SK3802002A3 - Benzodiazepin derivatives, the production and use thereof - Google Patents

Abstract

The invention relates to compounds of formula (I) as well as to the tautomeric forms thereof, possible enantiomeric and diastereomeric forms and the prodrugs thereof, the production and use thereof, whereby the values have the meaning as given in the description.

Description

Technical field

The present invention relates to novel benzodiazepine derivatives, their preparation and use as inhibitors of the enzyme poly (ADP-ribose) polymerase or PARP (EC 2.4.2.30) for the preparation of medicaments.

BACKGROUND OF THE INVENTION

Poly (ADP-ribose) polymerase (PARP) or, as it is also called poly (ADPribose) synthase (PARS), is a regulatory enzyme found in the cell nucleus (K. Ikai et al., J. Hístochem. Cytochem. 1983, 31, 1261-1264). PARP is believed to be involved in DNA repair repair (M. S. Satoh et al., Nature 1992, 356, 356-358). Damage or disruption of the DNA strands activates the enzyme PARP, which, when activated, catalyzes the transfer of ADP-ribose from NAD (S. Shaw, Adv. Radiat. Biol., 1984, H, 1-69). During this, nicotinamide is released from NAD. Nicotinamide is converted back to NAD, using other enzymes, with the consumption of the ATP energy carrier. Accordingly, overactivation of PARP should result in a non-physiologically high consumption of ATP, and in extreme cases this leads to cell damage and cell death.

It is known that free radicals, such as the hyperoxide anion, NO, and hydrogen peroxide, can lead to DNA damage in cells and thus to activation of PARP. The generation of large amounts of free radicals has been observed in a variety of pathophysiological conditions and it is believed that this accumulation of free radicals results in or contributes to the observed damage to cells or organs. These include, for example, ischemic conditions of organs such as stroke, myocardial infarction (C. Thiemermann et al., Proc. Natl. Acad. Sci. USA 1997, 94 (1997), 679-683) or renal ischemia as well as reperfusion injury, such as occurs, for example, after lysing myocardial infarction (see above: C. Thiemermann et al.). Thus, inhibition of the PARP enzyme may be, at least in part, a means of preventing or reducing that damage. Thus, PARP inhibitors could represent a new therapeutic principle in the treatment of a variety of diseases.

The PARP enzyme affects DNA repair repair and could therefore also play a role in the treatment of cancer, since a higher potent potential against tumor tissues has been observed (G. Chen et al. Cancer Chemo. Pharmacol. 1988, 22, 303) in combination with agents. with cytostatic activity.

Non-limiting examples of tumors are leukemia, glioblastomas, lymphomas, melanomas, breast cancers and cervical cancers.

It has also been found that PARP inhibitors may exert an immunosuppressive effect (D. Weltin et al. Int. J. Immunopharmacol. 1995, 17, 265-271).

PARP has also been implicated in immunological diseases or diseases in which the immune system plays an important role, such as rheumatoid arthritis and septic shock, and that PARP inhibitors may show

A beneficial effect on disease progression (H. Kroger et al. Inflammation 1996, 20, 203-215; W. Ehrlich et al. Rheumatol. Int. 1995, 15, 171-172; C. Szabo et al., Proc. Natl. Acad Sci USA 1998, 95, 3867-3323; S. Cuzzocrea et al., Eur. J. Pharmacol. 1998, 342, 67-76).

For the purposes of the present invention, PARP is also understood to be the PARP enzyme isoenzymes described above.

In addition, the PARP inhibitor 3-aminobenzamide exhibits protective effects in the circulatory shock model (S. Cuzzocrea et al., Br. J. Pharmacol. 1997, 121, 1065-1074). There is also experimental evidence that inhibitors of the enzyme PARP may be useful as agents for the treatment of diabetes mellitus (V. Burkart et al. Nature Med. 5, 314-319).

Benzodiazepines and benzodiazepinones and their derivatives are a class of chemicals that are widely used in organic synthesis. However, derivatives of these compounds, which additionally have a fused imidazole ring, i.e. imidazobenzodiazepinones, have hardly been described. Aminodibenzodiazepinones were prepared as described in P. V. Khadikar et al. J. Heterocycl. Chem. 1998, 35, 675. Thus, the basic derivatives containing substituents such as chlorine or nitro on the fused benzene ring and the methyl group on the imidazole ring are prepared as described in

-3 Geneste et al., Eur. J. Chem. Chim. Ther. 1978, 13, 53. In the M.J. Kukla et al., J. Med. Chem. 1991, 34, 3187, dihydroimidazobenzodiazepinone was prepared as an intermediate for active compounds that exhibit anti-HIV activity.

The compounds of the formula I according to the invention have not been described so far and are therefore novel.

I ¹ ''

In addition, it has surprisingly been found that benzodiazepine derivatives having a fused ring are very potent inhibitors of the enzyme PARP.

The present invention provides novel benzodiazepine derivatives of formula I which are potent PARP inhibitors.

SUMMARY OF THE INVENTION

The present invention relates to substituted benzodiazepine derivatives of formula I

in which

A may be a C-C 1 -C 3 chain, wherein each carbon atom may carry one or two of the following substituents, such as C ₁ -C ₄ -alkyl, OH, OC-C ₁ -C ₄ -alkyl, COOH, COO-C 1 -C ₄ -alkyl and phenyl or one carbon atom may also carry the group = O, and

X ¹ can be S, O and NH, and

R ¹ represents hydrogen, chlorine, fluorine, bromine, iodine, branched and unbranched C 1 -C 6 -alkyl, OH, nitro, CF ₃ , CN, NR ¹¹ R ¹² , NH-CO-R ¹³ , O-C 1 -C 4 alkyl,

- where R ¹¹ and R ¹² are, independently of one another, hydrogen or C 1 -C ₄ -alkyl, and R ¹³ is hydrogen, C 1 -C ₄ -alkyl, C 1 -C ₄ -alkylphenyl or phenyl, and

B may be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 14 carbon atoms and 0 to 5 nitrogen atoms, 0 up to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may also be substituted by one substituent R ⁴ and a maximum of 3 different or the same substituents R ⁵ , and one or two carbon or sulfur atoms may also carry one or two = O, such as keto groups, sulfones or sulfoxides, or represents the residue Lv-YM _w in which

L may be a linear or branched, saturated or unsaturated carbon chain containing 1 to 8 carbon atoms, each carbon atom being substituted by one or two substituents R ⁴ and at most two different or the same substituents R ⁵ , and

M, independently of L, has the same meaning as L, and

Y is a bond, may represent S, O or NR ^3, wherein R ³ denotes hydrogen, branched and unbranched C _r C6 alkyl, Cl-C4 alkylphenyl, phenyl, and denotes H and 1, and w can be O and 1, and when Y is a bond, R ⁴ and R ^{5 are} not both hydrogen, and when B is Lv-Y-Mw, R ^{1 is} not chlorine or NO 2, and

R ⁴ is hydrogen and - (D) p- (E) s- (F ¹ ) q -G ¹ - (F ² ) _r (G ² ) -G ³ , wherein

-5D may be S, NR ⁴³ and O

E can be phenyl, \

C = O, -SO 2 -, -SO 2 NH-, -NHCO-, -CONH-, 1,

NHSO2 -, - NHCOCH2X, and

X ⁴ can be S, O or NH, and

F ¹ may be a linear or branched, saturated or unsaturated carbon chain containing 1 to 8 carbon atoms, and

F ² , independently of F ¹ , has the same meaning as F ¹ ,

G ¹ represents a bond and or may represent an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring having a maximum of 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring having a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may be substituted by a maximum of 3 different or the same substituents R ⁵ , and one or two carbon or sulfur atoms may also carry one or two = O, and

G ² is NR ⁴¹ R ^42a

or a bond, and o

G may be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 14 carbon atoms and 0 to 5 nitrogen atoms, 0 up to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may also be substituted by a maximum of 3 different or the same R ⁵ substituents, and one or two carbon or sulfur atoms may also carry one or two = O, or hydrogen, and can mean 0 and 1 and can mean 0 and 1 and q can mean 0 and 1 and ar can mean 0 and 1 and

R ⁴¹ can be hydrogen, C 1 -C 6 -alkyl, wherein each carbon atom can also carry up to two R ⁶ substituents, phenyl which can also carry a maximum of two R ⁶ substituents, and (CH ₂ ) i K and

R ⁴² can be hydrogen, C 1 -C 6 -alkyl, -CO-R ⁸ , CO 2 -R ⁸ , SO ₂ NH ₂ , SO ₂ R ⁸ , - (C = NH) -R ^8, and - (C = NH) -NHR ⁸ and

R ⁴³ can be hydrogen and C ₁ -C ₄ -alkyl can be 1,2,3,4a

-7K may be NR ¹¹ R ¹² , NR ¹¹ -C 1 -C 4 -alkylphenyl, pyrrolidine, piperidine,

1,2,5,6-tetrahydropyridine, morpholine, homopiperidine, piperazine, which may also be substituted by an alkyl radical _C-R -C 6 alkyl, and homopiperazine, which can also be substituted with alkyl radicals C ₁ -C ₆ -alkyl, and

R ⁵ can be hydrogen, chloro, fluoro, bromo, iodo, OH, nitro, CF ₃ ,

CN, NR ¹¹ R ¹² , NH-CO-R ¹³ , C 1 -C 4 -alkyl-CO-NH-R ¹³ , COR ⁸ , C 0 -C ₄ -alkyl-OCO-R ¹³ , C 1 -C ₄ -alkylphenyl, phenyl, CO ₂ -CrC ₄ alkyl, and branched and unbranched dripped-alkyl, O-Ci-C ₄ alkyl, SC ₁ -C ₄ alkyl, wherein each carbon atom of the alkyl chains may carry up to two R ⁶ substituents, and the alkyl chain may also be unsaturated, and

