CA2915419A1 - Substituted phenyl-2,3-benzodiazepines - Google Patents

Substituted phenyl-2,3-benzodiazepines Download PDF

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CA2915419A1
CA2915419A1 CA2915419A CA2915419A CA2915419A1 CA 2915419 A1 CA2915419 A1 CA 2915419A1 CA 2915419 A CA2915419 A CA 2915419A CA 2915419 A CA2915419 A CA 2915419A CA 2915419 A1 CA2915419 A1 CA 2915419A1
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alkyl
phenyl
benzodiazepine
dihydro
amino
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Stephan Siegel
Stefan Baurle
Arwed Cleve
Bernard Haendler
Amaury Ernesto FERNANDEZ-MONTALVAN
Ursula Monning
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Bayer Pharma AG
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Abstract

The invention relates to BET-protein-inhibiting, in particular BRD4-inhibiting, substituted phenyl-2,3-benzodiazepines of general formula (I), in which X, R1a, R1b, R1c, R2, R3, R4, and R5 have the meanings specified in the description, to pharmaceutical agents containing the compounds according to the invention, and to the prophylactic and therapeutic use of said pharmaceutical agents for hyperproliferative diseases, in particular tumor diseases. The invention further relates to the use of BET protein inhibitors in benign hyperplasias, atherosclerotic diseases, sepsis, autoimmune diseases, vascular diseases, viral infections, neurodegenerative diseases, inflammatory diseases, atherosclerotic diseases, and male fertility control.

Description

Substituted pheny1-2,3-benzodiazepines The present invention relates to BET protein-inhibitory, especially BRD4-inhibitory, substituted pheny1-2,3-benzodiazepines, to pharmaceutical compositions comprising the compounds according to the invention, and to the prophylactic and therapeutic use thereof for hyperproliferative disorders, especially for neoplastic disorders. The present invention further relates to the use of BET protein inhibitors in benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, in neurodegenerative disorders, in inflammatory disorders, in atherosclerotic disorders and in male fertility control.
The human BET family (bromo domain and extra C-terminal domain family) has four members (BRD2, BRD3, BRD4 and BRDT) containing two related bromo domains and one extraterminal domain (Wu and Chiang, J. Biol. Chem., 2007, 282:13141-13145). The bromo domains are protein regions which recognize acetylated lysine residues. Such acetylated lysines are often found at the N-terminal end of histones (e.g. histone 3 or histone 4), and they are features of an open chromatin structure and active gene transcription (Kuo and Allis, Bioessays, 1998, 20:615-626). The different acetylation patterns recognized by BET proteins in histones were investigated in depth (Umehara et al., J. Biol. Chem., 2010, 285:7610-7618; Filippakopoulos et al., Cell, 2012, 149:214-231). In addition, bromo domains can recognize further acetylated proteins. For example, BRD4 binds to RelA, which leads to stimulation of NF-03 and transcriptional activity of inflammatory genes (Huang et al., Mol. Cell. Biol., 2009, 29:1375-1387; Zhang et al., J. Biol.
Chem., 2012, 287:
28840-28851; Zou et al., Oncogene, 2013, doi:10.1038/onc.2013.179). The extraterminal domain of BRD2, BRD3 and BRD4 interacts with several proteins involved in chromatin modulation and the regulation of gene expression (Rahman et al., Mol. Cell. Biol., 2011, 31:2641-2652).
In mechanistic terms, BET proteins play an important role in cell growth and in the cell cycle. They are associated with mitotic chromosomes, suggesting a function in epigenetic memory (Dey et al., Mol. Biol. Cell, 2009, 20:4899-4909; Yang et al., Mol. Cell. Biol., 2008, 28:967-976). BRD4 is important for post-mitotic reactivation of gene transcription (Zhao et al., Nat. Cell. Biol., 2011, 13:1295-1304). It has been shown that BRD4 is essential for transcription elongation and for the recruitment of the elongation complex P-TEFb consisting of CDK9 and cyclin T1, which leads to activation of RNA polymerase II (Yang et al., Mol. Cell, 2005, 19:535-545;
Schroder et al., J. Biol.
Chem., 2012, 287:1090-1099). Consequently, the expression of genes involved in cell proliferation is stimulated, for example of c-Myc and aurora B (You et al., Mol. Cell.
Biol., 2009, 29:5094-5103;
Zuber et al., Nature, 2011, 478:524-528). BRD2 and BRD3 bind to transcribed genes in hyperacetylated chromatin regions and promote transcription by RNA polymerase II (LeRoy et al., Mol. Cell, 2008, 30:51-60).
- 2 -Knock-down of BRD4 or the inhibition of the interaction with acetylated histones in various cell lines leads to G1 arrest and to cell death apoptosis (Mochizuki et al., J.
Biol. Chem., 2008, 283:9040-9048; Mertz et al., Proc. Natl. Acad. Sci. USA, 2011, 108:16669-16674). It has also been shown that BRD4 binds to promoter regions of several genes which are activated in the G1 phase, for example cyclin D1 and D2 (Mochizuki et al., J. Biol. Chem., 2008, 283:9040-9048). In addition, inhibition of the expression of c-Myc, an essential factor in cell proliferation, after BRD4 inhibition has been demonstrated (Dawson et al., Nature, 2011, 478:529-533;
Delmore et al., Cell, 2011, 146:1-14; Mertz et al., Proc. Natl. Acad. Sci. USA, 2011, 108:16669-16674).
BRD2 and BRD4 knockout mice die early in embryogenesis (Gyuris et al., Biochim. Biophys.
Acta, 2009, 1789:413-421; Houzelstein et al., Mol. Cell. Biol., 2002, 22:3794-3802). Heterozygotic BRD4 mice have various growth defects attributable to reduced cell proliferation (Houzelstein et al., Mol. Cell. Biol., 2002, 22:3794-3802).
BET proteins play an important role in various tumour types. Fusion between the BET proteins BRD3 or BRD4 and NUT, a protein which is normally expressed only in the testes, leads to an aggressive form of squamous cell carcinoma, called NUT midline carcinoma (French, Cancer Genet. Cytogenet., 2010, 203:16-20). The fusion protein prevents cell differentiation and promotes proliferation (Yan et al., J. Biol. Chem., 2011, 286:27663-27675; Grayson et al., 2013, doi:10-1038/onc.2013.126). The growth of in vivo models derived therefrom is inhibited by a BRD4 inhibitor (Filippakopoulos et al., Nature, 2010, 468:1067-1073). Screening for therapeutic targets in an acute myeloid leukaemia cell line (AML) showed that BRD4 plays an important role in this tumour (Zuber et al., Nature, 2011, doi:10.1038). Reduction in BRD4 expression leads to a selective arrest of the cell cycle and to apoptosis. Treatment with a BRD4 inhibitor prevents the proliferation of an AML xenograft in vivo. Amplification of the DNA region containing the BRD4 gene was detected in primary breast tumours (Kadota et al., Cancer Res, 2009, 69:7357-7365). For BRD2 too, there are data relating to a role in tumours. A transgenic mouse which overexpresses BRD2 selectively in B cells develops B cell lymphomas and leukaemias (Greenwall et al., Blood, 2005, 103:1475-1484).
BET proteins are also involved in viral infections. BRD4 binds to the E2 protein of various papillomaviruses and is important for the survival of the viruses in latently infected cells (Wu et al., Genes Dev., 2006, 20:2383-2396; Vosa et al., J. Virol., 2012, 86:348-357;
McBride und Jang, Viruses, 2013, 5:1374-1394). The herpes virus, which is responsible for Kaposi's sarcoma, also interacts with various BET proteins, which is important for disease survival (Viejo-Borbolla et al., J. Virol., 2005, 79:13618-13629; You et al., J. Virol., 2006, 80:8909-8919).
Through binding to P-TEFb, BRD4 also plays an important role in the replication of HIV (Bisgrove et al., Proc. Natl.
Acad. Sci. USA, 2007, 104:13690-13695).
BET proteins are additionally involved in inflammation processes. BRD2-hypomorphic mice show reduced inflammation in adipose tissue (Wang et al., Biochem. J., 2009, 425:71-83). Infiltration of macrophages in white adipose tissue is also reduced in BRD2-deficient mice (Wang et al.,
- 3 -, Biochem. J., 2009, 425:71-83). It has also been shown that BRD4 regulates a number of genes involved in inflammation. In LPS-stimulated macrophages, a BRD4 inhibitor prevents the expression of inflammatory genes, for example IL-1 or IL-6 (Nicodeme et al., Nature, 2010, 468:1119-1123).
BET proteins also regulate the expression of the ApoAl gene which plays an important role in atherosclerosis and inflammatory processes (Chung et al., J. Med. Chem, 2011, 54:3827-3838).
Apolipoprotein Al (ApoAl) is a major component of high density lipoproteins (HDL), and increased expression of ApoAl leads to elevated blood cholesterol values (Degoma and Rader, Nat. Rev. Cardiol., 2011, 8:266-277). Elevated HDL values are associated with a reduced risk of atherosclerosis (Chapman et al., Eur. Heart J., 2011, 32:1345-1361).

-4_ Prior art The nomenclature employed in the assessment of the structural prior art is illustrated by the following figure:

2 \ l 4 is 6 --"N
4-phenyl-6H-thieno[3,2-j]- 6-pheny1-4H-isoxazolo-[5,4-a][1,4]diazepine d] [2]benzazepine 410 1 2 3N¨R3 Ar R6 R4 substituted 3-amino-2,3-dihydro-1H-1- substituted 3,5-dihydro-4H-2,3-ben7a7epin-2-ones benzodiazepin-4-ones
5 Based on the chemical structure, only very few types of BRD4 inhibitors have been described to date (Chun-Wa Chung et al., Progress in Medicinal Chemistry 2012, 51, 1-55).
The first published BRD4 inhibitors are phenylthienotriazolo-1,4-diazepines (4-pheny1-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepines) as described in W02009/084693 (Mitsubishi Tanabe Pharma Corporation) and as compound JQ1 in W02011/143669 (Dana Farber Cancer Institute). Replacement of the thieno moiety by a benzo moiety also leads to active inhibitors (J.
Med. Chem. 2011, 54, 3827 ¨ 3838; E. Nicodeme et al., Nature 2010, 468, 1119).
These and one further publication show that the pyrazole unit fused to the 1,4-benzodiazepine or thieno-1,4-diazepine ring system is actively involved in binding of the target protein BRD4 (P.
Filippakopoulos et al., Nature 2010, 468, 1067). Further 4-pheny1-6H-thieno[3,2-[1,2,4]triazolo[4,3-a][1,4]diazepines and related compounds having alternative rings as a fusion partner rather than the benzo unit are described both in a general manner and in some cases as examples in W02012/075456 (Constellation Pharmaceuticals). W02012/075383 (Constellation Pharmaceuticals) describes 6-substituted 4H-isoxazolo[5,4-d][2]benzazepines and 4H-isoxazolo[3,4-4[2]benzazepines, including compounds which have optionally substituted phenyl at position 6 as BRD4 inhibitors, and also analogues with alternative heterocyclic fusion partners rather than the benzo unit, for example thieno- or pyridoazepines.

Another structural class of BRD4 inhibitors described is that of 7-isoxazoloquinolines and related quinolone derivatives (W02011/054843, Bioorganic & Medicinal Chemistry Letters 22 (2012) 2963-2967, GlaxoSmithKline).
The compounds according to the invention are novel substituted phenyl-2,3-benzodiazepines (1-pheny1-4,5-dihydro-3H-2,3-benzodiazepines) which, inter alia, are not fused at the benzodiazepine skeleton to a second heterocyclic moiety, specifically an isoxazole or triazole, and are still, surprisingly, BET, in particular BRD4, inhibitors.
The compounds according to the invention differ from known 2,3-benzodiazepines which have been described as A_MPA receptor antagonists. Thus, US 5,536,832 / EP 0492485, US 5,639,751, US 5,459,137 (Gyogyszerkutato Intezet Kft) disclose substituted 1-phenyl-2,3-benzodiazepines which have a mandatory methylenedioxy bridge condensed to the benzo moiety of the benzodiazepine.
US 2004/0152693 / WO 2004/069197, US 2007/0027143 and HU 2004000338 (Sandor Solyom et al.) disclose substituted 1-phenyl-2,3-benzodiazepines which have a mandatory heterocyclic group as a substituent at the nitrogen in position 3. The exemplary compounds disclosed and the intermediates not having the abovementioned heterocyclic group at N-3 are substituted at the 1-phenyl group inter alia by -NH2, acetamido or nitro groups, but not by the ether, amide or substituted amino groups present in the compounds according to the invention.
HU 199700688 only describes 2,3-benzodiazepines in a very general manner as AMPA
antagonists, without disclosing any specific exemplary compounds.
The exemplary compounds disclosed in WO 1997/028135 (Schering AG), WO

(Annovis, Inc.) and EP 0802195 / US 5,807,851 (EGIS Gyogysergyar, Rt) have nitro or -NH2 groups at the 1-phenyl group, but not substituted amino groups or acylamines;
the ether, amino and amide substituents claimed in a generic manner likewise differ from the corresponding substituents in the compounds according to the invention.
The compounds according to the invention furthermore differ from the known psychopharmacological 1-pheny1-2,3-benzodiazepine derivatives which are inhibitors of the adenosine transporter and the MT2 receptor (W02008/124075, Teva Pharmaceutical Industries, Inc). The exemplary compounds disclosed therein are substituted at the 1-phenyl group inter alia by NH2- acetamido, methoxy or nitro groups, but not by the ether, amide or substituted amino groups present in the compounds according to the invention. The amino and amide substituents claimed in a generic manner also differ from the corresponding substituents in the compounds according to the invention.
- 6 W094/26718/EP0703222A1 (Yoshitomi Pharmaceutical Industries) describes substituted 3-amino-2,3-dihydro-1H-1-benzazepin-2-ones or the corresponding 2-thiones and analogues in which the benzo unit has been replaced by alternative monocyclic systems, and in which the 2-ketone or the 2-thione together with the substituted nitrogen atom in the azepine ring may form a heterocycle, as CCK and gastrin antagonists for the treatment of CNS disorders, such as states of anxiety and depression, and of pancreatic disorders and of gastrointestinal ulcers.
Ligands of the gastrin and the cholecystokinin receptor are described in W02006/051312 (James Black Foundation). They also include substituted 3,5-dihydro-4H-2,3-benzodiazepin-4-ones which differ from the compounds according to the invention mainly by the obligatory oxo group in position 4 and by an obligatory carbonyl group-containing alkyl chain in position 5.
Finally, substituted 3,5-dihydro-4H-2,3-benzodiazepin-4-ones are also described as AMPA
antagonists in W097/34878 (Cocensys Inc.). The generic claim is very wide with respect to the possible substitution patterns at the benzodiazepine skeleton; however, the working examples are limited to just a narrow range.
In spite of the multifarious compounds of the prior art, there is still a need for further highly effective compounds, and it is therefore desirable to provide novel compounds having prophylactic and therapeutic properties.
Accordingly, it is an object of the present invention to provide compounds and pharmaceutical compositions comprising these compounds used for prophylactic and therapeutic applications for hyperproliferative disorders, in particular for tumour disorders, and as BET
protein inhibitors for viral infections, for neurodegenerative disorders, for inflammatory disorders, for atherosclerotic disorders and for male fertility control.
The structurally most similar compounds of the prior art have not been disclosed in the context of the prophylaxis and therapy of tumour disorders.
From the prior art described above, there was no reason to modify the structures of the prior art such that structures suitable for the prophylaxis and therapy of neoplastic disorders are obtained.
Surprisingly, the compounds according to the invention inhibit the interaction between BET
proteins, in particular BRD4, and an acetylated histone 4 peptide and inhibit the growth of cancer cells. Accordingly, they provide novel useful and effective compounds for the therapy of human and animal disorders, in particular of cancers.
It has now been found that compounds of the general formula (I) , BHC123073FC
- 7 -, X
R5 14111 ¨N" R3 Ric elk Rla Rlb (I) in which X represents an oxygen or sulphur atom, Ria represents -0R6 or -NR71e, Rib and Ric independently of one another represent hydrogen, halogen, hydroxy, cyano, nitro or represent a C1-C6-alkyl, C1-C6-alkoxy, C1-C6-alkoxy-C1-C6-alkyl, halo-C1-C6-alkyl, halo-Ci-C6-alkoxy, C3-C10-cycloallcyl radical or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, le represents a C1-C3-alkyl or trifluoromethyl or a C3- or C4-cycloalkyl radical, R3 represents C1-C3-alkyl-, Ci-C3-alkoxy-, amino- or C1-C3-alkylamino-, R4 and le independently of one another represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent Ci-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or C1-C6-alkylaminosulphonyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-C1-C6-alkyl-, C1-C6-alkoxY-, Ci-C6-alkoxy-C1-C6-alkyl-, CI-C6-alkylamino-, amino-Ci-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by C1-C3-alkyl-, or represent C3-Circycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, Ci-C6-alkyl-, C1-C6-alkoxy-, Ci-C6-alkoxy-CI-C6-alkyl-, Cr-C6-allcylamino-, amino-Ci-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-Ci-C6-alkyl-, halo-C1-alkoxy- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be
- 8 mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, C1-alkoxy-, C1-C6-alkoxY-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, C1-C6-allcylamino-, amino-Ci-C6-alkyl-, C1-C6-allcylamino-CI-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, Ci-C6-alkyl-, C1-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-alkylamino-C1-C6-alkyl-, hydroxy-C,-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-Cio-cycloallcyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, Or represent phenyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, Ci-C6-alkyl-, Ci-C6-alkoxy-, Ci-C6-alkoxy-CI-C6-allcyl-, C1-C6-alkylamino-, amino-Ci-C6-alkyl-, Ci-C6-alkylaminocarbonyl-, C1-C6-alkylaminosulphonyl-, Ci-C6-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-a1lcy1-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R6 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by Ci-C6-alkylamino-, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, CI-C3-alkyl-, Ci-C3-alkylcarbonyl-, CI-Cr alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, fluoro-C1-C3-alkyl, hydroxy-Ci-C3-alkyl, C1-C3-alkoxy-, CI-C3-alkylamino-, amino-Ci-C3-alkyl-, C1-alkylaminocarbonyl-, Ci-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-allcylsulphonylamino-, Ci-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, or represents a benzyl radical, where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-allcyl, hydroxy-C1-C3-= BHC123073FC
- 9 alkyl, CI-C3-alkoxy-, CI -C3-alkylarnino-, amino-CI-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, CI-C3-alkylsulphonyl- and trifluoromethoxy-, and where the methylene group contained therein may optionally be substituted by a hydroxy group or one or two Ci-C3-alkyl groups, R7 represents C3-C7-cycloalkyl- or C2-C6-alkyl-monosubstituted by - RNR9 or represents a -C(=0)It'1 group, or represents a -S(=0)2R'2 group, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloallcyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-CI-C3-alkyl-and C3-C7-cycloalkyl-, Or represents a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, CI-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, Ci-C3-alkoxy-, CI-C3-alkylamino-, amino-CI-C3-alkyl-, C1-C3-alkylaminocarbonyl-, CI-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, CI-C3-allcylsulphonylamino-, C1-C3-alkylcarbonyl-, C,-C3-allcylsulphonyl- and trifluoromethoxy-, or represents fluoro-C1-C3-alkyl or CI-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and C1-C3-alkoxy-, represents hydrogen or CI-C6-alkyl, R9 and RI independently of one another represent hydrogen or Ci-C6-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, C1-C3-alkylcarbonyl-, Ci-C4alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-,
- 10 -Rii represents C3-C7-cycloalkyl- or CI-C6-alkyl- monosubstituted by - RNR9 or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-Cp-heterocycloalkyl radical, a C5-Cu-heterospirocycloalkyl radical or a C6-C12-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, CI-C4alkoxycarbonyl-, phenyl-Ci-C3-alkyl-and C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, CI-C3-alkyl, fluoro-CI-C3-alkyl, hydroxy-Ci-C3-alkyl, CI-C3-alkoxy-, CI-C3-alkylamino-, amino-C1-C3-alkyl-, C1-alkylaminocarbonyl-, CI-C3-alkylaminosulphonyl-, CI-C3-alkylcarbonylamino-, CI-C3-alkylsulphonylamino-, Ci-C3-alkylcarbonyl-, Ci-C3-alkylsulphonyl- and trifluoromethoxy-, and represents CI-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, carboxy, cyano, Ci-C6-alkoxy-, -NR91e, phenyl, a monocyclic heteroaryl radical having 5 or 6 ring atoms and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, where phenyl and the monocyclic heteroaryl radical having 5 or 6 ring atoms for their part may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, Ci-C3-alkyl, trifluoromethyl, Ci-C3-alkoxy- and trifluoromethoxy-, and in which the monocyclic heterocyclyl radical for its part may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, CI-C4-alkoxycarbonyl-, phenyl-Ci-C3-alkyl- and C3-C7-cycloalkyl-, Or represents fluoro-C1-C3-alkyl-, or represents C3-Clo-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, Ci-C3-alkyl-, Ci-C3-alkoxy- and -NR9RM, Or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-
- 11 -C17-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-Cir heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, Ci-C3-alkyl-, C1-C3-alkylcarbonyl-, Ci-C4-alkoxycarbonyl-, phenyl-Ci-C3-alkyl-and C3-C7-cycloalkyl-, or represents an aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, Ci-C3-alkyl, fluoro-Ci-C3-alkyl, hydroxy-C1-C3-alkyl, Ci-C3-alkoxy-, Ci-C3-alkylamino-, amino-Ci-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, Ci-C3-alkylcarbonylamino-, CI-C3-alkylsulphonylamino-, Ci-C3-alkylcarbonyl-, Ci-C3-alkylsulphonyl- and trifluoromethoxy-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts are particularly suitable for a large number of prophylactic and therapeutic applications, in particular for hyperproliferative disorders, for neoplastic disorders and as BET protein inhibitors for viral infections, for neurodegenerative disorders, for inflammatory disorders, for atherosclerotic disorders and for male fertility control.
- 12 -The invention is based on the following definitions:
Alkyl:
Alkyl represents a straight-chain or branched saturated monovalent hydrocarbon radical having generally 1 to 6 carbon atoms (C1-C6-alkyl), preferably 1 to 4 (C1-C4-alkyl), 2 to 4 (C2-C4-alkyl) or 1 to 3 carbon atoms (C1-C3-alkyl).
Preferred examples include:
methyl-, ethyl-, propyl-, butyl-, pentyl-, hexyl-, isopropyl-, isobutyl-, sec-butyl, tert-butyl-, isopentyl-, 2-methylbutyl-, 1-methylbutyl-, 1-ethylpropyl-, 1,2-dimethylpropyl, neopentyl-, 1,1-dimethylpropyl, 4-methylpentyI, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl-, 1,3-dimethylbutyl-, 1,2-dimethylbutyl-.
Particular preference is given to a methyl, ethyl, propyl, isopropyl or tert-butyl radical.
Very particular preference is given to a methyl radical.
Cycloalkyl:
Cycloalkyl represents a mono- or bicyclic saturated monovalent hydrocarbon radical having generally 3 to 10 (C3-Cio-cycloalkyl), preferably 3 to 8 (C3-C9-cycloalkyl) and particularly preferably 3 to 7 (C3-C7-cycloalkyl) carbon atoms.
Preferred examples of monocyclic cycloalkyl radicals include:
cyclopropyl-, cyclobutyl-, cyclopentyl-, cyclohexyl- and cycloheptyl-.
Particular preference is given to a cyclopropyl, cyclopentyl or cyclohexyl radical.
Examples of bicyclic cycloalkyl radicals include:
perhydropentalenyl-, decalinyl-.
Phenylalkyl:
Phenyl-Ci-C3-alkyl is understood to mean a group composed of an optionally substituted phenyl radical and a CI-C3-alkyl group, and bonded to the rest of the molecule via the Ci-C3-alkyl group. The alkyl radical here is as defined above under alkyl.
Examples include benzyl, phenethyl, phenylpropyl, particular preference being given to benzyl.
Alkoxy:
Alkoxy represents a straight-chain or branched saturated alkyl ether radical of the formula ¨0-alkyl having generally I to 6 (Ci-C6-alkoxy-), preferably 1 to 3 (C1-C3-alkoxy-) carbon atoms.
Preferred examples include:
methoxy-, ethoxy-, n-propoxy, isopropoxy-, tert-butoxy-, n-pentyloxy- and n-hexyloxy-.
- 13 -Alkoxyalkyl:
Alkoxyalkyl represents an alkyl radical which is substituted by alkoxy.
Here, C1-C6-alkoxy-C1-C6-alkyl- means that the bond to the remainder of the molecule is via the alkyl moiety.
Oxo:
Oxo, an oxo group or an oxo substituent, is understood to mean a double-bonded oxygen atom =0.
Oxo may be bonded to atoms of suitable valency, for example to a saturated carbon atom or to sulphur.
Preference is given to the bond to carbon with formation of a carbonyl group -C(r=0)- and to the bond of two double-bonded oxygen atoms to sulphur with formation of a sulphonyl group -(S=0)2-.
Allglamino:
Alkylamino represents an amino radical having one or two (independently selected) alkyl substituents having generally 1 to 6 (C1-C6-alkylamino) and preferably 1 to 3 (C1-C3-allcylamino) carbon atoms.
(C1-C3)-Alkylamino represents, for example, a monoalkylamino radical having 1 to 3 carbon atoms or a dialkylamino radical having 1 to 3 carbon atoms each per alkyl substituent.
Examples include:
methylamino-, ethylamino-, n-propylamino-, isopropylamino-, tert-butylamino-, n-pentylamino-, n-hexylamino-, N,N-dimethylamino-, N,N-diethylamino-, N-ethyl-N-methylamino-, N-methyl-N-n-propylamino-, N-isopropyl-N-n-propylamino-, N-tert-butyl-N-methylamino-, N-ethyl-N-n-pentylamino- and N-n-hexyl-N-methylamino-.
Particular preference is given to methylamino and N,N-dimethylamino-.
Alkvlaminocarbonyl:
Alkylaminocarbonyl represents the alkylamino-C(=0)¨ group having one or two (independently selected) alkyl substituents having generally 1 to 6 (Ci-C6-allcylaminocarbonyl-) and preferably 1 to 3 (C1-C3-alkylaminocarbonyl-) carbon atoms.
Aminocarbonvl:
Aminocarbonyl represents the group H2N-C(=0)¨.
Alkvicarbonyl:
Allcylcarbonyl represents the ¨C(=0)-alkyl group having generally 1 to 3 carbon atoms in the alkyl moiety.
Examples include acetyl- and propanoyl-. Preference is given to acetyl-.
- 14 Alkylcarbonylamino:
Alkylcarbonylamino represents the alkyl-C(=0)-NH¨ group having generally 1 to (C1-C6-alkylcarbonylamino-), preferably 1 to 3 carbon atoms in the alkyl moiety.
Alkoxycarbonyl:
Alkoxycarbonyl represents the ¨C(=0)-0-alkyl group having generally I to 6, preferably 1 to 4 carbon atoms in the alkyl moiety.
Examples include:
methoxycarbonyl-, ethoxycarbonyl-, propoxycarbonyl-, isopropoxycarbonyl-, tert-butoxycarbonyl, n-pentyloxycarbonyl- and n-hexyloxycarbonyl-.
Particular preference is given to tert-butoxycarbonyl-.
Alkylsulphonyl:
Alkylsulphonyl represents a straight-chain or branched saturated radical of the formula ¨S(=0)2-alkyl having generally 1 to 3 (C1-C3-alkylsulphonyl-) carbon atoms.
Preferred examples include:
methylsulphonyl-, ethylsulphonyl-, propylsulphonyl-.
Preference is given to methylsulphonyl-.
Alkylsulphonylamino:
Alkylsulphonylamino represents a straight-chain or branched saturated radical of the formula -NH¨

