo [4,5-h] [2,3] - benzodiazepine 4.0 g (8.96 mmoles) of the compound prepared according to Example 64 are transferred into 160 cm 3 of ethanol, 9.0 g (40.0 mmoles) of crystalline tin (II) chloride (SnCl2.2H20) are added and the mixture is subjected to Boil for 90 minutes. After cooling, the reaction mixture is evaporated under reduced pressure. To the residue is added 120 cm3 of water and the mixture is extracted twice using 150 cm3 of dichloromethane each time. The organic phase is washed twice with 30 cm.sup.3 of an aqueous solution of 5% sodium hydroxide each time, and then once with 100 cm.sup.3 of water. The pH of the aqueous phase is adjusted with an aqueous solution of 10% sodium hydroxide to a value of 10, and extracted three times using 70 cm 3 of dichloromethane each time. The dichloromethane layers obtained before and after the alkylation are combined, dried and evaporated under reduced pressure. 50 cm 3 of diisopropyl ether are added to the evaporation residue and after 60 minutes of stirring the crystals are filtered and washed three times using 10 cm 3 of diisopropyl ether each time. 1.7 g (45.6%) of the crude product obtained is transferred to a column of silica gel eluting with pure chloroform. The Rf value of the product constitutes 0.53 in a mixture of toluene and methanol, in a ratio of 7: 3. The fraction containing the product is evaporated under reduced pressure, the residue is crisatlized from 10 cm 3 of n-hexane. The crystals are filtered and washed with 10 cm 3 of n-hexane. In this way 0.7 g (18.7%) of the title compound are obtained. P.f .: 129-130 ° C. Analysis: for C20H1SF3N403 (416.36) Calculated: N 13.46%; found: N 13.12%. 'H-NMR (CDC13): d 7.49 (2H, d, J = 8.7 Hz), 6.98 (1H, s), 6.67 (2H, d, J = 8.7 Hz), 6.66 (1H, s), 6.09 (1H , d, J = 1.3 Hz), 6.05 (1H, d, j = 1.3 Hz), 4.14 (2H, broad s), 3.15 (1H, d, J = 14.4 Hz), 2.98 (1H, broad s), 1.89 (3H, s).

Example 97 (±) - 7-acetyl-5 - (4-aminofenyl) -7,8-dihydro-8-met-il-9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine - 8 -carboxamide 1.5 g (3.66 mmol) of the compound prepared according to Example 62 are transferred into 50 cm3 of ethanol, 3.31 g (14.67 mmol) of crystalline tin (II) chloride (SnCl2.2H20) are added and the mixture is subjected to at boiling for 5 hours. After cooling, the reaction mixture is evaporated under reduced pressure. To the residue 50 cm 3 of water are added and the mixture is extracted three times using 70 cm 3 of dichloromethane each time. The pH of the aqueous phase is adjusted with an aqueous solution of 30% sodium hydroxide to a value of 11, and the solution is extracted three times with 100 cm 3 of dichloromethane each time. The aqueous phase is saturated with sodium chloride and extracted again three times using 70 cm 3 of dichloromethane each time. The dichloromethane phases are combined, dried and evaporated under reduced pressure. 1.25 g of the evaporation residue are transferred to a column of silica gel which is eluted with a mixture of chloroform and methanol in a ratio of 9: 1. The fraction containing the product is evaporated under reduced pressure and the residue is crystallized from 10 cm3 of ether. The crystals are filtered and washed three times using 10 cm3 of ether each time. The 0.6 g (43.1%) of crude product obtained is boiled in 4 cm3 of isopropanol for 5 minutes and then cooled, filtered and washed three times with 3 cm3 of ether each time. In this way, 0.4 g (28.8%) of the title compound is obtained. P.f .: 182-184 ° C. 'H-NMR (DMSO-d6, 140 ° C): d 7.31 (2H, d, J = 8.8 Hz), 6.86 (1H, s), 6.63 (2H, d, J = 8.8 Hz), 6.57 (1H, s), 6.11 (2H, broad s), 6.03 (2H, s), 5.23 (2H, broad s), 2.84 (1H, d, J = 13.6 Hz), 2.71 (1H, d, J = 13.6 Hz), 2.08 (3H, s), 1.52 (3H, S).