R ⁶ can be hydrogen, chloro, fluoro, bromo, iodo, branched and unbranched

C 1 -C 6 -alkyl, OH, nitro, CF ₃ , CN, NR ¹¹ R ¹² , NH-CO-R ¹³ , O-C 1 -C 8 alkyl,

R ⁷ can be hydrogen, C 1 -C ₆ -alkyl, phenyl, wherein the ring can be substituted with up to two R ⁷¹ radicals, and the amine NR ¹¹ R ¹² or a cyclic saturated amine having 3 to 7 members, and can also be substituted with alkyl C 1 -C 6 -alkyl, and homopiperazine, which may also be substituted by C 1 -C 6 -alkyl, and wherein the residues R ¹¹ , R ¹² and R ¹³ in K, R ⁵ , R ⁶ and R ⁷ may, independently of one another, have the same meaning as for R ^1, and

R ⁷¹ can be OH, C ₁ -C ₆ -alkyl, O-C 1 -C ₄ -alkyl, chlorine, bromine, iodine, fluorine, CF ₃ , nitro, NH ₂ , and

R ⁸ can be C 1 -C ₆ -alkyl, CF ₃ , phenyl, C 1 -C ₄ -alkylphenyl, wherein the ring can also be substituted with up to two R ⁸¹ radicals, and

R ⁸¹ denotes OH, C _r C ₆ -alkyl, _O-C-C4 alkyl, chloro, bromo, iodo, fluoro, CF _3, nitro, NH _2, and

R ⁹ denotes hydrogen, C6-alkyl, -C ₄ -alkyl-phenyl, CO ₂ -CrC ₄ alkyl-phenyl, CO _{2 R} C, -C ₄ -alkyl, SO ₂ -phenyl, COR ^8, and phenyl, wherein the phenyl rings may also be substituted by up to two residues R ⁹¹ , a

-8R ⁹¹ can be OH, C 1 -C 6 -alkyl, O-C 1 -C ₄ -alkyl, chloro, bromo, iodo, fluoro, CF ₃ , nitro, NH 2, and their tautomeric forms, possible enantiomeric and diastereoisomeric forms, and their precursors.

, 'I

Preferred compounds of formula I are those in which

A represents a C ₂ chain which may be substituted, and

X ¹ represents O, and

^R1 is hydrogen.

Preferred compounds of formula I are those described above in which

B may be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 14 carbon atoms and 0 to 5 nitrogen atoms, 0 up to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may also be substituted with one substituent R ⁴ and a maximum of 3 different or the same R ⁵ , and one or two carbon or sulfur atoms may also carry one or two = O groups.

Particularly preferred residues for B are:

B phenyl, cyclohexyl, piperidine, pyridine, pyrimidine, pyrrole, pyrazole, thiophene, furan, oxazole, naphthalene, piperazine, quinoline, pyrazine, which may also be substituted with one R ⁴ or a maximum of two R ⁵ substituents.

Particularly particularly preferred compounds of formula I are those in which hydrogen or D is ₀ , iF ¹⁰ i-G ² -G ³ wherein G ³ represents hydrogen, and

-9D represents O and NR ⁴³ , wherein R ⁴³ represents hydrogen and C 1 -C 3 -alkyl, and

F ¹ represents C 2 -C 4 -alkyl.

Other particularly preferred compounds of formula I are those wherein B is L _in -YM _W1 wherein v is 0, aw is 1, and

Y is a bond, and

M may be a linear or branched carbon chain of 2 to 8 carbon atoms containing at least one double bond, each carbon atom being substituted by one or two R ⁴ radicals and at most two different or the same R ⁵ radicals, and

R ¹ is hydrogen, and

R ⁴ represents Do, iF ¹⁰ , iG ¹ -G ² -G ³ wherein G ³ represents hydrogen, and

D is O and NR ⁴³ , wherein R ⁴³ is hydrogen and C 1 -C 6 -alkyl and

F ¹ represents C 2 -C ₄ -alkyl.

The use of compounds of formula I for the manufacture of a medicament having PARP inhibitory activity is also claimed, wherein R ¹ , X ¹ and A have the same meaning as above, and B can be hydrogen and a C 1 -C 6 -alkyl chain.

The compounds of formula I can be used in the form of racemates, enantiomerically pure compounds or diastereoisomers. If enantiomerically pure compounds are required, these are obtained, for example, by carrying out conventional racemate resolution with compounds of formula I or intermediates thereof using a suitable optically active base or acid.

The alkyl chains may in each case be branched or unbranched. Unbranched alkyl chains are preferred. Accordingly, the present invention relates to compounds that are mesomers or tautomers of the compounds of Formula I.

The present invention relates to physiologically acceptable salts of compounds of formula I, which may be obtained by reacting compounds of formula I with a suitable acid or base. Suitable acids and bases are disclosed, for example, in Fortschritte der Arzneimittelforschung, 1966, Birkäuser Verlag, volume 10, p. These include, for example, hydrochloric acid, citric acid, tartaric acid, lactic acid, phosphoric acid, methanesulfonic acid, acetic acid, formic acid, maleic acid, fumaric acid and the like, and sodium hydroxide, lithium hydroxide, potassium hydroxide and tris. .

Prodrugs are compounds that are metabolized in vivo to compounds of Formula I. Typical prodrugs are phosphates, amino acid carbamates, esters, and others.

The benzodiazepine derivatives of formula (I) of the present invention can be prepared by a variety of methods as outlined in Synthesis Schemes 1-3.

Possible synthesis methods are, in principle, already known or based on analogous procedures known.

Synthesis scheme 1

B

The condensation of the aldehyde II with the diamines III provides benzimidazole I, which is preferably carried out in polar solvents such as ethanol or dimethylformamide with the addition of acids such as acetic acid at elevated temperature, usually at 80 to 120 ° C. It is preferred that weak oxidizing agents such as copper salts are added in the reaction, for example in the form of aqueous solutions.

Scheme 2 coo-Alkyl

I

B

COOH

(iv) (I J

As an alternative to the aldehydes II shown in Scheme I, acids such as the acid of formula V (see Scheme 2) or nitriles such as the nitriles of formula VII (see Scheme 3) can also be used in place of the aldehyde. The reaction of these derivatives is carried out analogously to the preparation of the substituted aldehydes of formula II. starting from compounds of formula V, condensation to compounds of formula II is carried out in two stages. First, the acid of formula V is reacted with an aniline of formula III by coupling similar to peptide coupling to give the amide of formula VI. This is done under conventional conditions that are

See, for example, Houben-Weyl, Methoden der Organischen Chemie, 4 ^th Edition, E5, Chapter V, and RC Larock, Comprehensive Organic Transformations, VCH Publisher, 1989, p. The ring closure to the benzimidazole is then carried out at an elevated temperature, for example at 60 to 180 ° C, with or without solvents such as dimethylformamide, with the addition of acids such as acetic acid or directly in acetic acid itself,

Scheme 3

CN

I

B

(VII)

The reaction of the diamine of formula III with the nitrile of formula VII is similarly carried out under conventional conditions. These may include the use of solvents such as dimethylformamide with the addition of acids or, in addition, the use of polyphosphoric acid at an elevated temperature such as 60 to 200 ° C. However, conventional procedures for preparing amidines from benzonitriles as described in HoubenWeyl, Methoden der Organischen Chemie, E5, p. 1304 et seq., J. Amer. Chem. Bathroom. 1957, 427 and J. Org. Chem. 1987, 1017.

Compounds of formula III are synthesized as shown in Scheme 4 by reacting a substituted nitrobenzic acid ester of formula IX with a suitable diamine in a polar solvent such as dimethylformamide in the presence of a base such as potassium carbonate at a temperature of 100 ° C to 150 ° C, preferably at 110 ° C to 130 ° C, particularly preferably at about 120 ° C, followed by hydrogenation in the presence of a suitable catalyst such as 10% palladium on carbon.

Scheme 4

1) η ₂ ν ^ ^ νη ₂

-> 2) Η ₂ - Pd / C

(m)

The present invention further relates to intermediates of formula III

(m) in which:

A represents a C 1 -C 3 chain, wherein each carbon atom can carry one or two of the following substituents, such as C 1 -C 4 -alkyl, OH, O-C 1 -C 4 -alkyl, COOH, COO-C 1 -C 4 -alkyl and phenyl or one carbon atom may also carry the group = O, and

X ¹ and R ¹ have the meanings given above, excluding the following compounds

9-amino-3-methyl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one, 9-amino-3-methyl-3,4-dihydro-1H-1,4-benzodiazepine -2,5-dione, 6,8-diamino-2,4- (1H, 3H) quinazolinedione, 8-amino-2,4- (1H, 3H) -quinazolinedione and salts thereof.

In addition, the present invention relates to a process for the preparation of compounds of formula III and salts thereof, wherein 2-halo-3-nitrobenzoic acid esters are reacted with a suitable diamine in a polar solvent in the presence of a base and then

The 14-nitro group hydrogenates with hydrogen in the presence of a suitable catalyst, and the use of compounds of formula III in the synthesis of PARP inhibitors.

The substituted benzodiazepine derivatives of formula I described in the present invention are inhibitors of the enzyme poly (ADP-ribose) polymerase or PARP (EC 2.4.2.30).

t ·,

The inhibitory effect of substituted benzodiazepine derivatives of formula I can be determined using an enzymatic assay already described in the literature, where K i is determined as an activity criterion. The benzodiazepine derivatives of formula I were measured in this way for the inhibitory effect on the enzyme poly (ADP-ribose) polymerase or PARP (EC 2.4.2.30).

The substituted benzodiazepine derivatives of formula I are inhibitors of poly (ADP-ribose) polymerase (PARP) or, as it is also called poly (ADP-ribose) synthase (PARS) and can therefore be used for the treatment and prophylaxis of diseases associated with increased activity of these enzymes.