S(0)2-alkyl having generally 1 to 3 (Ci-C3-alkylsulphonylamino-) carbon atoms in the alkyl group.
Preferred examples include:
methylsulphonylamino-, ethylsulphonylamino-, propylsulphonylamino-.
Alkylaminosulphonyl:
Allcylaminosulphonyl represents the alkylamino-S(=--0)2¨ group having one or two (independently selected) alkyl substituents having generally 1 to 6 (C1-C6-alkylaminosulphonyl) and preferably 1 to 3 carbon atoms.
Preferred examples include:
methylaminosulphonyl-, ethylaminosulphonyl-, N,N-dimethylaminosulphonyl-.
Heteroatoms:
Heteroatoms are understood to mean oxygen, nitrogen or sulphur atoms.
Aryl An aryl radical or aryl- means a monovalent mono- or bicyclic aromatic ring system which consists
- 15 -..
of carbon atoms. Examples are naphthyl-, biphenyl- and phenyl-.
Preference is given to phenyl-.
Heteroaryl:
A heteroaryl radical or heteroaryl- means a monovalent mono- or bicyclic aromatic ring system having at least one heteroatom. The heteroatoms may be nitrogen atoms, oxygen atoms and/or sulphur atoms. The bonding valency may be located at any aromatic carbon atom or at a nitrogen atom.
A monocyclic heteroaryl radical according to the present invention has 5 or 6 ring atoms.
Heteroaryl radicals having 5 ring atoms include, for example, the following rings:
thienyl-, thiazolyl-, furyl-, pyrrolyl-, oxazolyl-, imidazolyl-, pyrazolyl-, isoxazolyl-, isothiazolyl-, oxadiazolyl-, triazolyl-, tetrazolyl- and thiadiazolyl-.
Heteroaryl radicals having 6 ring atoms include, for example, the following rings:
pyridyl-, pyridazinyl-, pyrimidinyl-, pyrazinyl- and triazinyl-.
A bicyclic heteroaryl radical in accordance with the present invention has 9 or 10 ring atoms.
Heteroaryl radicals having 9 ring atoms include, for example, the following rings:
phthalidyl-, thiophthalidyl-, indolyl-, isoindolyl-, indazolyl-, benzothiazolyl-, benzofuryl-, benzothienyl-, benzimidazolyl-, benzoxazolyl-, azocinyl-, indolizinyl-, purinyl-.
Heteroaryl radicals having 10 ring atoms include, for example, the following rings:
isoquinolinyl-, quinolinyl-, quinolizinyl-, quinazolinyl-, quinoxalinyl-, cinnolinyl-, phthalazinyl-, 1,7- and 1,8-naphthyridinyl-, pteridinyl-.
Monocvclic heterocyclyl:
Monocyclic heterocyclyl- or a monocyclic heterocyclyl radical means a non-aromatic monocyclic ring system having at least one heteroatom or a hetero group. The heteroatoms may be nitrogen atoms, oxygen atoms and/or sulphur atoms.
A monocyclic heterocyclyl ring according to the present invention may have 3 to 8, preferably 4 to 7, especially preferably 5 or 6 ring atoms.
Preferred examples of monocyclic heterocyclyl radicals having 3 ring atoms are as follows:
aziridinyl-.
Preferred examples of monocyclic heterocyclyl radicals having 4 ring atoms are as follows:
- 16 azetidinyl-, oxetanyl-.
Preferred examples of monocyclic heterocyclyl radicals having 5 ring atoms are as follows:
pyrrolidinyl-, imidazolidinyl-, pyrazolidinyl-, dioxolanyl- and tetrahydrofuranyl-.
Preferred examples of monocyclic heterocyclyl radicals having 6 ring atoms are as follows:
piperidinyl-, piperazinyl-, morpholinyl-, dioxanyl-, tetrahydropyranyl- and thiomorpholinyl-.
Preferred examples of monocyclic heterocyclyl radicals having 7 ring atoms are as follows:
azepanyl-, oxepanyl-, 1,3-diazepanyl-, 1,4-diazepanyl-.
Preferred examples of monocyclic heterocyclyl radicals having 8 ring atoms are as follows:
oxocanyl-, azocanyl-.
From among the monocyclic heterocyclyl radicals, preference is given to 4- to 7-membered saturated heterocyclyl radicals having up to two heteroatoms from the group consisting of 0, N and S.
Particular preference is given to morpholinyl-, piperidinyl-, piperazinyl- and pyrrolidinyl-.
Heterospirocycloalkyl:
C5-C12-Heterospirocycloalkyl- is to be understood as meaning a fusion of two saturated ring systems sharing a common atom, where C5-C12 denotes the number of ring members, where 1-4 carbon atoms are replaced by heteroatoms as defined above in any combination.
Examples are azaspiro[2.3]hexyl-, azaspiro[3.3]heptyl-, oxaa72spiro[3.3]heptyl-, thiaazaspiro[3.3]heptyl-, oxaspiro[3.3]heptyl-, oxazaspiro[3.5]nonyl-, oxazaspiro[3.4]octyl-, oxazaspiro[5.5]undecyl-, diazaspiro[3.3]heptyl-, thiazaspiro[3.3]heptyl-, thia72spiro[3.4]octyl-, azaspiro[5.5]decyl-, and the further homologous spiro[3.4]-, spiro[4.4]-, spiro[5.5]-, spiro[6.6]-, spiro[2.4]-, spiro[2.5]-, spiro[2.6]-, spiro[3.5]-, spiro[3.6]-, spiro[4.5]-, spiro[4.6]- and spiro[5.6]-systems in which 1-4 carbon atoms are replaced by heteroatoms. Preference is given to C6-C8-heterospirocycloalkyl-.
Bicycloalkyl and heterobicycloalkyl:
C5-C12-Heterobicycloallcyl- is to be understood as meaning a fusion of two saturated ring systems jointly sharing two directly adjacent atoms, where C6-C12 denotes the number of ring members, where 1-4 carbon atoms are replaced by heteroatoms as defined above in any combination.
Examples are systems derived from bicyclo[2.2.0]hexyl, bicyclo[3.3.0]octyl, bicyclo[4.4.0]clecyl, bicyclo[5.4.0]undecyl, bicyclo[3.2.0]heptyl, bicyclo[4.2.0]octyl, bicyclo[5.2.0]nonyl, bicyclo[6.2.0]decyl, bicyclo[4.3.0]nonyl, bicyclo[5.3.0]decyl, bicyclo[6.3.0]undecyl and bicyclo[5.4.0]undecyl in which 1-4 carbon atoms are replaced by heteroatoms, for example
- 17 -azabicyclo[3.3.0]octyl, azabicyclo[4.3.0]nonyl, diazabicyclo[4.3.0)nonyl, oxazabicyclo[4.3.0]nonyl, thia7abicyclo[4.3.0]nonyl or azabicyclo[4.4.0]decyl, and the further possible combinations as per the definition. Preference is given to C6-C10-heterobicycloalkyl.
Bridged heterocycloalkyl:
Bridged C6-C12-heterocycloalkyl- is to be understood as meaning a fusion of at least two saturated rings sharing two atoms which are not directly adjacent to one another, where C6-C12 denotes the number of ring members, and where 1-4 carbon atoms are replaced by heteroatoms as defined above in any combination. Examples are azabicyclo[2.2.1]heptyl-, oxazabicyclo[2.2.1]heptyl-, thiazabicyclo[2.2.1]heptyl-, diazabicyclo[2.2.1]heptyl-, azabicyclo[2.2.2]octyl-, dia7nbicyclo[2.2.2]octyl-, oxazabicyclo[2.2.2]octyl-, thiazabicyclo[2.2.2]octyl-, azabicyclo[3.2.1]octyl-, diazabicyclo[3.2.1]octyl-, oxazabicyclo[3.2.1]octyl-, thiazabicyclo[3.2.1]octyl-, azabicyclo[3.3.1]nonyl, diazabicyclo[3.3.1]nonyl-oxazabicyclo[3.3.1]nonyl-, thiazabicyclo[3.3.1]nonyl-, azabicyclo[4.2.1]nonyl-, diazabicyclo[4.2.1]nonyl-, oxazabicyclo[4.2.1]nonyl-, thiazabicyclo[4.2.1]nonyl-, a7abicyclo[3.3.2]decyl-, diazabicyclo[3.3.2]decyl-, oxazabicyclo[3.3.2]decyl-, thiazabicyclo[3.3.2]decyl- or azabicyclo[4.2.2]decyl- and the further possible combinations according to the definition. Preference is given to bridged C6-Cio-heterocycloalkyl-, by way of example and with particular preference azabicyclo[2.2.2]octyl-.
Halogen The term "halogen" includes fluorine, chlorine, bromine and iodine.
Preference is given to fluorine and chlorine.
Haloalkyl:
Haloalkyl represents an alkyl radical having at least one halogen substituent.
A halo-C1-C6-alkyl radical is an alkyl radical having 1-6 carbon atoms and at least one halogen substituent. If two or more halogen substituents are present, these may also be different from one another. Preference is given to fluoro-Ci-C3-alkyl radicals.
Preferred examples include:
the trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 4,4,5,5,5-pentafluoropentyl or 3,3,4,4,5,5,5-heptafluoropentyl group.
Particular preference is given to trifluoromethyl-.
Halogenalkoxy:
Haloalkoxy represents an alkoxy radical having at least one halogen substituent.
A halo-C1-C6-alkoxy radical is an alkoxy radical having 1-6 carbon atoms and at least one halogen substituent. If two or more halogen substituents are present, these may also be different from one . BHC123073FC
- 18 -,.
another. Preference is given to fluoro-C1-C3-alkoxy radicals.
Particularly preferred examples include:
trifluoromethoxy- or 2,2,2-trifluoroethoxy-.
Hydroxyalkyl:
Hydroxyalkyl represents an alkyl radical having at least one hydroxyl substituent A hydroxy-C1-C6-alkyl radical is an alkyl radical having 1-6 carbon atoms and at least one hydroxyl substituent Aminoalkyl:
Aminoalkyl represents an alkyl radical having at least one amino substituent An amino-C1-C6-alkyl radical is an alkyl radical having 1-6 carbon atoms and at least one amino substituent.
Alkylaminoalkyl:
Alkylaminoalkyl represents an alkyl radical having at least one alkylamino substituent.
A Ci-C6-alkylamino-C1-C6-alkyl radical is an alkyl radical having 1-6 carbon atoms and at least one C1-C6-alkylamino substituent as defined above.
Preference is given to those compounds of the general formula I in which X represents an oxygen atom, R1a represents -0R6 or -NR7R8, Rib and Ric independently of one another represent hydrogen, halogen, hydroxy, cyano, or represent a CI-C3-alkyl-, C1-C3-alkoxy-, fluoro-C1-C3-alkyl- or fluoro-C1-C3-alkoxy-radical, R2 represents methyl- or ethyl-, R3 represents Ci-C3-alkyl-, Ci-C3-alkoxy-, amino- or C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, Or represent C1-C6-alkyl-, Ci-C6-alkoxy-, Ci-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or Ci-C6-alkylaminosulphonyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-CI-C6-alkyl-, C1-C6-alkoxy-, CI-C6-alkoxy-Ci-C6-alkyl-, Ci-C6-alkylamino- or amino-C1-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by CI-C3-alkyl-,
- 19 or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, C1-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxY-, C3-C10-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, C1-C6-alkyl-, C1-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-Ci-C6-alkyl-, halo-C1-C6-alkoxy-, C3-Ci0-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R6 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by C1-C3-alkylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-alkoxycarbonyl-, benzyl- or C3-C7-cycloalkyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of CrC3-alkyl-, halogen and alkoxy-, or represents a benzyl radical, where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and C1-C3-alkoxy-, R7 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by -NR9R16, or represents a -C(=0)R11 group, Or represents a -S(-0)2R12 group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, Ci-C3-alkyl-, C1-C3-alkylcarbonyl-, benzyl- or CI-Cr alkoxycarbonyl-, = BHC123073FC
- 20 or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and alkoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and alkoxy-, R8 represents hydrogen or Ci-C3-alkyl, R9 and le independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, benzyl- or C1-C4-alkoxycarbonyl-, R" represents C3-C7-cycloallcyl- or C1-C6-alkyl-monosubstituted by -NR9R10 , Or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-Ci2-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, phenyl-Ci-C3-alkyl-or CI -C4-alkoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and alkoxy-, and R12 represents C1-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, Ci-C3-alkoxy-and -NR9R10 , or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, C1-C3-alkoxy- and -NR9R10 ,
- 21 or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkylcarbonyl-, CI-C4-alkoxycarbonyl-and phenyl-C1-C3-alkyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, CI-C3-alkyl- and alkoxy-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is given to those compounds of the general formula I in which X represents an oxygen atom, Rja represents -0R6 or -WIZ' and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, Ric represents hydrogen, R2 represents methyl-, R3 represents Ci-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R6 represents C2-C4-alkyl- monosubstituted by C1-C3-alkylamino-, Or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, or represents a benzyl radical where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9R10 ,
- 22 -, or represents a -C(=0)R" group, or represents a -S(=0)2R12 group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-, or represents fluoro-Ci-C3-alkyl or Ci-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine, R8 represents hydrogen or C1-C3-alkyl, R9 and 12.1 independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, R" represents CI-Ca-alkyl monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and Ri2 represents Ci-C3-alkyl-, or represents fluoro-Ci-C3-alkyl-,
- 23 -or represents C3-C7-cycloallcyl, which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, methyl-, ethyl-, methoxy-, ethoxy- and N,N-dimethylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, R'a represents -0R6 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, Ric represents hydrogen, R2 represents methyl-, represents C1-C3-alkylamino-, R4 and 12.5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, and R6 represents C2-C4-alkyl- monosubstituted by Ci-C3-alkylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, represents a benzyl radical where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group = BHC123073FC
- 24 -consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Ria represents -NleR8 and is located in the meta- or para-position with respect to the benzodiazepine, Rlb represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R represents hydrogen, represents methyl-, represents CI-C3-alkylamino-, R4 and le independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, represents a -C(=0)R11 group, R8 represents hydrogen or CI-C3-alkyl, R9 and Rm independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and R" represents Ci-C4-alkyl monosubstituted by -N-R9Rio, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-CI o-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to those compounds of the general formula I in which = BHC123073FC
- 25 -X represents an oxygen atom, R1a represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R1` represents hydrogen, R2 represents methyl-, represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R7 represents a -S(=0)2R12 group, R8 represents hydrogen or C1-C3-alkyl-, and represents C1-C3-alkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, methyl-, ethyl-, methoxy-, ethoxy- and N,N-dimethylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-Cio-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Ria represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-,
- 26 -Rlc represents hydrogen, R2 represents methyl-, represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R7 represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-, or represents fluoro-Ci-C3-alkyl or Ci-C3-allcyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine, R8 represents hydrogen or CI-C3-alkyl-, and R9 and le independently of one another represent hydrogen or C1-C3-alkyl-, Or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Very particular preference is given to those compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 or -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen or fluorine, Ric represents hydrogen, represents methyl-, = BHC123073FC
- 27 -R3 represents rnethylamino-, R4 and le independently of one another represent hydrogen, chlorine, methoxy or trifluoromethoxy, R6 represents N,N-dimethylaminoethyl-, or represents a monosubstituted monocyclic heterocyclyl radical selected from * __________________________ CN¨CH3 ( /N¨CH3 or represents a phenyl radical which may optionally be substituted by a fluorine atom, or represents a benzyl radical, represents N,N-dimethylaminoethyl- or N,N-dimethylaminopropyl-, or represents a -C(=-0)R11 group, or represents a -S(=0)2R12 group, or represents a radical selected from \ / __ \
/
C N¨ CH3 N\ /N ¨CH3 N N¨CH3 N¨ CH3 0 \ 0 * _______________________ C * __ ( N , CH3 , 0¨ tButyl CF:

or represents fluorophenyl-, pyridyl-, fluoropyridyl-, dimethyloxazolyl-, methylpyrazolyl-, methoxyoxadiazolyl-, pyridazinyl- or methylimidazolyl-, represents hydrogen or methyl, and R'' represents -CH2-NH(CH3), -CH2-N(CH3)2, methylpiperidinyl-, methylpyrrolyl-, thiadiazolyl-, or represents a radical selected from
- 28 -(N 0 /
* _______________________ ( \ N N/ 0 N N¨ CH3 / OtButyl \ __ /
\ _____________________________________________________________ /
where "*" in each case indicates the point of attachment to the remainder of the molecule, R12 represents methyl-, trifluoromethyl-, phenyl-, benzyl-, cyclopropyl-, tetrahydropyran-4-y1 or pyrid-3-y1-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Exceptional preference is given to those compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 or -Nlele and is located in the para-position with respect to the benzodiazepine, Rib and Ri c represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents hydrogen or methoxy-, represents methoxy- or trifluoromethoxy-, R6 represents C2-C4-alkyl- which is monosubstituted by CI-C3-alkylamino- or represents a monocyclic heterocyclyl radical having 6 ring atoms which may optionally be monosubstituted by methyl-, R7 represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -, or represents a -C(=0)R11 group, or represents a -S(=0)2R12 group, or represents a monocyclic heterocyclyl radical having 6 ring atoms or represents azabicyclo[2.2.2]oct-3-y1-, where the radicals mentioned may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or
- 29 -different substituents from the group consisting of methyl-, fluoro or methoxy-, R8 represents hydrogen or methyl-, R9 and R1 independently of one another represent hydrogen or CI-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, RH
represents C1-C2-alkyl monosubstituted by -NR9R10 , or represents a monocyclic heterocyclyl radical having 5 or 6 ring atoms which may optionally be monosubstituted by methyl-, benzyl-, acetyl- or tert-butoxycarbonyl-, and represents Ci-C3-alkyl, fluoro-Ci-C3-alkyl- or C3-C7-cycloalkyl-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl or tert-butoxycarbonyl-, or represents a phenyl or pyridyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 and is located in the para-position with respect to the benzodiazepine, Rib and RI c represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents methoxy-, R5 represents methoxy-, and R6 represents C2-C4-allcyl- which is monosubstituted by CI-C3-alkylamino- or represents a monocyclic heterocyclyl radical having 6 ring atoms which may optionally be . BHC123073FC
- 30 -, monosubstituted by methyl-, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to 11.2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Rla represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rlb and Rle represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents methoxy-, R5 represents methoxy-, R7 represents a -C(=0)R1' group, or represents a -S(=0)2R12 group, R8 represents hydrogen, R9 and 11.1 independently of one another represent hydrogen or Cl-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, represents C1-C2-alkyl monosubstituted by -NR R9 io, or represents a monocyclic heterocyclyl radical having 5 or 6 ring atoms which may optionally be monosubstituted by methyl-, benzyl-, acetyl- or tert-butoxycarbonyl-, and R12 represents CI-C3-alkyl, fluoro-Ci-C3-alkyl- or C3-C7-cycloalkyl-, represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl or tert-butoxycarbonyl-, or represents a phenyl or pyridyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting
- 31 -, of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Rla represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rib and R lc represent hydrogen, R2 represents methyl-, le represents methylamino-, R4 represents hydrogen or methoxy-, R5 represents methoxy- or trifluoromethoxy-, represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9R10 , or represents a monocyclic heterocyclyl radical having 6 ring atoms or represents azabicyclo[2.2.2]oct-3-y1-, where the radicals mentioned may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, fluoro or methoxy-, R8 represents hydrogen or methyl, and R9 and RI independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
- 32 Exceptional preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Rla represents -0R6 or -NR7R8 and is located in the para-position with respect to the benzodiazepine, RH' and R1c represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents hydrogen or methoxy-, R5 represents methoxy- or trifluoromethoxy-, R6 represents a radical selected from ( 7¨CH3 CH
\CH3 R7 represents a radical selected from / \
/N¨CH3 .-0¨N N¨CH, \ ______________________________________________ /
CH

CH3 , or represents a -C(=0)R" group, or represents a -S(=0)2R12 group, or represents a radical selected from (k) = _______________________________________ ( 7¨CH3 CH,CN
0 ' N
or represents a radical selected from ' BHC123073FC
-33..

\
H,C
NN .¨ m ,CH, \
* _____________________ u *--- 1 --N
, N" ' *--___, 1 z_N
-- N
*% ____________________________________________________________ ? , H3C¨O
F
N
* /= , * \\
____,si , . ____ _ \ _ \
/7N , *---C ,!`l N ' F F
* , N¨N
or represents the radical F F
F
*
.CH3 / N
/
R8 represents hydrogen or methyl, and R" represents a radical selected from ,CH, N¨CH, N
*_./ N
, or represents a radical selected from _______________________________________________________________ III
* ( )N¨CH, , * ( )N¨CH,/NH , \/\
CH, ( _______________________________________ \ p (CH, * N CH,
- 34 -, where "*" in each case indicates the point of attachment to the remainder of the molecule, represents methyl-, trifluoromethyl-, phenyl-, benzyl-, cyclopropyl-, tetrahydropyran-4-y1 or pyrid-3-y1-, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 and is located in the para-position with respect to the benzodiazepine, Rib and R lc represent hydrogen, represents methyl-, R3 represents methylamino-, R4 represents methoxy-, R5 represents methoxy-, and R6 represents a radical selected from CH
*_<\7¨CH3 N/ 3 CH, where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those compounds of the general formula I in which X represents an oxygen atom, Rla represents -INFIele and is located in the para-position with respect to the benzodiazepine,
- 35 -Rib and R lc represent hydrogen, R2 represents methyl-, represents methylamino-, R4 represents methoxy-, R5 represents methoxy-, R7 represents a -C(---0)R11 group, or represents a -S(=0)2R12 group, R8 represents hydrogen, R13 represents a radical selected from CH, i0) H3C, or represents a radical selected from = ( /N¨CH, NH N
CH, 0 ( CH, = (/N CH, and R12 represents methyl-, trifluoromethyl-, phenyl-, benzyl-, cyclopropyl-, tetrahydropyran-4-y1 or pyrid-3-y1-, where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those compounds of the general formula I in which
- 36 -X represents an oxygen atom, Rla represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, leb and R 1c represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents hydrogen or methoxy-, R5 represents methoxy- or trifluoromethoxy-, R7 represents a radical selected from / \
/ ______________________ NI\ 7¨CH3 /
N¨CH3 CH, or represents a radical selected from _______________________ p¨CH, _______ CH3 * __ <\/6 0 ' N
or represents a radical selected from 3 \ H 3C
N¨ ,CH3 * *
/
I
N"

N-* N /_N
111 * F __ * ___________________________________________________ ' H3C¨
* * * * __ C
N ' N
*
N¨N
or represents the radical
- 37 -F F
CH

and represents hydrogen or methyl-, where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
A subgroup of compounds of the general formula I are those in which X represents an oxygen or sulphur atom, Ria represents -OR' or -NR7R8, Rib and R'' independently of one another represent hydrogen, halogen, hydroxy, cyano, nitro or represent a C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl radical or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R2 represents a C1-C3-alkyl or trifluoromethyl or a C3- or Crcycloalkyl radical, R3 represents C3-C3-alkyl-, C1-C3-alkoxy-, amino- or C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent C1-C6-alkyl-, CI-C6-alkoxy-, Ci-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or C1-C6-alkylaminosulphonyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-Ci-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by C1-C3-alkyl,
- 38 -or represent C3-C10-cycloallcyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-CI-C6-alkyl-, halo-C1-alkoxy- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, Ci-C6-alkyl-, Ci-alkoxy-, Ci-C6-alkoxy-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, Ci-C6-alkylamino-, amino-Ci-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-Ci-C6-alkyl-, halo-CI-C6-alkoxY-, C3-Clo-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, C1-C6-alkyl-, C1-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-Ci-C6-alkyl-, C1-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-Ci0-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent phenyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, Cj-C6-alkoxy-, C,-C6-alkoxy-Ci-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylaminocarbonyl-, Ci-C6-alkylaminosulphonyl-, Ci-C6-alkylamino-Ci-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-Ci-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R6 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by C1-C6-alkylamino-, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, CI-C3-alkyl-, Ci-C3-allcylcarbonyl-, C1-alkoxycarbonyl-, phenyl-Ci-C3-alkyl- or C3-C7-cycloallcyl-, or represents a mono- or bicyclic aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, Ci-C3-alkyl, fluoro-Ci-C3-alkyl, hydroxy-Ci-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-Ci-C3-alkyl-, C1-, BHC123073FC
,
- 39 -alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, R7 represents C3-C7-cycloalkyl- or C2-C6-alkyl-monosubstituted by -NR9R10 , or represents a -C(=0)RI I group, or represents a -S(=0)2RI2 group, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C,2-heterospirocycloalkyl radical or a C6-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, CI-C3-alkyl-, CI -C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-Ci-C3-alkyl-and C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-Ci-C3-alkyl, hydroxy-C1-C3-alkyl, Ci-C3-alkoxy-, CI-C3-alkylamino-, amino-C1-C3-alkyl-, CI-C3-allcylaminocarbonyl-, C1-C3-allcylaminosulphonyl-, CI-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, CI-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, or represents fluoro-Ci-C3-alkyl or CI-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of CI-C3-alkyl-, halogen and CI-C3-alkoxY-, R8 represents hydrogen or Ci-C6-alkyl, R9 and RI independently of one another represent hydrogen or Ci-C6-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, Ci-C4-alkoxycarbonyl-, phenyl-Ci-C3-alkyl- or C3-C7-cycloallcyl-, R11 represents C3-C7-cycloalkyl- or C,-C6-alkyl-monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-. BHC123073FC
.
- 40 -C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, CI-C4-alkoxycarbonyl-, phenyl-Ci-C3-alkyl-and C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, Ci-C3-alkyl, fluoro-Ci-C3-alkyl, 1 0 hydroxy-Ci-C3-allcyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-CI-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, CI
-C3-alkylsulphonylamino-, Ci-C3-alkylcarbonyl-, Ci-C3-alkylsulphonyl- and trifluoromethoxy-, and R12 represents Ci-C6-alkyl- which may optionally be mono-or disubstituted by identical or 1 5 different substituents from the group consisting of halogen, hydroxy, carboxy, cyano, C1-C6-alkoxy-, -N11.1 R11, phenyl, a monocyclic heteroaryl radical having 5 or 6 ring atoms or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, where phenyl and the monocyclic heteroaryl radical having 5 or 6 ring atoms for 20 their part may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, Ci-C3-alkyl, trifluoromethyl, C1-C3-alkoxy- and trifluoromethoxy-, and in which the monocyclic heterocyclyl radical for its part may optionally be mono- or 25 disubstituted by identical or different substituents from the group consisting of oxo, Cj-C3-alkyl-, CI-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-Ci-C3-alkyl- and C3-C7-cycloalkyl-, or represents C3-Cio-cycloalkyl- which may optionally be mono- or polysubstituted by 30 identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, C1-C3-alkoxy- and -NR10R1 I, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-35 heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-CI-C3-allcyl-and C3-C7-cycloalkyl-,
- 41 or represents an aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, Ci-C3-alkoxy-, C1-C3-allcylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-allcylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
A further subgroup thereof are those compounds of the general formula I in which X represents an oxygen atom, R1a represents -0R6 or -Nlele, RI6 and RI' independently of one another represent hydrogen, halogen, hydroxy, cyano, or represent a Ci-C3-alkyl-, C1-C3-alkoxy-, fluoro-C1-C3-alkyl- or fluoro-C1-C3-alkoxy-radical, represents methyl- or ethyl-, le represents Ci-C3-alkyl-, C1-C3-alkoxy-, amino- or Ci-C3-alkylamino-, R4 and le independently of one another represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent Ci-C6-alkyl-, C1-C6-alkoxy-, CI-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or C1-C6-alkylaminosulphonyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-Ci-C6-alkyl-, C1-C6-alkoxy-Ci-C6-alkyl-, CI-C6-alkylamino- or amino-Ci-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by Ci-C3-alkyl, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkoxy-, Ci-C6-alkoxy-Ci-C6-alkyl-, hydroxy-Ci-C6-alkyl-, Ci-C6-alkylamino-, amino-Ci-C6-alkyl-, Ci-C6-alkylamino-Ci-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-Cio-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, ' BHC123073FC
- 42 -, or represent monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, C1-C6-alkyl-, C1-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, CI-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-Cio-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R6 represents C3-C7-cycloallcyl- or C2-C6-alkyl-monosubstituted by C1-C3-alkylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, Ci-C3-alkylcarbonyl-, C1-alkoxycarbonyl-, benzyl- or C3-C7-cycloallcyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and alkoxy-, R7 represents C3-C7-cycloalkyl- or C2-C6-alkyl-monosubstituted by -NR9R10 , or represents a -C(=0)R" group, or represents a -S(=0)2R12 group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkyl-, CI-C3-alkylcarbonyl-, benzyl- or CI-C4-alkoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and alkoxy-, or represents fluoro-C1-C3-alkyl or Ci-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of CI-C3-alkyl-, halogen and CI-C3-alkoxy-, R8 represents hydrogen or CI-C3-alkyl,
- 43 -R9 and le independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, C1-C3-alkylcarbonyl-, benzyl- or Ci-C4-alkoxycarbonyl-, R" represents C3-C7-cycloallcyl- or CI-C6-alkyl- monosubstituted by -NR9R16, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, Ci-C3-alkyl-, Ci-C3-allcylcarbonyl-, phenyl-Ci-C3-alkyl- or C1-C4-alkoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and alkoxy-, and represents Ci-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, C1-C3-alkoxy-and -NR10R11, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Also of interest are subgroups of the general formula I in which X represents an oxygen atom, Rla represents -0R6 or -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R16 represents hydrogen, R2 represents methyl-, represents C,-C3-alkylamino-, R4 and le independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C,-C3-alkoxy-, fluoro-Ci-C3-alkoxy-, R6 represents C2-C4-alkyl- which is monosubstituted by C,-C3-alkylamino- or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-,
- 44 or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, R.' represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9Rio, or represents a -C(=0)R11 group, or represents a -S(=0)2R12 group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine, R8 represents hydrogen or CI-C3-alkyl, R9 and R1 independently of one another represent hydrogen or Ci-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, R."
represents CI-Ca-alkyl monosubstituted by -NR9RIO, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or
- 45 different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and represents C1-C3-alkyl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Rla represents -0R6 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, Ric represents hydrogen, R2 represents methyl-, R3 represents CI-C3-allcylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R6 represents C2-C4-allcyl- which is monosubstituted by C1-C3-allcylamino- or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, R9 and R1 independently of one another represent hydrogen or Ci-C3-allcyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to those subgroups of compounds of the general formula I in which .
- 46 -X represents an oxygen atom, Rla represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, RIb represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, RIC represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and le independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-CI-C3-alkoxy-, represents a -C(=O)R11 group, R8 represents hydrogen or C1-C3-alkyl, R9 and RI independently of one another represent hydrogen or Ci-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and R" represents Ci-C4-alkyl monosubstituted by -NR9R10 , or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6' C10-heterocycloallcyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particular preference is furthermore given to a subgroup of compounds of the general formula I in which X represents an oxygen atom, RI.
represents -N12.71t8 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, . BHC123073FC
. - 47 -R1` represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, Ci-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R7 represents a -S(=0)2R12 group, R8 represents hydrogen or C1-C3-alkyl, R9 and le independently of one another represent hydrogen or Ci-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and R12 represents C1-C3-alkyl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Particularly preferred subgroups are furthermore those compounds of the general formula I in which X represents an oxygen atom, Rla represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, Rib represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, Ric represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and le independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, Ci-C3-alkoxy-, fluoro-Ci-C3-alkoxy-, le represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR91e, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-Ci0-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, . BHC123073FC
-, - 48 -bromine, methoxy and ethoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine, R8 represents hydrogen or C1-C3-alkyl-, and R9 and It'9 independently of one another represent hydrogen or Ci-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Very particular preference is given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 or -NR7R8 and is located in the meta-or para-position with respect to the benzodiazepine, RI b represents hydrogen or fluorine, Rk represents hydrogen, , R2 represents methyl-, R3 represents methylamino-, R4 and R5 independently of one another represent hydrogen, chlorine, methoxy or trifluoromethoxy, R6 represents NN-dimethylaminoethyl-, or represents a monosubstituted monocyclic heterocyclyl radical selected from * _______________________________ C N¨CH3N¨CH
\
* _____________________________________________________ ( 3 or represents a phenyl radical which may optionally be substituted by a fluorine atom, R7 represents N,N-dimethylaminoethyl- or N,N-dimethylaminopropyl-, or represents a -C(=0)R" group, or represents a -S(=0)2CH3 group, or represents a radical selected from / \\
/
N- CH, / __________________________ N __ /N- CH3 *--0---N N- CH3 __ * ( N -CH, , *
*¨( 0 CF, \/b * ___________ CN 04 * < __________________________________________ \/ ) CH, , 0¨ tButyl H,C
or represents fluorophenyl-, pyridyl-, fluoropyridyl-, dimethyloxazoly1-, methylpyrazolyl-, methoxyoxadiazolyl-, pyridazinyl- or methylimidazolyl-, R8 represents hydrogen or methyl, and R" represents -CH2-NH(CH3), -CH2-N(CH3)2, rnethylpiperidinyl-, methylpyrrolyl-, thiadiazolyl-, or represents a radical selected from * = 0 * ________________________________________ \N¨ CH
"N zr--N 0 / 3 OtButyl \ __ /
\ ___________________________________________________________________ where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
Exceptional preference is given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Rla represents -0R6 or -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents hydrogen or methoxy-, represents methoxy- or trifluoromethoxy-, R6 represents C2-C4-alkyl- which is monosubstituted by CI-C3-alkylamino- or represents a monocyclic heterocyclyl radical having 6 ring atoms which may optionally be monosubstituted by methyl-, represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9R10 , or represents a -C(=0)RI group, or represents a -S(=0)2R'2 group, or represents a monocyclic heterocyclyl radical having 6 ring atoms or represents azabicyclo[2.2.2]oct-3-y1-, where the radicals mentioned may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, fluor or methoxy-, R8 represents hydrogen or methyl-, R9 and le independently of one another represent hydrogen or Ci-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, R" represents Cl-C2-alkyl monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 5 or 6 ring atoms which may optionally be monosubstituted by methyl-, benzyl-, acetyl- or tert-butoxycarbonyl-, and R'2 represents CI-C3-alkyl, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.

Exceptional preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents methoxy-, R5 represents methoxy-, R6 represents C2-C4-alkyl- which is monosubstituted by C1-C3-allcylamino- or represents a monocyclic heterocyclyl radical having 6 ring atoms which may optionally be monosubstituted by methyl-, and R9 and RI independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Ria represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents methoxy-, represents methoxy-, R7 represents a -C(-0)R11 group, or represents a -S(=0)2R12 group, R8 represents hydrogen, *

, R9 and R1 independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, and Rn represents C1-C7-alkyl monosubstituted by -NR
9R10, or represents a monocyclic heterocyclyl radical having 5 or 6 ring atoms which may optionally be monosubstituted by methyl-, benzyl-, acetyl- or tert-butoxycarbonyl-, and R12 is Ci-C3-alkyl;
and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Rla represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 represents hydrogen or methoxy-, 12. represents methoxy- or trifluoromethoxy-, R7 represents C3-C7-cycloalkyl- or C2-C4-alkyl-monosubstituted by -NR9R10 , or represents a monocyclic heterocyclyl radical having 6 ring atoms or represents azabicyclo[2.2.2]oct-3-y1-, where the radicals mentioned may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, fluoro or methoxy-, R8 represents hydrogen or methyl, and R9 and le independently of one another represent hydrogen or C1-C3-alkyl-, Or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those subgroups of compounds of the general formula 1 in which X represents an oxygen atom, Ria represents -0R6 or -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, R2 represents methyl-, R3 represents methylamino-, represents hydrogen or methoxy-, R5 represents methoxy- or trifluoromethoxy-, R6 represents a radical selected from CH
( /N¨CH, \ __ NI 3 represents a radical selected from / \
7¨CH3 \N¨CH, \ ______________________________________________ /
,CH, N\
CH, , or represents a -C(=0)R11 group, or represents a radical selected from , , CH3 _______________________________________________________ *-( \ C
N-CH, * N
or represents a radical selected from H 3C\

N.- N,... ,CH, 3 \
___________________________________________________________________ ?
* _________________________ Ul , _ 11 N-...,.
*
*-i l ---N
N---H,C
N._ F

* ___________________________ / 1 --N , * 4/1 * 40 F . _____________________________________________________ c) , , H,C-C) F
* N
____1 _________________________ ) /
*-- *
/7 , *
_____________________________________________________________ N ' F F
* µ , N-N
or represents the radical F F
F
*
,CH, / N
/
R8 represents hydrogen or methyl, and R" represents a radical selected from CH, 0 Ni H,C
N-CH, N--) _____/ N
õ
, or represents a radical selected from ( 7¨CH3 (\ NH
/ ' ( CH, \ 0 ( CH, 7,1¨ CH3 o where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Ria represents -0R6 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, represents methyl-, R3 represents methylamino-, R4 represents methoxy-, R5 represents methoxy-, and R6 represents a radical selected from \_ CH3 * 7¨CH, where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.