Example 98 (±) -7-Acetyl-5- (4-aminophenyl) -7,8-dihydro-8-methyl-9H-l, 3-dioxolo [4,5-h] [2,3] -benzodiazepine- monohydrochloride 8 -carboxamide cm3 of concentrated hydrochloric acid are cooled to -20 ° C and 1.0 g (2.76 mmol) of the compound prepared according to Example 81 are added in 10 minutes. The mixture is allowed to warm to 5 to 10 ° C, and then it is stirred at 10 ° C for 2 hours. The suspension is again cooled to -20 ° C and, after 15 minutes of stirring, the crystals are filtered. The crude product is stirred in 30 cm3 of diethyl ether for 30 minutes, then filtered and washed with diethyl ether. In this way 0.8 g (69.5%) of the title compound are obtained. P.f .: 240-244 ° C. Analysis: for C20H21C1N404 (416.87) Calculated: Cl 8.50%, N 13.44% found: Cl 8.11%, N 13.80%. 'H-NMR (DMS0-d6): d 7.59 (2H, d, J = 8.4 Hz), 7.25 (2H, d, J = 8.4 Hz), 7.00 (1H, s), 6.95-6.70 (2H, broad) , 6.61 (1H, s), 6.11 (1H, s), 6.10 (1H, s), 3.1-2.88 (1H, m), 2.83 (1H, d, J = 14.0 Hz), 2.20 (3H, s), 1.47 (3H, s).

Example 99 (±) -5- (4-Aminophenyl) -8-cyano-7,8-dihydro-8-methyl-7-chloroacetyl-9H-1,3-dioxolo [4,5-h] [2,3] - benzodiazepine 4.28 g (10.0 mmol) of the compound prepared according to Example 73 are transferred into 120 cm3 of ethanol, 11.26 g (50 mmol) of crystalline tin (II) chloride (SnCl2.2H20) are added and the mixture is subjected to at boiling for 120 minutes. After cooling, the reaction mixture is evaporated under reduced pressure. To the residue is added 120 cm 3 of water, the pH is adjusted by the addition of an aqueous solution of 10% sodium hydroxide to a value of 11, and the mixture is extracted 5 times using 200 cm 3 of dichloromethane each time. The dichloromethane phase is washed twice with 100 cm.sup.3 of water each time, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. To the evaporation residue is added 70 cm 3 of diisopropyl ether, the mixture is stirred for 30 minutes, the crystals are filtered and washed three times using 10 cm 3 of diisopropyl ether each time. The crude product is boiled in 20 cm3 of methanol, cooled and filtered. In this manner, 0.6 g (15.2%) of the title compound is obtained. P.f .: 238-242 ° C. Analysis: for C20H17C1N403 (396.84) Calculated: Cl 8.93%, N 14.12%; found: Cl 8.72%, N 13.54%. 'H-NMR (CDC13 + DMS0-d6): d 7.41 (2H, d, J = 6.8 Hz), 6. 97 (1H, s), 6.68 (2H, d, J = 6.8 Hz), 6.66 (1H, s), 6.09 (1H, s), 6.07 (1H, s), 4.97 (2H, broad s), 4.40 (1H, d, J = 14.4 Hz), 4.35-4.15 (1H, broad s), 3.15-2.85 (2H, m), 1.82 (3H, s).

Example 100 (±) -7-acetyl-5- (4-aminophenyl) -8-cyano-7,8-dihydro-8-methyl-9H-1,3-dioxolo [4,5-h] [2,3] -benzodiazepine 2.5 g (6.9 mmol) of the compound prepared according to Example 81 are transferred to 25 cm 3 of anhydride acetic After 20 minutes of stirring, a solution is obtained. The solution is stirred for 18 hours, and then poured into 250 cm 3 of water. The mixture is stirred at 5 to 10 ° C for 30 minutes, the precipitated crystals are filtered, washed three times with 60 cm3 of water each time, and twice with water. 40 cm3 of ether each time. 2.69 cm3 (96.4%) of the crude product are stirred in 30 cm3 of ethyl acetate for one hour, the crystals are filtered, washed with ethyl acetate and ether. In this manner, 1.88 g (67.3%) of the title compound are obtained. P.f .: 162-163 ° C 25 Analysis: for C22H20N4O4 (404.43) Calculated: N 13.85%; found: N 13.32%. 'H-NMR (DMS0-d6): d 10.23 (1H, s), 7.71 (2H, d, J = 8. 7 Hz), 7.58 (2H, d, J = 8.7 Hz), 7.16 (1H, s), 6.67 (1H, s), 6.15 (1H, s), 6.14 (1H, s), 3.17 (1H, d, J = 14.2 Hz), 3.05 (1H, d, J = 14.2 Hz), 2.14 (3H, s), 2.09 (3H, s), 1.71 (3H, s).