The compounds of formula I may be used for the manufacture of medicaments for treating damage following ischemia and for the prophylaxis of expected ischemia in various organs.

Accordingly, the present benzodiazepine derivatives of formula (I) may be used for the treatment and prophylaxis of neurodegenerative diseases that occur after ischemia, trauma (craniocerebral trauma), massive bleeding, subarachnoid haemorrhage and stroke, and neurodegenerative diseases more than a multiple of, heart attacks, Alzheimer's disease, Huntington's disease and epilepsy, such as, in particular, generalized epileptic seizures, such as, for example, small epileptic seizures and tonic-clonic seizures, and partial epileptic seizures, such as temporal lobe seizures, and complex partial seizures, and further for treatment. and prophylaxis of cardiac damage following cardiac ischemia and renal damage following renal ischemia, such as acute renal insufficiency due to drug therapies, such as in connection with cyclosporine, acute renal failure, or in damage occurring during and after kidney transplantation. The compounds of formula I can further be used to treat acute myocardial infarction and damage occurring during and after its therapeutic lysis (e.g. with TPA,

-15 reteplasia, streptokinase or mechanically with laser or rotablator) and micro-infarcts during and after heart valve replacement, aneurysm resections and heart transplants. The present benzodiazepine derivatives of formula I can likewise be used for treatment in cases of revascularization of critically narrowed coronary arteries, for example in PTCA and bypass operations, and critically narrowed peripheral arteries, for example leg arteries. In addition, the benzodiazepine derivatives of formula I may be useful in the treatment of tumors and their metastases and may be used to treat inflammation and rheumatic diseases such as rheumatoid arthritis, and to treat diabetes mellitus, to treat multiorgan failure, for example associated with septic shock, and for the treatment of ARDS ("acute respiratory distress syndrome", "acute distress syndrome respirators, shock lungs).

The pharmaceutical compositions of the present invention contain, in addition to conventional pharmaceutical excipients, a therapeutically effective amount of the compounds of Formula I.

For topical topical use, for example, gelling powders, ointments or sprays, the active compounds may be present in the usual concentrations. The active compounds are usually present in an amount of from 0.001 to 1% by weight, preferably 0.001 to 0.1% by weight.

For oral use, the preparations are administered in single doses. In a single dose, they are administered from 0.1 to 100 mg per kilogram of body weight. The composition may be administered in one or more doses each day, depending on the nature and severity of the disease.

Accordingly to the desired mode of administration, the pharmaceutical compositions of the present invention contain, in addition to the active ingredient, conventional carriers and diluents. For topical local use, pharmaceutical excipients such as ethanol, isopropanol, ethoxylated castor oil, ethoxylated hydrogenated castor oil, polyacrylic acid, polyethylene glycol, polyethylene glycol stearate, ethoxylated fatty alcohols, liquid paraffin, petrolatum and lanolin can be used. Examples suitable for internal use are lactose, propylene glycol, ethanol, starch, talc and polyvinylpyrrolidone.

Antioxidants such as tocopherol and butylated hydroxyanisole, and butylated hydroxytoluene, flavor enhancers, stabilizers, emulsifying agents and lubricating agents may also be present.

Substances which are present in the preparation in addition to the active substance and substances which are used in the preparation of pharmaceutical preparations are toxicological, acceptable and compatible with the active substance concerned. The pharmaceutical preparations are prepared in a conventional manner, for example by mixing the active ingredient with conventional carriers and diluents.

The pharmaceutical preparations can be administered by various routes, for example, orally, parenterally, such as by intravenous infusion, subcutaneously, intraperitoneally and topically. Thus, possible forms are tablets, emulsions, infusions and injectable solutions, pastes, ointments, gels, creams, lotions, powders and sprays.

T

Pharmacological example:

Inhibition of the enzyme poly (ADP-ribose) polymerase or PARP (EC 2.4.2.30)

A 96 well microtiter plate (Falcon) was coated with histones (type II-AS; SIGMA H7755). For this purpose, the histones were dissolved at a concentration of 50 µg / ml in carbonate buffer (0.05 M NaHCl 3; pH 9.4). Individual wells of the microtiter plates were incubated overnight with 100 μΙ of this histone solution. The histone solution was then removed and the individual wells were incubated with 200 μ teplote of a 1% BSA (bovine serum albumin) solution in carbonate buffer for two hours at room temperature. This was followed by a three-fold wash with wash buffer (0.05% Tween10 in PBS). For the enzyme reaction, 50 μΙ enzyme reaction solution (5 μΙ reaction buffer (1 M Tris-HCl, pH 8.0, 100 mM _MgCl2, 10 mM DTT), 0.5 μΙ of PARP (c = 0.22 pg / 4 μΙ activated DNA (SIGMA D-4522, 1 mg / ml in water),

40.5 μΙ H ₂ O) preincubated in each well for 10 minutes with 10 μΙ inhibitor solution. The enzyme reaction was started by adding 40 μΙ of substrate solution (4 μΙ of reaction buffer (see above), 8 μΙ of NAD solution (100 μΜ in H ₂ O), 28 μΙ H ₂ O). The reaction time was 20 minutes at room temperature. The reaction was stopped by washing three times with wash buffer (see above).

-17 followed by incubation at room temperature with specific anti-poly (ADPribose) antibody for one hour. The antibodies used were 10H monoclonal anti-poly (ADP-ribose) antibodies (Kawamaitsu H. et al. (1984), Monoclonal antibodies to poly (adenosine diphosphate ribose) recognize different structures. Biochemistry 23, 3771-3777). Similarly, they can also be used

I polyclonal antibodies. . .

Antibodies were used at a 1: 5000 dilution in antibody buffer (1% BSA in PBS; 0.05% Tween20). Washing three times with wash buffer was followed by incubation at room temperature with the secondary antibody for one hour. In this case, the monoclonal antibody used was anti-mouse IgG coupled with peroxidase (Boehringer Mannheim) and the rabbit antibody was anti-rabbit IgG coupled with peroxidase (SIGMA A-6154), each diluted 1:10 000 in antibody buffer. After washing three times with the washing buffer, a color reaction was performed using činidlaμΙ / well color reagent (SIGMA, TMB mixture, T8540) at room temperature for approximately 15 minutes. The color reaction was stopped by adding 100 μ 100 of 2 M H2SO4. Immediately thereafter, measurements were made (450 nm vs 620 nm; ELI SA Easy Reader EAR340AT plate reader, SLTLabinstruments, Austria). The IC _{50 of the} inhibitor to be measured is the concentration of inhibitor at which half the maximum change in color concentration occurs.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

2- (4- (4-Methyl-piperazin-1-yl) phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

a) 9-Nitro-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one g (0.11 mol) of methyl 2-chloro-3-nitrobenzoate was dissolved in 250 ml of dimethylformamide. 15.4 g (0.11 mol) of potassium carbonate and 22.3 ml (0.33 mol) of ethylenediamine were added successively and the mixture was heated at

-18120 ° C for 3 hours. The mixture was then concentrated to half volume in vacuo and the residue was poured into water to precipitate the product. 19.7 g of product were obtained.

b) 9-Amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one

1.7 g of 10% palladium / carbon was added to 19 g (91.7 mmol) of intermediate 1a in 500 ml of ethanol, and the mixture was then hydrogenated with hydrogen. The mixture was then filtered. The filtrate was concentrated in vacuo and the residue was recrystallized from isopropanol / ether. The crystals that separated were filtered off with suction. 14.4 g of product were obtained.

c) 2- (4- (4-Methylpiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepin-7- (4H) -one

2.0 g (11.3 mmol) of intermediate Ib and 2.8 ml (45.15 mmol) of concentrated acetic acid were dissolved in 200 ml of methanol and a solution of 3.0 g (14.7 mmol) was added dropwise at room temperature. 4- (4-methylpiperazin-1-yl) benzaldehyde in 50 mL of methanol. The mixture was stirred at room temperature for one hour. Then, 2.9 g (14.7 mmol) of copper acetate dissolved in 100 ml of water was added dropwise and the mixture was refluxed for 30 minutes. During this time, a solution of 4.1 g (17 mmol) of sodium sulphide x 9 H ₂ O in 70 ml of water and a solution of 17 ml of 1 M hydrochloric acid in 50 ml of water were added in parallel. After cooling, the resulting precipitate was filtered off with suction and the filtrate was concentrated in vacuo. The remaining residue was partitioned between aqueous sodium bicarbonate and ethyl acetate. The organic phase was separated, dried and concentrated in vacuo. The residue was crystallized from ethyl acetate / ether. 2.4 g of product were obtained.

¹ H-NMR (D 6 -DMSO): δ = 2.2 (3H), 2.5 (4H), 3.3 (4H), 3.5 (2H), 4.4 (2H), 7.1 (2H);

7.3 (1H), 7.7-7.9 (4H) and 8.4 (1H) ppm.

[M * = 364]

Example 2

2- (4-Nitrophenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin7- (4H) -one

The product was obtained analogously to Example 1c, from 9 amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 4-nitrobenzaldehyde. ^{@ 1} H-NMR (D6 -DMSO): .delta. = 3.6 (2H), 4.5 (2H), 7.4 (1H) and 7.9-8.6 (7H) ppm.

[M ⁺ = 308]

Example 3

2- (4- (2-N, N-Diethylaminoeth-1-yloxy) phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

The product was obtained analogously to Example 1c from 9 amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 4- (2-N, N-diethylamino-ethyl-1-yloxy) -benzaldehyde .

¹ H-NMR (D ₆ -DMSO): δ = 1.0 (6H), 2.6 (4H), 2.8 (1H), 3.5 (2H), 4.1 (2H), 4, Δ (2H), 7.1 (2H), 7.4 (1H), 7.7-7.9 (4H), and 8.4 (1H) ppm.