Exceptional preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, Ria represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, R and R1c represent hydrogen, R2 represents methyl-, le represents methylamino-, R4 represents methoxy-, represents methoxy-, 12.2 represents a -C(=0)RI I group, or represents a -S(----0)2R12 group, R8 represents hydrogen, represents a radical selected from 0\
H3C\
N¨CH3 ' or represents a radical selected from N¨CH3 NH ' \N
/

0 __ CH, and represents methyl-, where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
Exceptional preference is furthermore given to those subgroups of compounds of the general formula I in which X represents an oxygen atom, RI a represents -NR7R8 and is located in the para-position with respect to the benzodiazepine, Rib and Ric represent hydrogen, represents methyl-, R3 represents methylamino-, R4 represents hydrogen or methoxy-, R5 represents methoxy- or trifluoromethoxy-, le represents a radical selected from \
/¨N\ /N¨CH3 \N¨CH, /
CH, \
CH, , OT
represents a -C(=0)R11 group, or represents a radical selected from CH
\N¨CH3 CN

or represents a radical selected from \ H C
,CF13 3 \
* ________________ SI , * 11 N, * I * __ N"--- ' N-... F

*1___I 1 --N , * , . = F, * _______ c¨N_? , H3C ¨
F
N
* *
* N * ____ K /N
F F
* , N¨N
or represents the radical F F
F
/ N
/
and R8 represents hydrogen or methyl-, where "*" in each case indicates the point of attachment to the remainder of the molecule, and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts, with the proviso that the stereocentre represented by the carbon atom, attached to R2, of the benzodiazepine skeleton is present either in racemic form or predominantly or completely in the (S) configuration.
The following compounds are of interest:
- ( )-7,8-dimethoxy-N,4-dimethy1-1-{4-[(1-methylpiperidin-4-yDamino]phenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4.9-7,8-dimethoxy-N,4-dimethy1-1-{4-[(1-methylpiperidin-4-yDamino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3-earboxamide, - (4R)-7,8-dimethoxy-N,4-dimethy1-1- {4-[(1-methylpiperidin-4-y0amino]phenyll -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1- { 4-[methyl(pyridin-3-yDamino]phenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-{4-[(2-fluorophenyl)amino]phenyl } -7,8-dimethoxy-N,4-di methy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4R)-1-{4-[(2-fluorophenypamino]phenyll -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodi azepine-3 -carboxami de, - (4S)-1- {4-[(2-fl uorophenypamino]phenyll-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1- {4-[(3,5-dimethylisoxazol-4-yDamino]phenyl 1 -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4R)-1- {4-[(3,5-dimethyli soxazol-4-yDamino]phenyl 1 -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1- {4-[(3,5-dimethylisoxazol-4-yDamino]phenyl } -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-1-(4-{ [2-(dimethylamino)ethyl] amino { pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-(4-{ [2-(dimethylamino)ethyl]amino{ pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-14-[(4-fluorophenypmethylamino]phenyll -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1-{4-[(1-methyl-1H-pyrazol-5-yDamino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4R)-7,8-dimethoxy-N,4-dimethy1-1- {4-[(1-methy1-1H-pyrazol-5-y0amino]phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethy1-1- 14-[(1-methy1-1H-pyrazol-5-yflamino]phenyll -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-1-[4-(1-azabicyclo[2.2.2]oct-3-ylamino)pheny1]-7,8-dimethoxy-N,4-dimethyl-4,5-=

=
dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (45)-144-(1-azabicycl o [2.2.2] oct-3-ylamino)pheny1]-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-1- {4-[(4-methoxy-1,2,5-oxadi azol-3-yDamino]phenyll-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-1- {4-[(4-methoxy-1,2,5-oxadiazol-3-yDamino]phenyl } -N,4-dimethyl-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - (4S)-7,8-dimethoxy-1- {4-[(4-methoxy-1,2,5-oxadi azol-3-yDamino]phenyll-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-144-(pyridazin-4-ylamino)pheny1]-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-144-(pyridazin-3-ylamino)pheny1]-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {4-[methyl(1-methyl-1H-imidazol-2-yDamino]phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4R)-7,8-dimethoxy-N,4-dimethy1-1-14-[methyl(1-methyl-1H-imidazol-2-yl)amino]phenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4,5)-7,8-dimethoxy-N,4-dimethy1-1-{4-[methyl(1-methyl-1H-imidazol-2-yDamino]phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1 -14-[(1-methyl-1H-pyrazol-3-yDamino]pheny11-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4S)-7,8-dimethoxy-N,4-dimethy1-1- {4-[(1-methy1-1H-pyrazol-3-yDamino]phenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-1- {4[(2-fluoropyri din-3-y Daminolpheny11-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-{4-[(2-fluoropyridin-3-yDamino]phenyll-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1- {4- [(2-fluoropyri din-3-y Damino]pheny11-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-14-[(3-fluoropyridin-4-yDamino]phenyl -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-{4-[(3-fluoropyridin-2-yDamino]pheny11-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1- {4-[(3-fluoropyridin-2-yDamino]phenyl -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (45)-1-14-[(3-fluoropyri din-2-yDamino]pheny11-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [2,2,2-tri fluor-1-(1-methy1-1H-pyrrol-2-ypethyl] amino} phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1 -(4- { [2-(dimethylamino)ethyl] methylamino} pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (45)-144- [2-(dimethylamino)ethyl] methylamino} pheny1)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [2-(4-methylpiperazin-1-ypethyl]
amino} pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4S)-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [2-(4-methylpiperazin-1-ypethyl]amino pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {44methyl(1-methylpiperidin-4-yDamino]phenyll -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-di methyl-1- 14-[methyl(1-methylpiperidin-4-y Damino]phenyll-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - (45)-7,8-dimethoxy-N,4-di methyl-1- {4- [methyl(1-methylpiperi din-4-yDamino]phenyll-4,5-dihydro-3H-2,3-benzo diazepine-3-carboxami de, - ( )-tert-butyl 4-[ {4-[7,8-dimethoxy-4-methy1-3-(methylcarbamoy1)-4,5-dihydro-3H-2,3-benzodiazepin-l-yliphenyllmethylamino]piperidine-1-carboxylate, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {4-[(1-methyl azetidin-3-yl)aminolphenyl -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1- {4-[(1-acetylazeti din-3-y parnino]phenyl -7,8-dimethoxy-N,4-dimethy1-4, 5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [trans-4-(4-methylpiperazin-1-yl)cyclohexyl]amino pheny1)-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {3-[methyl(pyridin-3-yl)amino]phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-{3-[(1-methylpiperidin-4-yDamino]phenyl} -4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - ( )-1-(3-1[3-(dimethylamino)propylimethyl amino } -4-fluoropheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-(3- [2-(dimethylamino)ethyl]methylamino}-4-fluoropheny1)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-(4-{ [(dimethylamino)acetyl] amino } pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-(4-1[(dimethylamino)acetyl]amino} pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-(4- [(dimethylamino)acetyl]amino} pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [(1-methylpiperidin-4-yl)carbonyl]amino pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [(1-methylpiperi di n-4-yl)carbonyl]
amino} pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-dimethy1-1-(4-{[(1-methylpiperidin-4-yl)carbonyllamino}pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {4-[(piperi din-4-ylcarbonyl)amino]
phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1-14-[(morpholin-4-ylacetyl)amino]phenyl } -4,5-dihydro-3H-2,3-benzodi a zi-pine-3-carboxami de, - ( )-1-(4-{ [(1-benzylpiperidin-4-y Dcarbonyl] amino pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-(4- [(1-benzy lpiperidin-4-yl)carbonyl] amino pheny1)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - (4R)-1-(4- {[(1-benzylpiperidin-4-Acarbonyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (+)-7,8-dimethoxy-N,4-dimethy1-1-(4-1 methyl [(methylamino)acetyl]amino pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [(4-methylpiperazin-1-yDacetyl]aminol pheny1)-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - (4R)-7,8-dimethoxy-N,4-dimethy1-1-(4- [(4-methylpiperazin-1-ypacetyl]am i no } pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4S)-7,8-dimethoxy-N,4-dimethy1-1-(4-{[(4-methylpiperazin-1-y1)acetyllaminolpheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-tert-butyl 4-({447,8-dimethoxy-4-methy1-3-(methylcarbamoy1)-4,5-dihydro-3H-2,3-benzodiazi-pin-1-yl]phenylIcarbamoyDpiperidine-1-carboxylate, - (4S)-tert-butyl {447,8-dimethoxy-4-methy1-3-(methy lcarbamoy1)-4,5-di hydro-3H-2,3-benzodiazepin-1 -yl] phenyl } carbamoyl)piperidine-1-carboxyl ate, - (4R)-tert-butyl 4-({447,8-dimethov-4-methyl-3-(methylcarbamoy1)-4,5-dihydro-3H-2,3-benzodiazepin-1-yllphenyl} carbamoyl)piperidine-1-carboxyl ate, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {4-[(1-methylpiperidin-4-ypoxy]phenyl -4,5-dihydro-3H-2,3-benzo di azepine-3-carboxami de, - (45)-7,8-dimethoxy-N,4-dimethy1-1- { 4-[(1-methy lpiperi din-4-y Doxy]phenyll -4,5-di hydro-3H-2,3 -benzodi azepine-3 -carboxamide, - ( )-1- {4[2-(dimethyl am ino)ethoxylphenyll -7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1- {4[2-(dimethyl amino)ethoxy]phenyl I -7,8-di methoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - (4S)-1- {442-(dimethylamino)ethoxy]pheny1}-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-{4-[(1-methylazetidin-3-ypoxy]phenyll-4,5-dihydro-3H-2,3 -benzodiazepine-3-carboxami de, - (+)-7,8-dimethoxy-N,4-dimethy1-1-(4-phenoxypheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-144-(4-fluorophenoxy)pheny1]-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3 -carboxamide, - ( )-8-chloro-1- {4-[(2-fluoropyri din-3-yDamino]phenyl 1 -N,4-dimethy1-7-(trifluoromethoxy)-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-14-[methyl(1-methylpiperidin-4-yl)amino]phenyll-8-(tri fluoromethoxy)-4,5-dihydro-3H-2,3-benzodiazep ine-3-carboxami de, - (4S)-8-methoxy-N,4-dimethy1-1-(4-{ [(1-methy1-1H-pyrrol-2-ypcarbonyl]amino}pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (45)-8-methoxy-N,4-dimethy1-1- {4-[(1,2,3-thi adiazol-4-ylcarbonypamino]phenyl 1 -4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - ( )-1-(4-{ [(dimethylamino)acetyl] amino} pheny1)-8-methoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodia7epine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-{44(methyl sulphonyDamino]phenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethy1-1- {4-[(pyri din-3-y lsulphony Damino]pheny11-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxami de, - (4S)-7,8-dimethoxy-N,4-dimethy1-1- {4-[(tetrahydro-2H-pyran-4-ylsulphonyl)amino]phenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxami de, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {4-[methyl(methylsulphonyl)amino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1- {41(phenylsulphonyl)aminolphenyl 1 -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-{4-[(benzylsulphonyDamino]phenyll-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethy1-1-(4-{ [(trifluoromethypsulphonyl]
amino 1 pheny1)-4,5-dihydro-3H-2,3-benzo diazepine-3-carboxami de, - ( )-1-{44(cyclopropylsulphonyl)aminolpheny11-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-144-(berizyloxy)pheny1]-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1- {4-[(N,N-dimethylglycyl)(methyDamino] phenyl 1 -4-ethy1-7,8-dimethoxy-N-methy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide and - ( )-4-isopropy1-7,8-dimethoxy-N-methyl-1-14-[methyl(1-methyl-1H-imidazol-2-yDamino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide and their polymorphs, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
In the general formula (I), X may represent an oxygen or sulphur atom.
In the general formula (I), X preferably represents an oxygen atom.
In the general formula (I), Rla may represent -OR' or -NR7R8.
In the general formula (I), Rla preferably represents -OR'.
In the general formula (I), R." preferably represents -NR7R8.
In the general formula (I), R'" preferably represents hydrogen, halogen, hydroxy, cyano, or represents a C1-C3-alkyl-, C1-C3-alkoxy-, fluoro-C1-C3-alkyl- or fluoro-C1-C3-alkoxy radical.
In the general formula (I), RI" particularly preferably represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-.
In the general formula (I), RI" particularly preferably represents hydrogen, fluorine, chlorine, bromine or cyano.
In the general formula (I), RI" particularly preferably represents hydrogen, fluorine, methyl-, methoxy- or trifluoromethyl-.
In the general formula (I), Rth particularly preferably represents hydrogen, fluorine or chlorine.

In the general formula (I), Rib very particularly preferably represents hydrogen or fluorine.
In the general formula (I), Rib very particularly preferably represents hydrogen.
In the general formula (I), leb very particularly preferably represents fluorine.
In the general formula (I), Ric preferably represents hydrogen, halogen, hydroxy, cyano, or represents a C1-C3-alkyl-, C1-C3-alkoxy-, fluoro-C1-C3-alkyl- or fluoro-C1-C3-alkoxy radical.
In the general formula (I), RIC particularly preferably represents hydrogen.
In the general formula (I), R2 may represent a C1-C3-alkyl- or trifluoromethyl-or a C3- or C4-cycloalkyl radical.
In the general formula (I), R2 preferably represents methyl- or ethyl-.
In the general formula (I), R2 particularly preferably represents methyl-.
In the general formula (I), R3 may represent Ci-C3-alkyl-, C1-C3-alkoxy-, amino- or C1-C3-alkylamino-.
In the general formula (I), R3 particularly preferably represents CI-C3-alkylamino-.
In the general formula (I), R3 particularly preferably represents CI-C2-alkylamino-.
In the general formula (I), R3 very particularly preferably represents methylamino-.
In the general formula (I), R4 and le independently of one another may represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent C1-C6-alkyl-, C/-C6-alkoxy-, C1-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or Ci-C6-alkylaminosulphonyl- which may optionally be mono-or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-, Ci-C6-alkoxy-Ci-C6-alkyl-, C1-C6-allcylamino-, amino-C1-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by C1-C3-alkyl, or represent C3-C10-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1 amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-Ci-C6-alkyl-, halo-C1-C6-alkoxy- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, Ci-C6-alkoxy-, Ci-C6-alkoxy-Ci-C6-alkyl-, hydroxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-Ci-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-C1-C6-1 5 alkyl-, halo-Ci-C6-alkoxy-, C3-C10-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represents monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, C1-C6-alkyl-, CI -C6-alkoxy-, C1-C6-alkoxy-Ci-C6-alkyl-, CI-C6-alkylamino-, amino-Ci-C6-alkyl-, Ci-C6-alkylamino-Ci-C6-alkyl-, hydroxy-Ci-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represents phenyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, Ci-C6-alkoxy-, C1-C6-alkoxy-CI-C6-alkyl-, Ci-C6-alkylamino-, amino-CI-C6-alkyl-, C1-C6-allcylaminocarbonyl-, C1-C6-alkylaminosulphonyl-, CI-C6-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-Ci-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloallcyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms.
In the general formula (I), le and R5 independently of one another preferably represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent C1-C6-alkyl-, C1-C6-alkoxy-, Ci-C6-alkylamino-, Ci-C6-alkylcarbonylamino-, Ci-C6-alkylaminocarbonyl- or Ci-C6-alkylaminosulphonyl- which may optionally be mono-or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-CI-C6-alkyl-, Ci-C6-alkoxy-, Ci-C6-alkoxy-Ci-C6-alkyl-, C1-C6-allcylamino- or amino-C1-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by C1-C3-alkyl, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, CI-C6-alkyl-, Ci-C6-alkoxy-, Ci-C6-alkoxy-C1-C6-alkyl-, hydroxy-Ci-C6-alkyl-, C1-C6-allcylamino-, amino-Ci-C6-alkyl-, CI-C6-alkylamino-Ci-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-Cio-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represents monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, Ci-C6-alkyl-, Ci-C6-alkoxy-, Ci-C6-alkoxy-C1-C6-alkyl-, Ci-C6-allcylamino-, amino-Ci-C6-alkyl-, C1-C6-allcylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-Ci-C6-alkoxy-, C3-Cio-cycloallcyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms.
In the general formula (I), R4 and le independently of one another particularly preferably represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, Ci-C3-alkoxy-, fluoro-C1-C3-alkoxy-.
In the general formula (I), R4 particularly preferably represents hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-.
In the general formula (I), le particularly preferably represents hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, Ci-C3-alkoxy-, fluoro-CI-C3-alkoxy-.
In the general formula (I), R4 and le independently of one another very particularly preferably represent hydrogen, chlorine, methoxy- or trifluoromethoxy-.
In the general formula (I), R4 very particularly preferably represents hydrogen, chlorine, methoxy-or trifluoromethoxy-.
In the general formula (I), R5 very particularly preferably represents hydrogen, chlorine, methoxy-or trifluoromethoxy-.
In the general formula (I), R4 exceptionally preferably represents hydrogen or methoxy-.

In the general formula (I), R4 exceptionally preferably represents hydrogen.
In the general formula (I), R4 exceptionally preferably represents methoxy-.
In the general formula (I), R5 very particularly preferably represents methoxy-or trifluoromethoxy-.
In the general formula (I), R5 very particularly preferably represents methoxy-.
In the general formula (I), R5 very particularly preferably represents trifluoromethoxy-.
In the general formula (I), R6 may represent C3-C7-cycloalkyl- or C2-C6-alkyl-which is monosubstituted by C1-C6-alkylamino-, or a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-, or a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, Ci-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl-and trifluoromethoxy-.
In the general formula (I), R6 may also represent C3-C7-cycloalkyl- or C2-C6-alkyl- which is monosubstituted by CI-C6-alkylamino-, or a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, Ci-C4alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-, or a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-CI-C3-alkyl-, C1-C3-alkylaminocarbonyl-, CI-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, Ci-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl-and trifluoromethoxy-, or a benzyl radical, where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-Ci-C3-alkyl, hydroxy-C1-C3-alkyl,C1-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-allcylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-alkylcarbonylamino-, CrC3-allcylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, and where the methylene group contained therein may optionally be substituted by a hydroxy group or one or two Cl-C3-alkyl groups.
In the general formula (I), R6 preferably represents C3-C7-cycloalkyl- or C2-C6-alkyl- which is monosubstituted by CI-C3-alkylamino-, or represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, Ci-C4alkoxycarbonyl-, benzyl- or C3-C7-cycloalkyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and C1-C3-alkoxy-.
In the general formula (I), R6 furthermore preferably represents C3-C7-cycloallcyl- or C2-C6-alkyl-which is monosubstituted by C1-C3-alkylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, Ci-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, benzyl- or C3-C7-cycloalkyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of CrC3-alkyl-, halogen and Ci-C3-alkoxy-, or represents a benzyl radical, where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and Ci-C3-alkoxy-.
In the general formula (I), R6 particularly preferably represents C2-C4-alkyl-which is monosubstituted by Ci-C3-alkylamino- or represents a monocyclic heterocyclyl radical haying 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-.
In the general formula (I), R6 particularly preferably represents C2-C4-alkyl-which is monosubstituted by C1-C3-allcylamino- or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, or represents a benzyl radical where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-.
In the general formula (I), R6 particularly preferably represents C2-C4-alkyl-which is monosubstituted by Ci-C3-alkylamino- or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbony1-.
In the general formula (I), R6 particularly preferably represents C2-C4-alkyl which is monosubstituted by C1-C3-alkylamino-, In the general formula (I), R6 particularly preferably represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), R6 particularly preferably represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-.
In the general formula (I), R6 particularly preferably represents a benzyl radical where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-.
In the general formula (I), R6 very particularly preferably represents /V,N-dimethylaminoethyl-, or represents a monosubstituted heterocyclyl radical selected from * ________________________________ N¨CH3 * ( N¨CH3 where "*" in each case indicates the point of attachment to the remainder of the molecule, or represents a phenyl radical which may optionally be substituted by a fluorine atom.
In the general formula (I), R6 very particularly preferably represents /V,N-dimethylaminoethyl-or represents a monosubstituted heterocyclyl radical selected from * C N¨CH3* N¨CH

where "*" in each case indicates the point of attachment to the remainder of the molecule, or represents a phenyl radical which may optionally be substituted by a fluorine atom, or represents a benzyl radical.
In the general formula (I), le very particularly preferably represents N,N-dimethylaminoethyl-.
In the general formula (I), R6 very particularly preferably represents a monosubstituted heterocyclyl radical selected from * ________________________________ C N¨CH3* ( N¨CH

where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R6 very particularly preferably represents a phenyl radical which may optionally be substituted by a fluorine atom.
In the general formula (I), R6 very particularly preferably represents a benzyl radical.
In the general formula (I), R6 exceptionally preferably represents C2-C4-alkyl-which is monosubstituted by C1-C3-alkylamino- or represents a monocyclic heterocyclyl radical having 6 ring atoms which may optionally be monosubstituted by methyl-.

, In the general formula (I), R6 exceptionally preferably represents a monocyclic heterocyclyl radical having 6 ring atoms which may optionally be monosubstituted by methyl-.
In the general formula (I), R6 furthermore exceptionally preferably represents a radical selected from CH
( 7¨CH, 3 N
CH, where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R7 may represent C3-C7-cycloalkyl- or C2-C6-alkyl-which is monosubstituted by -NR9Rio, or represents a -C(0)R" group, or represents a -S(=0)2R12 group, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C)2-heterospirocycloalkyl radical or a C6-C12-heterobicycloallcyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl--, C1-C3-alkylcarbonyl-, CI-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- and C3-C7-cycloalkyl-, or a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, Ci-C3-alkyl, fluoro-CI-C3-aIkyl, hydroxy-Ci-C3-alkyl, C1-C3-alkoxy-, C1-C3-allcylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-allcylaminosulphonyl-, CI-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C,-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl-and trifluoromethoxy-, or represents fluoro-C1-C3-alkyl or Ci-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of CI-C3-alkyl-, halogen and CI-C3-alkoxy-.
In the general formula (I), le preferably represents C3-C7-cycloallcyl- or C2-C6-alkyl- which is monosubstituted by -NR9R1 , or represents a -C(=0)R11 group, or represents a -S(=0)2RI2 group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-Cu-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, benzyl- or CI-C4alkoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and CI-C3-alkoxy-, or represents fluoro-C1-C3-alkyl or CI-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and CI-C3-alkoxy-.
In the general formula (I), R7 preferably represents C3-C7-cycloalkyl- or C2-C6-alkyl- which is monosubstituted by -NR9R' .
In the general formula (I), R7 preferably represents a -C(=0)0RII group.
In the general formula (I), R7 preferably represents a -S(=0)2RI2 group.
In the general formula (I), R7 preferably represents a monocyclic heterocyclyl =radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloallql radical, where the radicals mentioned may optionally be monosubstituted by oxo, CI-C3-alkyl-, CI-C3-alkylcarbonyl-, benzyl- or CI-Cr-alkoxycarbonyl-.
In the general formula (I), R7 preferably represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono-or disubstituted by identical or different substituents from the group consisting of Ci-C3-allcyl-, halogen and CI-C3-alkoxy-.
In the general formula (I), R7 preferably represents fluoro-CI-C3-alkyl or CI-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-.
In the general formula (I), R7 particularly preferably represents C3-07-cycloalkyl- or C2-C4-alkyl-which is monosubstituted by -NR9R10 , or represents a -C(---0)R1' group, or represents a -S(=0)21C group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-Cio-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine.
In the general formula (I), R7 particularly preferably represents C3-C7-cycloalkyl- or C2-C4-alkyl-which is monosubstituted by -NR9RI .
In the general formula (I), R7 particularly preferably represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), le particularly preferably represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-.
In the general formula (I), le particularly preferably represents fluoro-C1-C3-alkyl or CI-C3-alkyl monosubstituted by a phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine.

In the general formula (I), It7 very particularly preferably represents /V,N-dimethylaminoethyl or /V,N-dimethylaminopropyl, or represents a -C(----0)R11 group, or represents a -S(---0)2R12 group, or represents a radical selected from = \ CN¨CH3 _________________ /¨N\ /N¨CH3 --0--N /N¨CH3 N¨ CH3 =
, \ , 7 \ \

, CF3 N
*-0 * __ CN - __ ( \N ) CH3 , / 0¨
tButyl , * N---/

where "*" in each case indicates the point of attachment to the remainder of the molecule, or represents fluorophenyl-, pyridyl-, fluoropyridyl-, dimethyloxazoly1-, methylpyrazolyl-, methoxyoxadiazolyl-, pyridazinyl- or methylimidazolyl-.
In the general formula (I), lee very particularly preferably represents N,N-dimethylaminoethyl- or N,N-dimethylaminopropyl-.
In the general formula (I), le very particularly preferably represents a radical selected from / \ / \
\
= ______________ * __ / / __________________ N CN CH, \ /N¨CH3 *-0---N
/N¨ CH3 , . 7 \
N¨CH3 , *---0 * CN __ * __ K \N / CF3 ) _____________________________________________________________ -0 N , CH3 , / 0¨ tButyl , - N--/
H3c where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), le very particularly preferably represents fluorophenyl-, pyridyl-, fluoropyridyl-, dimethyloxazolyl-, methylpyrazolyl-, methoxyoxadiazolyl-, pyridazinyl- or methylimidazolyl-.
In the general formula (I), le exceptionally preferably represents C3-C2-cycloalkyl- or C2-C4-alkyl-which is monosubstituted by -1\11ele , .
or represents a -C(=0)12.11 group, or represents a -S(=0)12.12 group, or represents a monocyclic heterocyclyl radical having 6 ring atoms or represents azabicyclo[2.2.2]oct-3-y1-, where the radicals mentioned may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, fluoro or methoxy-.
In the general formula (I), R7 exceptionally preferably represents a monocyclic heterocyclyl radical having 6 ring atoms or represents azabicyclo[2.2.2]oct-3-y1-, where the radicals mentioned may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), R.7 exceptionally preferably represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono-or disubstituted by identical or different substituents from the group consisting of methyl-, fluorine and methoxy-.
In the general formula (I), R7 furthermore exceptionally preferably represents a radical selected from \
N¨CH3\N¨CH3 / \ __ /
CH

f-N\

or represents a -C(--=0)R" group, Or represents a radical selected from ( CH3 '\/0 or N¨CH3 *
represents a radical selected from N ,CH3 3\
* ________________________________ I N
N"

N-* I
* 111 * 411 *
\
H3C ¨
*
* N /jµi N % N
*<N
or represents the radical F F
CH
= 3 where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R7 furthermore exceptionally preferably represents a radical selected from / \
/ ________________________________________ \
N\ 71¨CH3 N¨CH, /"--N\/

where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (1), R7 furthermore exceptionally preferably represents a radical selected from CH
* ______________ ( \N¨CH3 * _____ CN 3 * __ (\/0 where "*" in each case indicates the point of attachment to the remainder of the molecule.

In the general formula (I), R7 furthermore exceptionally preferably represents a radical selected from HC
N¨ CH3 I
N
N"

N-__________ 0 N
= ________________________________________ F
H3C ¨
¨
*
¨N
N ' N¨N
where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R7 furthermore exceptionally preferably represents a radical F F
,CH3 N
where "*" denotes the point of attachment to the remainder of the molecule.
In the general formula (I), R8 may represent hydrogen or C1-C6-alkyl-.
In the general formula (I), R8 preferably represents hydrogen or C1-C3-alkyl.
In the general formula (I), R8 particularly preferably represents hydrogen or C1-C2-alkyl.
In the general formula (I), R8 particularly preferably represents hydrogen.
In the general formula (I), R8 particularly preferably represents methyl-.
In the general formula (I), R8 particularly preferably represents ethyl-.

In the general formula (1), R9 and RI independently of one another may represent hydrogen or C1-C6-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-.
In the general formula (I), R9 and R.1 independently of one another preferably represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, Ci-C3-alkyl-, C1-C3-alkylcarbonyl-, benzyl- or C1-C4-alkoxycarbonyl-.
In the general formula (1), R9 and le independently of one another preferably represent hydrogen or CI-C3-alkyl-.
In the general formula (I), R9 and R.1 preferably together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, Ci-C3-alkylcarbonyl-, benzyl- or CI-Cr alkoxycarbonyl-.
In the general formula (I), R9 and RI independently of one another particularly preferably represent hydrogen or CI-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), R9 and RI particularly preferably together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), R9 and RI particularly preferably together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, acetyl- or tert-butoxycarbonyl-.

In the general formula (I), R9 and 12.1 independently of one another particularly preferably represent hydrogen or C1-C2-alkyl-.
In the general formula (I), R9 and RI very particularly preferably represent hydrogen or methyl-.
In the general formula (I), R9 very particularly preferably represents methyl.
In the general formula (I), RI very particularly preferably represents methyl.
In the general formula (I), R9 very particularly preferably represents hydrogen.
In the general formula (I), RI very particularly preferably represents hydrogen.
In the general formula (I), R9 and RI very particularly preferably represent hydrogen or methyl-.
In the general formula (I), R9 and le very particularly preferably together with the nitrogen atom to which they are attached represent morpholinyl- or N-methylpiperazinyl.
In the general formula (I), R11 may represent C3-C7-cycloalkyl- or Ci-C6-alkyl-which is monosubstituted by - RN-R9 or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-C,2-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, Ci-C3-alkyl-, C,C3-alkylcarbonyl-, CI-C4-alkoxycarbonyl-, phenyl-CI-C3-alkyl- and C3-C7-cycloalkyl-, Or a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, CI-C3-alkyl, fluoro-Ci-C3-alkyl, hydroxy-C1-C3-alkyl, Ci-C3-alkoxy-, CI-C3-alkylamino-, amino-Ci-C3-allcyl-, C,C3-alkylaminocarbonyl-, CI-C3-alkylaminosulphonyl-, CI-C3-alkylcarbonylamino-, CI-C3-alkylsulphonylamino-, CI-C3-alkylcarbonyl-, CI-C3-alkylsulphonyl-and trifluoromethoxy-.
In the general formula (I), R" preferably represents C3-C7-cycloalkyl- or Ci-C6-alkyl- which is monosubstituted by -NR9R10 , or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-.

heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkyl-, Ci-C3-alkylcarbonyl-, phenyl-C1-C3-alkyl- or C1-Ca-alkoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of CI-C3-alkyl-, halogen and CI-C3-alkoxy-, In the general formula (I), R" preferably represents C3-C7-cycloalkyl- or Ci-C6-alkyl- which is monosubstituted by -NR R9 io.
In the general formula (I), R" preferably represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloallcyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, CI-C3-alkyl-, CI-C3-alkylcarbonyl-, phenyl-Ci-C3-alkyl- or CI-Ca-alkoxycarbonyl-.
In the general formula (I), Rn preferably represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono-or disubstituted by identical or different substituents from the group consisting of Ci-C3-alkyl-, halogen and C1-C3-alkoxy-.
In the general formula (I), R" particularly preferably represents CI-Ca-alkyl which is monosubstituted by -NR
9R' , or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine.
In the general formula (I), R" particularly preferably represents CI-Ca-alkyl which is monosubstituted by -NR R9 io.
In the general formula (I), R" particularly preferably represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-Cio-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-.

In the general formula (1), R11 particularly preferably represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono-or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, or bromine.
In the general formula (I), R11 very particularly preferably represents -CH2-NH(CH3), -CH2-N(CH3)2, -S(-0)2.-CH3, methylpyrrolyl- or thiadiazolyl-, or represents a radical selected from ( (0 / \
N¨ CH3 N-1( 0 /- N\
/¨N"
OtButyl where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R" very particularly preferably represents -CH2-NH(CH3), -CH2-N(CH3)2, -S(=0)2-CH3, methylpyrrolyl- or thiadiazolyl-.
In the general formula (I), Ril very particularly preferably represents a radical selected from ( ('N 0 N¨CH3 /- \/ //- N/ \ \
OtButyl where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R" exceptionally preferably represents CI-C2-alkyl which is monosubstituted by -NR9Rio, or represents a monocyclic heterocyclyl radical having 5 or 6 ring atoms which may optionally be monosubstituted by methyl-, benzyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), R" exceptionally preferably represents CI-C2-alkyl which is monosubstituted by -NR9R1 .
In the general formula (I), R" exceptionally preferably represents a monocyclic heterocyclyl radical having 5 or 6 ring atoms which may optionally be monosubstituted by methyl-, benzyl-, acetyl- or tert-butoxycarbonyl-.
In the general formula (I), Ril furthermore exceptionally preferably represents a radical selected from /CH, cO\
H,C\
N-CH, N
or represents a radical selected from \N¨CH3 \N
' /
CH, 0 (CH, CH, where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), R1' furthermore exceptionally preferably represents a radical selected from CH, cO\ NI
H,C
\N-CH, *_/ N
where "*" in each case indicates the point of attachment to the remainder of the molecule.
In the general formula (I), Ru furthermore exceptionally preferably represents a radical selected from = N-CH, NH
/ ____________________________________________ /
CH, 0 __ (CH, = ( N CH, / \O
where "*" in each case indicates the point of attachment to the remainder of the molecule.

In the general formula (I), RI2 may represent CI-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, carboxy, cyano, Cl-C6-alkoxy-, -NRI R11, phenyl, a monocyclic heteroaryl radical having 5 or 6 ring atoms or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, where phenyl and the monocyclic heteroaryl radical having 5 or 6 ring atoms for their part may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, CI-C3-alkyl, trifluoromethyl, CI-C3-alkoxy- and trifluoromethoxy-, and in which the monocyclic heterocyclyl radical for its part may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, CI-C3-alkyl-, C,-C3-alkylcarbonyl-, CI-C4alkoxycarbonyl-, phenyl-C1-C3-alkyl- and C3-C7-cycloalkyl-, or represents C3-C10-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, CI-C3-alkoxy- and -NRI RI I, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-Cu-heterospirocycloallcyl radical or a C6-C12-heterobicycloallcyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, Ci-C3-alicyl-, CI-C3-allcylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C,-C3-alkyl- and C3-C7-cycloalkyl-, or represents an aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, CI-C3-alkoxy-, C1-C3-alkylamino-, amino-CI-C3-alkyl-, CI-C3-alkylaminocarbonyl-, CI-C3-alkylaminosulphonyl-, CI-alkylcarbonylamino-, CI-C3-alkylsulphonylamino-, Cl-C3-alkylcarbonyl-, CI-C3-alkylsulphonyl-and trifluoromethoxy-.
In the general formula (I), RI' may represent CI-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, carboxy, cyano, CI-C6-alkoxy-, -NR9e, phenyl, a monocyclic heteroaryl radical having 5 or 6 ring atoms or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, where phenyl and the monocyclic heteroaryl radical having 5 or 6 ring atoms for their part may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, C1-C3-alkyl, trifluoromethyl, C1-C3-alkoxy- and trifluoromethoxy-, and in which the monocyclic heterocyclyl radical for its part may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- and C3-C7-cycloalkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C10-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, CI-C3-alkoxy- and -NR9R1 , or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-C12-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, Ci-C3-alkyl-, CI-C3-alkylcarbonyl-, CI-C4-alkoxycarbonyl-, phenyl-CI-C3-alkyl- and C3-C7-cycloalkyl-, or represents an aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-Ci-C3-alkyl, hydroxy-Ci-C3-alkyl, CI-C3-alkoxy-, CI-C3-allcylamino-, amino-Ci-C3-alkyl-, CI-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-alkylcarbonylamino-, CI-C3-alkylsulphonylamino-, C1-C3-allcylcarbonyl-, Ci-C3-alkylsulphonyl-and trifluoromethoxy-.
In the general formula (I), R12 preferably represents Ci-C6-alkyl- which may optionally be mono-or disubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, Ci-C3-alkoxy- and -NRIGRII.
In the general formula (I), R12 preferably represents CI-C6-alkyl- which may optionally be mono-or disubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, Ci-C3-alkoxy- and _N-R9Rio.
In the general formula (I), R12 preferably represents CI-C6-alkyl- which may optionally be mono-or disubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, C1-C3-alkoxy- and -NR9R1 , or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, C1-C3-alkoxy- and -NR9R1 , or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloallcyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, Ci-C3-alkyl-, Ci-C3-alkylcarbonyl-, CI-C3-alkoxycarbonyl- and phenyl-Ci-C3-alkyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, C1-C3-alkyl- and CI-C3-alkoxy-.
In the general formula (I), R12 particularly preferably represents Ci-C3-alkyl-.
In the general formula (I), R12 particularly preferably represents Ci-C3-alkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloallcyl which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, methyl-, ethyl-, methoxy-, ethoxy- and N,N-dimethylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine.
In the general formula (I), R.12 very particularly preferably represents methyl.

In the general formula (I), 12.12 very particularly preferably represents methyl-, trifluoromethyl-, phenyl-, benzyl-, cyclopropyl-, tetrahydropyran-4-y1 or pyrid-3-y1-.
In the general formula (I), R'2 exceptionally preferably represents CI-C3-alkyl, fluoro-C1-C3-alkyl-or C3-C7-cycloalkyl-, OT
represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl or tert-butoxycarbonyl-, or represents a phenyl or pyridyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine.
In the general formula (I), R'2 furthermore exceptionally preferably represents CI-C3-alkyl, fluoro-CI-C3-alkyl- or C3-C7-cycloallcyl-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms, or represents a phenyl or pyridyl radical.
The specific radical definitions given in the particular combinations or preferred combinations of radicals are, irrespective of the particular combinations of radicals specified, also replaced as desired by radical definitions of other combination.
Very particular preference is given to combinations of two or more of the abovementioned preferred ranges.
Compounds according to the invention are the compounds of the formula (I) and their salts, solvates and solvates of the salts, the compounds, comprised by formula (I), of the formulae mentioned below and their salts, solvates and solvates of the salts and the compounds comprised by the formula (I), mentioned below as embodiments and their salts, solvates and solvates of the salts if the compounds, comprised by the formula (I), mentioned below are not already salts, solvates and solvates of the salts.
The present invention is likewise considered to encompass the use of the salts of the compounds according to the invention.
Preferred salts in the context of the present invention are physiologically acceptable salts of the ..
compounds according to the invention. However, the invention also encompasses salts which themselves are unsuitable for pharmaceutical applications but which can be used, for example, for the isolation or purification of the compounds according to the invention.
Physiologically acceptable salts of the compounds according to the invention include acid addition salts of mineral acids, carboxylic acids and sulphonic acids, for example salts of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulphonic acid, toluenesulphonic acid, benzenesulphonic acid, naphthalenedisulphonic acid, acetic acid, trifluoroacetic acid, propionic acid, lactic acid, tartaric acid, malic acid, citric acid, fumaric acid, maleic acid and benzoic acid.
Physiologically acceptable salts of the compounds according to the invention furthermore include base addition salts, for example of alkali metals such as sodium or potassium, of alkaline earth metals such as calcium or magnesium, or of ammonium salts derived from ammonia or organic amines having 1 to 16 carbon atoms, for example methylamine, ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, ethylenediamine, N-methylpiperidine, N-methylglucamine, dimethylglucamine, ethylglucamine, 1,6-hexadiamine, glucosamine, sarcosine, serinol, tris(hydroxymethyDaminomethane, aminopropanediol, Sovak base and/or 1-amino-2,3,4-butanetriol. Furthermore, the compounds according to the invention may form base addition salts with quaterary ammonium ions which can be obtained, for example, by quatemization of corresponding amines with agents such as lower alkyl halides, for example methyl, ethyl, propyl and butyl chlorides, methyl, ethyl, propyl and butyl bromides, and methyl, ethyl, propyl and butyl iodides, dialkyl sulphates such as dimethyl, diethyl, dibutyl and diamyl sulphate, long-chain halides such as decyl, lauryl, myristyl and stearyl chlorides, decyl, lauryl, myristyl and stearyl bromides, and decyl, lauryl, myristyl and stearyl iodides, or arylalkyl halides such as benzyl bromide or phenethyl bromide. Examples of such quaternary ammonium ions are tetramethylarnmonium, tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium and also benzyltrimethylammonium.
The present invention furthermore provides all the possible crystalline and polymorphous forms of the compounds according to the invention, where the polymorphs may be present either as single polymorphs or as a mixture of a plurality of polymorphs in all concentration ranges.
The present invention furthermore provides medicaments comprising the compounds according to the invention and at least one or more further active compounds, in particular for the prophylaxis and/or therapy of neoplastic disorders.