Example 101 (±) - 8-cyano-7, 8-dihydro-7 - [2 - [4 - (2-fluoro-phenyl) piperazinyl] acetyl] -8-methyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4, 5-h] [2,3] -benzodiazepine To 5.33 g (12.5 mmol) of the compound that is prepared according to Example 73, 75 cm3 of acetonitrile and 4.05 g (22.5 mmoles) of 2-fluorophenylpiperazine are added. The reaction mixture is boiled for 7 hours, and then evaporated under reduced pressure. The evaporation residue is stirred in 20 cm3 of water for 1.5 hours, the precipitated crystals are filtered and washed with water. The crude product is transferred to a column of silica gel which is eluted with a mixture of cyclohexane and ethyl acetate. The appropriate fraction is evaporated under reduced pressure, the residue is crystallized from 25 cm 3 of ethanol, the crystals are filtered and washed with ethanol.

In this manner, 2.70 g (37.9%) of the title compound are obtained. Mp: 148-150 ° C 'H-NMR (CDC13): d 8.31 (2H, d, J = 8.8 Hz), 7.81 (2H, d, J = 8.8 Hz), 7.10-6.90 (4H, m), 7.00 (1H, s), 6.53 (1H, s), 6.10 (1H, s), 6.07 (1H, s), 3.67 (1H, d, J = 16.7 Hz), 3.41 (1H, d, J = 16.7 Hz), 3.20-3.05 (6H, m), 2.95-2.80 (2H, m), 2. 80-2.6 (2H, m) 1.88 (3H, s).

Example 102 (±) -5- (4-Aminophenyl) -8-cyano-7,8-dihydro-7- [2- [4- (2-fluorophenyl) piperazinyl] -acetyl] -8-methyl- 5- (4 - nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] -benzodiazepine g (8.8 mmol) of the compound prepared according to Example 101 are dissolved in a mixture of 230 cm.sup.3 of methanol and 50 cm.sup.3 of water, and a suspension of 3 g of 10% palladium / carbon catalyst is added to the mixture. cm3 of methanol. To the mixture is added 10 cm3 (200 mmol) of hydrazine hydrate, dropwise, in 15 minutes, and the reaction mixture is stirred vigorously at room temperature for 3.5 hours. The catalyst is filtered, washed three times using 40 cm3 of methanol each time, and the filtrate is evaporated under reduced pressure. To the residue is added 200 cm3 of water, and the mixture is stirred for 1 hour. The crystals that are obtained are filtered. The crude product is transferred to a column of silica gel which is eluted with a mixture of chloroform and methanol in a ratio of 9: 1. The appropriate fraction is evaporated under reduced pressure, the residue is crystallized from 20 cm 3 of diisopropyl ether, filtered and washed with diisopropyl ether. In this way 1.9 g (40.2%) of the title compound are obtained. P.f .: 124-126 ° C. 'H-NMR (CDC13): d 7.46 (2H, d, J = 8.5 Hz), 7.1-6.8 (4H, m), 6.96 (1H, s), 6.68 (2H, d, J = 8.5 Hz), 6.67 (1H, s), 6.06 (1H, S), 6.02 (1H, s), 4.19 (2H, broad s), 3.64 (1H, d, J = 16.6 Hz), 3.0 (1H, m), 3.3-2.6 (10H, m), 1.84 (3H, s).

Claims (14)