[M ⁺ = 379]

The following additional examples were carried out analogously to the procedures described above:

Example 4

2- (4- (2-Piperidin-1-yl-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepine-7- (4H) -one

The product was obtained analogously to Example 1c from 9 amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 4- (2-piperidin-1-ylet-1-yloxy) benz -aldehyde.

¹ H-NMR (D ₆ -DMSO): δ = 1.3 - 1.6 (6H), 2.5 (4H), 2.7 (2H), 3.6 (2H), 4.2 (2H) ), 4.5 (2H), 7.1 (2H), 7.4 (1H), 7.7-7.9 (4H), and 8.4 (1H) ppm.

[M ⁺ = 390]

-20Example 5

2- (4- (N- (2-N, N-Diethylaminoeth-1-yl) -N-methylamino) phenyl) -5,6-dihydro-imidazo [4,5,1jk] - [1,4] benzodiazepin 7 (4H) -one

The product was obtained analogously to Example 1c from 9 amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 4 (N- (2-N, N-diethylaminoethyl) yl). N-methylamino) benzaldehyde.

¹ H-NMR (D 6 -DMSO): δ = 0.9 (6H), 2.5 (6H), 3.0 (3H), 3.4 - 3.6 (4H), 4.45 (2H) 6.8 (2H), 7.3 (1H), 7.6-7.9 (4H), and 8.45 (1H) ppm.

[M ⁺ = 392]

Example 6

2- (4- (4- (tert-Butyloxycarbonyl) piperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1 jk] [1,4] benzodiazepin-7- (4H) -one

The product was obtained analogously to Example 1c from 9 amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 4- (4- (tert-butyloxycarbonyl) -piperazin-1-yl) benzaldehyde.

¹ H-NMR (D 6 -DMSO): δ = 1.4 (9H), 3.3 (4H), 3.4 - 3.6 (6H), 4.45 (2H), 7.1 (2H) 7.3 (1H), 7.7-7.9 (4H) and 8.4 (1H) ppm.

[M ⁺ = 446]

Example 7

2- (4- (4- (tert-butyloxycarbonyl) homopiperazine-1-yl) phenyl) -5,6-dihydro-imidazo [4,5,1jk] - [1,4] benzodiazepin-7 (4H) -one

The product was obtained analogously to Example 1c from 9 amino-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one and 4- (4- (tert-butyloxycarbonyl) homopiperazin-1-yl). ) benzaldehyde.

¹ H-NMR (D ₆ -DMSO): δ = 1.2 - 1.3 (9H), 1.8-1.9 (2H), 3.2 - 3.8 (10H), 4.45 ( 2H), 6.9 (2H), 7.3 (1H), 7.7 (2H), 7.8 (2H), and 8.4 (1H) ppm.

-21 [Μ ⁺ = 462]

Example 8

2- (4- (Homopiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-k] [1,4] benzodiazepin-7 (4H) -one

The product was prepared from the product of Example 7, analogously to Example 9.

[M ⁺ = 364]

Example 9

2- (4- (Piperazin-1-yl) phenyl-5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one ₁ trihydrochloride

0.5 g of the product of Example 6 was added to 30 ml of a solution of hydrogen chloride in isopropanol at room temperature and the mixture was stirred for several hours. The mixture was then concentrated in vacuo and the remaining residue was recrystallized from ethanol. The product was obtained as the trihydrochloride.

¹ H-NMR (D 6 -DMSO): δ = 3.2 - 3.8 (10H), 4.5 (2H), 7.2 (2H), 7.5 - 8.0 (5H), Δ (1H) and 9.6 (broad) ppm.

[M ⁺ = 346]

Example 10

2- (4-Aminophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x 2 HCl; · [M ⁺ = 280]

Example 11

2- (Piperidin-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 271]

Example 12

-222- (1- / 7-Propylpiperidin-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 313] ]

Example 13 i

2- (1-Benzylpiperidin-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 361]

Example 14

2- (Pyridin-4-yl) _-5) 6-dihydro-imidazo _[4,5-) 1-jk] [1,4] benzodiazepin-7 (4H) -one x HCl [M ⁺ = 265]

Example 15

2- (Thien-3-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 270]

Example 16

2- (Quinolin-3-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 315]

Example 17

2- (Naphth-2-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ = 313]

Example 18

2- (1H-Imidazol-1-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x HCl

-23 [Μ ⁺ = 330]

Example 19

2- (4- (3-Formylpyrrol-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ = 356]

Example 20

2- (4- (3-Trifluóracetamidometylpyrol-1-butyl) phenyl) -5 _l 6-dihydro-imidazo _[4) 5 _l 1-jk] _[1) 4] benzodiazepin-7 (4H) -one x HCl [M ⁺ = 453]

Example 21

2- (4- (4- (piperidin-1-yl) -piperidin-1-yl) phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 ( 4H) -one x 2 HCl [M ⁺ = 432]

Example 22

2- (4- (3- (Piperidin-1-ylmethyl) pyrrol-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzo diazepine-7- (4H) ) -one x HCl [M ⁺ = 427]

Example 23

2- (4- (3-Aminomethyl-pyrrol-1-yl) -phenyl) -5,6-dihydro-imidazo [4,5,1b] [1,4] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 358]

Example 24

-242- (3- (2- (N, N-Dimethylamino) et-1-yl) -4-nitrophenyl) -5,6-dihydroimidazo [4,5,1,4] benzodiazepine-7- (4H) - ion x HCl [M ⁺ = 380]

Example 25 t

5,6-Dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M < ⁺ &^gt; = 187]

Example 26

2- (Pyrazin-2-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one x HCl [M ⁺ = 266]

Example 27

2- (2- (tert-butyloxycarbonylaminomethyl) -thiazol-4-yl) -5,6-dihydro-imidazo [4,5 ₁ 1 jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ = 399 ]

Example 28

2- (2- (Aminomethyl) thiazol-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one x HCl [M ⁺ = 300]

Example 29 .1

2- (2-Fluoro-4- (pyridin-4-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ = 358]

Example 30

-252- (1- (1-Methyl-piperidin-4-yl) piperidin-4-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one x 2 HCl [M ⁺ = 369]

Example 31 f

2 - [(Z) -1- (4-Fluorophenyl) -2- (pyridin-3-yl) ethenyl] -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M < ⁺ &^gt; = 384]

Example 32

2- (1-Benzyl-piperidin-3-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ = 360]

Example 33

2- (1-phenylcyclopent-1-yl) -5,6-dihydro-imidazo [4,5,1-jk] _[1) 4] benzodiazepin-7 (4H) -one [M ⁺ = 331]

Example 34

2- (1-Phenylcyclohex-1-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M < ⁺ &^gt; = 345]

Example 35

6- (4- (Aminomethyl) cyclohex-1-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ = 298]

Example 36

2 - [(E) -2- (Pyridin-4-yl) ethenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

-26 [Μ ⁺ = 290]

Example 37

2- [3-Cyanophenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 288];

Example 38

2- (2-phenyl-1 H-imidazol-4-yl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 329 ]

Example 39

2- [2- (4-Methylphenyl) -1,3-oxazol-4-yl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M] ⁺ -1 = 344]

Example 40

2- [1- (4-Fluoro-phenyl) -5-methyl-1 H -pyrazol-4-yl] -5 _l 6-dihydro-imidazo [4,5,1-jk] (1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 361]

Example 41

2- [1- (4-Chlorophenyl) -1H-pyrazol-5-yl] -5,6-dihydroimidazo [4,5,1-k] [1,4] benzodiazepine

7 (4H) -one

IM ⁺ 1 = 363]

Example 42

2- (3-Propyl-5-isoxazolyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 296]

-27Example 43

2- [1- (4-Methoxyphenyl) -1H-pyrrol-3-yl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 358]

Example 44

2- (1.2 _l 5-trimethyl-1 H-pyrrol-3-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1 _I, 4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 294]

Example 45

2- (4-benzoyl-1-methyl-1H-pyrrol-2-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepine

7- (4H) -one [M ⁺ -1 = 370]

Example 46

2- {4-Methyl-5- [4- (trifluoromethyl) phenyl] -3-isoxazolyl} -5,6-dihydroimidazo [4 _] 5,1-jk] [1,4] benzodiazepine-7- (4H) - O [M ⁺ -1 = 412]

Example 47

2- (5-Methyl-2-furyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one. !

[M ⁺ -1 = 267]

Example 48

2- [1- (2-Chlorophenyl) -5- (trifluoromethyl) -1 H -pyrazol-4-yl] 5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 431]

-28Example 49

2- (5-Methyl-1H-imidazol-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 267] ]

Example 50

2- (1-Methyl-1H-pyrazol-4-yl) -5,6-dihydroimidazo [4 _] 5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 267 ]

Example 51

2- (1-Methyl-1H-indol-3-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 316]

Example 52

2 ~ 6 - [(4-chlorophenyl) thio] imidazo [2,1-b] [1,3] thiazol-5-yl} 5,6-dihydro-imidazo [4,5,1jk] [1,4] - Benzodiazepin-7- (4H) -one [M ⁺ -1 = 451]

Example 53

2- [1- (4-Chlorophenyl) -1H-pyrrol-3-yl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M] ⁺ -1 = 363]

Example 54

2- [2- (4-Fluorobenzoyl) -1-benzofuran-5-yl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M] ⁺ - 1 = 425]

-29Example 55

2- (2,5-Dibromo-3-thienyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 427]

Example 56

2- (2-Phenyl-1,3-oxazol-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1] = 330]

Example 57

2- (6-Methyl-2-pyridinyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 278]

Example 58

2- (1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) -5,6-dihydro-imidazo [4,5- _l ] jk - [1,4] ] Benzodiazepin-7- (4H) -one [M ⁺ -1 = 373]