Solvates in the context of the invention are described as those forms of the compounds according to the invention which form a complex in the solid or liquid state by coordination with solvent molecules.
Hydrates are a specific form of the solvates in which the coordination is with water. Solvates preferred in the context of the present invention are hydrates.
The compounds according to the invention may, depending on their structure, exist in different stereoisomeric forms, i.e. in the form of configurational isomers or else optionally as conformational isomers. The compounds according to the invention may have a centre of asymmetry at the carbon atom to which R2 is attached (C-4). They may therefore take the form of pure enantiomers, racemates, or else of diastereomers or mixtures thereof when one or more of the substituents described in the formula (I) contains a further element of asymmetry, for example a chiral carbon atom. The present invention therefore also encompasses enantiomers and diastereomers, and the respective mixtures thereof The pure enantiomers and diastereomers can be isolated from such mixtures in a known manner; chromatography processes are preferably used for this, in particular HPLC chromatography on a chiral or achiral phase.
In general, the enantiomers according to the invention inhibit the target to different degrees and have different activity in the cancer cell lines studied. The more active enantiomer is preferred, which is often that in which the centre of asymmetry represented by the carbon atom bonded to R2 has (S) configuration.
If the compounds according to the invention can occur in tautomeric forms, the present invention encompasses all the tautomeric forms.
The present invention also encompasses all suitable isotopic variants of the compounds according to the invention. An isotopic variant of a compound according to the invention is understood here as meaning a compound in which at least one atom within the compound according to the invention has been exchanged for another atom of the same atomic number, but with a different atomic mass than the atomic mass which usually or predominantly occurs in nature. Examples of isotopes which can be incorporated into a compound according to the invention are those of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulphur, fluorine, chlorine, bromine and iodine, such as 2H (deuterium), 314 (tritium), 13C, 14C, 1 sN, 170, 180, 32F, 33F, 33s, 34s, 35s, 36s, 18F, 36C1, 82Br, 123/, 1241, 129/ and 131/.
Particular isotopic variants of a compound according to the invention, especially those in which one or more radioactive isotopes have been incorporated, may be beneficial, for example, for the examination of the mechanism of action or of the active ingredient distribution in the body; due to comparatively easy preparability and detectability, especially compounds labelled with 3H or 14C isotopes are suitable for this purpose. In addition, the incorporation of isotopes, for example of deuterium, can lead to particular therapeutic benefits as a consequence of greater metabolic stability of the compound, for example an extension of the half-life in the body or a reduction in the active dose required; such modifications of the compounds according to the invention may therefore in some cases also constitute a preferred embodiment of the present invention. Isotopic variants of the compounds according to the invention can be prepared by the processes known to those skilled in the art, for example by the methods described further below and the procedures described in the working examples, by using corresponding isotopic modifications of the respective reagents and/or starting compounds.
In addition, the present invention also encompasses prodrugs of the compounds according to the invention. The term "prodrugs" encompasses compounds which for their part may be biologically active or inactive but are converted during their residence time in the body into compounds according to the invention (for example by metabolism or hydrolysis).
The compounds according to the invention can act systemically and/or locally.
For this purpose, they can be administered in a suitable manner, for example by the oral, parenteral, pulmonary, nasal, sublingual, lingual, buccal, rectal, dermal, transdermal, conjunctival or otic route, or as implant or stent.
The compounds according to the invention can be administered in suitable administration forms for these administration routes.
Suitable administration forms for oral administration are those which function according to the prior art and deliver the compounds according to the invention rapidly and/or in modified fashion, and which contain the compounds according to the invention in crystalline and/or amorphized and/or dissolved form, for example tablets (uncoated or coated tablets, for example having enteric coatings or coatings which are insoluble or dissolve with a delay and control the release of the compound according to the invention), tablets which disintegrate rapidly in the mouth, or films/wafers, films/Iyophilizates, capsules (for example hard or soft gelatin capsules), sugar-coated tablets, granules, pellets, powders, emulsions, suspensions, aerosols or solutions.
Parenteral administration can be accomplished with avoidance of a resorption step (for example by an intravenous, intraarterial, intracardiac, intraspinal or intralumbar route) or with inclusion of a resorption (for example by an intramuscular, subcutaneous, intracutaneous, percutaneous or intraperitoneal route). Administration forms suitable for parenteral administration include preparations for injection and infusion in the form of solutions, suspensions, emulsions, lyophilizates or sterile powders.
Suitable administration forms for the other administration routes are, for example, pharmaceutical forms for inhalation (including powder inhalers, nebulizers), nasal drops, solutions or sprays;

tablets for lingual, sublingual or buccal administration, films/wafers or capsules, suppositories, preparations for the ears or eyes, vaginal capsules, aqueous suspensions (lotions, shaking mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic systems (for example patches), milk, pastes, foams, dusting powders, implants or stents.
The compounds according to the invention can be converted to the administration forms mentioned. This can be accomplished in a manner known per se by mixing with inert, nontoxic, pharmaceutically suitable excipients. These excipients include carriers (for example microcrystalline cellulose, lactose, mannitol), solvents (e.g. liquid polyethylene glycols), emulsifiers and dispersing or wetting agents (for example sodium dodecylsulphate, polyoxysorbitan oleate), binders (for example polyvinylpyrrolidone), synthetic and natural polymers (for example albumin), stabilizers (e.g. antioxidants, for example ascorbic acid), colourants (e.g. inorganic pigments, for example iron oxides) and flavour and/or odour correctants.
The present invention furthermore provides medicaments which comprise the compounds according to the invention, typically together with one or more inert, nontoxic, pharmaceutically suitable auxiliaries, and the use thereof for the aforementioned purposes.
The compounds according to the invention are formulated to give pharmaceutical preparations in a manner known per se, by converting the active compound(s) to the desired administration form with the excipients customary in the pharmaceutical formulation.
The excipients used may, for example, be carrier substances, fillers, disintegrants, binders, humectants, glidants, absorbents and adsorbents, diluents, solvents, cosolvents, emulsifiers, solubilizers, taste correctors, colourants, preservatives, stabilizers, wetting agents, salts for modifying the osmotic pressure or buffers. Reference should be made to Remington's Pharmaceutical Science, 15th ed. Mack Publishing Company, East Pennsylvania (1980).
The pharmaceutical formulations can be present in solid form, for example as tablets, sugar-coated tablets, pills, suppositories, capsules, transdermal systems or in semisolid form, for example as ointments, creams, gels, suppositories, emulsions or in liquid form, for example as solutions, tinctures, suspensions or emulsions.
Excipients in the context of the invention may, for example, be salts, saccharides (mono-, di-, tri-, oligo- and/or polysaccharides), proteins, amino acids, peptides, fats, waxes, oils, hydrocarbons and derivatives thereof, and the excipients may be of natural origin or be obtained by synthetic or partially synthetic means.

Useful forms for oral or peroral administration are especially tablets, sugar-coated tablets, capsules, pills, powders, granules, pastilles, suspensions, emulsions or solutions.
Useful forms for parenteral administration are especially suspensions, emulsions, and particularly solutions.
The present invention relates to the compounds according to the invention.
They can be used for the prophylaxis and therapy of human disorders, in particular neoplastic disorders.
The compounds according to the invention can be used in particular for inhibiting or reducing cell proliferation and/or cell division and/or to induce apoptosis.
The compounds according to the invention are suitable in particular for the prophylaxis and/or therapy of hyper-proliferative disorders such as, for example, - psoriasis, - keloids and other skin hyperplasias, - benign prostate hyperplasias (BPH), - solid tumours and - haematological tumours.
Solid tumours that can be treated in accordance with the invention are, for example, tumours of the breast, the respiratory tract, the brain, the reproductive organs, the gastrointestinal tract, the urogenital tract, the eye, the liver, the skin, the head and the neck, the thyroid gland, the parathyroid gland, the bones, and the connective tissue and metastases of these tumours.
Haematological tumours which can be treated are, for example, - multiple myelomas - lymphomas or - leukaemias Breast tumours which can be treated are, for example:
- breast carcinomas with positive hormone receptor status - breast carcinomas with negative hormone receptor status - Her-2 positive breast carcinomas - hormone receptor and Her-2 negative breast carcinomas - BRCA¨associated breast carcinomas - inflammatory breast carcinomas.
Tumours of the respiratory tract which can be treated are, for example, .

a - non-small-cell bronchial carcinomas such as, for example, squamous cell carcinoma, adenocarcinoma, large-cell carcinoma and - small-cell bronchial carcinomas.
Tumours of the brain which can be treated are, for example, - gliomas, - glioblastomas, - astrocytomas, - meningiomas and - medulloblastomas.
Tumours of the male reproductive organs which can be treated are, for example:
- prostate carcinomas, - malignant epididymal tumours - malignant testicular tumours and - penis carcinomas.
Tumours of the female reproductive organs which can be treated are, for example:
- endometrial carcinomas - cervix carcinomas - ovarian carcinomas - vaginal carcinomas - vulvar carcinomas Tumours of the gastrointestinal tract which can be treated are, for example:
- colorectal carcinomas - anal carcinomas - stomach carcinomas - pancreas carcinomas - oesophagus carcinomas - gall bladder carcinomas - carcinomas of the small intestine - salivary gland carcinomas - neuroendocrine tumours - gastrointestinal stroma tumours Tumours of the urogenital tract which can be treated are, for example:
- urinary bladder carcinomas A
- kidney cell carcinomas - carcinomas of the renal pelvis and lower urinary tract Tumours of the eye which can be treated are, for example:
- retinoblastomas - intraocular melanomas Tumours of the liver which can be treated are, for example:
- hepatocellular carcinomas - cholangiocellular carcinomas Tumours of the skin which can be treated are, for example:
- malignant melanomas - basaliomas - spinaliomas - Kaposi sarcomas - Merkel cell carcinomas Tumours of the head and neck which can be treated are, for example:
- larynx carcinomas - carcinomas of the pharynx and the oral cavity - carcinomas of the middle line structures (e.g. NMC, C.A.
French, Annu. Rev. Pathol. 2012, 7:247-265) Sarcomas which can be treated are, for example:
- soft tissue sarcomas - osteosarcomas Lymphomas which can be treated are, for example:
- non-Hodgkin lymphomas - Hodgkin lymphomas - cutaneous lymphomas - lymphomas of the central nervous system - AIDS-associated lymphomas Leukaemias which can be treated are, for example:
- acute myeloid leukaemias - chronic myeloid leukaemias A

a - acute lymphatic leukaemias - chronic lymphatic leukaemias - hairy cell leukaemias Advantageously, the compounds according to the invention can be used for prophylaxis and/or treatment of leukaemia, especially acute myeloid leukaemia, prostate carcinoma, especially androgen receptor-positive prostate carcinoma, cervical carcinoma, mammary carcinoma, especially hormone receptor-negative, hormone receptor-positive or BRCA-associated mammary carcinoma, pancreatic carcinoma, renal cell carcinoma, hepatocellular carcinoma, melanoma and other skin tumours, non-small-cell bronchial carcinoma, endometrial carcinoma and colorectal carcinoma.
Particularly advantageously, the compounds according to the invention can be used for prophylaxis and/or treatment of leukaemia, especially acute myeloid leukaemia, prostate carcinoma, especially androgen receptor-positive prostate carcinoma, mammary carcinoma, especially oestrogen receptor alpha-negative mammary carcinoma, melanoma or multiple myeloma.
The compounds according to the invention are also suitable for prophylaxis and/or treatment of benign hyperproliferative diseases, for example endometriosis, leiomyoma and benign prostate hyperplasia.
The compounds according to the invention are also suitable for male fertility control.
The compounds according to the invention are also suitable for prophylaxis and/or treatment of systemic inflammatory diseases, especially LPS-induced endotoxic shock and/or bacteria-induced sepsis.
The compounds according to the invention are also suitable for prophylaxis and/or treatment of inflammatory or autoimmune disorders, for example:
- pulmonary disorders associated with inflammatory, allergic and/or proliferative processes:
chronic obstructive pulmonary disorders of any origin, particularly bronchial asthma;
bronchitis of different origin; all forms of restrictive pulmonary disorders, particularly allergic alveolitis; all forms of pulmonary oedema, particularly toxic pulmonary oedema;
sarcoidoses and granulomatoses, particularly Boeck's disease, - rheumatic disorders/autoimmune disorders/joint disorders associated with inflammatory, allergic and/or proliferative processes: all forms of rheumatic disorders, especially rheumatoid arthritis, acute rheumatic fever, polymyalgia rheumatica; reactive arthritis;
inflammatory soft-tissue disorders of other origin; arthritic symptoms in the case of =

degenerative joint disorders (arthroses); traumatic arthritides; collagenoses of any origin, e.g. systemic lupus erythematosus, scleroderma, polymyositis, dermatomyositis, Sjogren's syndrome, Still's syndrome, Felty's syndrome - allergies associated with inflammatory and/or proliferative processes: all forms of allergic reactions, e.g. angiooedema, hay fever, insect bites, allergic reactions to medicaments, blood derivatives, contrast agents, etc., anaphylactic shock, urticaria, contact dermatitis - vascular inflammation (vasculitis): panarteritis nodosa, temporal arteritis, erythema nodosum - dermatological disorders associated with inflammatory, allergic and/or proliferative processes: atopic dermatitis; psoriasis; pityriasis rubra pilaris;
erythematous disorders triggered by different noxae, for example radiation, chemicals, burns, etc.;
bullous dermatoses; lichenoid disorders; pruritus; seborrhoeic eczema; rosacea;
pemphigus vulgaris; erythema exsudativum multiforme; balanitis; vulvitis; hair loss, such as alopecia areata; cutaneous T-cell lymphoma - renal disorders associated with inflammatory, allergic and/or proliferative processes:
nephrotic syndrome; all nephritides - hepatic disorders associated with inflammatory, allergic and/or proliferative processes:
acute hepatic disintegration; acute hepatitis of different origin, for example viral, toxic, medicament-induced; chronic aggressive and/or chronic intermittent hepatitis - gastrointestinal disorders associated with inflammatory, allergic and/or proliferative processes: regional enteritis (Crohn's disease); ulcerative colitis;
gastritis; reflux oesophagitis; gastroenteritides of other origin, e.g. indigenous sprue - proctological disorders associated with inflammatory, allergic and/or proliferative processes: anal eczema; fissures; haemorrhoids; idiopathic proctitis - ocular disorders associated with inflammatory, allergic and/or proliferative processes:
allergic keratitis, uveitis, iritis; conjunctivitis; blepharitis; optic neuritis; chlorioditis;
sympathetic ophthalmia - disorders of the ear-nose-throat region associated with inflammatory, allergic and/or proliferative processes: allergic rhinitis, hay fever; otitis externa, for example caused by contact eczema, infection, etc.; otitis media - neurological disorders associated with inflammatory, allergic and/or proliferative processes: cerebral oedema, particularly tumour-related cerebral oedema;
multiple sclerosis; acute encephalomyelitis; meningitis; various forms of seizure, for example West's syndrome - haematological disorders associated with inflammatory, allergic and/or proliferative processes: acquired haemolytic anaemia; idiopathic thrombocytopenia - neoplastic disorders associated with inflammatory, allergic and/or proliferative processes:
acute lymphatic leukaemia; malignant lymphomas; lymphogranulomatoses;

- 98 ¨
Is lymphosarcoma; extensive metastases, particularly in the case of mammary, bronchial and prostate carcinoma - endocrine disorders associated with inflammatory, allergic and/or proliferative processes:
endocrine orbitopathy; thyrotoxic crisis; de Quervain's thyroiditis;
Hashimoto's thyroiditis;
Basedow's disease - organ and tissue transplants, graft-versus-host disease - severe states of shock, for example anaphylactic shock, systemic inflammatory response syndrome (SIRS) - substitution therapy in the case of: congenital primary adrenal insufficiency, for example congenital adrenogenital syndrome; acquired primary adrenal insufficiency, for example Addison's disease, autoimmune adrenalitis, postinfectious, tumours, metastases, etc;
congenital secondary adrenal insufficiency, for example congenital hypopituitarism;
acquired secondary adrenal insufficiency, for example postinfectious, tumours, etc.
- emesis associated with inflammatory, allergic and/or proliferative processes, for example in combination with a 5-HT3 antagonist in the case of cytostatic-induced vomiting - pain of inflammatory origin, for example lumbago.
The compounds according to the invention are also suitable for the treatment of viral disorders, for example infections caused by papilloma viruses, herpes viruses, Epstein-Barr viruses, hepatitis B or C viruses, and human immunodeficiency viruses.
The compounds according to the invention are also suitable for the treatment of atherosclerosis, dyslipidaemia, hypercholesterolaemia, hypertriglyceridaemia, peripheral vascular disorders, cardiovascular disorders, angina pectoris, ischaemia, stroke, myocardial infarction, angioplastic restenosis, hypertension, thrombosis, obesity, endotoxaemia.
The compounds according to the invention are also suitable for the treatment of neurodegenerative diseases, for example multiple sclerosis, Alzheimer's disease and Parkinson's disease.
These disorders are well characterized in man, but also exist in other mammals.
The present application furthermore provides the compounds according to the invention for use as medicaments, in particular for the prophylaxis and/or therapy of tumour disorders.
The present application furthermore provides the compounds according to the invention for prophylaxis and/or therapy of leukaemia, especially acute myeloid leukaemia, prostate carcinoma, especially androgen receptor-positive prostate carcinoma, cervical carcinoma, mammary carcinoma, especially hormone receptor-negative, hormone receptor-positive or BRCA-associated mammary carcinoma, pancreatic carcinoma, renal cell carcinoma, hepatocellular carcinoma, .4 melanoma and other skin tumours, non-small-cell bronchial carcinoma, endometrial carcinoma and colorectal carcinoma.
The present application furthermore provides the compounds according to the invention for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemias, prostate carcinomas, especially androgen receptor-positive prostate carcinomas, mammary carcinomas, especially oestrogen receptor alpha-negative mammary carcinomas, melanomas or multiple myelomas.
The invention furthermore provides for the use of the compounds according to the invention for production of a medicament.
The present application furthermore provides for the use of the compounds according to the invention for production of a medicament for prophylaxis and/or therapy of neoplastic disorders.
The present application furthermore provides for the use of the compounds according to the invention for production of a medicament for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemias, prostate carcinomas, especially androgen receptor-positive prostate carcinomas, cervical carcinomas, mammary carcinomas, especially hormone receptor-negative, hormone receptor-positive or BRCA-associated mammary carcinomas, pancreatic carcinomas, renal cell carcinomas, hepatocellular carcinomas, melanomas and other skin tumours, non-small-cell bronchial carcinomas, endometrial carcinomas and colorectal carcinomas.
The present application furthermore provides for the use of the compounds according to the invention for production of a medicament for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemias, prostate carcinomas, especially androgen receptor-positive prostate carcinomas, mammary carcinomas, especially oestrogen receptor alpha-negative mammary carcinomas, melanomas or multiple myelomas.
The present application furthermore provides for the use of the compounds according to the invention for prophylaxis and/or therapy of neoplastic disorders.
The present application furthermore provides for the use of the compounds according to the invention for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemias, prostate carcinomas, especially androgen receptor-positive prostate carcinomas, cervical carcinomas, mammary carcinomas, especially hormone receptor-negative, hormone receptor-positive or BRCA-associated mammary carcinomas, pancreatic carcinomas, renal cell carcinomas, hepatocellular carcinomas, melanomas and other skin tumours, non-small-cell bronchial %
carcinomas, endometrial carcinomas and colorectal carcinomas.
The present application furthermore provides for the use of the compounds according to the invention for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemias, prostate carcinomas, especially androgen receptor-positive prostate carcinomas, mammary carcinomas, especially oestrogen receptor alpha-negative mammary carcinomas, melanomas or multiple myelomas.
The present application furthermore provides pharmaceutical formulations in the form of tablets comprising one of the compounds according to the invention for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemia, prostate carcinoma, especially androgen receptor-positive prostate carcinoma, cervical carcinoma, mammary carcinoma, especially hormone receptor-negative, hormone receptor-positive or BRCA-associated mammary carcinoma, pancreatic carcinoma, renal cell carcinoma, hepatocellular carcinoma, melanoma and other skin tumours, non-small-cell bronchial carcinoma, endometrial carcinoma and colorectal carcinoma.
The present application furthermore provides pharmaceutical formulations in the form of tablets comprising one of the compounds according to the invention for prophylaxis and/or therapy of leukaemias, especially acute myeloid leukaemias, prostate carcinomas, especially androgen receptor-positive prostate carcinomas, mammary carcinomas, especially oestrogen receptor alpha-negative mammary carcinomas, melanomas or multiple myelomas.
The invention furthermore provides for the use of the compounds according to the invention for treatment of disorders associated with proliferative processes.
The invention furthermore provides for the use of the compounds according to the invention for treatment of benign hyperplasias, inflammation disorders, autoimmune disorders, sepsis, viral infections, vascular disorders and neurodegenerative disorders.
The compounds according to the invention can be used alone or, if required, in combination with one or more other pharmacologically active substances, provided that this combination does not lead to undesirable and unacceptable side effects. The present invention therefore furthermore provides medicaments comprising an inventive compound and one or more further active ingredients, especially for prophylaxis and/or treatment of the disorders mentioned above.
For example, the compounds according to the invention can be combined with known antihyperproliferative, cytostatic or cytotoxic substances for treatment of cancer. The combination of the compounds according to the invention with other substances commonly used for cancer treatment, or else with radiotherapy, is particularly appropriate.
An illustrative but nonexhaustive list of suitable combination active ingredients is as follows:
abiraterone acetate, abraxane, acolbifene, Actimmune, actinomycin D
(dactinomycin), afatinib, affinitak, Afinitor, aldesleukin, alendronic acid, alfaferone, alitretinoin, allopurinol, Aloprim, Aloxi, alpharadin, altretamine, aminoglutethimide, aminopterin, amifostine, amrubicin, amsacrine, anastrozole, anzmet, apatinib, Aranesp, arglabin, arsenic trioxide, Aromasin, arzoxifen, asoprisnil, L-asparaginase, atamestane, atrasentane, avastin, axitinib, 5-azacytidine, azathioprine, BCG or Tice BCG, bendamustine, bestatin, beta-methasone acetate, betamethasone sodium phosphate, bexarotene, bicalutamide, bleomycin sulphate, broxuridine, bortezomib, bosutinib, busulfan, cabazitaxel, calcitonin, campath, camptothecin, capecitabine, carboplatin, carfilzomib, carmustine, casodex, CCI-779, CDC-501, cediranib, cefesone, celebrex, celmoleukin, cerubidine, cediranib, chlorambucil, cisplatin, cladribine, clodronic acid, clofarabine, colaspase, corixa, crisnatol, crizotinib, cyclophosphamide, cyproterone acetate, cytarabine, dacarbazine, dactinomycin, dasatinib, daunorubicin, DaunoXome, Decadron, Decadron Phosphate, decitabine, degarelix, delestrogen, denileukin diftitox, depomedrol, deslorelin, dexrazoxane, diethylstilbestrol, diflucan, 2",2"-difluorodeoxycytidine, DN-101, docetaxel, doxifluridine, doxorubicin (Adriamycin), dronabinol, dSLIM, dutasteride, DW-166HC, edotecarin, eflornithine, Eligard, Elitek, Ellence, Emend, enzalutamide, epirubicin, epoetin-alfa, Epogen, epothilone and derivatives thereof, eptaplatin, ergamisol, erlotinib, erythro-hydroxynonyladenine, estrace, oestradiol, oestramustine sodium phosphate, ethinyloestradiol, Ethyol, etidronic acid, etopophos, etoposide, everolimus, exatecan, exemestane, fadrozole, farston, fenretinide, filgrastim, finasteride, fligrastim, floxuridine, fluconazole, fludarabine, 5-fluorodeoxyuridine monophosphate, 5-fluorouracil (5-FU), fluoxymesterone, flutamide, folotin, formestane, fosteabine, fotemustine, fulvestrant, Ganunagard, gefitinib, gemcitabine, gemtuzumab, Gleevec, Gliadel, goserelin, gossypol, granisetrone hydrochloride, hexamethylmelamine, histamine dihydrochloride, histrelin, holmium-166-DOTPM, hycamtin, hydrocortone, erythro-hydroxynonyladenine, hydroxyurea, hydroxyprogesterone caproate, ibandronic acid, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib, iniparib, interferon-alpha, interferon-alpha-2, interferon-alpha-2a, interferon-a1pha-21, interferon-alpha-nl, interferon-alpha-n3, interferon-beta, interferon-gamma-la, interleukin-2, intron A, iressa, irinotecan, ixabepilone, keyhole limpet haemocyanin, lcytril, lanreotide, lapatinib, lasofoxifene, lentinan sulphate, lestaurtinib, letrozole, leucovorin, leuprolide, leuprolide acetate, levamisole, levofolic acid calcium salt, levothroid, levoxyl, Libra, liposomal MTP-PE, lomustine, lonafarnib, lonidamine, marinol, mechlorethamine, mecobalamine, medroxyprogesterone acetate, megestrol acetate, melphalan, Menest, 6-mercaptopurine, mesna, methotrexate, metvix, miltefosine, minocycline, minodronate, miproxifen, mitomycin C, mitotan, mitoxantrone, modrenal, MS-209, MX-6, myocet, nafarelin, nedaplatin, nelarabine, nemorubicin, neovastat, neratinib, neulasta, neumega, neupogen, nilotimib, nilutamide, nimustine, nolatrexed, nolvadex, NSC-631570, obatoclax, oblimersen, OCT-43, octreotide, olaparib, ondansetron hydrochloride, Onco-TCS, Orapred, Osidem, oxaliplatin, paclitaxel, pamidronate disodium, pazopanib, pediapred, pegaspargase, pegasys, pemetrexed, pentostatin, N-phosphonoacetyl-L-aspartate, picibanil, pilocarpine hydrochloride, pirarubicin, plerixafor, plicamycin, PN-401, portimer sodium, prednimustine, prednisolone, prednisone, Premarin, procarbazine, Procrit, QS-21, quazepam, R-1589, raloxifene, raltitrexed, ranpirnas, RDEA119, Rebif, regorafenib, 13-cis-retinoic acid, rhenium-186 etidronate, rituximab, roferon-A, romidepsin, romurtide, ruxolitinib, salagen, salinomycin, sandostatin, sargramostim, satraplatin, semaxatinib, semustine, seocalcitol, sipuleucel-T, sizofiran, sobuzoxan, Solu-Medrol, sorafenib, streptozocin, strontium-89 chloride, sunitinib, Synthroid, T-138067, tamoxifen, tamsulosin, Tarceva, tasonermin, tastolactone, Taxoprexin, Taxoter, teceleukin, temozolomide, temsirolimus, teniposide, testosterone propionate, Testred, thalidomide, thymosin alpha-1, thioguanine, thiotepa, thyrotropin, tiazorufin, tiludronic acid, tipifarnib, tirapazamine, TLK-286, toceranib, topotecan, toremifen, tositumomab, tastuzumab, teosulfan, transMID-107R, tretinoin, Trexall, trimethylmelamine, trimetrexate, triptorelin acetate, triptorelin pamoate, trofosfamide, UFT, uridine, valrubicin, valspodar, vandetanib, vapreotide, vatalanib, vemurafinib, verte-porfin, vesnarinone, vinblastine, vincristine, vindesine, vinflumine, vinorelbine, virulizin, vismodegib, Xeloda, Z-100, Zinecard, zinostatin stimalamer, zofran, zoledronic acid.
The combination of the compound according to the invention with a P-TEFb or CDK9 inhibitor, or with a BCL6 inhibitor, is likewise particularly preferred.
In a promising manner, the compounds according to the invention can also be combined with biologics such as antibodies (for example aflibercept, alemtuzumab, bevacizumab, brentuximumab, catumaxomab, cetuximab, denosumab, edrecolomab, gemtuzumab, ibritumomab, ipilimumab, ofatumumab, panitumumab, pertuzumab, rituximab, tositumumab, trastuzumab) and recombinant proteins.
The compounds according to the invention can also achieve positive effects in combination with other therapies directed against angiogenesis, for example with bevacizumab, axitinib, regorafenib, cediranib, sorafenib, sunitinib or thalidomide. Combinations with antihormones and steroidal metabolic enzyme inhibitors are particularly suitable because of their favourable profile of side effects.
Generally, the following aims can be pursued with the combination of the compounds according to the invention with other cytostatically or cytotoxically active agents:

= improved efficacy in slowing the growth of a tumour, in reducing its size or even in completely eliminating it, compared with treatment with an individual active ingredient;
= the possibility of using the chemotherapeutics used in a lower dosage than in the case of monotherapy;
= the possibility of a more tolerable therapy with fewer side effects compared with individual administration;
= the possibility of treatment of a broader spectrum of tumours;
= the achievement of a higher rate of response to the therapy;
= a longer survival time of the patient compared with present-day standard therapy.
In addition, the compounds according to the invention can also be used in conjunction with radiotherapy and/or surgical intervention.

=

Preparation of the compounds of the general formula I according to the invention Synthesis routes for preparing the compounds of the general formula (I) The following schemes and general procedures illustrate general synthetic routes to the compounds of the formula (I) according to the invention; however, this should not be interpreted as meaning that the synthesis of the compounds according to the invention is limited to these.
4,5-Dihydro-3H-2,3-benzodiazepines of the general formula (I) can be prepared analogously to processes described in the literature. Depending on the substituents present, protective group strategies may optionally be required; however, these are known to the person skilled in the art (T.
W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3.
Edition, Wiley 1999).
Scheme 1 shows the synthesis of 4,5-dihydro-3H-2,3-benzodiazepines using a 3,4-dihydro-1H-2-benzopyran intermediate (III), where the radicals Rla, Rlb, RC, R2, R4 and R5 have the meanings given in the general formula (I). Corresponding approaches are described, for example, in F. Gatta et al. 11 Farmaco ¨ Ed. Sc. 1985, 40, 942, and in WO 1997028135, W02008124075 or W0200198280.
The benzaldehydes of the formula (Ilb) used are commercially available, or their preparation is known to the person skilled in the art. R1a can also be introduced at a later stage of the synthesis, for example as described in Scheme 5.
The substituted phenethyl alcohols (II) used are either commercially available or are prepared in a manner generally known to the person skilled in the art, for example by reduction of the corresponding ketones (Ha), e.g. by reduction with lithium aluminium hydride in THF;
alternatively, they can also be obtained by reacting the corresponding phenylacetaldehydes with organomagnesium compounds of the formula R2Mg-halogen where halogen represents chlorine, bromine or iodine (see, for example, Organic Letters 2007, 2103-2106; for the preparation of the corresponding phenylacetaldehydes see, for example, Monatshefte fur Chemie 2004, 1289-1295).
This synthesis route is preferably used for phenethyl alcohols (II) having electron-rich substituents (e.g. with alkoxy).
3,4-Dihydro-1H-2-benzopyrans (III) are obtained by condensation of the substituted phenethyl alcohols (11) with benzaldehydes (1Ib) under acidic conditions. The reaction is preferably carried out in solvents such as toluene or dioxane in the presence of hydrochloric acid or anhydrous zinc chloride. Further conversion of the 3,4-dihydro-1H-2-benzopyrans (III) can be by various routes:
oxidative ring-opening using chromium(VI) oxide/sulphuric acid affords the diketone (IV) which =

can be cyclized with hydrazine to give 4-methyl-1-pheny1-5H-2,3-benzodiazepine (V) (cf.
US5288863). Reduction, for example with sodium cyanoborohydride (Synthetic Communications, 2002, 32, 527), then yields the desired 4,5-dihydro-3H-2,3-benzodiazepine derivative (VI).
Oxidation of (III) with atmospheric oxygen affords the 1-ary1-3,4-dihydro-1H-2-benzopyran-1-o1 (VII) which, under elimination of water, can be reacted with a monoprotected hydrazine, for example H2NNHBoc, to give the corresponding hydrazone derivatives, such as the N-Boc-hydrazone (VIII). This can be cyclized, for example by mesylation and subsequent treatment with base, to give the Boc-protected 4,5-dihydro-3H-2,3-benzodiazepine derivative, such as (IX), which in turn can be converted by deprotection, for example removal of Boc in the presence of an acid, in a generally known manner into the corresponding 4,5-dihydro-3H-2,3-benzodiazepine derivative (VI).