1. An 8-substituted-9H-l, 3-dioxolo- [4, 5 h] [2,3] benzodiazepine derivative of the formula I characterized in that X represents a carbonyl group or a methylene group, and R 'denotes a hydrogen atom, a hydroxy group, a C1-4 alkoxy group, a C1-4 alkanoyloxy group, a group (C 1-4 alkyl) sulfonyloxy or a group of the formula -NR 4 R 5, wherein R 4 and R 5 signify, independently, a hydrogen atom, a C 1-4 alkoxy group, a C 1-4 alkanoyl group, or a C 1-6 alkyl group, the latter which is optionally substituted by a saturated or unsaturated heterocyclic group having 5 or 6 members and comprising 1 or 2 nitrogen atoms or a nitrogen atom and an oxygen atom as the heteroatom, or by a N- [phenyl- (C 1-4 alkyl)] -N- (C 1-4 alkyl) amino group, wherein the phenyl group is optionally substituted by 1 to 3 substituents, wherein the substituent consists of a C1-4 alkoxy group, or R4 and Rs form with the adjacent nitrogen atom and optionally with an additional nitrogen atom or an oxygen atom, a saturated or unsaturated heterocyclic group having 5 to 10 members, or X forms together with R 'a cyano group, a tetrazolyl group, a group of the formula -CHNOH, or a group of the f COR6, wherein R6 means a hydroxy group, a C1-4 alkoxy group, a phenoxy group, a naphthyloxy group or an amino group which is optionally substituted by an alkyl group of C ^, R2 denotes a group nitro, an amino group or a group (C 1-4 alkanoyl) amino, R 3 represents a hydrogen atom, a C 1-4 alkyl group, or a group of the formula -COR 7, wherein R 7 represents a hydrogen atom, a C 1-6 alkyl group, an alkyl group substituted by 1 to 3 halo atoms, a C 1-4 alkoxy group, a phenoxy group, a pyridyl group, a phenyl group or a naphthyl group these last two groups which are optionally substituted by 1 to 3 substituents or a group of the formula - (CH2) n-NR8R9, wherein R8 and R9 independently represent a hydrogen atom, a C1-4 alkyl group optionally substituted by a phenyl group or a group saturated heterocyclic having 5 or 6 members and containing a nitrogen group or a nitrogen group and an oxygen group, and the phenyl group is optionally substituted by 1 to 3 substituents wherein the substituents consist of a C 1-4 alkoxy group, or R 8 and R 9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen atom, a saturated or unsaturated heterocyclic group having 5 or 6 members and which is optionally substituted by a phenyl group which is optionally substituted by 1 to 3 substituents, wherein the substituent consists of a halo atom or a C1-4 alkoxy group, n has a value of 0, 1 or 2, Y is a hydrogen atom, or a methyl group, or Y forms together with R3 a valence bond between the carbon atom in the 8-position and the nitrogen atom in the 7-position, with the proviso that: 1) if Y denotes a hydrogen atom or forms together with R3 a valence bond and X represents a methylene group, then R 'is different from a hydrogen atom; hydrogen, and 2) yes Y denotes a hydrogen atom or a methyl group and R3 represents a C1-4 alkyl group, or a group of the formula -COR7, then X is different from a methylene group, and pharmaceutically acceptable acid addition salts and derivatives of quaternary ammonium thereof.

2. The derivative of 8-substituted-9H-1, 3-dioxolo [4,5-h] [2, 3] benzodiazepine, according to claim 1, characterized in that: X represents a carbonyl group or a methylene group, and R1 denotes a hydrogen atom, a hydroxy group, a methoxy group, an acetoxy group, a methylsulfonyloxy group or a group of the formula -NR4R5, wherein R4 and RB signify, independently, a hydrogen atom, a methoxy group, a acetyl group or a C1-4 alkyl group, the latter which is optionally substituted by a morpholino group or a N- (dimethoxyphenylethyl) -N- (methyl) amino group, or R4 and R5 form with the adjacent nitrogen atom and optionally with an additional nitrogen atom or an atom of oxygen, a saturated or unsaturated heterocyclic group having 5 to 9 members, or X forms together with R 'a cyano group, a tetrazolyl group, or a group of the formula -CHNOH, R2 denotes a nitro group, or an amino group , R3 represents a hydrogen atom, or an acetyl group, Y is a hydrogen atom, or Y together with R3 form a valence bond between the carbon atom at position 8 and the nitrogen atom at position 7, with the condition that: 1) if Y indicates a hydrogen atom or form together with R3 a valence bond and X represents a methylene group, then R 'is different from a hydrogen atom, and 2) if Y indicates an atom of hydrogen or a methyl group and R3 represents an alkyl group of C 1-4, or a group of the formula -COR7, then X is different from a methylene group, and pharmaceutically acceptable acid addition salts and quaternary ammonium derivatives thereof.