Example 59

2- [1- (Benzylaminocarbonylmethyl) pyrrol-2-yl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzo-diazepin-7- (4H) -one [M ⁺ -1 = 399]

Example 60

2- (1-Phenyl-1H-pyrazol-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 329] ]

Example 61

-302- [1- (3-cyano-4-methoxy-pyridin-2-yl) pyrrol-2-yl] -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepine-7- ( 4H) -one [M ⁺ -1 = 384]

Example 62

2- {1 - [(4-methylphenyl) sulfonyl] -1 H-indol-3-yl} -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) - O [M ⁺ -1 = 456]

Example 63

2- (5-Methoxy-1H-indol-3-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 332] ]

Example 64

2- [4-Bromo-1- (4-chlorobenzyl) -1 H -pyrazol-5-yl) -5,6-dihydro-imidazo _[I, 4 5,1jk] [1,4] benzodiazepine-7 (4 H) -one [M ⁺ -1 = 456]

Example 65

2- [1- (4-Methylphenyl) -1H-pyrrol-2-yl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 342]

Example 66

2- (5-Chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one (M ⁺ -1 = 377)

-31 Example 67

2- [4- (4-Qhlórbenzoyl) -1-methyl-1H-pyrrol-2-yl] -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepine-7 (4 H) -one [M ⁺ -1 = 404]

Example 68

2- (4- (diethylamino) phenyl] _-5) 6-dihydro-imidazo [5,1-4 _I jk] _[1> 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 334]

Example 69

2- (4-Methoxy-1-naphthyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 343]

Example 70

2- (4-Methoxy-2,5-dimethylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 321]

Example 71

2- [3- (4-Chloro-phenoxy) -phenyl] -5,6-dihydro-imidazo [4,1,5,1- _k ] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 389]

Example 72

2- [4- (Methylthio) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 309]

Example 73

-322- [4- (Acetyloxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 321]

Example 74

2- [2,5-Bis (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 399]

Example 75

2- (2,3-Dimethoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 323]

Example 76

2- (2-Methylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 277]

Example 77

2- [4- (Benzyloxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 369]

Example 78

2- (2-Chloro-6-fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 315]

Example 79

2- (2-Ethoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 307]

-33Example 80

2- (4-Isopropylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 305]

Example 81

2- (6-Nitro-1,3-benzodioxol-5-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 352]

Example 82

2- (2,3-dihydro-1 _l 4-benzodioxin-6-yl) -5,6-dihydro-imidazo [4.5 _l 1jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 321]

Example 83

2- [4- (dimethylamino) -1-naphthyl] -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 355]

Example 84

2- [4- (Difluoromethoxy) phenyl] -5,6-dihydroimidazo [4,5- _l -jk] [1,4-] benzodiazepin-7- (4H) -one [M ⁺ -1 = 329]

Example 85

2- (3,7-Dichloro-8-quinolinyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 383]

-34Example 86

2- [4-chloro-3- (trifluoromethyl) phenyl] -5,6-dihydro-imidazo [5,1-4 _I jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 365]

Example 87

2- (1-tert-Butyl-1H-pyrazol-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1] = 309]

Example 88

2- (4-Chloro-5-nitro-1-benzothien-2-yl) -5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 398]

Example 89

2- [1- (4-Phthalimidobutan-1-yl) indol-3-yl] -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepin-7- (4H) -one [M] ⁺ -1 = 504]

Example 90

2- (3-isobutyl-5-isoxazolyl) -5,6-dihydro-imidazo [4,5,1-jk] _[1) 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 310]

Example 91

2- [1- (4-Methoxyphenyl) -5- (trifluoromethyl) -1 H -pyrazol-4-yl] -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7 (4 H ) -one [M ⁺ -1 = 427]

-35Example 92

2- [2- (Dimethylamino) -1,3-thiazol-5-yl] -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepine

7- (4 H) -one [M ⁺ -1 = 313]

Example 93

2- [3- (4-tert-Butylphenyl) -5-isoxazolyl] -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepine-7- (4H) -one [M ⁺ -1 = 386] ]

Example 94

2- [1- (4-Chlorophenyl) -3,5-dimethyl-1 H -pyrazol-4-yl] -5 _l 6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepine-7- ( 4H) -one [M ⁺ -1 = 391]

Example 95

2- (3-Chlorophenyl) -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 297]

Example 96

2- (3-Fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepine-7- (4H) -one [M ⁺ -1 = 281]

Example 97

2- (3-Phthalimidophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 408]

Example 98

-362- {4- [3-Chloro-5- (trifluoromethyl) -2-pyridinyl] phenyl} -5,6-dihydroimidazo [4,5,1 jk] [1,4] benzodiazepine-7- (4H) ) -one [M ⁺ -1 = 442]

Example 99

2- [5- (6-methyl-nicotinamide) -2-chlorophenyl] -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 431]

Example 100

2- (4-tert-Butoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 335]

Example 101

4- (7-Oxo-4,5,6,7-tetrahydroimidazo [4,5,1-jk] [1,4] benzodiazepin-2-yl) benzonitrile [M ⁺ -1 = 288]

Example 102

2- [3- (Trifluoromethoxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 347]

Example 103

2- (3- (3,5-Dichlorophenoxy) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 423]

Example 104

-372- (3-bromo-4,5-dimethoxyphenyl) -5,6-dihydro-imidazo [4,5 ₁ 1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 402]

Example 105

2- [5- (allyloxy) -1,3-dimethyl-1 H -pyrazol-4-yl] -5,6-dihydro-imidazo [4th ₍ 5,1-jk) [1,4] Benzodiazepin-7- (4H) -one [M ⁺ -1 = 337]

Example 106.

2- {2- [3- (Trifluoromethyl) anilino] phenyl} -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 422]

Example 107

2- [2- (2-Phenylethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 367]

Example 108

2- (3-Benzoyl-phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 367]

I

Example 109

2- (4-Acetamidophenyl) -5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 320]

Example 110

2 ₍₁₎ 3-benzodioxol-5-yl) -5,6-dihydro-imidazo [4,5,1-jk] _[1) 4] benzodiazepin-7 (4H) -one

-38 [ ⁺ 1 = 307]

Example 111

2- (5-Aminosulfonyl-2,4-dichlorophenyl) -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 411]

Example 112

2- (2-Benzoyloxymethylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 397]

Example 113

2- (2-N, N-Diethylaminocarbonyl-3,6-difluorophenyl) -5,6-dihydroimidazo [4,5,1- _t ] [1,4] benzodiazepin-7- (4H) -one [M] ⁺ -1 = 398]

Example 114

2- (2- (N-2,2,2-Trifluoroacetamido) phenyl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1] = 374]

Example 115

2- [4- (Trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 331]

Example 116

2- [2-Fluoro-4- (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

-39 [ ⁺ - 1 = 349]

Example 117

2- (3-Chloro-4-methoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 327]

Example 118

2- (3-Bromo-4-fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 360]

Example 119

2- (2,5-Dimethyl-1-phenyl-1H-pyrrol-3-yl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [M] ⁺ - 1 = 356]

Example 120

2- (4- (2,4-dichlorobenzoyl) -1-methyl-1H-pyrrol-2-yl] -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepine-7- ( 4H) -one [M ⁺ -1 = 439]

Example 121

2- (1- (2-Fluorophenyl) -1H-pyrrol-2-yl) -5,6-dihydroimidazo [4,5 _] 1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 346]

Example 122

2- (3,5-Dimethoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 323]

-40Example 123

2- (4-Bromo-2-fluorophenyl) -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 360]

Example 124 '

2- (2-Chloro-4-fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 315]

Example 125

2- [2- (Benzyloxy) -3-methoxyphenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 399]

Example 126

2- (2,4-diethoxy-3-methyl-phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1 _I, 4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 365]

Example 127

2- (5-Bromo-2,4-dimethoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 402]

Example 128

2- [4- (dimethylamino) -2-methoxyphenyl] -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepine

7- (4H) -one [M ⁺ -1 = 336]

Example 129

-41 2- [2-Chloro-5- (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 366]

Example 130 '

2- (3,5-Dimethyl-phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 291]

Example 131

2- [4-Fluoro-2- (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 349]

Example 132

2- (5-Bromo-2-fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 360]

Example 133

2- [4- (1-pyrrolidinyl) phenyl] -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 332]

Example 134

2- (4-lzopropoxyfenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 321]

Example 135

2- (3,5-Dibromophenyl) -5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 421]

-42Example 136

2- [4- (Benzyloxy) -2-methoxyphenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 399] t

Example 137

2- [3-Fluoro-4- (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 349]

Example 138

2- [5- (4-Nitrophenyl) -2-furyl] -5,6-dihydroinnidazo [4,5,1-jk] _[1) 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 374]

Example 139

2- (3-Acetyloxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 321]

Example 140

2- [2- (tert-Butylthio) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 351]

Example 141

2- [2-Fluoro-5- (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 349]

Example 142

-432- (3,4-Dimethylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 291]

Example 143

2- [4- (ethylthio) phenyl] -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 323]

Example 144

2- {4 - [(trifluoromethyl) thio] phenyl} -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 363]

Example 145

2- {2 - [(4-Chlorophenyl) thio] phenyl} _-5> 6-dihydro-imidazo [4,5,1-jk] [1 _l 4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 406 ]

Example 146

2- (4-Chloro-3-fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 316]

Example 147

2- (2- (4-Ethoxycarbonylpiperidine-1-yl) -thiazol-5-yl) -5,6-dihydro-imidazo [4.5 _l 1jk] [1,4] benzodiazepine-7 (4H) -one [M ⁺ -1 = 425]

Example 148

2- {1S-Dimethyl-5- (4-trifluoromethyl-phenoxy) -1H-pyrazol-4-yl} -5,6-dihydro-imidazo [4,5,1jk] - [1,4] benzodiazepine-7- (4H) -one