, Scheme I: 4,5-Dihydro-3H-2,3-benzodiazepines via 3,4-dihydro-1H-2-benzopyrans Rs 0Reduction Ila II 0 I R'e * ell Rla Ilb R

Jones R5 Atmospheric all 0 Oxidation oxidation Rs 0 .ii---- OH
Rs ir 1101 Ric 111 Rib IV * Ric lit Feb R" Ria Rib Ria III
Rie 1 H2N ¨NHBoc N2114 i \ N R4 A
3)<CH3 I
R5 * -- r4 v , N
VIII
RS =
Ric ill Rib Ric * R15 Ri' NaCNB\H3 Ria 1 1. MsCI
2. Base NH ,N-Rs .I --- Ni HCI RS = "*". N'l4 O---VI

Ric * Ric elit Ix Ria Ria Scheme 2 describes the synthesis of 4,5-dihydro-3H-2,3-benzodiazepines from indanones (X).
Scheme 2: 4,5-Dihydro-3H-2,3-benzodiazepines from indanones FF FF (js, IP. R2 Ric it B(OH)2 F)c)Ci(4`F R 5 r Ilc F
F F F F

R2 ioe R2 MgHal F F 5 so R2 Rie * Rlb *le R2 Olip Rib R" Ild R5 OH p-Ts0H R
R* ,OK

R"
R1' XIII
RuCI, / Na104 R2 0 R2 or R4 R4 0s04 Ma 104 Si N2H4 -101 NaCNBH3NH
o N

Fee * Rie R1 * Rib R Rib IV R" la R VI
V
The radicals RI., Rib, Ric, R2, lean a = R5 in Scheme 2 have the meanings given in the general formula (I).
The indanone (X) can be converted into the corresponding 3-phenyl-1H-indene (XII). To this end, the following processes may be used:
- the indanone derivative (X) can, for example, be converted in a generally known manner into the corresponding enol nonaflate (XI) and then be converted by palladium-catalysed Suzuki coupling with the appropriate boronic acid derivatives (Hc) into the indene (XII).
- the indanone derivative (X) can be converted by addition of organomagnesium reagents (Hd) in a generally known manner into the corresponding indanols (XIII) which, via acid-catalysed elimination, readily form the corresponding indenes (XII).
The 3-phenyl-1H-indenes (XII) can be converted by oxidative methods using, for example, ruthenium(III) chloride/sodium periodate (Bioorganic and Medicinal Chemistry Letters, 2011, 21, 2554) into the corresponding diketones (IV). These can be converted analogously to Scheme 1 into the corresponding 4,5-dihydro-3H-2,3-benzodiazepine derivatives (VI).

The indanones used for preparing the working examples are either commercially available or can be prepared as shown, for example, in Scheme 3, where the radicals R2, R4 and 125 have the meanings given in the general formula (I).
Scheme 3: Synthesis of indanones Br EtO¨P=0 H,C OH
OEt 0 0RZ sio OH _____________ Rz Hydrogenation : Base R' XV
CH_ CH, =
1.T.y A-C, 0 OH
R' 2. Reduction R5=0 0 H R' 4i 0 XIV CH, CH_ XVI XVII XVIII
Polyphosphoric acid Or \1/4 chlorosulphoric acid//, 1. SOCI, 2. AICI, O. R2 R' Using processes known from the literature, e.g. via Perkin reaction (Medicinal Chemistry Research, 2004, Vol. 13, 660) or Wittig reaction (Journal of Organic Chemistry, 2001, Vol. 66, 3682), it is possible to prepare the 2-methyl-3-phenylpropanoic acids (XVIII) from the corresponding aromatic aldehydes (XIV) . These can be cyclized using, for example, chlorosulphonic acid or polyphosphoric acid, giving the corresponding indanones (X) (cf. Synthesis 2009, 627 and Org.
Process Res. Dev. 2011, 15, 570-580, J. Org. Chem. 2005, 70, 1316 and Bioorg.
Med. Chem. Lett.
2011, 21, 2554-2558).
Scheme 4 illustrates the preparation of the exemplary compounds according to the invention starting with 4,5-dihydro-3H-2,3-benzodiazepines (VI) using generally known reactions, for example with acid chlorides, anhydrides, chloroformates or isocyanates or isothiocyanates, where the radicals RI, aIR b, Ric, R2, R3, I(-4 and R5 have the meanings giving in general formula (I). The corresponding alkylureas (lb) can also be obtained by reacting a reactive intermediate such as, for example, the 4-nitrophenyl carbamate, with alkylamines.

, Scheme 4: Synthesis of 4,5-dihydro-3H-2,3-benzodiazepine-3-carbonyl compounds R4 R3¨ R4 0 VI NH a N-4 Rs * ¨1\11 Or R5 I. --14 R3 la Ric * R3¨g Ric *

Rlb 0--Rlb Rla R3 Rla R4 1 . R4 0 -,0 .
R5 0 -,NH 0 ci p-4 R = Alkyl R5 * --- N N- R
H
vi Ric Rlb 02N * Ric *
______________________________________________ IN
Rla 2. RNH2 Rla Rlb lb R4= R R4 X X =
o,s NH Alkyl isocyanate 5 ,N-4 R = Alkyl Or H
alkyl isothiocyanate VI Ric ___________________ 0-- Ric * ic Rlb Rlb Rla Rla Rla can also be introduced at a later stage of the synthesis, for example as described in Scheme 5.
The starting materials (XXI), (XXII) and (XXIII) used can be prepared using the synthesis methods discussed above and illustrated in Schemes 1 to 4. The radicals RI', Rlb, Ric, R2, R3, R4, R5, R6, R7, R8, RH, R12 in Scheme 5 have the meanings given in the general formula (I).

. BHC123073FC

Scheme 5:

Fe 0 R4 0 R5 101 ¨ 4 R3 R7R8NH R5 44 * --- N R3 )0(1 ____________________________ r le R" *Pd catalyst complex R" *
RTh Rib Y R7¨ N

Y = CI, Br, I, OTf R8 1\14 R5 (16 --- N R3 NH(R8)-00R11 R5 (III/ 3 ¨ N
R if XXII ____________________________ 3.-Fec * Rib Cu catalyst complex R" *
R"
Y R8¨N
Y = Cl. Br, I 0 ¨ ,N
N Fe 11 11 R6-OH R5 10 --- 4 R3 1g XXII , Fee * Pd catalyst complex R" *
R" or Cu catalyst complex Rib Y C

Y = CI, Br, I

R4 r" 0 XXIII R5 R4 *I 0 R12-S02-NH(R8) i 3 -- N R
A
I h Ric *Pd catalyst complex Ric *
Rib Feb Br R¨N
µs=-=:,'0 R121 (3 Scheme 5 illustrates the preparation of working examples which can be prepared by palladium-catalysed coupling reactions generally known to the person skilled in the art starting, for example, with brominated intermediates (XXI) by reaction with the appropriate amines (Chem. Sci. 2011, 2, 27; Angew. Chem. 2008, 47, 6338, Accounts of Chemical Research 2008, 41, 1534). Using copper-catalysed reactions, it is possible to convert intermediates of type XXII by reaction with amides into the corresponding coupled derivatives (If) (JACS 2001, 123, 7727; JACS
2002, 124, 7421).
Via palladium-catalysed reactions, intermediates of type XXII can be converted by reaction with alcohol derivatives or by copper-catalysed couplings by reaction with phenol derivatives into the respective corresponding ether derivatives (Ig) (JACS 1997, 119, 3395;
Angewandte Chemie, International Edition 2006, 45, 1276). N-Arylated sulphonamides (Ih) can be prepared from intermediates of type XXIII by palladium-catalysed reaction with sulphonamides (Org. Lett. 2011, 2564). Intermediates XXI, XXII and XXIII can be prepared analogously to the synthesis routes shown.
Scheme 6 illustrates the preparation of working examples which can be prepared by palladium-catalysed coupling reactions generally known to the person skilled in the art starting, for example, with brominated intermediates (XXIV, XXV) by reaction with the appropriate amines (Chem. Sci.
2011, 2, 27; Angew. Chem. 2008, 47, 6338, Accounts of Chemical Research 2008, 41, 1534, Journal of Organometallic Chemistry (1999), 576(1-2), 125-146). The starting materials (XXIV) and (XXV) used can be prepared using the synthesis methods discussed above and illustrated in Schemes 1 to 4. Starting with XXIV and XXV, it is possible to obtain, by palladium-catalysed reaction with boronic acid derivatives, the corresponding coupling products Ii and lj, respectively (Chem. Rev. 1995, 95, 2457-2483; Angewandte Chemie, International Edition (2002), 41(22), 4176-4211).
Scheme 6: Synthesis of 4,5-dihydro-3H-2,3-benzodiazepine-3-carbonyl compounds Boronic acid derivative , 3 =
R5 111-1 N R3 or amine R5 N R
Ii XXIV
R" Pd catalyst complex Ric it Rib R 1 b Rla R1 a Y= Br, Cl, I

=R 11101 4 0 Boronic acid derivative 5 ,N.-4 3 y N R or amine N R lj XXV
Ric Pd catalyst complex Ric =
R1 b Rib Rla R1 a Y= Br. Cl, I

Boronic acid derivatives are commercially available or can be prepared in a generally known manner; for a review, see, for example, D. G. Hall, Boronic Acids, VCH-Wiley-Verlag GmbH &
Co. KGaA, Weinheim 2005, ISBN 3-527-30991-8, and the literature cited therein.
Scheme 7 illustrates a method for preparing Working Examples (lk) from amino intermediates ()OCVI) by amide coupling reactions generally known to the person skilled in the art, using carboxylic acids of the formula It11-C(=0)0H in the presence of coupling agents familiar to the person skilled in the art, for example propanephosphonic acid cyc/o-anhydride or (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate.
The preparation of amino intermediates (Xm) is known to the person skilled in the art (see, for example, WO 1997/028135); carboxylic acids of the formula R11-C(=0)0H are likewise known to the person skilled in the art and commercially available in many different structures.
Scheme 7:

=4 p-4 ,N4 R11_C(=0)0H

XXVI p.
Ric *
Coupling agent R" *
lk Rlb Rib Ril Abbreviations:
ACN acetonitrile Boc tert-butoxycarbonyl CDC13 deuterochloroform CO2 carbon dioxide day DMF dimethylformamide DMSO dimethyl sulphoxide ESI electrospray ionization (in MS) sat. saturated hour HPLC high-pressure, high-performance liquid chromatography conc. concentrated LC-MS liquid chromatography-coupled mass spectrometry min minutes MS mass spectrometry MW molecular weight [g/mol]
NMP N-methylpyrrolidone NMR nuclear magnetic resonance spectroscopy RT room temperature Rt retention time (in HPLC) SFC supercritical fluid chromatography THF tetrahydrofuran LC-MS Methods:
Method 1: Instrument: Waters Acquity LCT; column: Phenomenex Kinetex C18, 50 mm x 2.1 mm, 2.6 ft; mobile phase A: water/0.05% FA, mobile phase B: ACN/0.05% FA;
gradient: 0.0 min 98%
A 4 0.2 min: 98% A 1.7 min: 10% A - 1.9 min: 10% A 2 min: 98% A 4 2.5 min:
98% A;
flow rate: 1.3 ml/min; column temperature: 60 C; UV detection: 200-400 nm.
Method 2: Instrument: Waters Acquity Platform ZQ4000; column: Waters BEHC 18, 50 mm x 2.1 mm, 1.7 II; mobile phase A: water/0.05% FA, mobile phase B: ACN/0.05% FA;
gradient: 0.0 min 98% A -) 0.2 min: 98% A -4 1.7 min: 10% A -4 1.9 min: 10% A - 2 min: 98% A
2.5 min:
98% A; flow rate: 1.3 ml/min; column temperature: 60 C; UV detection: 200-400 nm.

Method 3: UPLC-SQD-HCOOH; instrument: Waters Acquity UPLC-MS SQD; column:
Acquity LTPLC BEH C18 1.7 50x2.1 mm; mobile phase A: water + 0.1% by volume of formic acid (99%), mobile phase B: acetonitrile; gradient: 0-1.6 min 1-99% B, 1.6-2.0 min 99% B;
flow rate 0.8 ml/min; temperature: 60 C; injection: 2 ul; DAD scan: 210-400 nm.
Preparative HPLC methods:
Method III: System: Dionex Pump P 580, Gilson Liquid Handler 215, Knauer UV
detector K-2501;
column: Chiralpak IC 5i.tm 250x30 mm; mobile phase: hexane / ethanol 70:30 (v/v); flow rate: 50 ml/min; column temperature: 25 C; detection: UV 254 nm.
Method X: System: Agilent: Prep 1200, 2xPrep Pump, DLA, MWD, Prep FC; column:
Chiralpak IC 5 m 250x30 mm; mobile phase: ethanol/methanol/diethylamine 50:50:0.1 (v/v/v); flow rate: 30 ml/min; temperature: RT; detection: UV 280 nm.
Method XI: System: Agilent: Prep 1200, 2xPrep Pump, DLA, MWD, Prep FC; column:
Chiralpak IC 51.tm 250x20 mm; mobile phase: methanol/diethylamine 100:0.1 (v/v); flow rate: 20 ml/min;
temperature: RT; detection: UV 280 nm.
Method XII: System: Agilent: Prep 1200, 2xPrep Pump, DLA, MWD, Prep FC;
column: Chiralpak IC 51.tm 250x30 mm; mobile phase: hexane/ethanol/diethylamine 70:30:0.1 (v/v/v); flow rate: 50 ml/min; temperature: RT; detection: UV 280 nm.
Method XIII: System: Sepiatec: Prep SFC 100, Prep FC; column: Chiralpak IC Sum 250x20 mm;
mobile phase: CO2 / ethanol 7/3; flow rate: 80 ml/min; temperature: 40 C;
detection: UV 254 nm.
Method XIV: System: Agilent: Prep 1200, 2xPrep Pump, DLA, MWD, Prep FC;
column:
Chiralpak ID 51.1m 250x20 mm; mobile phase: hexane/2-propanol/diethylamine 70:30:0.1 (v/v/v);
flow rate: 25 ml/min; temperature: RT; detection: UV 280 nm.
Analytical HPLC methods:
Method C: System: Waters Alliance 2695, DAD 996; column: Chiralpak IC 31.tm 100x4.6 mm;
mobile phase: hexane / ethanol 70:30 (v/v); flow rate: 1.0 ml/min; column temperature: 25 C;
detection: DAD 254 nm.
Method F: System: Waters Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak ID 3 m 100x4.6 mm; mobile phase: hexane / 2-propanol 70:30 (v/v) +0.1% DEA; flow rate: 1.0 ml/min;
column temperature: 25 C; detection: DAD 254 nm.
Method G: System: Waters Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak IC 3 m 100x4.6 ntm; mobile phase: ethanol/methanol/DEA 50:50:0.1 (v/v/v); flow rate:
1.0 ml/min;
column temperature: 25 C; detection: DAD 254 nm.
Method H: System: Waters: Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak IA 5p.m 150x4.6 mm; mobile phase: hexane/2-propanol/diethylamine 70:30:0.1 (v/v/v);
flow rate: 1.0 ml/min; column temperature: 25 C; detection: DAD 210 nm.
Method I: System: Waters: Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak IC 5 m 150x4.6 mm; mobile phase: methanol 100 (v); flow rate: 1.0 ml/min; column temperature: 25 C;
detection: DAD 280 nm.
Method J: System: Waters: Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak IC 51tm 150x4.6 mm; mobile phase: hexane / ethanol 70:30 (v/v); flow rate: 1.0 ml/min;
column temperature: 25 C; detection: DAD 280 nm.
Method K: System: Waters: Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak IA 5 m 150x4.6 mm; mobile phase: methanol 100 (v); flow rate: 1.0 ml/min; column temperature: 25 C;
detection: DAD 280 nm.
Method L: System: Agilent: 1260 AS, MWD, Aurora SFC module; column: Chiralpak 1D 5 m 100x4.6 mm; mobile phase: CO2 / 2-propanol / diethylamine 6:4:0.2; flow rate:
4.0 ml/min;
pressure (outlet): 100 bar; column temperature: 37.5 C; detection: UV 254 nm.
Method M: System: Agilent: 1260 AS, MWD, Aurora SFC module; column: Chiralpak IC 5 m 100x4.6 mm; mobile phase: CO2 / methanol 70:30; flow rate: 4.0 ml/min;
pressure (outlet): 100 bar; column temperature: 37.5 C; detection: DAD 254 nm.
Method N: System: Agilent: 1260 AS, MWD, Aurora SFC module; column: Chiralpak ID 51.1m 100x4.6 mm; mobile phase: CO2 / 2-propanol 70:30; flow rate: 4.0 ml/min;
pressure (outlet): 100 bar; column temperature: 37.5 C; detection: DAD 254 nm.
Method 0: System: Alliance 2695, DAD 996, ESA: Corona; column: Chiralpak AD-H
Sum 150x4.6 mm; mobile phase: hexane/ethanol 70:30 (v/v) +0.1% DEA; flow rate: 1 ml/min;
temperature: 25 C; detection: DAD 280 nm.
Method P: System: Alliance 2695, DAD 996, ESA: Corona; column: Chiralpak IC
3nm 100x4.6 mm; mobile phase: methanol/diethylamine 100:0.1 (v/v); flow rate: 1 ml/min;
temperature: 25 C;
detection: DAD 280 nm.
Method Q: System: Waters: Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak IC 3 m 100x4.6 mm; mobile phase: hexane/ethanol/diethylamine 70:30:0.1 (v/v/v); flow rate: 1.0 ml/min;
column temperature: 25 C; detection: DAD 280 nm.
Method R: System: Agilent: 1260 AS, MWD, Aurora SFC module; column: Chiralpak IC 31.1m 100x4.6 mm; mobile phase: CO2 / ethanol 70:30; flow rate: 4.0 ml/min; pressure (outlet): 100 bar;
column temperature: 37.5 C; detection: DAD 254 nm.

Method S: System: Waters: Alliance 2695, DAD 996, ESA: Corona; column:
Chiralpak ID 311m 100x4.6 mm; mobile phase: hexane/2-propanol/diethylamine 70:30:0.1 (v/v/v);
flow rate: 1.0 ml/min; column temperature: 25 C; detection: DAD 280 nm.
Preparation of the intermediates Example 1A
(2E)-3[4-Chloro-3-(trifluoromethoxy)pheny1]-2-methylacrylic acid O
F
OH

CI
10.0 g (44.5 mmol) of 4-chloro-3-(trifluoromethoxy)benzaldehyde (CAS [886499-59-8]), 7.53 g (57.9 mmol) of propionic anhydride and 4.49 g (46.8 mmol) of sodium propionate (CAS [137-40-6]) were combined under argon and stirred at 150 C for 5 h. Water was added to the warm mixture and the mixture was extracted 3x with ethyl acetate. The combined organic phases were dried with sodium sulphate and the solvent was removed on a rotary evaporator. This gave 11.68 g (88% of theory) of the crude product which was converted further without further purification.
LCMS (Method 2): R, = 1.31 min; ni/z [ES] = 279 (M-H)-1H-NMR (300MHz, CDC13): ö = 2.13 (d, 3H), 7.30 (dd, 1H), 7.38 (s, 1H), 7.52 (d, 1H), 7.73 (s, 1H).
Example 2A
( )-3[4-Chloro-3-(trifluoromethoxy)pheny1]-2-methylpropanoic acid O
Fl CI
In the presence of 289 mg of palladium catalyst (10% Pd on activated carbon, 0.27 mmol), 10.0 g (35.6 mmol) of (2E)-3-[4-chloro-3-(trifluoromethoxy)pheny1]-2-methylacrylic acid (Example 1A) in 200 ml of ethyl acetate were hydrogenated at RT for 12 h with vigorous shaking (1 atm hydrogen atmosphere). The catalyst was then filtered off, the filtercake was washed with ethyl acetate and the filtrate was concentrated on a rotary evaporator. This gave 11.04 g (99%) of crude product which is reacted without further purification.

LCMS (Method 2): R, = 1.27 min; m/z [ES] = 281 (M-H)-1H-NMR (400MHz, CDC13): 5 = 1.21 (d, 3H), 2.67-2.81 (m, 2H), 2.98-3.09 (m, 1H), 7.08 (dd, 1H), 7.16 (s, 1H), 7.38 (d, 1H).
Example 3A
( )-6-Chloro-2-methy1-5-(trifluoromethoxy)indan-1-one F F
IP. CH3 C I

With ice bath cooling, 26.3 g (225.7 mmol) of chlorosulphonic acid (CAS [7790-94-5]) were added carefully to 10.0 g (35.38 mmol) of ( )-344-chloro-3-(trifluoromethoxy)pheny1]-methylpropanoic acid (Example 2A), and the mixture was stirred in the ice bath for a further 3 h.
Since the conversion was still incomplete, the mixture was stirred at 7 C for a further 12 h. The reaction was then terminated by careful additon of crushed ice, a little at a time. The mixture was extracted three times with ethyl acetate and the combined organic phases were washed with sat.
sodium bicarbonate solution and dried with sodium sulphate. The solvents were removed on a rotary evaporator and the residue (10 g) was used for the next synthesis step without further purification.
LCMS (Method 2): Rt = 1.36 min; m/z = 306 (M+ACN)+
'H-NMR (300MHz, CDC13): 5 = 1.32 (d, 3H), 2.68-2.84 (m, 2H), 3.33-3.47 (m, 1H), 7.40 (s, 1H), 7.85 (s, 1H).
Example 4A
2,2-Dimethy1-5[4-(trifluoromethoxy)benzy1)-1,3-dioxane-4,6-dione CH, CH, 25.4 g (134 mmol) of 4-(trifluoromethoxy)benzaldehyde (CAS [659-28-9]), 19.3 g (134 mmol) of Meldrum's acid (2,2-dimethy1-1,3-dioxane-4,6-dione, CAS [2033-24-1]) and 1.93 g (13.4 mmol) of piperidinium acetate (CAS [4540-33-4]) were dissolved in 500 ml of ethanol, and the mixture was stirred at RT for 30 min. The reaction solution was cooled to 0 C using an ice bath and stirred for a further 10 min. 12.6 g (200 mmol) of sodium cyanoborohydride were introduced a little at a time and the mixture was allowed to warm to RT and stirred for a further 1.5 h. 250 ml of 2M
hydrochloric acid were then added carefully and stirring was continued until the evolution of gas had ceased completely (about 30 min). The ethanol was removed on a rotary evaporator, the residue was taken up in 2M hydrochloric acid and the mixture was extracted repeatedly with dichloromethane. The combined organic phases were dried with sodium sulphate and the solvent was removed on a rotary evaporator. This gave 32.7 g (41% of theory) of crude product as a white solid which was converted further without further purification.
LCMS (Method 1): R = 1.33 min; m/z = 319 (M+H)+
Example 5A
2,2,5-Trimethy1-5[4-(trifluoromethoxy)benzy1]-1,3-dioxane-4,6-dione CH, FF>r0 = 0 0 At RT, 32.7 g (103 mmol) of 2,2-dimethy1-544-(trifluoromethoxy)benzy1]-1,3-dioxane-4,6-dione (Example 4A) and 21.3 g (154 mmol) of potassium carbonate were initially charged in 400 ml of DMF, and 72.9 g (514 mmol, 32.0 ml) of iodomethane were slowly added dropwise.
The mixture was stirred vigorously at RT for 1.5 h and then added to water. The mixture was extracted 3x with ethyl acetate, the combined organic phases were washed with sat. sodium chloride solution and dried with sodium sulphate. The solvents were removed on a rotary evaporator and the crude product (32.5 g colourless oil) was purified by flash chromatography (Si02, hexane/ethyl acetate).
This gave 20.0 mg (55% of theory) of the desired product as a colourless oil.
1H-NMR (300MHz, DMSO-d6): 8 = 0.99 (s, 3H), 1.57 (s, 3H), 1.63 (s, 3H), 3.22 (s, 2H), 7.12 (d, 2H), 7.31 (s, 2H).
Example 6A
( )-2-Methyl-3[4-(trifluoromethoxy)phenyl]propanoic acid 19.0 g (57.2 mmol) of 2,2,5-trimethy1-5[4-(trifluoromethoxy)benzy1]-1,3-dioxane-4,6-dione (Example 5A) were taken up in 90 ml of dioxane and 35 ml of conc. aqueous hydrochloric acid and heated under reflux at 125 C for 2 h. The mixture was allowed to cool and the solvents were removed on a rotary evaporator. The residue (19.5 g of a colourless resin) was heated at 200 C for 1 h. The crude product obtained was reacted further without further purification.
LCMS (Method 2): R, = 1.21 min; m/z [ES-] = 247 (M-H)-'H-NMR (300MHz, DMSO-d6): = 1.12 (s, 3H), 3.06 (s, 2H), 7.21 - 7.27 (m, 4H).
Example 7A
( )-2-Methy1-6-(trifluoromethoxy)indan-1-one F la* CH3 17.2 g (69.3 mmol) of crude ( )-2-methyl-3[4-(trifluoromethoxy)phenyl]propanoic acid (Example 6A) were dissolved in 100 ml of dichloromethane, and 12.1 ml (16.6 g, 166 mmol) of thionyl chloride and 0.16 ml of DMF were added dropwise at RT. The mixture was then heated under reflux for about 30 min until the evolution of gas had ceased. The solution was allowed to cool and the solvents were removed on a rotary evaporator. The residue (yellow solid) was taken up in 35 ml of dichloromethane and, at RT, added dropwise to a suspension of 10.2 g (76.2 mmol) of anhydrous aluminium chloride in 200 ml of dichloromethane. The dark-red solution was stirred for 30 min and then added to water and the phases were separated. The aqueous phase was extracted 3x with dichloromethane. The combined organic phases were washed with water, sat. sodium bicarbonate solution and sat. sodium chloride solution and dried with sodium sulphate. The solvents were removed and the residue (10.0 g) was purified by flash chromatography (Si02, hexane/dioxane). This gave 5.84 mg (14% of theory) of the product as a yellow oil.
LCMS (Method 2): R, = 1.27 min; m/z = 231 (M+H)'; 272 (M+ACN1H-H)+

Example 8A
5-Chloro-3-(4-chloropheny1)-2-methy1-6-(trifluoromethoxy)-1H-indene F F

CI
CI
Under argon, 10.6 g (40.06 mmol) of ( )-6-chloro-2-methy1-5-(trifluoromethoxy)indan-1-one (Example 3A) were initially charged in 30 ml of THF, and 60.1 ml of 4-chlorophenylmagnesium bromide (1M in diethyl ether, 60.1 mmol) were slowly added dropwise at RT such that the temperature of the solution stayed below 30 C. The solution was left to stir at RT for a further 16 h, and water was then added. The mixture was extracted 3x with ethyl acetate and the combined organic phases were dried with sodium sulphate and the solvent was removed on a rotary evaporator. The residue was taken up in 300 ml of dichloromethane, 55 mg of 4-toluenesulphonic acid monohydrate were added and the mixture was stirred at RT for 16 h. The reaction mixture was added to sat. sodium bicarbonate solution and extracted lx with dichloromethane and 2x with ethyl acetate, the combined organic phases were washed with sat. sodium chloride solution and dried with sodium sulphate and the solvent was removed on a rotary evaporator. The residue was purified by flash chromatography (Si02, hexane/ethyl acetate). This gave 11.19 g (65%
of theory) of the product.
LCMS (Method 2): R, = 1.81 min; m/z = 360 (M H)+
11-1-NMR (400MH.z, CDC13): 5 = 2.13 (s, 3H), 3.46 (s, 2H), 7.20 (s, 1H), 7.29 (d, 2H), 7.38 (s, br, 1H), 7.46 (d, 2H).

Analogously to Example 8A, the following compound was prepared from Example 7A:
No. Structure Name Analytical data 1 11011 CH, 3-(4-Chloropheny1)-2-methyl-5- LCMS
(Method 1): Rt = 1.76 min;

(trifluoromethoxy)-1H- miz = 325 (M+H)+
indene CI
Example 10A
144-Chloro-2-(4-chlorobenzoy1)-5-(trifluoromethoxy)phenyl]propan-2-one C I
C' 11 g (30.63 mmol) of 5-chloro-3-(4-chloropheny1)-2-methyl-6-(trifluoromethoxy)-1H-indene (Example 8A) were initially charged in 206 ml of a 2:2:3 mixture of n-hexane, acetonitrile and water, and 138 mg (0.61 mmol) of ruthenium(III) chloride hydrate (CAS 1j14898-67-0]) were added. The mixture was cooled to 0 C, and 13.1 g (61.3 mmol) of sodium periodate were added a little at a time over a period of 1 h. After 3 h of stirring with ice bath cooling, water was added and the mixture was extracted 3x with ethyl acetate. The combined organic phases were filtered through a water-separating filter and the solvents were then removed on a rotary evaporator. The residue was purified by flash chromatography. This gave 2.24 g (19% of theory) of the product.
LCMS (Method 1): R = 1.54 min; miz = 391, 393 (C1 isotope pattern, M+H)+
11-I-NMR (300MHz, CDC13): 8 -= 2.20 (s, 3H), 4.04 (s, 2H), 7.21 (s, br, 1H), 7.45-7.53 (m, 3H), 7.77 (d, 2H).

, Analogously to Example 10A, the following compound was prepared from the corresponding 2-methy1-1H-indene 9A:
No. Structure Name Analytical data 0 CH, 1H-NMR (400MHz, DMSO-d6): 8 = 2.05 (s, 3H), 3.98 (s, 2H), 7.31 ¨
*
0 1-[2-(4-Chlorobenzoy1)-4- 7.33 (m, 1H), 7.46 (d, 1H), 7.50 ¨
11A F-0F 7.56 (m, 1H), 7.60 (d, 2H), 7.68 (d, (trifluoromethoxy)phen 141 yl]propan-2-one 2H).
LCMS (Method 1): R, = 1. 45 min;
01 m/z = 357 (M+H)+
Example 12A
( )-1-(3,4-Dimethoxyphenyl)propan-2-ol At 0 C, 147 mg (3.86 mmol) of lithium aluminium hydride were initially charged in 30 ml of THF, and 1.00 g (5.15 mmol) of 1-(3,4-dimethoxyphenyl)propan-2-one (CAS [776-99-81), dissolved in 10 ml of Tiff, were added dropwise. The mixture was stirred at 0 C for 2 h, and 0.1 ml of water, 0.1 ml of 2M aqueous sodium hydroxide solution and a further 0.3 ml of water were then added carefully. After a further 30 min of stirring at RT, the mixture was filtered through silica gel/sodium sulphate, the filter cake was washed with ethyl acetate and the filtrate was concentrated on a rotary evaporator. This gave 950 mg of product (82% of theory) which was directly reacted further.
LCMS (Method 2): It, = 0.82 min; m/z = 197 (M+H)+; 179 (M-H2O+H)' 111-NMR (300MHz, DMSO-d6): 8 = 0.98 (d, 3H), 2.43 (dd, 1H), 2.59 (dd, 1H), 3.67 (s, 3H), 3.69 (s, 3H), 3.70 ¨ 3.79 (m, 1H), 4.43 (d, 1H), 6.65 (dd, 1H), 6.75 (d, 1H), 6.79 (d, 1H).

Example 13A
( )-1-(4-Bromopheny1)-3,4-dihydro-6,7-dimethoxy-3-methy1-1H-2-benzopyran H C

Br At RT, 349.2 g (1.779 mol) of ( )-1-(3,4-dimethoxyphenyl)propan-2-ol (Example 12A) and 329.2 g (1.779 mol) of 4-bromobenzaldehyde (CAS [1122-91-4]) were initially charged in 3 1 of toluene, 140 ml of hydrochloric acid (36% strength aqueous solution) were added and the mixture was stirred at RT for 2 days. The mixture was then poured into 2 1 of water and extracted 2x with in each case 2 1 of ethyl acetate, and the combined organic phases were washed lx with sat. aqueous sodium bicarbonate solution and lx with 2 1 of water and dried with sodium sulphate. The solvent was reduced on a rotary evaporator. The product precipitated as a colourless solid. Just before dryness, 1 1 of hexane was added and the mixture was cooled in an ice bath.
The solid was filtered off with suction, washed with hexane and then dried under reduced pressure at 50 C. This gave 598.9 g (93% of theory) of the product (isomer mixture) which was directly converted further without further purification.
LCMS (Method 2): R = 1.44 min; m/z = 363; 365 (Br isotope pattern, M+H)+
Analogously to Example 13A, the following compounds were prepared from Example 12A and 3-bromobenzaldehyde or 3-bromo-4-fluorobenzaldehyde:
No. Structure Name Analytical data CH3 ( )-1-(3-H C
H33C,..o 0 Bromopheny1)-3,4- LCMS (Method 3): R, = 1.40 min;
14A dihydro-6,7- m/z = 363; 365 (M+H, Br isotope dimethoxy-3-methyl- pattern)+
Br 1H-2-benzopyran No. Structure Name Analytical data H3C ( )-1-(3-bromo-4-H3C.,o 0 fluoropheny1)-6,7- LCMS
(Method 3): R, = 1.44 min;
15A dimethoxy-3-methyl- m/z = 381; 383 (Br isotope pattern, 1.1 3,4-dihydro-1H-2- M+H)+
Br benzopyran Example 16A
1-[2-(4-Bromobenzoy1)-4,5-dimethoxyphenyl]propan-2-one (10 Br Preparation ofJones reagent:
267g of chromium-VI oxide (Cr03) were carefully introduced into 230 ml of sulphuric acid (95-97%). Using water ice and water, the reaction was cooled such that the internal temperature was 35-40 C. Initially, orange crystals were formed, which slowly dissolved with addition of water.
After 500 ml of water had been added, everything apart from a small sediment had gone into solution. The mixture was stirred at RT for 30 min and then transferred into a bottle and made up to 1000 ml with water. This gave an about 2.6 M solution.
496.5 g (1.367 mol) of ( )-1-(4-bromopheny1)-3,4-dihydro-6,7-dimethoxy-3-methyl-IH-2-benzopyran (Example 13A) were initially charged in 5 1 of acetone, the mixture was cooled to 0 C
and 50 g of silica gel were added. 1.9 1 of chromium trioxide in sulphuric acid (Jones reagent) were then added dropwise over 4 h and the mixture was stirred at RT for 1 h. After the reaction had gone to completion, 4 1 of water were added slowly to the reaction mixture. The mixture was extracted 3x with 4 1 of ethyl acetate each time. The combined organic phases were washed with 4 1 of sat.
sodium bicarbonate solution and 3x with in each case 4 1 of aqueous sodium chloride solution and dried with sodium sulphate. The solvent was reduced on a rotary evaporator.
The product precipitated as a colourless solid. Just before dryness, 500 ml of hexane were added and the mixture was cooled in an ice bath. The solid was filtered off with suction, washed with hexane and then dried under reduced pressure at 50 C. This gave 334.1 g (65% of theory) of the product which was directly converted further without further purification.

LCMS (Method 2): R, = 1.26 min; m/z = 377; 379 (Br isotope pattern, M+H)+
'H-NMR (300MHz, DMSO-d6): 8 = 2.07 (s, 3H), 3.66 (s, 3H), 3.83 (s, 3H), 3.89 (s, 2H), 6.91 (s, 1H), 6.97 (s, 1H), 7.61 (d, 2H), 7.72 (d, 2H).