3. Amide 5- (4-aminophenyl) -H-1,3-dioxolo [4,5-h] [2,3] enzodiazepine-8-carboxylic acid, 5- (4-aminophenyl) -8-cyano-9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine, 5- (4-aminophenyl) -8- (5-tetrazolyl) -9H-1,3-dioxolo [4,5-h] [2, 3] benzodiazepine and pharmaceutically acceptable acid addition salts and quaternary ammonium derivatives thereof.

4. The 8-substituted-9H-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine derivative according to claim 1, characterized in that R3 represents a hydrogen atom or a group of the formula -COR7, wherein R7 denotes a hydrogen atom, a C1-4 alkyl group, a C1-4 alkyl group substituted by 1 to 3 halo atoms, or a group of the formula - (CH2) n-NR8R9, wherein R8 and R9 signifies, independently, a hydrogen atom, a C1-4 alkyl group, optionally substituted by a phenyl group or a morpholino group, and the phenyl group is optionally substituted by 1 or 2 methoxy groups, or R8 and R9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen atom, a saturated or unsaturated heterocyclic group having 5 or 6 members and which is optionally substituted by a phenyl group which is optionally substituted by a halo atom or a group methoxy, n has a value of 0, 1 or 2, X form together with R 'a cyano group, or a group of the formula -COR6, wherein R6 represents a hydroxy group, or an amino group, Y denotes a methyl group, R2 is a nitro group, an amino group or a group (C 1-4 alkanoyl) amino, and pharmaceutically acceptable acid addition salts thereof.

5. The substituted derivative 8-lH-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine according to claim 4, characterized in that: R3 represents a hydrogen atom or a group of the formula - COR7, wherein R7 denotes a hydrogen atom, an alkyl group of C ^, a C1-2 alkyl group substituted by a chlorine atom, a trifluoromethyl group, a trichloromethyl group or a group of the formula - (CH2) n -NR8R9, wherein R8 and R9 independently represent a hydrogen atom, a C1-2 alkyl group, optionally substituted by a phenyl group or a morpholino group, and the phenyl group is optionally substituted by 2 methoxy groups, or R8 and R9 form, together with the adjacent nitrogen atom and optionally an additional nitrogen or oxygen atom, a pyridinyl, pyrrolidinyl, morpholino or piperazinyl group, wherein the piperazinyl group is substituted by a fluorophenyl or methoxyphenyl group, n has a value of 0, 1 or 2, X forms together with R 'a cyano group, R2 means an amino group or a group (alkanoyl C1-4) amino, Y denotes a methyl group, and pharmaceutically acceptable acid addition salts thereof.

6. The substituted 8-9H-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine derivative according to claim 5, characterized in that: R 2 represents an acetylamino or propionylamino group, R ', R 3, X and And they are as defined in accordance with claim 5 and pharmaceutically suitable acid addition salts thereof.