-44 [ ⁺ 1 = 441]

Example 149

2- {1-methyl-3- (trifluoromethyl) -5- [3- (trifluoromethyl) phenoxy] -1 H -pyrazol-4-yl} -5,6-dihydro-imidazo [4,5,1-jk] [1, 4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 495]

Example 150

2- [2- (4-benzyl-1-piperazinyl) -1,3-thiazol-5-yl] -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 ( 4H) -one [M ⁺ -1 = 444]

Example 151

2- (5-isopropyl-2-methylcyclohexyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 325]

Example 152

2- (6,6-dimethyl [3.1.1] hept-2-yl) -5- _I, 6-dihydro-imidazo [4,5,1jk] [l, 4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 309]

Example 153

2- [5- (3-Nitrophenyl) -2-furyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 374]

Example 154

2- (2,5-dimethoxy-tetrahydro-3-furanyl) -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7 (4H) -one

-45 [ ⁺ 1 = 317]

Example 155

2- (2-Thienyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4 H) -one [M ⁺ -1 = (269)

Example 156

2- (1,3-Thiazol-2-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 270]

Example 157

2 _L (4-methoxycyclohexyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 299]

Example 158

2- (3,5-Dimethoxy-2-methoxycarbonylphenyl) -5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 381]

Example 159

2- {5- [1-methyl-3- (trifluoromethyl) -1 H -pyrazol-5-yl] -2-thienyl} 5 _l 6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7 - (4H) -one [M ⁺ -1 = 417]

Example 160

2- (2-Fluoro-5-methoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 311]

Example 161

-462- (4-Butylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 319]

Example 162

2- [2- (Trifluoromethoxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 347]

Example 163

2- (4-quinolinyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 314]

Example 164

2- (2-quinolinyl) -5 _l 6-dihydro-imidazo _[4,5-I, 1 jk] [1 ₁ 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 314]

Example 165

2- (2-Chloro-3-quinolinyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 348]

Example 166

2- [4- (1H-Pyrol-1-yl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1] = 328]

Example 167

2- (1H-Indol-6-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 302]

Example 168

-472- (4- (1,1-Dioxo-1,2-thiazinan-2-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepine-7- (4H) -one [M ⁺ -1 = 396]

Example 169

2- (1,3-Benzothiazol-6-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 320]

Example 170

2- (2,3-Dihydro-1-benzofuran-5-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 305]

Example 171

2- (4- (2- (2-Furylmethylthio) acetamido) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ - 1 = 432]

Example 172

2 - {[5- (2-Fluorobenzoyl) -2-thienyl] methyl} -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [M * -1] = 405]

Example 173

2- (2- (2-Acetamidopyridin-5-ylthio) pyridin-5-yl) -5,6-dihydroimidazo [4,5,1b] [1,4] benzodiazepin-7- (4H) -one ( M ⁺ 1 = 430]

Example 174

-482- (4- (N- (3,4-Dioxo-2-ethoxy-1-cyclobuten-1-yl) amino) phenyl) -5,6-dihydroimidazo [4,5,1jk] - (1,4 Benzodiazepin-7- (4H) -one [M ⁺ -1 = 402]

Example 175

I

2 - [(2-Quinoxalinylthio) methyl] -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepin-7- (4H) -one [M ⁺ -1 = 361]

Example 176

2- [4- (Methylamino) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 292]

Example 177

2- (5- (4-Aminosulfonylphenyl) furan-2-yl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 408] ]

Example 178

2- {2,5-Dimethyl-1- [4- (trifluoromethyl) phenyl] -1H-pyrrol-3-yl} 5,6-dihydroimidazo [4,5,1jk] [1,4] -benzodiazepin-7- (4H) -one [M ⁺ -1 = 424]

Example 179

2- {1 - [(2,4-Difluorophenyl) sulfonyl] -1H-pyrrol-2-yl} -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepine-7 (4 H ) -one [M ⁺ -1 = 428]

Example 180

-492-1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -2,5-dimethyl-1H-pyrrol-3-yl} -5,6dihydroimidazo- [4,5,1-jk] [1 4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 493]

Example 181

2- [5- (Phenylethynyl) -2-thienyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 369]

Example 182

2- {5- [2- (Trifluoromethoxy) phenyl] -2-furyl} -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1] = 413]

Example 183

2- (5- (2-Methoxycarbonylthiophen-3-yl) furan-2-yl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepin-7- (4H) -one [ M ⁺ -1 = 392]

Example 184

2- (2,5-Dimethyl-phenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1 _l 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 291]

Example 185

2- (4-Methoxycarbonylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 321]

Example 186

-502- (4-Methylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 277]

Example 187

2- (3 _l 4-Difluorophenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1 _l 4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 299]

Example 188

2- (4-Fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 281]

Example 189

2- (3-Chloro-4-fluorophenyl) -5,6-dihydroimidazo [4,5 _] 1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 315]

Example 190

2- (3-Bromo-4-methoxy-phenyl) -5 ₁ 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 372]

Example 191

2- [4- (Trifluoromethoxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 374]

Example 192

2- (2,5-Difluorophenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 299]

-51 Example 193

2- (4- (1,1,2,2-Tetrafluoroethoxy) phenyl) -5,6-dihydroimidazo [3,4-b] benzodiazepin-7 (4H) -one [M * -1 = 379]

Example 194

2- [4-Fluoro-3- (trifluoromethyl) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepin-7 (4H) -one [M ⁺ -1 = 349]

Example 195

2- (4-Cyanophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 288]

Example 196

2- (3-Bromo-4-fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 360]

Example 197

2- (4-tert-Butyl-2-methylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 333]

Example 198

2- [4- (1-methoxy-1-methylethyl) phenyl) -5,6-dihydro-imidazo _[4) 5,1-jk] _[1> 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 335]

Example 199

-522- (4-Bromophenyl) -5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 342]

Example 200

2- [4- (3,4-Dichlorophenoxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 424]

Example 201

2- [4- (2-Propinyloxy) phenyl] -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 317]

Example 202

2- {4- [Chloro (difluoro) methyl] phenyl} -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 347]

Example 203

2- (4-benzoylphenyl) -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 367]

Example 204

2- (4-Ethyl-phenyl) -5,6-dihydro-imidazo [5,1-4 _l jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 291]

Example 205

2- (2-hydroxy-5-methylphenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

-53 [ ⁺ - 1 = 293]

Example 206

2- (4- (2,6-Difluorobenzoyl) -1-methyl-1H-pyrrol-2-yl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepine-7 - (4H) -one [M ⁺ -1 = 406]

Example 207

2- [4- (3-Chlorobenzoyl) -1-methyl-1H-pyphol-4-yl] -5-dihydroimidazo [3,4-d] [1,4] benzo diazepin-7- (4H) -one [M ⁺ -1 = 404]

Example 208

2- (2-Ethoxy-1-naphthyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 357]

Example 209

2- [2- (Benzyloxy) -4,5-dimethoxyphenyl] -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 429]

Example 210

2- {4 - [(2-Chloroethyl) (ethyl) amino] -2-methylphenyl} -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M * -1 = 382]

Example 211

2- (4,5-dimethoxy-2-methyl-phenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

-54 [ ⁺ - 1 = 337]

Example 212

2- (7-ethyl-2-naphthyl) -5,6-dihydroimidazo [4,5,1-b] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 327]

Example 213

2- (2,4-Dimethoxy-5-methylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 337]

Example 214

2- (3-benzoyl-2,4-dichlorophenyl) -5,6-dihydro-imidazo [5,1 ₁ 4-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 436]

Example 215

2- (6-chloro-1,3-benzodioxol-5-yl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1 _l 4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 341]

Example 216

2- [4- (benzyloxy) _-3 '5-dimethoxy-phenyl) -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 429]

Example 217

2- (3,4-Diethoxyphenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 351]

- 55Example218

2- (2 - ((Pyridin-2-yl) aminocarbonyl) et-1-yl) -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepin-7- (4H) -one [M ⁺ -1 = 335]

Example 219

2- (3 - ((Pyridin-2-yl) aminocarbonyl) prop-1-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzo diazepine-7- (4H) - o [M ⁺ -1 = 349]

Example 220

2 - ((1,3-Dimethyl-3,7-dihydro-2,6-dioxo-1H-purin-8-yl) methyl-5,6-dihydroimidazo [4,5,1] - [1,4] ] Benzodiazepin-7- (4H) -one [M ⁺ -1 = 379]

Example 221

2- (2 - ((thiazol-2-yl) aminocarbonyl) eth-1-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepine-2-yl) -7- (4 H) -one [M ⁺ -1 = 341]

Example 222

2- {2 - [(1,3-Dimethyl-1 H-pyrazol-5-yl) amino] phenyl} -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepine-7- ( 4H) -one [M ⁺ -1 = 372]

Example 223

2- (2- (4-chlorophenyl) methylthio-3-cyano-pyridin-6-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

-56 [ ⁺ 1 = 445]

Example 224

2- (4-tert-Butyl-phenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1 _I, 4] benzodiazepin-7 (4H) -one

I [M ⁺ -1 = 319]

Example 225

2- {2,5-Dimethyl-1- [3- (trifluoromethyl) phenyl] -1H-pyrrol-3-yl} 5,6-dihydroimidazo [4,5,1jk] 4] -benzodiazepin-7- (4H) -one [M ⁺ -1 = 424]

Example 226 '

2- (5-Chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ -1 = 377]

Example 227

2- [2 _S 5-bis (trifluoromethyl) phenyl] -5,6-dihydro-imidazo _[4) 5,1-jk] [1,4] benzodiazepin-7 (4H) -one [M ⁺ - 1 = 399]

Example 228

2- [4- (4-tert-Butyl-1,3-thiazol-2-yl) phenyl] -5,6-dihydro-imidazo [4,5,1jk] [1,4] benzodiazepin-7 (4H) - O [M ⁺ - 1 = 402]