Analogously to Example 16A, Examples 14A and 15A were used to prepare the following diketones:
No. Structure Name Analytical data H,C 140 LCMS
(Method 3): Rt = 1.21 min;
Bromobenzoy1)-4,5-17A H3c,..0 0 m/z = 377;
379 (M-+H, Br isotope dimethoxyphenyl]prop a pattern) n-2-one Br H
H CCO 142-(3-Bromo-4- LCMS
(Method 3): R, = 1.25 min;
fluorobenzoy1)-4,5-18A 0 m/z = 395;
397 (Br isotope pattern, dimethoxyphenyl]prop M+H) an-2-one +
Br Example 19A
1-(4-Bromopheny1)-7,8-dimethoxy-4-methy1-5H-2,3-benzodiazepine o 0 " N

Br At 0 C, 471 g (1.249 mol) of 142-(4-bromobenzoy1)-4,5-dimethoxyphenyl]propan-2-one (Example 16A) were initially charged in 4.5 1 of ethanol, and 402 ml of hydrazine hydrate (6.62 mol) were added dropwise. The mixture was allowed to come to RT and stirred at this temperature for 2 days.
The mixture was decanted off from the solid and the clear supernatant was concentrated on a rotary evaporator. 8 I of ice-water were added, resulting in the precipitation of a beige solid. The suspension was stirred for 2 days, and the precipitate was filtered off with suction, washed with water and then dried under reduced pressure at 50 C. This gave 409.8 g (88% of theory) of the product which was directly converted further without further purification.

LCMS (Method 2): 12, = 1.20 min; m/z = 373; 375 (Br isotope pattern, M+H) 11-1-NMR (300MHz, DMSO-d6): 5 = 2.04 (s, 3H), 2.72 (d, 1H), 3.44 (d, 1H), 3.62 (s, 3H), 3.85 (s, 3H), 6.72 (s, 1H), 7.09 (s, 1H), 7.53 (d, 2H), 7.64 (d, 2H).
Analogously to Example 19A, Examples 10A, 11A, 17A and 18A were used to prepare the following 5H-2,3-benzodiazepines:
No. Structure Name Analytical data 'H-NMR (300MHz, CDC13): 6 =
2.15 (s, 3H), 2.98 (d, 1H), 3.27 (d, CH, 4;) 1H), 3.75 (s, 3H), 3.97 (s, 3H), H3C 40/\ 1-(3-Bromopheny1)-N 6.73 (s, 1H), 6.75 (s, 1H), 7.27 (dd, /
H3C0 ---"N 7,8-dimethoxy-4-20A 1H), 7.55 (dbr, 1H), 7.61 (dbr, 1H), methyl-5H-2,3-= benzodiazepine 7.86 (m, 1H).
LCMS (Method 3): R, = 1.15 min;
Br 111/Z = 373; 375 (M+H, Br isotope pattern)+
'H-NMR (400MHz, CDC13): 6 =

2.16 (s, 3H), 2.99 (d, 1H), 3.29 (d, ,0 H,C * \
1 -(3-bromo-4- 1H), 3.77 (s, 3H), 3.98 (s, 3H), H3C,.
0 ---N fluoropheny1)-7,8- 6.74 (s, 2H), 7.16 (dd, 1H), 7.62 dimethoxy-4-methyl- (ddd, 1H), 7.94 (dd, 1H).
5H-2,3-benzodiazepine LCMS (Method 3): 12, = 1.21 min;
Br = 381; 383 (Br isotope pattern, M+H)+
'H-NMR (300MHz, CDC13): 8 =

F
8-Chl oro-1 -(4- 2.20 (s, 3H), 3.10 (d, 1H), 3.40 (d, F N/N chloropheny1)-4- 1H), 7.29 (s, br, 2H), 7.45 (d, 2H), Ci 22A methyl-7- 7.62 (d, 2H).
4410 (trifluoromethoxy)-5H- LCMS (Method 1): R, = 1.55 min;
2,3-benzodiazepine m/z = 387 (C1 isotope pattern, Cl M+H)+

No. Structure Name Analytical data CH, 11-1-NMR
(400MHz, DMSO-d6): 8 F1 40 \ N 1-(4-chloropheny1)-4- = 2.05 (s, 3H), 2.89 (d, 1H), 3.61 F4.0N methyl-8- (d, 1H), 7.20 (s, br, 1H), 7.49 ¨
F
(trifluoromethoxy)-5H- 7.54 (m, 4H), 7.59 ¨ 7.66 (m, 2H).
2,3-benzodiazepine LCMS
(Method 1): Rt = 1.44 min;
ci m/z = 353 (M+H) Example 24A
( )-1-(4-Bromopheny1)-7,8-dimethoxy-4-methy1-4,5-dihydro-3H-2,3-benzodiazepine CH, FI,C
NH

Br At RT, 1.99 g (5.33 mmol) of 1-(4-bromopheny1)-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine (Example 19A) were initially charged in 200 ml of methanol, 3.0 ml of 2M
hydrochloric acid were added and 1.68 g (26.6 mmol) of sodium cyanoborohydride were introduced. The mixture was stirred at RT for 1 h and then made alkaline with 2M aqueous sodium hydroxide solution (pH about 8). Most of the methanol was removed on a rotary evaporator, and the residue was partitioned between water and dichloromethane. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with sat. sodium chloride solution and dried with sodium sulphate and the solvent was removed on a rotary evaporator. The residue was purified by flash chromatography (Si02, hexane/ethyl acetate). This gave 1.56 g(78% of theory) of the product as a yellow resin which crystallized.
LCMS (Method 2): R, = 0.96 min; m/z = 375; 377 (Br isotope pattern, M+H) 11-1-NMR (400MHz, DMSO-d6): 8 = 1.09 (d, 3H), 2.58 (dd, 1H), 2.83 (dd, 1H), 3.27 (s, 3H), 3.51 (s, 3H), 3.77 ¨ 3.82 (m, 1H), 6.47 (s, 1H), 6.85 (s, 1H), 7.01 (d, 1H), 7.33 (d, 2H), 7.47 (d, 2H).

Analogously to Example 24A, Examples 20A, 21A, 22A and 23A were used to prepare the following 4,5-dihydro-3H-2,3-benzodiazepines:
No. Structure Name Analytical data 'H-NMR (300MHz, CDC13): ö =
1.28 (d, 3H), 2.62 (dd, 1H), 2.89 /10 ( )-1-(3- (dd, 1H), 3.71 (s, 3H), 3.94 (s, 3H), NH
H C Bromopheny1)-7,8- 4.11 (m, 1H), 6.59 (s, 1H), 6.76 (s, N

25A dimethoxy-4-methyl- 1H), 7.22 (dd, 1H), 7.45 (dbr, 1H), 4,5-dihydro-3H-2,3- 7.48 (dbr, 1H), 7.75 (m, 1H).
benzodiazepine LCMS (Method 3): R, = 0.99 min;
Br rniz 375; 377 (M+H, Br isotope pattern)+
'H-NMR (400MHz, CDC13): ö =
0-13 1.29 (d, 3H), 2.61 (dd, 1H), 2.89 H3C.- *NH
( )-1-(3-Bromo-4- (dd, 1H), 3.72 (s, 3H), 3.95 (s, 3H), H3C, fluoropheny1)-7,8- 4.12 (m, 1H), 6.57 (s, 1H), 6.77 (s, 26A dimethoxy-4-methyl- 1H), 7.10 (dd, 1H), 7.45 (ddd, 1H), = 4,5-dihydro-3H-2,3- 7.81 (dd, 1H).
benzodiazepine LCMS (Method 3): R, = 1.03 min;
Br rniz = 393; 395 (Br isotope pattern, M+H)+
'H-NMR (300MHz, CDCI3): 8 =
CH3 ( )-8-Chloro-1-(4- 1.34 (d, 3H), 2.72 (dd, 1H), 2.99 Fe.õ0 NH chloropheny1)-4- (dd, 1H), 4.07-4.21 (m, 1H), 7.24 F 401:1 ci N methyl-7- (s, br, 2H), 7.39 (d, 2H), 7.49 (d, (trifluoromethoxy)-4,5- 2H).
dihydro-3H-2,3- LCMS (Method 1): R, = 1.63 min;
01 benzodiazepine m/z = 389 (C1 isotope pattern, M+H)+
III-NMR (400MHz, DMSO-d6):
CH3 ( )-1-(4-= 1.10 (d, 3H), 2.75 (dd, 1H), 2.99 NH Chloropheny1)-4-(dd, 1H), 3.76 ¨ 3.83 (m, 1H), 6.84 F4=0 =--N methyl-8-28A F (s, br, 1H), 7.21 ¨ 7.24 (m, 1H), 411k1 (trifluoromethoxy)-4,5-dihydro-3H-2,3- 7.32 ¨ 7.38 (m, 5H), 7.64 (s, br, 1H).
benzodiazepine Cl LCMS (Method 2): R, = 1.50 min;

No. Structure Name Analytical data m/z = 355 (WH)' Example 29A
( )-1-(4-Bromopheny1)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide Br At RT, 1.56 g (4.16 mmol) of ( )-1-(4-bromopheny1)-7,8-dimethoxy-4-methy1-4,5-dihydro-3H-2,3-benzodiazepine (Example 24A) were dissolved in 50 ml of THF, 1.68 g (8.31 mmol) of 4-nitrophenyl chloroformate (CAS [7693-46-1]) were added dropwise and the mixture was stirred at RT for 1 h. During this time, the clear yellow solution slowly became turbid.
20.8 ml (41.6 mmol) of a 2M solution of methylamine in THF were added dropwise and the mixture was stirred at 60 C
for 5 h. The mixture was allowed to cool to RT, concentrated on a rotary evaporator and partitioned between water and ethyl acetate and the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with sat. sodium chloride solution and dried with sodium sulphate and the solvent was removed on a rotary evaporator. Since the reaction was incomplete (monitored by UPLC/MS), the reaction was carried out once more in an analogous manner using the crude product/intermediate/starting material mixture obtained to achieve complete conversion. The crude product then obtained was purified by flash chromatography (Si02, hexane/ethyl acetate). This gave 1.90 g (100% of theory) of the desired product as a yellow foam.
LCMS (Method 2): R, = 1.33 min; m/z = 432; 434 (Br isotope pattern, M+H) 1H-NMR (400MHz, DMSO-d6): 5 = 0.92 (d, 3H), 2.64 (d, 3H), 2.67 (dd, 1H), 2.91 (dd, 1H), 3.53 (s, 3H), 3.80 (s, 3H), 5.03 ¨ 5.11 (m, 1H), 6.47 (s, 1H), 6.60 (q, 1H), 6.98 (s, 1H), 7.56 (s, 4H).
Enantiomer separation 19.9 g of the compound prepared under 29A were separated into the enantiomers by chiral preparative HPLC under the following conditions:
System: SFC Prep 400; column: Chiralpak AZ-H 5 im 250x50 mm; mobile phase: CO2 /

isopropanol 75:25 (v/v); flow rate: 300 ml/min; temperature: 38 C; pressure 80 bar; solution: 5 g /
100 ml of methanol / acetonitrile 50:50 (v/v); detection: UV 220 nm.

Example 29-1A:
(4R)-1-(4-Bromopheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 9.29 g, light-yellow solid, HPLC (Method F): R = 3.29 min, purity > 99%
optical rotation: [a]D2 = -89.3 (c = 1.00; methanol) Example 29-2A:
(45)-1-(4-Bromopheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 9.9 g, light-yellow solid, HPLC (Method F): Rt = 4.55 min, purity 96%
optical rotation: [a]D2 = +81.3 (c = 1.00; methanol) Analogously to Example 29A, the following compounds were prepared from the corresponding 4,5-dihydro-3H-2,3-benzodiazepines 25A, 26A, 27A und 28A. Completeness of the conversion into the 4-nitrophenylcarbamate formed as an intermediate or to the methylurea was checked by UPLC/MS. If the conversion was incomplete, the reaction was once more carried out analogously using the crude product mixture.
No. Structure Name Analytical data 1H-NMR (500MHz, CDC13): =
0.95 (d, 3H), 2.86 (dd, 1H), 2.90 ( )-1-(3-(d, 3H), 3.12 (dd, 1H), 3.66 (s, N¨<
Bromopheny1)-7,8-I-1,C
dimethoxy-N,4- 3H), 3.93 (s, 3H), 5.48 (m, 1H), H,c, 0 ¨N NH6.50 (m, 1H), 6.54 (s, 1H), 6.71 (s, H3C/ dimethy1-4,5-dihydro-1H), 7.26 (dd, 1H), 7.39 (dbr, 1H), 3H-2,3-benzodiazepine-3- 7.52 (dbr, 1H), 7.64 (m, 1H).
Br LCMS (Method 3): Rt = 1.27 min;
carboxamide m/z = 432; 434 (M+H, Br isotope pattern)+

No. Structure Name Analytical data 1H-NMR (400MHz, CDC13): =
0.95 (d, 3H), 2.86 (dd, 1H), 2.90 (+)-1-(3-bromo-4-CH3 (d, 3H), 3.10 (dd, 1H), 3.67 (s, H:o' * dimethoxy-N,4-o fluoropheny1)-7,8-3H), 3.93 (s, 3H), 5.48 (m, 1H), H C
0 N NH 6.44 (m, 1H), 6.52 (s, 1H), 6.71 (s, 31A H,C dimethy1-4,5-dihydro-* 3H-2,3- 1H), 7.14 (dd, 1H), 7.39 (ddd, 1H), 7.69 (dd, 1H).
benzodiazepine-3-Br LCMS (Method 3): R, = 1.31 min;
carboxamide m/z = 450; 452 (Br isotope pattern, WH)' 1H-NMR (400MHz, CDC13): 5 =
( )-8-Chloro-1-(4- 0.95 (d, 3H), 2.92 (d, 3H), 2.96 CH, FO 0 chloropheny1)-N,4- (dd, 1H), 3.16 (dd, 1H), 5.51-5.60 1.1 714 dimethy1-7- (m, 1H), 6.50 (q, 1H), 7.22 (s, 1H), Cl N NH
32A H,C (trifluoromethoxy)-4,5- 7.23 (s, 1H), 740 (d, 2H), 7.43 (d, = dihydro-3H-2,3- 2H).
benzodiazepine-3- LCMS (Method 1): R, = 1.61 min;
Cl carboxamide m/z = 446 (CI isotope pattern, M+H)+
1H-NMR (300MHz, CDC13): 5 =
0.91 (d, 3H), 2.90 (d, 3H), 2.96 cH3 ( )-1-(4-chloropheny1)-o (dd, 1H), 3.14 (dd, 1H), 5.46 -5.55 7-4 N,4-dimethy1-8-(m, 1H), 6.47 - 6.52 (m, 1H), 6.94 --N /NH (trifluoromethoxy)-4,5-33A F H3C (s, br, 1H), 7.17 - 7.29 (m, 2H), dihydro-3H-2,3-benzodiazepine-3- 7.39 (s, 4H).
LCMS (Method 2): Rt = 1.53 min;
Cl carboxamide m/z = 412;414 (CI isotope pattern, M+H)+

Example 34A
( )-1-(4-Aminopheny1)-8-methoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-carboxamide H3C =7¨<

The preparation of the title compound is described in W097/28135 Al (Schering AG) as Example 5.
UPLC/MS (Method 3): Rt = 0.92 min; miz = 339 (M+H) 1H-NMR (300MHz, DMSO-d6): 5 = 1.07 (d, 3H), 2.37 (dd, 1H), 2.60 (d, 3H), 2.81 (dd 1H), 3.69 (s, 3H), 4.74 (m, 1H), 5.70 (sbr, 2H), 6.19 (qbr, 1H), 6.53 (d, 1H), 6.57 (d, 2H), 6.98 (dd, 1H), 7.28 (d, 1H), 7.45 (d, 2H).
Enantiomer separation (Preparative Method III) Example 34-1A: (4R)-1-(4-Aminopheny1)-8-methoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodi __ 71-pine-3-carboxamide 1.64 g, yellow solid, HPLC (Method C): R = 5.05 min, purity 99%
optical rotation: [01]32 = -637.8 0.12 (c = 1.040; Me0H) Example 34-2A: (4S)-1-(4-Aminopheny1)-8-methoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 1.71 g, yellow solid, HPLC (Method C): R, = 6.75 min, purity 95%
optical rotation: [a]D2 = +604.9 0.100 (c = 1.030; Me0H) The examples which follow describe the preparation of the compounds according to the invention, without restricting the invention to these examples.
Working examples Example 1 ( )-7,8-Dimethoxy-N,4-dimethy1-1- {4-[(1-methylpiperidin-4-yl)amino]phenyII-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide CH, H CO
[00 N NH

H,C
HN
0 c.3 Under argon, 100 mg (231 mol) of ( )-1-(4-bromopheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 29A) was initially charged in 5 ml of degassed toluene. 32 ul (29 mg, 254 mol) of 4-amino-l-methylpiperidine, 31 mg (324 mop of sodium tert-butoxide and 9 mg (12 mop of chloro-(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-bipheny1)[2-(2-amino-1,1-biphenyl)]palladium(11) (CAS [1310584-14-5]) were added. The mixture was degassed again, saturated with argon and then stirred at 110 C for 16 hours. After cooling, the mixture was partitioned between 15 ml of sat. sodium bicarbonate solution and 15 ml of ethyl acetate, and the phases were separated. The aqueous phase was extracted with ethyl acetate, and then the combined organic phases were washed with water and sat.
sodium chloride solution and dried with sodium sulphate. The solvents were removed on a rotary evaporator and the residue (126 mg, yellow oil) was purified by flash chromatography (Si02, hexane/ethyl acetate).
This gave 79 mg (73% of theory) of the desired product as a yellow solid.
LCMS (Method 2): 11, = 0.70 min; m/z = 466 (M+H)+
1H-NMR (500MHz, CDC13): 8 = 1.20 (d, 3H), 1.55 ¨ 1.67(m, 4H), 2.17 ¨ 2.24 (m, 2H), 2.09 ¨
2.17 (m, 2H), 2.37 (s, 31{), 2.73 (dd, 1H), 2.84 ¨ 2.91 (m, 1H), 2.90 (d, 3H), 2.93 (dd, 1H), 3.40 (s, br, 1H), 3.76 (s, 3H), 3.98 (s, 3H), 5.23 ¨ 5.30 (m, 1H), 5.98 (q, 1H), 6.63 (d, 2H), 6.70 (s, 1H), 6.80 (s, 1H), 7.49 (d, 2H).
Enantiomer separation 78 mg of ( )-7,8-dimethoxy-N,4-dimethy1-1-{4-[(1-methy1piperidin-4-y1)amino]pheny11-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 1) were separated into the enantiomers by chiral preparative HPLC under the following conditions:
System: Dionex: pump P 580, Gilson: Liquid Handler 215, Knauer: UV detector K-2501; column:
Chiralpak IC 5m 250x30 mm; mobile phase: ethanol/methanol/diethylamine 50:50:0.1 (v/v/v);
flow rate: 40 ml/min; temperature: RT; solution: 78 mg / 3.3 ml of Me0H;
injection: 3 x 1.1 ml;
detection: UV 254 nm.
Example 1-1: (45)-7,8-Dimethoxy-N,4-dimethy1-1-{4-[(1-methylpiperidin-4-yl)amino]phenyll-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide mg, yellowish solid, HPLC (Method G): Rt = 2.38 min, purity >99.9%
optical rotation: [4)2 = 362.3 0,55 (c = 1.00; methanol) 15 Example 1-2: (4R)-7,8-Dimethoxy-N,4-dimethy1-1-{4-[(1-methylpiperidin-4-yDamino]pheny1}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 24 mg, yellowish solid, HPLC (Method G): Rt = 2.86 min, purity 98.5%
optical rotation: [0E]02 = -360,4 0.44 (c = 1.00; methanol) 20 Analogously to Example 1, the racemic Example 29A (optionally with subsequent enantiomer separation) or the enantiomerically pure Example 29-2A and the appropriate commercially available amines gave the following exemplary compounds:
No. Structure Name Analytical data CH, ( )..78-Dimethoxy- 1H-NMR (300MHz, DMS0-4): 8 ,o H,C 401) N,4-dimethy1-1-{4- = 1.00 (d, 3H), 2.43 - 2.53 (m, 1H), H3c [methyl(pyridin-3- 2.60 (d, 3H), 2.83 (dd, 1H), 3.33 (s, =cH3 yl)amino]pheny1}-4,5- 3H), 3.58 (s, 3H), 3.80 (s, 3H), dihydro-3H-2,3- 4.85 -4.97 (m, 1H), 6.33 (q, 1H), benzodiazepine-3- 6.53 (s, 1H), 6.94 (d, 2H), 6.99 (s, carboxamide 1H), 7.34 (dd, 1H), 7.54 - 7.58 (m, No. Structure Name Analytical data 1H), 7.60 (d, 2H), 8.24 (dd, 1H), 8.42 (d, 1H).
LCMS (Method 2): R, = 0.87 min;
rniz = 460 (M+H) 1H-NMR (300MHz, DMSO-d6):
= 1.02 (d, 3H), 2.40 - 2.50 (m, 1H), CH3 (+)-1-{4-[(2- 2.60 (d, 3H), 2.82 (dd, 1H), 3.58 (s, H3c,o =7,4 Fluorophenyl)amino]ph 3H), 3.80 (s, 3H), 4.82 ¨ 4.92 (m, ¨N NH
H3C eny1}-7,8-dimethoxy- 1H), 6.27 (q, 1H), 6.53 (s, 1H), =CH3 N,4-dimethy1-4,5- 6.93 (d, 2H), 6.99 (s, 1H), 6.98 -F dihydro-3H-2,3- 7.04 (m, 111), 7.11 (dt, 1H), 7.22 HN
benzodiazepine-3- (ddd, 1H), 7.34 (dt, 1H), 7.57 (d, carboxamide 2H), 8.29 (s, 1H).
LCMS (Method 2): R, = 1.28 min;
m/z = 463 (M-FH)+
cH3 (4R)-1-{4-[(2-H3c,o Fluorophenyl)amino]ph N H3C/NH eny1}-7,8-dimethoxy-Chiral HPLC (Method K):

N,4-dimethy1-4,5-= 3.58 min dihydro-3H-2,3 R.(-HN
benzodiazepine-3-carboxamide cH3 (4S)-1-{4-[(2-o 0 H3C, /1,1-- Fluorophenypamino]ph N H3C /NH enyl 1-7,8-dimethoxy-CH3 Chiral HPLC (Method K):

410 N,4-dimethy1-4,5-dihydro-3H-2,3-= 7.10 min HN
benzodiazepine-3-carboxamide , No. Structure Name Analytical data 1H-N (300MHz, DMSO-d6): 8 = 1.03 (d, 3H), 2.03 (s, 3H), 2.22 ( )-1-{4-[(3,5-CH, (s, 3H), 2.41 (dd, 1H), 2.58 (d, ,0 N4 Dimethylisoxazol-4-3H), 2.78 (dd, 1H), 3.58 (s, 3H), H3C o ¨ N1 NH yl)amino]phenyl} -7,8-1 / 3.79 (s, 3H), 4.77 -4.89 (m, 1H), CH, H3C

4#1 dimethoxy-N,4-dimethy1-4,5-dihydro- 6.18 (q, 1H), 6.53 (s, 1H), 6.94 (d, 2H), 6.99 (s, 1H), 6.52 (d, 2H), FINCH, 3H-2,3-6.53 (s, 1H), 6.98 (s, 1H), 7.53 (d, o benzodiazepine-3-H3C N 2H), 7.63 (s, 1H).
carboxamide LCMS (Method 2): R, = 1.10 min;
m/z = 464 (M+H)+
(4R)-1-{4-[(3,5-CH, ,0 Dimethylisoxazol-4-O --- N1 NH yl)amino]pheny1}-7,8-dim CH, 4-1 H3C Chiral HPLC (Method M):
40 dimethoxy-N,4-ethy1-4,5-dihydro- R, = 2.96 min HNz(CH, 3H-2,3-o benzodiazepine-3-,.
H3C N, carboxamide (4S)-1-14-[(3,5-õcH3 H3C' 4111 ___0 Dimethylisoxazol-4-N
O --- N1 NH ypaminolpheny1}-7,8-CH, 4-2 H3C Chiral RPLC (Method M):
* dim dimethoxy-N,4-ethy1-4,5-dihydro- R, = 3.95 min HN,.....z...,<CH3 3H-2,3-o benzodiazepine-3---., H3C N, carboxamide 1H-NMR (300MHz, DMSO-d6): 8 ( )-1-(4- { [2-CH, = 1.04 (d, 3H), 1.19¨ 1.22 (m, H3C' 0 ____ (Dimethylamino)ethyl]
N 2H), 2.15 (s, 6H), 2.38 - 2.42 (m, /
o 11 11 ----N NH aminolpheny1)-7,8-CH, H3C 1H), 2.58 (d, 3H), 2.77 (dd, 1H), * dimethoxy-N,4-dimethy1-4,5-dihydro- 3.11 (q, 2H), 3.58 (s, 3H), 3.80 (s, 3H), 4.76 - 4.84 (m, 1H), 5.94 ¨
j--NH 3H-2,3-1-1,c\ 5.98 (m, 1H), 6.13 (q, 1H), 6.51 (s, N benzodiazepine-3-/
H3C 1H), 6.57 (d, 2H), 6.98 (s, 1H), carboxamide 7.47 (d, 2H).

No. Structure Name Analytical data LCMS (Method 2): 12, = 0.68 min;
ink = 440 (M+H)+
(4S)-1-(4-1[2-.õ CH, H, Co 4111 4 (Dimethylamino)ethyl]
0 N NH aminolpheny1)-7,8-cH3 5-1 =H3c dimethoxy-N,4-dimethy1-4,5-dihydro- [a]D2 = 434.9 0.36 (c = 1.00; methanol) NH 3H-2,3-H3C, benzodiazepine-3-carboxamide 1H-NMR (300MHz, DMSO-d6): 8 cH3 ( )-1-{4-[(4-= 1.01 (d, 3H), 2.40 - 2.44 (m, 1H), ,o H3c Fluorophenyl)methyla 2.59 (d, 3H), 2.81 (dd, 1H), 3.57 (s, 0 N NH minolpheny11-7,8-CH3 =H3C 3H), 3.80 (s, 3H), 4.82 ¨ 4.92 (m, dimethoxy-N,4-dimethy1-4,5-dihydro- 1H), 6.25 (q, 1H), 6.52 (s, 1H), 6.75 (d, 2H), 6.99 (s, 1H), 7.18 ¨
H3c¨N1 3H-2,3-benzodiazepine-3- 7.26 (m, 4H), 7.55 (d, 2H).
LCMS (Method 2): 12, = 1.39 min;
carboxamide m/z = 477 (M+H)+
1H-NMR (400MHz, DMSO-d6): 5 = 1.02 (d, 3H), 2.43 - 2.47 (m, 1H), CH, ( )-7,8-Dimethoxy-,o =714 2.60 (d, 3H), 2.81 (dd, 1H), 3.58 (s, N,4-dimethy1-1-{4-[(1-3H), 3.62 (s, 3H), 3.80 (s, 3H), N /NH methyl-1H-pyrazol-5-CH, H3C 4.82 ¨ 4.91 (m, 1H), 6.03 (d, 1H), 4110 yl)aminolpheny11-4,5-6.25 (q, 1H), 6.52 (s, 1H), 6.81 (d, dihydro-3H-2,3-CH, 2H), 6.99 (s, 1H), 7.57 (d, 2H), HN
benzodiazepine-3-t 8.32 (s, 1H).
I / carboxamide LCMS (Method 2): 12, = 1.00 min;
rn/z = 449 (M+H)+

=

No. Structure Name Analytical data CH3 (4R)-7,8-Dimethoxy-, 0 H,Co 0 ,N4 N,4-dimethy1-1-{4-[(1-o I ---- N /NH methyl-1H-pyrazol-5-cH, H3c Chiral HPLC
(Method N):

40 yl)amino]pheny11-4,5-R, = 3.06 min dihydro-3H-2,3-HN /CH, benzodiazepine-3-\C\N
I / carboxamide , CH3(4S)-7,8-Dimethoxy-, H,C0 0 ini40 N,4-dimethy1-1-{4-[(1-o I -----N /NH methyl-1H-pyrazol-5-cH3 H3c Chiral HPLC
(Method N):

. ypaminolphenyll-4,5-R, = 4.27 min dihydro-3H-2,3-benzodiazepine-3-t z.N\N
I / carboxamide 'H-NMR (300MHz, DMSO-d6): 8 = 1.03 (d, 3H), 1.23 ¨ 1.38 (m, 1H), 1.55 ¨ 1.66 (m, 2H), 1.70 -( )-1-[4-(1-0-13 1.83 (m, 1H), 1.85 ¨ 1.93 (m, 1H), ,o H3 C 4111 Azabicyclo[2.2.21oct-p-- 2.31 ¨2.45 (m, 1H), 2.57 (d, 3H), o ¨N NH 3-ylamino)pheny1]-7,8-I /
2.66 - 2.87 (m, 5H), 3.17 ¨ 3.29 CH, H3C
* dimethoxy-N,4-dimethy1-4,5-dihydro- (m, 2H), 3.43 ¨ 3.52 (m, 1H), 3.58 (s, 3H), 3.79 (s, 3H), 4.73 - 4.85 HN 3H-2,3-(m, 1H), 6.14 (q, 1H), 6.30 ¨ 6.33 benzodiazepine-3-N (m, 1H), 6.51 (s, 1H), 6.56 (d, 2H), carboxamide 6.98 (s, 1H), 7.47 (d, 2H).
LCMS (Method 2): R, = 0.73 min;
m/z = 478 (M+H)+
(4S)-1-[4-(1 -CH
,0 H3C 110 Azabicyclo[2.2.2]oct-N--0 -- N/ NH 3-ylamino)pheny1]-7,8-I /
cH, 8-1 * H3c [4)2 = 279.2 + 0.28 dimethoxy-N,4-dimethy1-4,5-dihydro- (c = 1.00; methanol) HN 3H-2,3-benzodiazepine-3-N
carboxamide e No. Structure Name Analytical data 11-1-NMR (300MHz, DMSO-d6): 6 (+)-7,8-Dimethoxy-1-CH, = 0.99 (d, 3H), 2.53 (dd, 1H), 2.62 ,o o {4-[(4-methoxy-1,2,5-,N_ (d, 3H), 2.84 (dd, 1H), 3.55 (s, H3c iii o ¨N NH oxadiazol-3-I / 3H), 3.80 (s, 3H), 4.12 (s, 3H), CH, H3C yl)amino]pheny1}-N,4-#1 dimethy1-4,5-dihydro-4.88 ¨ 5.00 (m, 1H), 6.40 (q, 1H), 6.50 (s, 1H), 6.99 (s, 1H), 7.60 (d, HN 3H-2,3------Nl'o benzodiazepine-3- 2H), 7.67 (d, 2H), 9.59 (s, 1H).
,0 ----, LCMS (Method 2): R, = 1.16 min;

carboxamide m/z = 467 (M+H) (4R)-7,8-Dimethoxy-1-H3c, 410 0 0 14-[(4-methoxy-1,2,5-IN--O ---N / NH oxadiazol-3-I
CH, H3C yl)amino]phenyll-N,4- Chiral HPLC
(Method I):

40 dimethy1-4,5-dihydro- It, = 2.40 min HN 3H-2,3-,Z,....-N\0 benzodiazepine-3-H3c,0 ----N, carboxamide (45)-7,8-Dimethoxy-1-cH3 ,o o {44(4-[(4-1,2,5-H3c o O¨N/NNH
/ oxadiazol-3-I
cH, H3c yl)amino]pheny1}-N,4- Chiral HPLC
(Method I):

. dimethy1-4,5-dihydro- R, = 3.08 min HN 3H-2,3-benzodiazepine-3-H3c,,0õ),-..---.N, carboxamide 1H-NMR (400MHz, DMSO-d6): 6 = 1.02 (d, 3H), 2.58 (dd, 1H), 2.65 CH3 ( )-7,8-Dimethoxy-,o o (d, 3H), 2.89 (dd, 1H), 3.60 (s, H,C /10 N-- N,4-dimethy1-144-[4 /
3H), 3.83 (s, 3H), 4.94¨ 5.03 (m, o ¨ N NH (pyr I / idazin-4-cH3 H3c 1H), 6.47 (q, 1H), 6.55 (s, 1H), . ylamino)pheny1]-4,5-7.03 (s, 111), 7.22 (dd, 1H), 7.28 (d, dihydro-3H--2,3-HN 2H), 7,71 (d, 2H), 8.73 (d, 1H), C-- benzodiazepine-3-N 8.90 (d, 1H), 9.39 (s, 1H).
141 carboxamide LCMS (Method 2): R, = 0.74 min;
m/z = 447 (M+H)+

, No. Structure Name I Analytical data 1H-NMR (400MHz, DMSO-d6): 8 = 1.02 (d, 3H), 2.52 (dd, 1H), 2.63 CH, ( )-7,8-Dimethoxy-H3C,0 7 N,4-dimethy1-1-[4-0 0 (d, 3H), 2.85 (dd, 1H), 3.57 (s, O ¨N NH
3H), 3.81 (s, 3H), 4.88 ¨ 4.97 (m, I / (pyridazin-3-CH, H,C 1H), 6,38 (q, 1H), 6,54 (s, 1H), . ylamino)pheny1]-4,5-7.01 (s, 1H), 7.15 (dd, 1H), 7.45 dihydro-3H-2,3-HN (dd, 1H), 7.67 (d, 2H), 7.81 (d, N benzodiazepine-3-\
2H), 8.68 (dd, 1H), 9.51 (s, 1H). /
carboxamide LCMS (Method 2): R, = 0.87 min;
m/z = 447 (M+H)+
1H-NMR (300MHz, DMSO-d6): 8 ( )-7,8-Dimethoxy- = 1.01 (d, 3H), 2.46 - 2.50 (m, 1H), CH, -0 0 N,4-dimethy1-1-14- 2.59 (d, 3H), 2.82 (dd, 1H), 3.21 (s, H,C 0 ___ N1N¨NH [methyl(1-methyl-1H- 3H), 3.34 (s, 3H), 3.56 (s, 3H), o I
/
CH, H3C imidazol-2-3.80 (s, 3H), 4.83 ¨ 4.94 (m, 1H), 40 yl)aminolpheny11-4,5-6.26 (q, 1H), 6.50 (d, 2H), 6.51 (s, cH3 dihydro-3H-2,3- 1H), 6.83 (d, 1H), 6.99 (s, 1H), H3c¨N /
)01 benzodiazepine-3- 7.10 (d, 1H), 7.57 (d, 2H).
carboxamide LCMS (Method 2): R, = 0.76 min;
m/z = 463 (M+H)+
(4R)-7,8-Dimethoxy-CH, -0 0 N,4-dimethy1-1-14-o N NH
H3c 0 N¨