7. A process for the preparation of 8 substituted-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine derivatives of the formula I wherein X, R ', R2, R3 and Y are as defined in accordance with claim 1 and pharmaceutically suitable acid salts and quaternary ammonium derivatives thereof, the process is characterized in that: a) for the preparation of 8-formyl-5- (4-nitrophenyl) -9H- 1,3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula II are within the scope of the compounds of the formula I, 8-methyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine is reacted with an agent oxidant; or b) for the preparation of 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid of the formula III being within the scope of the compounds of the formula I, 8-formyl-5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula is reacted II with an oxidizing agent; or c) for the preparation of compounds of formula I, wherein R 'is an imidazolyl group, R 2 represents a nitro group, X denotes a carbonyl group and Y forms together with R 3 a valence bond, 5- (4-nitrophenyl) acid -9H-1, 3-dioxolo [4, 5-h] [2,3] benzodiazepine-8-carboxylic acid of the formula III is reacted with 1,1 '-carbonyldiimidazole; od) for the preparation of compounds of formula I, wherein R1 is a group of the formula -NR4R5, R2 represents a nitro group, X denotes a carbonyl group, and forms together with R3 a valence bond, R4 and R5 are as are defined in relation to formula I, 5- (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid of formula III or a derivative reagent thereof of formula IV wherein Y1 is a leaving group, which is reacted with an amine of the formula V R 'HN7 5 wherein R4 and R5 are as stated above; e) for the preparation of compounds of formula I, wherein R 1 is a C 1-4 alkoxy group, R 2 represents a nitro group, X denotes a carbonyl group, and forms together with R 3 a valence bond, 5- (4 -nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine-8-carboxylic acid of the formula III which is esterified with a C1-4 alkanol; of) for the preparation of compound of formula I, wherein R 1 is a group (C 1-4 alkyl) sulfonyloxy, R 2 represents a nitro group, X denotes a methylene group, and forms together with R 3 a valence bond, 8- formyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula II which is reacted with a reducing agent and the 8- (hydroxymethyl) - 5- (4-nitrophenyl) -9H-1,3-dioxolo [4, 5-h] [2,3] benzodiazepine obtained is reacted with a halide of (C 1-4 alkyl) sulfonyl; og) for the preparation of compounds of the formula I, wherein R 'represents a C1-4 alkoxy group, a C1-4 alkanoyloxy group, or a group of the formula -NR4RS, R2 denotes a nitro group, and together with R3 a valence bond, R4 and R5 are as stated in relation to the formula I, 8-formyl-5- (4-nitrophenyl) -9H-1, 3-dioxolo [4, 5-h] [2 , 3] benzodiazepine of formula II which is reacted with a reducing agent, and 8- (hydroxymethyl) -5- (4-nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2, 3] benzodiazepine obtained or a reactive alkylating derivative thereof of formula VI wherein Q denotes a leaving group, a (C1_) alkane-substituted alkane or a reactive acylating derivative thereof or an amine of the formula V are reacted with a C1_alkanol, wherein R4 and Rs are as defined above. establish before; oh) for the preparation of a compound of formula I, wherein X forms together with R 'a group of the formula -CHNOH, R2 represents a nitro group, and forms together with R3 a valence bond, 8-formyl-5 - (4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine of the formula II which is reacted with hydroxylamine; oi) for the preparation of a compound of formula I, wherein X forms together with R 'a cyano group, R2 represents a nitro group, and forms together with R3 a valence bond, 8- (hydroxymethyl) -5- ( 4-nitrophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine which is reacted with a dehydrating agent; oj) for the preparation of a compound of the formula I, wherein X forms together with R 'a tetrazolyl group, R 2 represents a nitro group, and forms together with R 3 a valence bond, 8-cyano- 5 - (4- nitrophenyl) -9H-1, 3-dioxolo [4,5-h] [2,3] benzodiazepine which is reacted with an alkali metal azide; ok) for the preparation of 7,8-dihydro compounds of the formula VI, which have a narrower group of the compounds of the formula I, wherein X represents a carbonyl group or a methylene group, and R 'is as defined in relation to formula I, a compound of formula VII VII wherein X and R are as indicated above, which is reacted with a reducing agent; or 1) for the preparation of 7,8-dihydro-7-acyl derivatives of the formula VIII, which are a narrower group of the compounds of formula I, wherein X represents a carbonyl group or a methylene group, R 'is as stated in relation to formula I, R3 denotes a C1-4 alkanoyl group, 7,8-dihydro derivative of the formula VI, wherein X and R 'are as defined above, and reacted with alkane (C ^-carboxylic acid or a reactive acylating derivative thereof; om) for the preparation of the formula I, wherein R 'is a group of the formula -NR4R5, R2 represents a nitro group, X denotes a carbonyl group or a methylene group, one of R4 and R5 represents a C1-4 alkanoyl group, while the other is as defined in relation to formula I, Y means a hydrogen atom and in this case R3 denotes an alkanoyl group of C1-4, or Y forms together with R3 a valence bond, a compound of formula I, wherein R1 is a group of the formula -NR4R5, wherein one of R4 and RB means a hydrogen atom, while and the other is as defined above, X, R2, Y and R3 are as indicated above, and reacted with a (1-4C) alkane carboxylic acid or a reactive acylating derivative thereof; n) for the preparation of compounds of the formula I, wherein Y represents a methyl group, -X-R 'denotes a cyano group, R3 is a hydrogen atom and R2 signifies a nitro group, the compound of fromula IX is reacted IX is reacted with hydrogen cyanide; oo) for the preparation of compounds of formula I, wherein Y represents a methyl group, R3 denotes a hydrogen atom, R2 means a nitro group and -XR 'represents a group of the formula -COR6, wherein R6 is as is defined in relation to formula I, the compound of formula X it is hydrolyzed with a mineral acid, and the carboxylic acid which is obtained is optionally converted into an ester or a carboxylic amide; op) for the preparation of compounds of the formula I, wherein Y represents a methyl group, -XR 'denotes a cyano group or a group of the formula -COR6, R2 signifies a nitro group, R3 is a C1-6 alkyl group 4, and R6 is as defined in relation to formula I, a compound of formula I is reacted, wherein Y and R2 are as indicated above, R3 represents a hydrogen atom, is reacted with a halide ( C1-4 alkyl); or) for the preparation of compounds of the formula I, wherein Y represents a methyl group, -X-R1 denotes a cyano group or a group of the formula -COR6, R2 means a nitro group, R3 is a group of the formula -COR7, R7 represents a group of the formula - (CH2) n-NR8R9, R6, R8, R9 and n are as defined in relation to formula I, a compound of formula XI wherein -X-R ', R2 and n are as indicated above, X1 is a leaving group, preferably a chlorine atom, and is reacted with an amine of the formula HNR8R9; and if desired, a compound obtained from formula I, wherein R 2 represents a nitro group, R ', R 3, X and Y are as defined in relation to formula I, is transformed into a compound of formula I, wherein R2 represents an amino group, by reduction; and if desired, a compound obtained from the formula I, wherein R 2 represents an amino group, R 1, R 3, X and Y are as stated in relation to the formula I, are reacted with a (C 1-4) alkane ) carboxylic or an acylating derivative thereof; and if desired, a base obtained from formula I is converted to a pharmaceutically acceptable acid addition salt or freed from the acid addition salt; and if desired, a compound obtained from the formula I or a pharmaceutically acceptable acid addition salt thereof is converted to a quaternary ammonium derivative.