Example 229

2- (3-Cyano-4-N, N-dimethylamino-2-fluorophenyl) -5,6-dihydroimidazo [4 _] 5,1jk] [1,4] benzodiazepin-7- (4H) -one

-57 [ ⁺ -1 = 349]

Example 230

2- (6-Methoxy-2-naphthyl) -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepin-7- (4H) -one [M ⁺ -1 = 343] ¹

Example 231

2- (4-isobutylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 319]

Example 232

2- (3-Bromo-4-methoxyphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one [M ⁺ -1 = 372]

The following compounds of the invention can be prepared in analogy to the procedures described above:

2- (4- (4-n-propylpiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

2- (4- (4-Isopropylpiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-k] [1,4] benzodiazepin-7- (4H) -one

2- (4- (4-Benzylpiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

4. 2- (4- (4-n-butyl-piperazin-1-yl) phenyl) -5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

5. 2- (4- (4-ethylpiperazin-1-yl) phenyl) -5,6-dihydroimidazo- [4,5,1] k [1,4] benzodiazepin-7- (4H) -one

6. 2- (4- (2-N, N-dimethylaminoet-1-yloxy) phenyl) -5,6-dihydropyrimazo [4,5,1k] [1,4] benzodiazepine-7- (4H) - one

-587. 2- (4- (2-pyrrolidin-1-yl-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepine-7- (4H) -one

8. 2- (4- (2-piperazin-1-ylet-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepine-7- (4H) - one

I

9. 2- (4- (2- (4-Methylpiperazin-1-yl) et-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepine-7- (4H) -one

10. 2- (4- (2- (4-propylpiperazin-1-yl) et-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1 jk] [1,4] benzodiazepine-7 - (4H) -one

11. 2- (4- (2- (4-ethylpiperazin-1-yl) et-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepine-7 - (4H) -one

12. 2- (4- (2- (4-Benzylpiperazin-1-yl) et-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepine-7- (4H) -one

13. 2- (4- (2- (4-acetamidopiperazin-1-yl) et-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1] -k- [1,4] benzodiazepine-7- (4H) -one

14. 2- (4- (2- (4-Benzamidopiperazin-1-yl) et-1-yloxy) phenyl) -5,6-dihydroimidazo [4,5,1- b] [1,4] benzodiazepine- 7 (4H) -one

15. 2- (4- (4-methylhomopiperazin-1-yl) phenyl) -5,6-dihydro-imidazo [4,5,1-jk] _[1) 4] benzodiazepin-7 (4H) -one

16. 2- (4- (4-Phenylpropan-1-yl) phenyl) -5,6-dihydro-imidazo [4 _l 5,1jk] [1,4] benzodiazepine-7 (4H) -one

17. 2- (4- (4-n-butylhomopiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepin-7- (4H) -one

18. 2- (4- (4-ethylhomopiperazin-1-yl) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

19. 2- (4-Methoxyphenyl) -5,6-dihydroimidazo [4,5,1-k] [1,4] benzodiazepin-7- (4H) -one

20. 2- (4-Chlorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

-5921. 2- (4-aminophenyl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

22. 2- (4-Isopropylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepin-7- (4H) -one

23. 2- (3-Chlorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

24. 2- (3-Methylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

25. 2- (3-Phenylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

26. 2- (3-Isopropylphenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

27. 2- (3-Fluorophenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

28. 2-piperidin-4-yl-5 _l 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

29. 2- (1-ethylpiperidin-4-yl) -5,6-dihydroimidazo [4,5,1-b] [1,4] benzodiazepin-7- (4H) -one

30. 2- (1-n-Propylpiperidin-4-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

31. 2- (1-Isopropyl-piperidin-4-yl) -5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

32. 2-Pyridin-4-yl-5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

33. 2-Pyridin-2-yl-5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

34. 2-Thien-2-yl-5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

35. 2-Indol-5-yl-5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

36. 2-Indol-2-yl-5,6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

37. 2-Quinolin-3-yl-5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

38. 2-Isoquinolin-1-yl-5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

39. 2-Quinoxalin-2-yl-5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one

-6040. 2-naphth-2-yl-5,6-dihydroimidazo [4,5- _l -jk] [1,4] benzodiazepin-7- (4H) -one

41. 2- (2- (N, N-dimethylamino) et-1-ylamino) phenyl) -5,6-dihydroimidazo [4,5,1-k] [1,4] benzodiazepin-7- (4H) -one

42. 2- (2- (N, N-Diethylamino) et-1-ylamino) phenyl) -5,6-dihydroimidazo [4,5,1jk] [1,4] benzodiazepine-7- (4H) - one

43. 2- (2-piperidin-1-ylethyl-1-ylamino) phenyl) _-5) 6-dihydro-imidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

44. 2- (2-Pyrrolidin-1-ylet-1-ylamino) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

45. 2- (3- (N, N-dimethylamino) prop-1-ylamino) phenyl) -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepin-7- (4H) -one

46. 2- (3- (N, N-Diethylamino) prop-1-ylamino) phenyl) -5,6-dihydroimidazo [4,5,1-jk] [ _1,4 ] benzodiazepine-7- (4H) - one

47. 2- (3-piperidin-1-yl-prop-1-ylamino) -phenyl] -6-ε-dihydro-imidazo [theta], 1k] [1,4] benzodiazepin-7- (4H) -one

48. 2- (3-pyridin-1-ylprop-1-ylamino) phenyl) -5,6-dihydroimidazo [4,5,1] k [1,4] benzodiazepine-7- (4H) ) -one

49. 2-Cyclohexyl-5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7- (4H) -one

50. 2- (cis-4-amino-cyclohex-1-yl) -5- _I, 6-dihydro-imidazo [5,1-4 _I jk] [1,4] benzodiazepin7- (4H) -one

51. 2- (4-Methoxycyctohex-1-yl) -5,6-dihydroimidazo [4,5,1-jk] [1,4] benzodiazepin-7 (4H) -one

52. 2-Phenyl-5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

53. 2- (3-Aminophenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

-61 54. 2- (4-N, N-dimethylaminomethylphenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

55. 2- (4- (2-N, N-dimethylaminoet-1-yl) phenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepine-7- (4H) ) -one

56. 2- (4-Hydroxyphenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

57. 2- (4-pyrrolidinomethylphenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7 (4H) -one

58. 2- (2-methylthiophenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

59. 2- (4-Carboxyphenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

60. 2- (3 _l 5-bis (trifluoromethyl) phenyl) -5,6-dihydro-imidazo [5,4 ₁ 1 jk] [1,4] benzodiazepin7- (4H) -one

61. 2- (4-tert-Butylphenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepin-7- (4H) -one

62. 2- (3- (morpholin-4-ylmethyl) phenyl) -5,6-dihydroimidazo [5,4,1-jk] [1,4] benzodiazepine 7- (4H) -one

Claims (25)