/ [methyl (1-methy1-1 H----I /
CH, H,C imidazol-2- Chiral HPLC
(Method 1-1):

= yflaminolpheny11-4,5-R, = 2.97 min 3CH dihydro-3H-2,3-H3C -- N is\f/--,)N/
benzodiazepine-3-carboxamide (4S)-7,8-Dimethoxy-µ CH3 H,C.-C) - el , N,4-dimethy1-1 -{ 4-----1--% H [methyl(1-methy1-1 H-o I /
cH, H3c imidazol-2- Chiral HPLC
(Method H):

. yl)aminolpheny11-4,5-R, = 4.68 min cH3 dihydro-3H-2,3-H3c¨N /
benzodiazepine-3-carboxamide No. Structure Name Analytical data 1H-NIvIR (300MHz, DMSO-d6): 8 = 1.03 (d, 3H), 2.46 - 2.50 (m, 1H), CH, ( )-7,8-Dimethoxy-1-1,Co Ili o 2.60 (d, 3H), 2.80 (dd, 1H), 3.57 (s, /N- N,4-dimethy1-1-{4-[(1-3H), 3.71 (s, 3H), 3.80 (s, 3H), o I --- N /NH methyl-1H-pyrazol-3-CH, H3C
4.79 ¨ 4.89 (m, 1H), 5.79 (d, 1H), 40 yl)aminolphenyl} -4,5-6.23 (q, 1H), 6.52 (s, 1H), 6.99 (s, dihydro-3H-2,3-HN 1H), 7.32 (d, 2H), 7.50 (d, 1H), N) benzodiazepine-3-carboxamide H) 7.54 (d, 2H), 8.76 (s, 1.
LCMS (Method 2): R, = 1.03 min;
m/z = 449 (M+H)+
CH (4S)-7,8-Dimethoxy-,o 0 H3C el714 N,4-dimethy1-1- {44(1-o I -- N /NH methyl-1H-pyrazol-3-cH3 H3c [4)2 = 289.3 1.03 . yl)amino]pheny1}-4,5-(c = 1.00; methanol) dihydro-3H-2,3-HN
\ ...c...._;\ benzodiazepine-3-CH, carboxamide 11-1-NMR (300MHz, DMS046): 8 ( )-1-{4-[(2- =
1.02 (d, 3H), 2.43 - 2.53 (m, 1H), CH, ,0 0 Fluoropyridin-3-2.61 (d, 3H), 2.83 (dd, 1H), 3.57 (s, tc O

-- Ni NH yl)amino]pheny11-7,8-3H), 3.80 (s, 3H), 4.85 ¨ 4.96 (m, /
1-1, H3C dimethoxy-N,4- 1H), 6.32 (q, 1H), 6.53 (s, 1H), = dimethy1-4,5-dihydro- 7.00 (s, 1H), 7.04 (d, 2H), 7.24 (m, F
HN 3H-2,3-1H), 7.60 (d, 2H), 7.74 (m, 1H), benzodiazepine-3- 7.81 (m, 1H), 8.47 (s, 1H).
carboxamide LCMS (Method 2): R, = 1.13 min;
m/z = 464 (M+H)-' (4R)-1-{4-[(2-CH, ,0 0 Fluoropyridin-3-H3c N-el 0 --- N/ NH yl)amino]phenyl} -7,8-CH, /

dimethoxy-N,4-Chiral HPLC (Method J):

* dimethy1-4,5-dihydro- R., = 3.05 min F
HN 3H-2,3---1N benzodiazepine-3-\
carboxamide No. Structure Name Analytical data (4S)-1-{4-[(2-, CH3 N
,0 Fluoropyridin-3-i O ¨n NH ypamino]pheny11-7,8-I /
dimethoxy-N,4-CH, H3C Chiral HPLC (Method J):

. dimethy1-4,5-dihydro- R, = 6.01 min F
HN 3H-2,3---\ /N benzodiazepine-3-carboxamide 11-1-NMR (300MHz, DMSO-d6): 8 = 1.00 (d, 3H), 2.54-(dd, 1H), 2.62 ( )-1-{4-[(3-CI-13 (d, 3H), 2.86 (dd, 1H), 3.57 (s, o o Fluoropyridin-4-H3c-- 40 N- 3H), 3.80 (s, 3H), 4.89 ¨ 5.01 (m, o ¨1,1/ NH yl)amino]pheny11-7,8-I / 1H), 6.42 (q, 1H), 6.53 (s, 1H), CH3 H,C
dimethoxy-N,4-. dimethy1-4,5-dihydro- 7.00 (s, 1H), 7.23 ¨ 7.27 (m, 1H), F 7.25 (d, 2H), 7.67 (d, 2H), 8.08 -HN 3H-2,3--- 8.10 (m, 1H), 8.33 (d, 1H), 8.92 (s, , / benzodiazepine-3-, N 1H).
carboxamide LCMS (Method 2): R., = 0.76 min;
m/z = 464 (M+H)+
11-1-NMR (300MHz, DMSO-d6): 8 ( )-1-{4-[(3- = 1.01 (d, 3H), 2.44 - 2.54 (m, 1H), CH, O 0 Fluoropyridin-2- 2.62 (d, 3H), 2.84 (dd, 1H), 3.56 (s, H3c' .
N--yl)aminolpheny11-7,8- 3H), 3.80 (s, 3H), 4.86 ¨ 4.97 (m, I
/
cH3 H3c dimethoxy-N,4- 1H), 6.37 (q, 1H), 6.52 (s, 1H), = dimethy1-4,5-dihydro- 6.84 (m, 1H), 7.00 (s, 1H), 7.53 -F
HN 3H-2,3- 7.58 (m, 1H), 7.62 (d, 2H), 7.85 (d, N /
\ benzodiazepine-3- 2H), 7.99 (d, 1H), 9.10 (s, 1H).
carboxamide LCMS (Method 2): R, = 1.21 min;
m/z = 464 (M+H)+

No. Structure Name Analytical data _ (4R)-1- {44(3-CH, H3C o 4111 Fluoropyridin-2-N--?
o ¨ Ni NH ypamino]pheny11-7,8-CH, 16-1 H,C Chiral HPLC (Method J):
. dimethoxy-N,4-dimethy1-4,5-dihydro- R, = 4.91 min F
HN 3H-2,3-_ \ benzodiazepine-3-carboxamide (4S)-1-{4-[(3-_ CH, , 0 Fluoropyridin-2-H3c 40 r, j_.,c) o ¨NI NH ypamino]phenyll -7,8-I /

16-2 H3C Chiral linc (Method J):
. dimethoxy-N,4-dimethy1-4,5-dihydro- R, = 6.85 min F
HN 3H-2,3-N /
\ benzodiazepine-3-carboxamide 'H-NMR (600MHz, DMSO-d6): 8 .
= 1.07 (dd, 3H), 2.441(dd, 1H), CH, ( )-7,8-Dimethoxy-,o o 2.62 (d, 3H), 2.81 (dd, 114), 3.57 H3c 40 N,4-dimethy1-1-(4-(d. 3H), 3.61 (s,13H), 3.83 (s, 3H), o ¨ N /NH { [2,2,2-trifluor-1-(1-I
CH, H3C 4.87 (dquin, 1H), 5.65 - 5.74 (m, = methy1-1H-pyrrol-2-yDethyllaminolphenyl) 1H), 5.961- 6.01 (m, 1H), 6.21 -F 6.27 (m, 2H), 6.55 (d, 1H), 6.75 -HN F -4,5-dihydro-3H-2,3-F 6.811(m, 2H), 6.95 (dd, 2H), 7.02 H3C, N \ benzodiazepine-3-(d, 1H), 7.54 (dd, 2H).
carboxamide LCMS (Method 2): Rt = 1.29 min;
miz ¨ 530 (M+H)+
_ 1H-NMR (400MHz, CDC13): 8 =
CH3 ( )-1-(4-{ [2-,o o 1.17 (d, 3H), 2.36 (s, 6H), 2.51 ¨
H3C is N4 (Dimethylamino)ethyl]
/ 2.63 (m, 2H), 2.68 (dd, 1H), 2.86 o I ---N H3C/NH methylaminolpheny1)-cH3 (d, 3H), 2.88 (dd, 1H), 3.04 (s, 18 7,8-dimethoxy-N,4-3H), 3.53 ¨ 3.62 (m, 2H), 3.73 (s, dimethy1-4,5-dihydro-3H), 3.94 (s, 3H), 5.17 ¨ 5.26 (m, H3c¨N) 3H-2,3-1H), 5.91 (q, 1H), 6.67 (s, 1H), C= N.¨ CH3 benzodiazepine-3-i 6.70 (d, 2H), 6.76 (s, 1H), 7.52 (d, H3C carboxamide 2H).

=

No. Structure Name Analytical data LCMS (Method 2): R, = 0.73 min;
in/z = 454 (M+H) CH3 (4S)-1-(4- { [2-HsC,0 = NH
(Dimethylamino)ethyl]
01 H,C/ methylaminolpheny1)-18-1 =7,8-dimethoxy-N,4- [432 = 352.1 0.78 dimethy1-4,5-dihydro- (c = 0.503;
methanol) Ft3c¨N) 3H-2,3-CN--CH3 benzodiazepine-3-H3C carboxamide 1H-NMR (400MHz, CDC13): 8 =

1.16 (d, 3H), 1.44¨ 1.94 (m, br, , H3co N.4 ( )-7,8-Dimethoxy- 2H), 2.38 (s, 3H), 2.44 ¨ 2.77 (m, N,4-dimethy1-1-(4-{[2-8H), 2.69 (dd, IH), 2.86 (d, 3H), cH3 (4-methylpiperazin-1- 2.88 (dd, 1H), 3.20 ¨3.28 (m, 2H), ypethyl]amino}phenyl) 3.72 (s, 3H), 3.93 (s, 3H), 5.18 ¨
HN
-4,5-dihydro-3H-2,3- 5.27 (m, 1H), 4.63 (s, br, 1H), 5.94 benzodiazepine-3- (q, 1H), 6.62 (d, 2H), 6.66 (s, 1H), N carboxamide 6.76 (s, 1H), 7.46 (d, 2H).
µCH3 LCMS (Method 2): R, =
0.69 min;
m/z = 495 (M+H)-1 0 H3c 0 H3C el 71 (4S)-7,8-Dimethoxy-¨11 /NH N,4-dimethy1-1-(4- {[2-cH3 19-1 (4-methylpiperazin-l-[c]p2o = 384.6 0.38 ypethyljamino}phenyl) HN= 1.00; methanol) -4,5-dihydro-3H-2,3-benzodiazepine-3-7--)carboxamide No. Structure Name Analytical data 'H-NMR (300MHz, DMSO-d6): 5 = 1.03 (d, 3H), 1.50 ¨ 1.60 (m, CH, ( )-7,8-Dimethoxy- 2H), 1.67¨ 1.83 (m, 2H), 1.96 -o o H3c' 410 p4 N,4-dimethy1-1-{4- 2.08 (m, 2H), 2.16 (s, 3H), 2.33 ¨
o --- N /NH [methyl(1-2.52 (m, 2H), 2.58 (d, 3H), 2.76 (s, I
cH3 40 H3c methylpiperidin-4- 3H), 2.78 - 2.86 (m, 2H), 3.59 ¨
yl)amino]pheny11-4,5- 3.69 (m, 1H), 3.57 (s, 3H), 3.80 (s, H,C"-N dihydro-3H-2,3- 3H), 4.75 -4.88 (m, 1H), 6.19 (q, benzodiazepine-3- 1H), 6.52 (s, 1H), 6.75 (d, 2H), CH, carboxamide 6.99 (s, 1H), 7.54 (d, 2H).
LCMS (Method 2): R, = 0.74 min;
m/z = 480 (M+H)+
CH, (4R)-7,8-Dimethoxy-, 0 H3C0 p4 0 N,4-dimethy1-1-{4-o ¨ N /NH [methyl(1-i cH3 1-13c .methylpiperidin-4-yl)amino]phenyl} -4,5- Chiral HPLC (Method L):
R, = 1.72 min H,C"-N \r\1 dihydro-3H-2,3-C
rs benzodiazepine-3-CH, carboxamide s CH, le 11¨
(4S)-7,8-Dimethoxy-..
o H,C N,4-dimethy1-1-{4-O ¨ N / NH [methyl(1-I
cH3 H3c .methylpiperidin-4-HP
LC

-4,5- Chiral LC (Method L):
Ri = 2.76 min H3C --1µ10 dihydro-3H-2,3-benzodiazepine-3-CH3 carboxamide N--, CH ( )-tert-Butyl 4-[{4- '1-1-NMR
(300MHz, CDC13): 8 =
H,C.-(3 Ns 0 [7,8-dimethoxy-4- 1.15 (d, 3H), 1.48 (s, 9H), 1.21 ¨
/
0 ¨ N NH I
HaCi methyl-3- 1.29 (m, 2H), 1.65 ¨ 1.80 (m, 4H), 21 4* (methylcarbamoyI)- 2.74 ¨ 2.82 (m, 2H), 2.68 (dd, 1H), 4,5-dihydro-3H-2,3- 2.84 (s, 3H), 2.85 (d, 3H), 2.89 (dd, 1-130¨N
H,C xf., H3 benzodiazepin-1- 1H), 3.78 ¨
3.85 (m, 1H), 3.72 (s, \iro yl]phenyl}methylamin 3H), 3.93 (s, 3H), 5,19 - 5.26 (m, 0 o]piperidine-1- 1H), 5.95 (q, 1H), 6.66 (s, 1H), No. Structure Name Analytical data carboxylate 6.75 - 6.79 (m, 3H), 7.52 (d, 2H).
LCMS (Method 1): R= 1.36 min;
m/z = 566 (M+H)+
1H-NMR (400MHz, CDC13): 5 =-1.16 (d, 3H), 2.41 (s, 3H), 2.71 (dd, 1H), 2.88 (d, 3H), 2.91 (dd, 1H), CH3 ( oxy-)-7,8-Dimeth ,o 2.98 (dd, 2H), 3.73 (s, 3H), 3.78 140 714H N,4-dimethy1-1-{4-[(1-(dd, 2H), 3.95 (s, 3H), 4.11-4.20 methylazetidin-3-CH (m, 1H), 4.30 (d, 1H), 5.21-5.32 =yl)amino]pheny1}-4,5-(m, 1H), 6.01 (q, 1H), 6.55 (d, 2H), dihydro-3H-2,3-HN 6.66 (s, 1H), 6.77 (s, 1H), 7.46 (d, 1_1 benzodiazepine-3-2H).
cH, carboxamide LCMS (Method 1): R = 0.68 min;
m/z = 438 (M-i-HY
1H-NMR (400MHz, CDC13): 6 =
1.13 (d, 3H), 1.93 (s, 3H), 2.74 (dd, cH3 ( )-1-{4-[(1- 1H), 2.88 (d, 3H), 2.96 (dd, 1H), ,o 0 ,N4 Acetylazetidin-3- 3.73 (s, 3H), 3.88 (d, 1H), 3.96 (s, 3H), 3.97 (m, 1H), 4.32-4.40 (m, =H3c/NH ypamino]pheny1}-7,8-23 dimethoxy-N,4- 2H), 4.41-4.57 (m, 2H), 5.25-5.35 (m, 1H), 6.09 (q, 1H), 6.55 (d, 2H), dimethy1-4,5-dihydro-HN
3H-2,3- 6.65 (s, 1H), 6.77 (s, 1H), 7.48 (d, 2H).
sr benzodiazepine-3-H3C carboxamide LCMS (Method 1): R = 0.88 min;
m/z = 466 (M+H)+
111-NMR (300MHz, CDC13): 8 =
( )-7,8-Dimethoxy-1.18 (d, 3H), 1.53-1.71 (m, 4H), N,4-dimethy1-1-(4-1.71-1.83 (m, 2H), 1.89-2.01 (m, FI,C, 0 Ni NH [trans-4-(4-2H), 2.21-2.30 (m, 1H), 2.32 (s, H,C
40 methylpiperazin-1-3H), 2.41-2.56 (m, 4H), 2.56-2.67 Acyclohexyllamino}p (m, 4H), 2.69 (dd, 1H), 2.82-2.94 heny1)-4,5-dihydro-3H-(m, 1H), 2.87 (d, 3H), 3.63-2.72 2,3-benzodiazepine-3-C", (m, 1H), 3.75 (s, 3H), 3.95 (s, 3H), carboxamide 4.12 (d, 1H), 5.16-5.30 (m, 1H), No. Structure Name Analytical data 5.92 (q, 1H), 6.59 (d, 2H), 6.68 (s, 1H), 6.78 (s, 1H), 7.48 (d, 2H).
LCMS (Method 2): R, = 0.60 min;
m/z 549 (M+H)+

, ..

Analogously to Example 1, Example 30A or 31A and the appropriate commercially available amines gave the following exemplary compounds:
No. Structure Name Analytical data 'H-NMR (300MHz, CDC13): 8 =
0.97 (d, 3H), 2.83 (dd, 1H), 2.86 CH, ( )-7,8-Dimethoxy-N,4- (d, 3H), 3.10 (dd, 1H), 3.35 (s, -o 1N-- dimethyl-1- {3- 3H), 3.69 (s, 3H), 3.92 (s, 3H), I / [methyl(pyridin-3-5.44 (m, 1H), 6.44 (q, 1H), 6.62 (s, CH, H,C
= yl)aminolpheny1}-4,5-1H), 6.70 (s, 1H), 7.12 (d, 1H), N-CH, dihydro-3H-2,3- 7,19 (m, 3H), 7.28 (m, 1H), 7.36 abenzodiazepine-3- (dd, 1H), 8.15 (dd, 1H), 8.33 (d, carboxamide 1H).
LCMS (Method 3): R, = 0.85 min;
m/z = 460 (M+H)+
'H-NMR (400MHz, CDC13): 6 =
1.01 (d, 3H), 1.53 (m, 2H), 2.07 (d, CH, 2H), 2.15 (m, 2H), 2.32 (s, 3H), -o o ( )-7,8-Dimethoxy-N,4-,3c mol /71¨ 2.81 (dd, 111), 2.84 (m, 2H), 2.87 o ¨N NH
dimethy1-1-{3-[(1-I / (d, 3H), 3.07 (dd, 1H), 3.31 (m, CH, H3C methylpiperidin-4-26 40 ypamino]pheny11-4,5- 1H), 3.67 (s, 3H), 3.93 (s, 3H), NH 5.40 (m, 1H), 6.44 (m, 1H), 6.64 adihydro-3H-2,3-benzodiazepine-3- H) (dd, 1, 6.65 (s, 1H), 6.71 (s, 1H), 6.72 (dd, 1H), 6.79 (d, 1H), 7.18 N
/ carboxamide H3C (dd, 1H).
LCMS (Method 3): R, = 0.76 min;
m/z = 466 (M+H) 'H-NMR (300MHz, CDCI3): 6 =
CH, (1)-143-1[3- 1.02 (d, 3H), 1.89 (m, 2H), 2.40 ,o o itc 4111 7-4 (Dimethylamino)propyl] (m, 8H), 2.81 (s, 3H), 2.85 (m, o ¨N NH
I / methylamino}-4- 1H), 2.88 (d, 3H), 3.08 (dd, 1H), CH, H3C
27 . fluoropheny1)-7,8-3.18 (m, 2H), 3.67 (s, 3H), 3.93 (s, N_-CH3 dimethoxy-N,4-dimethyl- 3H), 5.43 (m, 1H), 6.41 (m, 11-1), F
N--CH. 4,5-dihydro-3H-2,3-6.58 (s, 1H), 6.72 (s, 1H), 6.97 ¨
benzodiazepine-3- 7.05 (m, 3H).
/
H3C carboxamide LCMS (Method 3): R, = 0.81 min;
m/z = 486 (M+H)+

No. Structure Name Analytical data 11-1-NMR (400MHz, CDC13): 5 =
CH, (+)-1-(3-{[2- 1.01 (d, 3H), 2.29 (s, 6H), 2.56 (m, H,C 410 (Dimethylamino)ethyl]m 2H), 2.85 (s, 3H), 2.82 (dd, 1H), ¨N NH ethylamino} -4- 2.88 (d, 31-1), 3.08 (dd, 1H), 3.29 CH, H,C

fluoropheny1)-7,8- (m, 2H), 3.67 (s, 3H), 3.93 (s, 3H), N--CH3 dimethoxy-N,4-dimethyl- 5.42 (m, 1H), 6.42 (m, 1H), 6.58 F 4,5-dihydro-3H-2,3- (s, 1H), 6.72 (s, 1H), 6.96 ¨ 7.06 benzodiazepine-3- (m, 3H).
nLA 3, ,--N

carboxamide LCMS (Method 3): It, = 0.79 min;
m/z = 472 (M+H)+
Example 29 ( )-1-(4-{ [(Dimethylamino)acetyljamino} pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide H/

HN
o Under argon, 150 mg (0.347 mmol) of ( )-1-(4-bromopheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Intermediate 29A), 39 mg (0.382 mmol) of N2,N2-dimethylglycinamide, 147 mg (0.69 mmol) of potassium phosphate and 132 mg (0.69 mmol) of copper(I) iodide were initially charged in 4 ml of degassed dioxane. 122 mg (1.39 mmol) of NA-dimethylethylenediamine were then added under argon and the mixture was degassed again and heated at 130 C for 3 hours. After cooling, 2M aqueous hydrochloric acid was added, and after brief stirring the mixture was made alkaline with 25% strength ammonia solution. The mixture was extracted twice with ethyl acetate, and the combined organic phases were dried with sodium sulphate. The solvent was removed on a rotary evaporator and the residue was purified by column chromatography (amino phase). This gave 115 mg (70% of theory) of the desired product as a solid.
LCMS (Method 2): R = 0.7 min; m/z = 454 (M+H)+
1H-NMR (300MHz, CDC13): 5 = 1.01 (d, 3H), 2.04 (s, 2H), 2.59 (s, br, 6H), 2.72-2.88 (m, 1H), 2.88 (d, 3H), 3.07 (dd, 1H), 3.66 (s, 3H), 3.93 (s, 3H), 5.34-5.48 (m, 1H), 6.40 (q, 1H), 6.59 (s, 1H), 6.72 (s, 1H), 7.48 (d, 2H), 7.68 (d, 2H), 9.71 (s, br, 1H).
Enantiomer separation:
91 mg of ( )-1-(4-{ [(dimethylamino)acetyl]amino}pheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 29) were separated into the enantiomers by chiral preparative HPLC under the following conditions:
System: Agilent: Prep 1200, 2xPrep Pump, DLA, MWD, Prep FC; column: Chiralpak AD-H 5p.m 250x30 mm; mobile phase: hexane/ethanol 70:30 (v/v) +0.1% DEA; flow rate: 50 ml/min;
temperature: RT; detection: UV 280 nm.
Example 29-1: (4R)-1-(4- [(Dimethylamino)acetyl]amino} pheny1)-7,8-dimethoxy-N,4-di methyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 36 mg, solid, HPLC (Method 0): R, = 4.66 min, purity >99%
optical rotation: [a]D2 = -181,7 0,59 (c = 1,00; methanol) Example 29-2: (45)-1-(4-{[(Dimethylamino)acetyl]aminolpheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 36 mg, solid, HPLC (Method 0): R, = 6.25 min, purity >99%
optical rotation: [c]u2 = 165,7 0,38 (c = 1,00; methanol) . CA 02915419 2015-12-14 , Analogously to Example 29, the racemic Intermediate 29A (optionally with subsequent enantiomer separation) and the appropriate commercially available carboxamides gave the following exemplary compounds:
No. Structure Name Analytical data 'H-NMR (300M1-1z, CDCI3): 5 =-CH, 1.01 (d, 3H), 1.85-2.05 (m, 4H), ,o o H,C 40 N4 ( )-7,8-Dimethoxy-N,4-2.05-2.20 (m, 2H), 2.25-2.40 (m, /
o ¨ N /NH dimethy1-1-(4-{[(1-1H), 2.33 (s, 3H), 2.78 (dd, 1H), C
I
CH, H, 40 methylpiperidin-4-2.86 (d, 3H), 2.95-3.09 (m, 3H), 30 yl)carbonyliaminolphen 3.64 (s, 3H), 3.92 (s, 3H), 5.30-HN
Z o y1)-4,5-dihydro-3H-2,3- 5.44 (m, 1H), 6.36 (q, 1H), 6.57 (s, benzodiazepine-3- 1H), 6.71 (s, 1H), 7.46 (d, 2H), Cr--1 carboxamide 7.59 (d, 2H), 9.80 (s, br, 1H).
/
Ito LCMS (Method 2): R, = 0.72 min;
m/z - 494 (M+H)+
,cH3 -0 = 0 H,C 0 ,N4 (4S)-7,8-Dimethoxy-N,4-o ¨ N /NH dimethy1-1-(4-{[(1-prep. 1-IPLC: Method XII
I H,C
CH, =methylpiperidin-4-analyt. HPLC (Method Q):
30-1 yOcarbonyllaminolphen HN R, = 10.83 min zo y1)-4,5-dihydro-3H-2,3-benzodiazepine-3-(N) carboxamide /
H,C
CH, -o 0 H3C 0--- N- (4R)-7,8-Dimethoxy- prep. HPLC:
Method XX110 N /NH
N,4-dimethy1-1-(4-1[(1-C1H, H,C analyt. HPLC
(Method Q):
40 methylpiperidin-4-R, 9.49 min yOcarbonyljaminolphen =

HN
optical rotation: [a]20 = -233.2 zo yI)-4,5-dihydro-3H-2,3-0.36 (c = 1.00; methanol) benzodiazepine-3-c) carboxamide /
H,C

. CA 02915419 2015-12-14 ' BHC123073FC
, No. Structure Name Analytical data 11-1-NMR (300MHz, CDC13): 8 =
cH3 1.01 (d, 3H), 1.73-2.05 (m, 4H), ,o /2 ( )-7,8-Dimethoxy-N,4-H,C 010 ,N, 2.31-2.55 (m, 4H), 2.67-2.83 (m, o ¨N , NH dimethy1-1- {4-2H), 2.86 (d, 3H), 3.04 (d, 1H), 31 O [(piperidin-4-ylcarbonyl)amino]phenyl 3.26 (d, 1H), 3.64 (s, 3H), 3.92 (s, CH, 3H), 5.36 (m, 1H), 6.38 (q, 1H), HN }-4,5-dihydro-3H-2,3-zo 6.57 (s, 1H), 6.71 (s, 1H), 7.47 (d, benzodiazepine-3-2H), 7.59 (d, 2H), 7.91 (s, br, 1H).
carboxamide 4') H
LCMS (Method 2): R, = 0.72 min;
nth = 480 (M-PH) 111-NMR (600MHz, DMSO-d6): 8 cH3 = 1.02 (d, 3H), 2.51-2.54 (m, 4H), , 0 o H3c ( )-7,8-Dimethoxy-N,4-2.59 (dd, 1H), 2.66 (d, 3H), 2.89 o ---- =

N NH dimethy1-1-{4-1 H,C1 (dd, 111), 3.16 (s, 2H), 3.58 (s, 3H), CH, [(morpholin-4-32 ( cl, FO, ( 3.64 d 4 3.84 s, 3H), 4.97-5-O ylacetypamino]phenyll-04 (m, 1H), 6.46 (q, 1H), 6.52 (s, HN 4,5-dihydro-3H-2,3-r benzodiazepine-3- 1H), 7.02 (s, 1H), 7.65 (d, 2H), 7.71 (d, 2H), 9.92 (s, 1H).
IN--) carboxamide LCMS (Method 2): R, = 0.76 min;
m/z = 496 (M+H)+
11-1-NMR (400MHz, CDC13): 8 =
cH3 1.04 (d, 3H), 1.88-2.02 (m, 41), ,o 40 o Hsc 2.03-2.17 (m, 2H), 2.25-2.37 (m, o .¨N NH ( )-1-(4-{[(1-1 H3c 1H), 2.82 (dd, 1H), 2.90 (d, 3H), cit ifi Benzy1piperidin-4-2.99-3.12 (m, 3H), 3.57 (s, 2H), yl)carbonyljamino}phen 3.68 (s, 3H), 3.95 (s, 3H), 5.38-33 HN z y1)-7,8-dimethoxy-N,4-o 5.47 (in, 1H), 6.40 (q, 1H), 6.61 (s, dimethy1-4,5-dihydro-1H), 6.74 (s, 1H), 7.30-7.34 (m, c) 3H-2,3-benzodiazepine-2H), 7.36 (m, 4H), 7.50 (d, 2H), 3-carboxamide 7.59 (d, 2H).
. LCMS (Method 2): R, = 0.85 min;
m/z = 570 (M+1-1)+
_ s CA 02915419 2015-12-14 , No. Structure Name Analytical data CH
,. 3 H3C-. 0 .N40 O _N NH (4S)-1-(4-{[(1-prep. HPLC: Method X
1 H3c, CH Benzylpiperidin-4-3 it yl)carbonyl]aminolphen analyt. HPLC
(Method G):
R, ---- 2.78 min 33-1 HN y1)-7,8-dimethoxy-N,-zo 4optical rotation: [a]D2 = 211.00 dimethy1-4,5-dihydro-0.470 (c = 1.00; methanol) 3H-2,3-benzodiazepine-(nri 3-carboxamide lit cH3 o 0 O --N NH (4R)-1-(4-{[(1-prep. HPLC: Method X
1 H,C1 CH3 OBenzylpiperidin-4-analyt. HPLC (Method G):
yl)carbonyljamino}phen Rt = 2.49 min 33-2 HN y1)-7,8-dimethoxy-N,4-optical rotation: [a]D2 = -192.5 dimethy1-4,5-dihydro-0.38 (c ¨ 1.00; methanol) 3H-2,3-benzodiazepine-ci 3-carboxamide 1H-NMR (600MHz, DMSO-d6): 5 = 0.98 (d, 3H), 2.20 (s, br, 3H), ,0 gair--r CH3o ( )-7,8-Dimethoxy-N,4-2.68 (d, 3H), 2.70 (dd, 1H), 2.94 N-- dimethy1-1-(4-? µP ¨N NH
3C (dd, 1H), 3.08 (s, br, 2H), 3.24 (s, H, {methyl[(methylamino)a CH, 3H), 3.58 (s, 3H), 3.84 (s, 3H), O cetyl] amino} phenyI)-5.05-5.12 (m, 1H), 6.52 (s, 1H), 4,5-dihydro-3H-2,3-H,C"'" N =\,. 0 6.61 (q, 1H), 7.03 (s, 1H), 7.37 (d, benzodiazepine-3-2H), 7.71 (d, 2H).
CN--CH3 carboxamide H
LCMS (Method 2): Rt = 0.75 min;
miz = 454 (M+H)+

. CA 02915419 2015-12-14 No. Structure Name Analytical data _ 1H-NMR (300MHz, CDC13): 8 =
cH3 1.01 (d, 3H), 2.43 (s, 3H2.61-oH3c- . o N4 ( )-7,8-Dimethoxy-N,4-2.71 (m, 3H), 2.72-2.81 (m, 5H), /
o --- N /NH
dimethy1-1-(4- {[(4- 2.83 (d, 1H), 2.88 (d, 3H), 3.07 thylpiperazin-1- (dd, 1H), 3.20 (s, 2H), 3.66 (s, 3H), yl)acetyl]aminolphenyly 3.93 (s, 3H), 5.35-5.46 (m, 1H), HN
\r0 4,5-dihydro-3H-2,3- 6.40 (q, 1H), 6.59 (s, 1H), 6.72 (s, benzodiazepine-3- 1H), 7.49 (d, 2H), 7.61 (d, 2H), /NMcarboxamide 9.16 (s, 1H).
s CH3 LCMS (Method 2): Rt =
0.75 min;
m/z = 509 (M+H)+

I-1,C ei 11,14 (4R)-7,8-Dimethoxy-prep. HPLC: Method XI
o --- N NH N,4-dimethy1-1-(4-{[(4-I it g analyt. HPLC (Method P):
cH3 . methylpiperazin-l-R, = 4.54 min ypacetyl]aminolpheny1)-HN optical rotation: [ode' = -227.5 ,ro 4,5-dihydro-3H-2,3-benzodiazepine-3- 0.300 (c = 1.00; methanol) N
c...,-N carboxamide ... 0 IV, o ill .7,4 (4S)-7,8-Dimethoxy-N,4- prep. HPLC: Method XI
O ¨ N /NH dimethy1-1-(4- {[(4-cH3 I H,C
analyt. HPLC (Method P):
35-2 O methylpiperazin-1-yl) acetyl] amino } phenyl)- Rt = 5.70 min HN optical rotation: loc1D2 = 213.1 ro 4,5-dihydro-3H-2,3-0.490 (c= 1.00; methanol) benzodiazepine-3-N
carboxamide C,, N
s CH3 , CA 02915419 2015-12-14 , No. Structure Name Analytical data 11I-NMR (300MHz, CDCI3): 5 =

,0 0 1.06 (d, 3H), 1.49 (s, 9H), 1.60-FI,C /10 o ---N NH ( )-tert-Butyl 44{447,8- 2.01 (m, 6H), 2.76-2.87 (m, 3H), i *
dimethoxy-4-methyl-3- 2.89 (d, 3H), 3.07 (dd, 1H), 3.69 (s, (methylcarbamoy1)-4,5- 3H), 3.96 (s, 3H), 4.16-4.29 (m, ZO dihydro-3H-2,3- 1H), 5.34-5.46 (m, 1H), 6.37 (m, benzodiazepin-1- 1H), 6.61 (s, 1H), 6.76 (s, 1H), yliphenyl}carbamoyDpip 7.53 (d, 2H), 7.64 (d, 2H), 7.71 (s, (nri o--"o eridine-l-carboxylate br, 1H).
El3CCH3 LCMS (Method 2): Rt = 1.25 min;

m/z = 580 (M+H)+
., CH3 itc,0 ga 'IV 40 / (45)-tert-Butyl 4-({4-o 1111111111 ¨ N NH
CI H3 H3g [7,8-dimethoxy-4- prep. HPLC:
Method XIII
Ili methy1-3-analyt. HPLC (Method R):
(methylcarbamoy1)-4,5-Zo R = 4.14 min dihydro-3H-2,3-optical rotation: [a]02 = 189.9 E
benzodiazepin-1-0.14 (c = 1.00; methanol) 1\ N-) yl]phenylIcarbamoyl)pip 0--ko eridine-l-carboxylate ,0 0 el O -- N1N4NH (4R)-tert-Butyl 4-({4-prep. HPLC: Method XIII
1 it CI [7,8-dimethoxy-4-CH, =methy1-3- analyt. HPLC (Method R):
(methylcarbamoy1)-4,5- Rt = 3.46 min dihydro-3H-2,3-optical rotation: [402 = -190.9 benzodiazepin-1- 0.21 (c = 1.00;
methanol) c--) yllphenyllcarbamoyl)pip o¨ko eridine-l-carboxylate Example 37 ( )-7,8-Dimethoxy-N,4-dimethy1-1-14-[(1-methylpiperidin-4-ypoxy]phenyl -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide O N NH

In a microwave vessel, 18.5 mg (0.463 mmol) of sodium hydride (60%) were initially charged in 1 ml of toluene, and 32 mg (0.278 mmol) of 1-methylpiperidin-4-ol were added and the suspension was degassed with argon and then heated at 70 C for 15 min. After cooling, 3 mg (0.003 mmol) of Pd2(dba)3 [CAS No: 51364-51-3], 6 mg (0.008 mmol) of (S)-Tol-B1NAP (CAS
[100165-88-6]) and 100 mg (0.231 mmol) of ( )-1-(4-bromopheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 29A) were added and the mixture was heated under argon in a microwave oven at 100 C for 5 h. The reaction was then acidified with 2N hydrochloric acid and then made alkaline using 25% aqueous ammonia solution. The blue solution was extracted twice with ethyl acetate. The combined organic phases were dried with sodium sulphate. The solvent was removed on a rotary evaporator and the residue was purified by prep. HPLC. This gave 44.7 mg (41% of theory) of the desired product as a solid.
LCMS (Method 2): R, = 0.74 min; ink = 467 (M+H) 111-NMR (400MHz, CDC13): 8 = 1.05 (d, 3H), 1.91-2.02 (m, 2H), 2.11-2.22 (m, 2H), 2.44 (s, 3H), 2.51-2.63 (m, 2H), 2.75 (dd, 1H), 2.79-2.85 (m, 2H), 2.87 (d, 3H), 2.99 (dd, 1H), 3.68 (s, 3H), 3.93 (s, 3H), 4.43-4.52 (m, 1H), 5.28-5.38 (m, 1H), 6.24 (q, 1H), 6.60 (s, 1H), 6.73 (s, 1H), 6.91 (d, 2H), 7.47 (d, 2H).