8. A pharmaceutical composition, characterized in that it comprises an 8-substituted-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine derivative of the formula I characterized in that X, Y, R 'and R3 are as defined in claim 1, or a pharmaceutically suitable acid addition salt or a quaternary ammonium derivative thereof as the active ingredient and one or more conventional carriers.

9. The pharmaceutical composition as described in claim 8, comprising an 8-substituted-9H-1,3-dioxolo [4,5] [2,3] benzodiazepine derivative of the formula I, wherein X, R ', R2, R3 and Y are as defined in claim 2, or a pharmaceutically suitable acid addition salt or a quaternary ammonium derivative thereof as the active ingredient.

10. The pharmaceutical composition as described in claim 8 or 9, comprising one of the following compounds: amide 5- (4-aminophenyl) -9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine -8-carboxylic acid, 5- (4-aminophenyl) -8-cyano-9H-l, 3-dioxolo [4, 5-h] [2,3] benzodiazepine, 5- (4-aminophenyl) -8- (5 -tetrazolyl) -9H-1, 3-dioxolo [4, 5-] [2,3] benzodiazepine or a pharmaceutically suitable acid addition salt or a quaternary ammonium derivative thereof as the active ingredient.

11. The pharmaceutical composition as described in claim 8, comprising an 8-substituted-9H-1,3-dioxolo [4,5-h] [2,3] benzodiazepine derivative of the formula I, wherein X, Y, R ', R2 and R3 are as defined in claim 4, or a pharmaceutically acceptable acid addition salt thereof as the active ingredient.

12. The pharmaceutical composition as described in claim 11, comprising a derivative of 8-substituted-9H-l, 3-dioxolo [4,5-h] [2,3] benzodiazepine wherein X, Y, R1, R2 and R3 are as defined in claim 5, or a pharmaceutically acceptable acid addition salt thereof as the active ingredient.

13. A method of treatment in which a patient who suffers especially from epilepsy or a neurodegenerative disease or is in a state after attack is treated with a non-toxic dose of an 8-substituted-9H-l, 3-dioxolo derivative [ 4, 5-h] [2, 3] benzodiazepine of the formula I wherein X, Y, R ', R2 and R3 are as defined in claim 1, or a pharmaceutically acceptable acid addition salt or a quaternary ammonium derivative thereof.

14. A process for the preparation of a pharmaceutical composition suitable for the treatment especially of epilepsy or a neurodegenerative disease or a post-attack state, characterized in that the derivative 8-substituted-9H-l, 3-dioxolo [4,5-h] [ 2,3] benzodiazepine of the formula I wherein X, Y, R ', R2 and R3 are as defined in claim 1 or a pharmaceutically acceptable acid addition salt or a quaternary ammonium derivative thereof, is converted to a pharmaceutical composition using one or more carriers used commonly in the preparation of medicines.