PATENT CLAIMS A compound of formula I wherein: A may be a C 1 -C 3 chain, wherein each carbon atom may carry one or two of the following substituents, such as C 1 -C ₄ -alkyl, OH, O-C 1 -C ₄ -alkyl, COOH, COO-C 1 -C ₄ - alkyl and phenyl or one carbon atom may also carry the group = O, and X ¹ can be S, O and NH, and R ¹ represents hydrogen, chloro, fluoro, bromo, iodo, branched and unbranched C 1 -C 6 -alkyl, OH, nitro, CF ₃ , CN, NR ¹¹ R ¹² , NH-CO-R ¹³ , O-C 4 -C 4 -alkyl, wherein R ¹¹ and R ¹² are, independently of one another, hydrogen or C 1 -C 4 -alkyl and R ¹³ represents hydrogen, C 1 -C ₄ -alkyl, C 1 -C ₄ alkylphenyl or phenyl, and B may be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 14 carbon atoms and 0 to 5 nitrogen atoms, O up to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may also be substituted by one substituent R ⁴ and a maximum of 3 different or the same substituents R ⁵ , and one or two carbon or sulfur atoms may also carry one or two groups = O, or represents a residue L _in -YM _w in which -63L may be a linear or branched, saturated or unsaturated carbon chain of 1 to 8 carbon atoms, each carbon atom being substituted by one or two substituents R ⁴ and at most two different or the same substituents R ⁵ , and M, independently of L, has the same meaning as L, and Y is a bond, can be S, O or NR ³ , wherein R ³ can be hydrogen, branched and unbranched C 1 -C 6 alkyl, C 1 -C 4 -alkylphenyl, phenyl, and can be 0 and 1, and w can be 0 and 1, and when Y is a bond, R ⁴ and R ^{5 are} not both hydrogen, and when B is Lv-Y-Mw, R ^{1 is} not chlorine or NO 2, and R ⁴ is hydrogen and - (D) p- (E) s- (F ¹ ) q -G ¹ - (F ² ) _r (G ² ) -G ³ , wherein D can be S, NR ⁴³ and O E may be phenyl, ^X C = O, -SO ₂ -, -SO ₂ NH-, -NHCO-, -CONH-, NHSO ₂ -, -NHCOCH ₂ X ⁴ , and X ⁴ can be S, O or NH, and F ¹ may be a linear or branched, saturated or unsaturated carbon chain containing 1 to 8 carbon atoms, and F ² , independently of F ¹ , has the same meaning as F ¹ , -64G ¹ is a bond or can be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring having at most 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring with a maximum of 14 carbon atoms and 0 up to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may be substituted by a maximum of 3 different or the same R ⁵ substituents, and one or two carbon or sulfur atoms may also carry one or two = O, and G ² is NR ⁴¹ R ⁴² a or a bond, a G ³ may be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring having a maximum of 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring having a maximum of 14 carbon atoms and 0 to 5 nitrogen atoms, 0 to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may also be substituted by a maximum of 3 different or -65 the same substituents R ⁵ , and one or two carbon or sulfur atoms may also carry one or two = O, or hydrogen, and p may be 0 and 1 and may be 0 and 1 and q may be 0 and 1 and may be 0 a 1 a R ⁴¹ can be hydrogen, C 1 -C 6 -alkyl, wherein each carbon atom can also carry up to two R ⁶ substituents, phenyl which can also carry a maximum of two R ⁶ substituents, and (CH 2) _t -K and R ⁴² can be hydrogen, C 1 -C 6 -alkyl, -CO-R ⁸ , CO 2 -R ⁸ , SO ₂ NH ₂₎ SO ₂ R ⁸ , - (C = NH) -R ^8, and - (C = NH) -NHR ⁸ and R ⁴³ can be hydrogen and C ₁ -C ₄ -alkyl and t can be 1,2,3,4a K may be NR ¹¹ R ¹² , NR ¹¹ -C 1 -C 4 -alkylphenyl, pyrrolidine, piperidine, 1,2,5,6-tetrahydropyridine, morpholine, homopiperidine, piperazine, which may also be substituted by an alkyl radical _C-R -C 6 alkyl, and homopiperazine, which can also be substituted by alkyl radicals C6-alkyl, and R ⁵ can be hydrogen, chloro, fluoro, bromo, iodo, OH, nitro, CF ₃ , CN, NR ¹¹ R ¹² , NH-CO-R ¹³ , C 1 -C 4 alkyl-CO-NH-R ¹³ , COR ⁸ , C 0 -C 4 -alkyl O-CO-R ¹³ , C 1 -C 4 -alkylphenyl, phenyl, CO ₂ - C 1 -C ₄ -alkyl, and branched and unbranched C 1 -C 6 -alkyl, O-C 1 -C 4 -alkyl, S-C 1 -C ₄ -alkyl, wherein each carbon atom of the alkyl chains may carry up to two R ⁶ substituents, and alkyl the chains may also be unsaturated, and -66R ⁶ denotes hydrogen, chloro, fluoro, bromo, iodo, branched and unbranched _Ci-C6-alkyl, OH, nitro, CF _3, CN, NR ¹¹ R ^12, NHCO-R ^13, O-C ₄ -C alkyl, R ⁷ may be hydrogen, C 1 -C ₆ -alkyl, phenyl, wherein the ring may be substituted with up to two R ⁷¹ radicals, and the amine NR ¹¹ R ¹² or a cyclic saturated amine having 3 to 7 members, and may also be substituted with alkyl C 1 -C ₆ -alkyl, and homopiperazine, which may also be substituted by C 1 -C 6 -alkyl, and wherein the radicals R ¹¹ , R ¹² and R ¹³ in K, R ⁵ , R ⁶ and R ⁷ may, independently of each other. of one another, have the same meaning as for R ^1, and R ⁷¹ can be OH, C 1 -C 6 -alkyl, O-C 1 -C ₄ -alkyl, chlorine, bromine, iodine, fluorine, CF ₃ , nitro, NH ₂ , and R ⁸ can be C 1 -C ₆ -alkyl, CF ₃ , phenyl, C 1 -C ₄ -alkylphenyl, wherein the ring can also be substituted with up to two R ⁸¹ radicals, and R ⁸¹ can be OH, C 1 -C ₆ -alkyl, O-C 1 -C ₄ -alkyl, chlorine, bromine, iodine, fluorine, CF ₃ , nitro, NH ₂ , and R ⁹ can be hydrogen, C 1 -C 4 -alkyl, C 1 -C ₄ -alkylphenyl, CO ₂ -C 1 -C ₄ alkylphenyl, CO ₂ -C 1 -C ₄ -alkyl, SO ₂ -phenyl, COR ⁸ and phenyl, wherein the phenyl rings can be also be substituted with up to two R ⁹¹ radicals, and R ⁹¹ can be OH, C 1 -C ₆ -alkyl, O-C 1 -C ₄ -alkyl _,; chlorine, bromine, iodine, fluorine, CF ₃ , nitro, NH ₂ , and tautomeric forms thereof, possible enantiomeric and diastereoisomeric forms, and prodrugs thereof. A compound of formula I according to claim 1, wherein A represents a C ₂ chain which may be substituted, and X ¹ represents O, and -67R ¹ is hydrogen. A compound of formula I according to any one of claims 1 or 2, wherein B may be an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 15 carbon atoms, an unsaturated, saturated or partially unsaturated mono-, bi- or tricyclic ring of up to 14 carbon atoms and 0 to 5 nitrogen atoms, 0 up to 2 oxygen atoms or 0 to 2 sulfur atoms, each of which may also be substituted by a maximum of 3 different or the same R ⁵ , and one or two carbon or sulfur atoms may also carry one or two = O groups. A compound of formula I according to claim 3, wherein> B phenyl, cyclohexyl, piperidine, pyridine, pyrimidine, pyrrole, pyrazole, thiophene, furan, oxazole, naphthalene, piperazine, quinoline, pyrazine, each of which may also be substituted with one R ⁴ or a maximum of two R ⁵ substituents. A compound of formula I according to claim 4, wherein R ⁴ is hydrogen or D ₁₁ -F ¹⁰ , G ² -G ³ , where G ³ is hydrogen, and D is O and NR ⁴³ , wherein R ⁴³ is hydrogen and C 1 -C ₃ -alkyl, and F ¹ represents C 2 -C ₄ -alkyl. A compound of formula I according to any one of claims 1 or 2, wherein B is L _in -YM _w , wherein v is 0, aw is 1, and Y is a bond, and M may be a linear or branched carbon chain containing 2 to 8 carbon atoms and containing at least one carbon atom; -68 is a double bond, each carbon atom being substituted by one or two R ⁴ radicals and at most two different or the same R ⁵ radicals, and R ¹ is hydrogen, and R ⁴ represents D _o , iF ¹ o, iG ¹ -G ² -G ³ , wherein G ³ represents hydrogen, and D is O and NR ⁴³ , wherein R ⁴³ is hydrogen and C 1 -C 6 -alkyl and F ¹ represents C 2 -C 4 -alkyl. A medicament comprising one or more compounds of formula (I) according to any one of claims 1 to 6, together with conventional carriers and excipients. Use of compounds of formula I according to any one of claims 1 to 6 or compounds of formula I, in which R ¹ , X ¹ and A are as defined above, and B can be hydrogen and a C 1 -C ₆ -alkyl chain, for the preparation of medicaments with PARP-inhibitory effect. Use of compounds of formula I according to claim 8 for the preparation of medicaments for the treatment of neurodegenerative diseases and neuronal damage. Use according to claim 8 for the treatment of neurodegenerative diseases and neuronal damage caused by ischemia, trauma or massive bleeding. Use according to claim 8, for the treatment of stroke and craniocerebral trauma. Use according to claim 8, for the treatment of Alzheimer's disease, Parkinson's disease and Huntington's disease. Use of compounds of formula I according to claim 8 for the preparation of medicaments for the treatment or prophylaxis of damage caused by ischemia. Use of compounds of formula I according to claim 8, for the preparation of medicaments for the treatment of epilepsy, in particular generalized epileptic seizures, such as, for example, minor epileptic seizure and tonic-clonic seizures, and partial -69 epileptic seizures such as temporal lobe attacks and complex partial seizures. Use of compounds of formula I according to claim 8, for the preparation of medicaments for the treatment of renal impairment after renal ischemia, damage caused by drug therapy, such as during cyclosporine therapy, and for treatment during and after kidney transplantation. Use of compounds of formula I according to claim 8, for the preparation of medicaments for the treatment of cardiac damage following cardiac ischemia. Use of the compounds of formula I according to claim 8, for the preparation of medicaments for the treatment of microinfarcts, such as during and after heart valve replacement, aneurysm resections and heart transplants. Use of compounds of formula I according to claim 8, for the preparation of medicaments for treatment in cases of revascularization of critically narrowed coronary arteries, such as in PTCA and bypass operations, or critically narrowed peripheral arteries, in particular leg arteries. Use of the compounds of formula I according to claim 8, for the preparation of medicaments for the treatment of acute myocardial infarction and injury during and after its therapeutic or mechanical lysis. Use of compounds of formula I according to claim 8 for the preparation of medicaments for the treatment of tumors and their metastases. Use of compounds of formula I according to claim 8, for the preparation of medicaments for the treatment of sepsis, multiorgan failure, such as during septic shock, and acute respiratory distress syndrome. Use of the compounds of formula I according to claim 8 for the preparation of medicaments for the treatment of immunological diseases such as inflammation and rheumatic diseases such as rheumatoid arthritis. Use of compounds of formula I according to claim 8 for the preparation of medicaments for the treatment of diabetes mellitus. -7024. A compound of formula III (xnj wherein A represents a C 1 -C 3 chain, wherein each carbon atom can carry one or two of the following substituents such as C 1 -C ₄ -alkyl, OH, OC 1 -C ₄ -alkyl, COOH, COO-C 1 -C ₄ -alkyl and phenyl or one carbon atom may also carry the group = O, and X ¹ and R ¹ have the meanings set forth in the preceding claims, excluding the following compounds 9-amino-3-methyl-1,2,3,4-tetrahydro-5H-1,4-benzodiazepin-5-one, 9-amino-23-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione, 6,8-diamino-2,4- (1H, 3H) -quinazolinedione. 8-amino-2,4- (1H, 3H) -quinazolinedione and salts thereof. 25. A process for the preparation of compounds of formula III and salts thereof, characterized in that 2-halo-3-nitrobenzoic acid esters are reacted with a suitable diamine in a polar solvent in the presence of a base, and then the nitro group is hydrogenated with hydrogen in the presence of a suitable catalyst. Use of compounds of formula III in the synthesis of PARP inhibitors.