=

, Analogously to Example 37, the racemic Example 29A (optionally with subsequent enantiomer separation) or the enantiomerically pure Example 29-2A and the appropriate commercially available alcohols gave the following exemplary compounds:
1, No. Structure Name Analytical data .' CH' , (45)-7,8-Dimethoxy-N,4-H3c- 40 4,-, / dimethy1-1-{4-[(1-o --- N-N NH LCMS (Method 2): R, = 0.78 min;
I H,C/ methylpiperidin-4-CH, ink - 467 (M+H)+

411 yl)oxylpheny11-4,5-optical rotation: [4)2 - 314.1 dihydro-3H-2,3-o nzodiazepine-3-be o 0.22 (c = 1.00; methanol) carboxamide CH, _ 'H-NMR (300MHz, CDC13): 5 =
cH3 ,o o ( )-I-{4-[2- 1.05 (d, 3H), 2.51 (s, 6H), 2.76 (dd, H,C el 1N4 , 0 ---N NH (Dimethylammo)ethoxy]
1H), 2.87 (d, 3H), 2.91-3.06 (m, cH3 H3c phenyl}-7,8-dimethoxy-3H), 3.68 (s, 3H), 3.93 (s, 3H), 38 #1 N,4-dimethy1-4,5- 4.24 (t, 2H), 5.28-5.41 (m, 1H), o dihydro-3H-2,3-6.26 (q, 1H), 6.58 (s, 1H), 6.73 (s, Zbenzodiazepine-3- 1H), 6.93 (d, 2H), 7.47 (d, 2H).

i carboxamide LCMS (Method 2): R, = 0.74 min;
H,C
miz = 441 (M+H) cii3 H,C prep. HPLC: Method XIV
o ,o is N4 o (4R)-1-{4-[2-____NNH (Dimethylamino)ethoxy] analyt. HPLC
(Method S):

CH, phenyl }-7,8-dimethoxy- R., - 5.79 min 38-1 =H,C N,4-dimethy1-4,5- LCMS (Method 2): R, =
0.73 min;
o dihydro-3H-2,3- rn/z = 441 (M+H)+
benzodiazepine-3-.,N.-c1-13 optical rotation:
[]D2 = -237.6 / carboxamide H3c 0.87 (c = 1.00;
methanol) . CA 02915419 2015-12-14 .

No. Structure Name Analytical data CH
, 0 H3C el ' N-4 0 (4S)- I -{4-[2- prep.
HPLC: Method XIV
o ¨ N NH /
(Di methylarnino)ethoxy] analyt. HPLC
(Method S):
1 t CH, =

phenyl}-7,8-dimethoxy- R, = 8.40 min 38-2 O H,C N,4-dimethy1-4,5-LCMS (Method 2): R, = 0.72 min;
o dihydro-3H-2,3- m/z ¨ 441 (M+H) Z
N--- cit benzodiazepine-3-optical rotation: [(1]132 = 218.5 / carboxamide Itc 0.41 (c = 1.00;
methanol) 111-NMR (400MHz, CDC13): 5 =
1.07 (d, 3H), 2.45 (s, 3H), 2.78 (dd, ( )-7,8-Dimethoxy-N,4-CH, 1H), 2.89 (d, 3H), 3.03 (dd, 1H), ,o 401) o dimethy1-1-{4-[(1-3.18 (dd, 2H), 3.70 (s, 3H), 3.84-/

o ¨ N
N NH H3C methylazetidin-3-1 / 3.90 (m, 2H), 3.95 (s, 3H), 4.78-=yl)oxylpheny11-4,5-dihydro-3H-2,3- 4.86 (m, 1H), 5.32-5.42 (m, 1H), 6.28 (q, 1H), 6.61 (s, 1H), 6.75 (s, benzodiazepine-3-1H), 6.81 (d, 2H), 7.49 (d, 2H).
carboxamide LCMS (Method 1): R, = 0.80 min;
m/z = 439 (M+H)+
Example 40 ( )-7,8-Dimethoxy-N,4-dimethy1-1-(4-phenoxypheny1)-4,5-dihydro-3H-2,3-benzodi azepine-3-carboxamide 0 N¨ CH3 H

C"
3 , el 0 ----. N 0 ES
O=
In a microwave vessel, 100 mg (0.231 mmol) of ( )-1-(4-bromopheny1)-7,8-dimethoxy-N,4-= CA 02915419 2015-12-14 dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 29A), 43.5 mg (0.463 mmol) of phenol, 226 mg (0.694 mmol) of caesium carbonate, 9.2 mg (0.093 mmol) of copper(I) chloride and 8.5 mg (0.046 mmol) of 2,2,6,6-tetramethylheptane-3,5-dione were initially charged in 4 ml of NMP, and the reaction solution was degassed carefully and heated at 205 C under argon for 20 min. The crude mixture was filtered and the filtrate was purified by prep. HPLC. This gave 15.8 mg (15% of theory) of the desired product as a solid.
LCMS (Method 2): 1Z, = 1.33 min; m/z = 446 (M+H) 1H-NMR (300MHz, CDCI3): = 1.07 (d, 3H), 2.82 (dd, 1H), 2.90 (d, 3H), 3.08 (dd, 1H), 3.72 (s, 3H), 3.96 (s, 3H), 5.36-5.50 (m, 1H), 6.33-6.43 (m, 1H), 6.64 (s, 1H), 6.76 (s, 1H), 7.04 (d, 2H), 7.10 (d, 2H), 7.19 (t, 1H), 7.41 (t, 2H), 7.53 (d, 2H).
Analogously to Example 40, Intermediate 29A and the appropriate commercially available phenol derivative gave the following exemplary compound:
No. Structure Name Analytical data 'H-NMR (300M1Hz, CDCI3): 8 CI) CH3 H ( )-1-[4-(4- 1.07 (d, 3H), 2.82 (dd, 1H), 2.90 N-CH3 (d, 3H), 3.08 (dd, 1H), 3.72 (s, Fluorophenoxy)phenyli-H3C.,o =¨N 0 3H), 3.96 (s, 3H), 5.35-5.50 (m, 7,8-dimethoxy-N,4-111101 dimethy1-4,5-dihydro-3H- 1H), 6.31-6.43 (m, 1H), 6.63 (s, 1H), 6.76 (s, 1H), 7.00 (d, 2H), 2,3-benzodiazepine-3-0 a 7.05-7.15 (m, 4H), 7.53 (d, 2H).
carboxamide "WI F LCMS (Method 2): R, =
1.34 min;
m/z = 464 (M+H)+
Example 42 ( )-8-Chloro-1- {4-[(2-fluoropyridin-3-yDamino]phenyl)-N,4-dimethyl-7-(trifluoromethoxy)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide F
F F
\./'"

ON¨

CI
¨N ,NH

HN
Fr¨) Under argon, 100 mg (0.224 mmol) of ( )-8-chloro-1-(4-chloropheny1)-N,4-dimethy1-7-(trifluoromethoxy)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 32A) were initially charged in 5 ml of degassed toluene. 50.2 mg (0.448 mmol) of 2-fluoropyridin-3-amine, 30 mg (0.314 mmol) of sodium tert-butoxide and 9 mg (0.011 mmol) of chloro-(2-dicyclohexylphosphino-2,4,6-triisopropy1-1,1-bipheny1)[2-(2-amino-1,1-biphenyl)Jpalladium(ll) (CAS [1310584-14-5]) were added. The mixture was degassed again and then stirred at 120 C for 1 hour. After cooling, sat. aqueous ammonium chloride solution and water were added and the mixture was extracted with ethyl acetate. The mixture was filtered off with suction through a WhatmanTM filter, and the filter was rinsed with ethyl acetate. The solvent was removed on a rotary evaporator and the residue was purified by prep. HPLC. This gave 24 mg (20% of theory) of the desired product as a solid.
LCMS (Method 1): R = 1.42 min; miz = 522 (M+H)+
'H-NMR (600MHz, CDC13): 5 = 1.02 (d, 3H), 2.84 - 2.91 (m, 4H), 3.08 (dd, 1H), 5.39 - 5.47 (m, 1H), 6.07 (br. s., 1H), 6.32 (br. s., 1H), 7.12 (dd, 1H), 7.16 (d, 2H), 7.22 (s, 1H), 7.29 (s, 1H), 7.47 (d, 2H), 7.72 - 7.78 (m, 2H).
Analogously to Example 42, Example 33A and the appropriate commercially available amine gave the following exemplary compound:

= CA 02915419 2015-12-14 -No. Structure Name Analytical data _ 1H-NMR (300MHz, CDC13): 8 =
1.13 (d, 3H), 1.77 (m, 2H), 1.95 CH3 (-7,8-Dimethoxy-N,4-(m, 2H), 2.14 (m, 2H), 2.37 (s, el N-/dimethy1-1-{4-[methyl(1-/ \ 3H), 2.74 (dd, 1H), 2.85 (d, 3H), o ¨ N /NH methylpiperidin-4-H3C H) 2.88 (s, 3, 2.94 (dd, 1H), 3.03 F4'T yOamino]pheny1}-8-43 F e (m, 2H), 3.69 (m, 1H), 5.23 (m, (trifluoromethoxy)-4,5-1H), 5.95 (m, 1H), 6.76 (d, 2H), oidihydro-3H-2,3-7.04 (d, 1H), 7.20 (dd, 1H), 7.28 benzodiazepine-3-(d, 1H), 7.47 (d, 2H).
CH3 carboxamide LCMS (Method 3): Rt = 0.96 min;
m/z = 504 (M+H)+

Example 44 (4S)-8-Methoxy-N,4-dimethy1-1-(4-{[(1-methy1-1H-pyrrol-2-ypcarbonyl]amino}pheny1)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide HC N

HN
)r 100 mg (0.295 mmol) of (4S)-1-(4-aminopheny1)-8-methoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 34-2A) and 40.7 mg (0.325 mmol) of 1-methy1-1H-pyrrole-2-carboxylic acid (CAS [6973-60-0]), 114 mg (0.355 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (CAS [130312-02-6]) and 61.8 ul (0.355 mmol) of N,N-diisopropylethylamine in 2 ml of N,N-dimethylformamide were stirred at 80 C for 23 h. After cooling, the mixture was concentrated under reduced pressure and the residue was purified by prep.
HPLC. This gave 68 mg (50% of theory) of the desired product as a solid.
LCMS (Method 3): R = 1.16 min; m/z = 446 (M+H)+
'H-NMR (300MHz, CDC13): = 0.99 (d, 3H), 2.81 (dd, 1H), 2.88 (d, 3H), 3.04 (dd, 1H), 3.69 (s, 3H), 4.00 (s, 3H), 5.36 (m, 1H), 6.16 (dd, 1H), 6.37 (br. q., 1H), 6.67 (d, 1H), 6.74 (dd, 1H), 6.81 (dd, 1H), 6.88 (dd, 1H), 7.14 (d, 1H), 7.51 (d, 2H), 7.59 (d, 2H), 7.70 (br.
s., 1H).

Analogously to Example 44, Example 34-2A and 1,2,3-thiadiazole-4-carboxylic acid (CAS [4100-13-4]) gave the following exemplary compound:
No. Structure Name Analytical data LCMS (Method 3): 124 = 1.08 min;
CH (45)-8-Methoxy-N,4- m/z = 451 (M+H)+
H.,C =
dimethy1-1-{44(1,2,3-[(1,2,3 'H-NMR
(300MHz, CDCI3): 8 =
- N NH thiadiazol-4- 0.98 (d, 3H), 2.84 (dd, 1H), 2.90 H,C
ylcarbonypamino]phenyl (d, 3H), 3.08 (dd, IH), 3.70 (s, }-4,5-dihydro-3H-2,3- 3H), 5.39 (m, 1H), 6.44 (m, 1H), benzodiazepine-3- 6.67 (d, 1H), 6.89 (dd, 1H), 7.15 carboxamide (d, 1H), 7.57 (d, 2H), 7.78 (d, 2H), 9.36 (s, 1H), 9.46 (br. s., 1H).
5 Example 46 ( )-1-(4-{[(Dimethylamino)acetyl]aminolpheny1)-8-methoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide 71¨( HN

At 0 C, 998 mg (2.95 mmol) of ( )-1-(4-aminopheny1)-8-methoxy-N,4-dimethy1-4,5-dihydro-3H-10 2,3-benzodiazepine-3-carboxamide (Example 34A) and 304 mg (2.95 mmol) of N,N-dimethylglycine (CAS [1118-68-9]) and 1.28 ml (7.39 mmol) of N,N-diisopropylethylamine were initially charged in 20 ml of tetrahydrofuran. With ice bath cooling, 2.07 ml (3.54 mmol) of a 50%
strength solution of propanephosphonic acid cyc/o-anhydride in N,N-dimethylformamide (CAS
[68957-94-8]) were added dropwise. The reaction mixture was then stirred at 60 C for 3 days. For workup, saturated aqueous sodium bicarbonate solution was added and the mixture was extracted three times with ethyl acetate. The combined organic phases were dried, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography. This gave 647 mg (50% of theory) of the desired product as a solid.
LCMS (Method 3): 124 = 0.74 min; m/z = 424 (M+H)+
'H-NMR (300MHz, CDC13): = 0.98 (d, 3H), 2.44(s, 6H), 2.81 (dd, 1H), 2.88 (d, 3H), 3.05 (dd, 1H), 3.68 (s, 3H), 5.36 (m, 1H), 3.16 (s, 2H), 6.38 (m, 1H), 6.65 (d, 1H), 6.88 (dd, 1H), 7.14 (d, 1H), 7.50 (d, 2H), 7.64 (d, 2H), 9.32 (br. s., 1H).
Example 47 ( )-7,8-Dimethoxy-N,4-dimethyl -1- {4-[(methylsulphonypaminolphenyll -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide CH

,N4 H C

N NH

HN
,S 3 Cr' "
o 100 mg (0.231 mmol) of ( )-1-(4-bromopheny1)-7,8-dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide (Example 29A), 26 mg (0.278 mmol) of methanesulphonamide, 64 mg (0.46 mmol) of potassium carbonate and 13 mg (0.023 mmol) of allylchloropalladium dimer (CAS [12012-95-2]) were initially charged in 3 ml of 2-methyltetrahydrofuran, and the suspension was degassed with argon for 10 min. 39 mg (0.093 mmol) of di-tert-buty1(2',4',6'-triisopropylbipheny1-2-yOphosphane (CAS [564483-19-8]) were then added, and the mixture was degassed again with argon and heated at 80 C for 16 h. The crude mixture was filtered, the solvent was then removed and the residue obtained was purified by prep. HPLC. This gave 16 mg (16% of theory) of the desired product as a solid.
LCMS (Method 2): R, = 0.84 min; m/z = 447 (M+H)+

'11-NMR (300MHz, CDC13): = 1.02 (d, 3H), 2.84 (dd, 1H), 2.91 (d, 3H), 3.06-3.15 (m, 1H), 3.10 (s, 3H), 3.69 (s, 3H), 3.96 (s, 311), 5.38-5.51 (m, 1H), 6.44 (q, 1H), 6.59 (s, 1H), 6.75 (s, 1H), 7.04 (s, br, 1H), 7.28 (d, 2H), 7.53 (d, 2H).
Analogously to Example 47, racemic Example 29 or enantiomerically pure Example 29-2A and the appropriate sulphonamides gave the following exemplary compounds.
No. Structure Name Analytical data LCMS (Method 1): R = 1.03 min;
m/z = 510 (M+H)+
cH3 (4S)-7,8-Dimethoxy-N,4-O cH,c) 'H-NMIR
(300MHz, CDC13): 8 =
dimethy1-1-14-[(pyridin-40'N4 1.00 (d, 3H), 2.83 (dd, 1H), 2.91 ¨No N- CH, 3-4840 (d, 3H), 3.09 (dd, 1H), 3.66 (s, ylsulphonyl)amino]pheny 3H), 3.95 (s, 3H), 5.38-5.51 (m, 11-4,5-dihydro-3H-2,3-HNõs 0 1H), 6.42 (q, 1H), 6.49 (s, 1H), , benzodiazepine-3-6.73 (s, 1H), 7.17 (d, 2H), 7.28 (m, carboxamide IH), 7.41-7.51 (m, 3H), 8.16 (m, 1H), 8.80 (d, 1H), 9.04 (d, 1H).
LCMS (Method 1): R, = 1.01 min;
m/z = 517 (M+H)+
CH, (4S)-7,8-Dimethoxy-N,4- 1H-NMR
(400MHz, CDC13): =
O aghm ,cH30 dimethy1-1-{4- 1.04 (d, 3H), 1.96-2.10 (m, 4H), H3c.,0 niN4N-cH, [(tetrahydro-2H-pyran-4- 2.85 (dd, 1H), 2.92 (d, 3H), 3.10 ylsulphonyDaminolpheny (dd, 1H), 3.29-3.42 (m, 3H), 3.70 11-4,5-dihydro-3H-2,3- (s, 3H), 3.96 (s, 3H), 4.07-4.15 (m, HN,s,0 benzodiazepine-3- 2H), 5.40-5.49 (m, 1H), 6.37-6.45 carboxamide (m, 1H), 6.60 (s, 1H), 6.76 (s, 1H), 6.80 (s, br, 1H), 7.28 (d, 2H), 7.52 (d, 2H).

, No. Structure Name Analytical data LCMS (Method 2): R, = 0.94 min;
( )-7,8-Dimethoxy-N,4- m/z = 461 (M+H)+
CH, I CH, dimethy1-1-{4- 'H-NMR (400MHz., CDCI3): 8 =
1-130,0 MPIP _ N [methyl(methylsulphonyl 1.02 (d, 3H), 2.86 (dd, 1H), 2.92 (s, IP )amino]pheny1}-4,5-dihydro-3H-2,3- 6H), 3.12 (dd, 1H), 3.40 (s, 3H), 3.70 (s, 3H), 3.96 (s, 3H), 5.42-,N .0 N.

benzodiazepine-3- 5.53 (m, 1H), 6.44-6.54 (m, 1H), o '-'3 carboxamide 6.61 (s, 1H), 6.75 (s, 1H), 7.73 (d, 2H), 7.55 (d, 2H).
LCMS (Method 2): R, = 1.05 min;
in/z = 509 (M+H)+
CH, 1H-NMR (300MHz, CDC13): 8 =
O abh cH30 ( )-7,8-Dimethoxy-N,4-1.02 (d, 3H), 2.83 (dd, 1H), 2.90 H3c.,0 1111V _...;
DIN4N-C It dimethy1-1- {4-(d, 3H), 3.08 (dd, 1H), 3.64 (s, 51 H [(phenylsulphonyl)amino ]phenyl}-4,5-dihydro-3H- 3H), 3.95 (s, 3H), 5.37-5.51 (m, 1H), 6.34-6.44 (m, 1H), 6.49 (s, HN - 0 2,3-benzodiazepine-3--s' g 40 carboxamide 1H), 6.73 (s, 1H), 6.99 (m, 1H), 7.14 (d, 2H), 7.43 (d, 2H), 7.46-7.54 (m, 2H), 7.55-7.63 (m, 1H), 7.88 (d, 2H).
_ LCMS (Method 2): Rt = 1.07 min;
m/z = 523.8 (M+H)+
( )-1-{4-cH
CH, , 'H-NMR (300MHz, CDC13): 8 =
I
0 0 [(Benzylsulphonyl)amino 1.05 (d 3H) 2.86 (dd 1H) 2.93 gi ¨ rsiN4 ' ' ' "
N_CH, ]pheny1}-7,8-dunethoxy-H ' (d, 3H), 3.11 (dd, 1H), 3.71 (s, benzodiazepine-3-1101 N,4-dimethy1-4,5-dihydro-3H-2,3- 3H), 3.96 (s, 3H), 4.42 (s, 2H), HNõF 0 el 5.39-5.52 (m, 1H), 6.39-6.47 (m, o 1H), 6.50 (s, br, 1H), 6.61 (s, 1H), carboxamide 6.76 (s, 1H), 7.18 (d, 2H), 7.30-7.45 (m, 5H), 7.53 (d, 2H).

. CA 02915419 2015-12-14 No. Structure Name Analytical data LCMS (Method 2): R, = 1.13 min;
( )-7,8-Dimethoxy-N,4- m/z = 501.8 (M+H)+

oI CH3 o N dimethy1-1-(4- 'H-NMR (300MHz, CDC13): 8 =

¶3 0 .--- 14 N-CH3 {
[(trifluoromethyl)sulpho 1.00 (d, 3H), 2.87 (dd, 1H), 2.92 40 nyl]aminolpheny1)-4,5-(d, 3H), 3.14 (dd, 1H), 3.67 (s, dihydro-3H-2,3-3H), 3.96 (s, 3H), 5.41-5.54 (m, HN,_...,0 g.,.,, FF benzodiazepine-3- 1H), 6.51 (q, 1H), 6.54 (s, 1H), F carboxamide 6.74 (s, 1H), 7.35 (d, 2H), 7.53 (d, 2H).
LCMS (Method 2): R., = 0.93 min;
m/z = 473 (M+H)+
( )-1-{4-CH
cH3 , 'H-NMR (400MHz, CDC13): 8 =
oI
o [(Cyclopropylsulphonyl)a N4 1.00-1.08 (m, 5H), 1.24-1.30 (m, H3c-0 VI ¨ rsi N-CH3 mino]pheny11-7,8-2H), 2.54-2.62 (m, 1H), 2.85 (dd, SI dimethoxy-N,4-dimethy1-4,5-dihydro-3H-2,3-1H), 2.92 (d, 3H), 3.10 (dd, 1H), HN,o 3.69 (s, 3H), 3.96 (s, 3H), 5.40-benzodiazepine-3-8 V 5.50 (m, 1H), 6.39-6.47 (m, 1H), carboxamide 6.60 (s, 1H), 6.72 (s, br, 1H), 6.76 (s, 1H), 7.30 (d, 2H), 7.52 (d, 2H).

Example 55 ( )-1-[4-(Benzyloxy)pheny1]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide CH
i 3 CH3 0 '14 N¨CH3 Analogously to Example 37, 100 mg (0.162 mmol) of racemic Example 29A gave, by reaction with 27 mg (0.243 mmol) of phenylmethanol and subsequent purification by reversed-phase prep.
HPLC, 32 mg (42% of theory) of the desired product as a solid.
LCMS (Method 2): R, = 1.32 min; m/z = 460.8 (M+H)+
1H-NMR (300MHz, CDC13): 6 = 1.10 (d, 3H), 2.79 (dd, 1H), 2.89 (d, 3H), 3.03 (dd, 1H), 3.71 (s, 3H), 3.96 (s, 3H), 5.16 (s, 2H), 5.31-5.44 (m, 1H), 6.27 (q, 1H), 6.63 (s, 1H), 6.77 (s, 1H), 7.03 (d, 2H), 7.34-7.51 (m, 5H), 7.53 (d, 2H).

Example 56 (1)-1 - {4-[(N,N-Dimethylglycyl)(methypamino] phenyl } -4-ethy1-7,8-dimethoxy-N-methy1-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide CH
i 3 0 41, N-C H3 fk H3C, CH3 Example 56 was prepared analogously to the synthesis sequence described for Example 29. The 1-(3,4-dimethoxyphenyl)butan-2-ol (cf. Formula II in Scheme 1) used for this purpose was prepared from (3,4-dimethoxyphenyl)acetaldehyde by reaction with ethylmagnesium bromide (Journal of Organic Chemistry 1976, 3201 - 3204). (3,4-Dimethoxyphenyl)acetaldehyde was prepared from commercial 2-(3,4-dimethoxyphenypethanol (CAS[7417-21-2]) by oxidation with Dess-Martin reagent (CAS[87413-09-0]) (cf. Monatshefte fijr Chemie 2004, 1289¨ 1295).
LCMS (Method 2): It, = 0.68 min; m/z = 482 (M+H)+
11-1-NMIt (300M1-Iz, CDC13): 5 = 0.88 (t, 3H), 1.04-1.21 (m, 1H), 1.32-1.48 (m, 1H), 2.38 (s, br, 6H), 2.64 (s, 2H), 2.93 (d, 3H), 3.02-3.15 (m, 2H), 3.36 (s, 3H), 3.68 (s, 3H), 3.96 (s, 3H), 5.26-5.37 (m, 1H), 6.60 (s, 1H), 6.59-6.67 (m, 1H), 6.75 (s, I H), 7.25 (d, 2H), 7.55 (d, 2H).

Example 57 ( )-4-Isopropyl-7,8-dimethoxy-N-methy1-1-{4-[methyl(1-methyl-IH-imidazol-2-yDamino]phenyll-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide H3CC) 0 CH3 H,C

H,C'N
\\ N"
Example 57 was prepared analogously to the synthesis sequence described for Example 12. The 1-(3,4-dimethoxyphenyI)-3-methylbutan-2-ol (cf. Formula II in Scheme 1) used for this purpose was prepared from (3,4-dimethoxyphenypacetaldehyde by reaction with 2-propylmagnesium chloride (cf. Organic Letters 2007, 2103 ¨ 2106). (3,4-Dimethoxyphenyl)acetaldehyde was prepared from commercial 2-(3,4-dimethoxyphenyl)ethanol (CAS[7417-21-2]) by oxidation with Dess-Martin reagent (CAS[87413-09-0]) (cf. Monatshefte fiir Chemie 2004, 1289¨ 1295).
LCMS (Method 2): R, = 0.75 min; m/z = 491 (M+H) 'H-NMR (400MHz, CDC13): 8 = 0.88 (t, 6H), 1.48-1.60 (m, 1H), 2.87 (d, 3H), 2.91 (dd, 1H), 3.01 (dd, 1H), 3.41 (s, 3H), 3.43 (s, 3H), 3.69 (s, 3H), 3.94 (s, 3H), 5.08-5.16 (m, 1H), 6.35 (q, 1H), 6.61 (d, 2H), 6.68 (s, 1H), 6.75 (s, 1H), 6.86 (d, 1H), 7.03 (d, 1H), 7.43 (d, 2H).

= BHC123073FC

Biological efficacy of the compounds according to the invention 1. Assays 1.1 Protein-Protein Interaction Assay Binding assay BRD4/acetylated peptide H4 ("PRO") To assess the BRD4 binding strength of the substances described in this application, the ability thereof to inhibit the interaction between BRD4 (BD1) and acetylated histone H4 in a dose-dependent manner was quantified (Filippakopoulos et al., Cell, 2012, 149:214-231).
For this purpose, a time-resolved fluorescence resonance energy transfer (TR-FRET) assay was used, which measures the binding between N-terminally His6-tagged BRD4 (BD1) (amino acids 67-152, longer constructs also being possible, preferably amino acids 44-168) and a synthetic acetylated histone H4 (Ac-H4) peptide with sequence GRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHGSGSK-biotin. The recombinant BRD4 protein produced in-house according to Filippakopoulos et al., Cell, 2012, 149:214-231 was expressed in E. coli and purified by means of (Ni-NTA) affinity and (Sephadex G-75) size exclusion chromatography. The Ac-H4 peptide can be purchased, for example, from Biosyntan (Berlin, Germany).
In the assay, typically 11 different concentrations of each substance (0.1 nM, 0.33 nM, 1.1 nM, 3.8 nM, 13 nM, 44 nM, 0.15 M, 0.51 M, 1.7 M, 5.9 M and 20 M) were analysed as duplicates on the same microtitre plate. For this purpose, 100-fold concentrated solutions in DMSO
were prepared by serial dilutions (1:3.4) of a 2 mM stock solution into a clear, 384-well microtitre plate (Greiner Bio-One, Frickenhausen, Germany). From this, 50 nl were transferred into a black test plate (Greiner Bio-One, Frickenhausen, Germany). The test was started by the addition of 2 I
of a 2.5-fold concentrated BRD4 solution (final concentration typically 10 nM
in the 5 .1 of reaction volume) in aqueous assay buffer [50 mM HEPES pH 7.5, 50 mM sodium chloride (NaC1), 0.25 mM CHAPS and 0.05% serum albumin (BSA)] to the substances in the test plate. This was followed by a 10-minute incubation step at 22 C for the pre-equilibration of putative complexes between BRD4 and the substances. Subsequently, 3 1 of a 1.67-fold concentrated solution (in assay buffer) consisting of Ac-H4 peptide (83.5 nM) and TR-FRET detection reagents [16.7 nM
anti-6His-XL665 and 3.34 nM streptavidin cryptate (both from Cisbio Bioassays, Codolet, France), and 668 mM potassium fluoride (KF)] were added.
The mixture was then incubated in the dark at 22 C for one hour and then at 4 C for at least 3 hours and for no longer than overnight. The formation of BRD4/Ac-H4 complexes was determined by the measurement of the resonance energy transfer from the streptavidin-Eu cryptate to the anti-- 174 -6His-XL665 antibody present in the reaction. For this purpose, the fluorescence emission was measured at 620 nm and 665 nm after excitation at 330-350 nm in a TR-FRET
measuring instrument, for example a Rubystar or Pherastar (both from BMG Lab Technologies, Offenburg, Germany) or a Viewlux (Perkin-Elmer). The ratio of the emissions at 665 nm and at 622 nm was taken as an indicator of the amount of BRD4/Ac-H4 complexes formed.
The data (ratios) obtained were normalized, with 0% inhibition corresponding to the mean from the measurements for a set of controls (typically 32 data points) in which all the reagents were present.
In these, in place of test substances, 50 n1 of DMS0 (100%) were used.
Inhibition of 100%
corresponded to the mean from the measurements for a set of controls (typically 32 data points) in which all the reagents except BRD4 were present. The IC50 was determined by regression analysis based on a 4-parameter equation (minimum, maximum, IC50, Hill; Y = max + (min -max) / (1 +
(X/ICõ)}")).
1.2 Cell assays Cell proliferation assays In accordance with the invention, the ability of the substances to inhibit cell proliferation was determined. Cell viability was determined by means of the alamarBlue reagent (Invitrogen) in a Victor X3 Multilabel Reader (Perkin Elmer). The excitation wavelength was 530 nm and the emission wavelength 590 nM.
The MOLM-13 cells (DSMZ, ACC 554) were sown at a concentration of 4000 cells/well in 100 1.11 of growth medium (RPMI1640, 10% FCS) on 96-well microtitre plates.
The Bl6F10 cells (ATCC, CRL-6475) were sown at a concentration of 300-500 cells/well in 100 [11 of growth medium (DMEM with phenol red, 10% FCS) on 96-well microtitre plates.
The LOX-IMVI cells (NCI-60) were sown at a concentration of 1000 cells/well in 100 1 of growth medium (RPMI1640, 10% FCS) on 96-well microtitre plates.
The CHL-1 cells (ATCC, CRL -9446) were sown at a concentration of 1000 cells/well in 100 I of growth medium (DMEM, 10% FCS) on 96-well microtitre plates.
The MOLP-8 cells (DSMZ, ACC 569) were sown at a concentration of 4000 cells/well in 100 I of growth medium (RPMI1640, 20% FCS) on 96-well microtitre plates.
The KMS-12-PE cells (DSMZ, ACC 606) were sown at a concentration of 4000 cells/well in 100 I of growth medium (RPMI1640, 20% FCS) on 96-well microtitre plates.
The LAPC-4 cells (ATCC, PTA-1441TM) were sown at a concentration of 4000 cells/well in 100 I of growth medium (RPMI1640, 2 mM L-glutamine, 10% cFCS) on 96-well microtitre plates. One day later, the LAPC-4 cells were treated with 1 nM
methyltrienolone and various substance dilutions.
The MDA-MB-231 cells (DSMZ, ACC 732) were sown at a concentration of 4000 cells/well in 100 I of growth medium (DMEM/Ham's F12 medium, 10% FCS) on 96-well microtitre plates.
After overnight incubation at 37 C, the fluorescence values (CI values) were determined. Then the plates were treated with various substance dilutions (1E-5 M, 3E-6 M, 1E-6 M, 3E-7 M, 1E-7 M, 3E-8 M, 1E-8 M) and incubated at 37 C for 72 (LOX-IMVI cells), 96 (MOLM-13, B16F10, CHL-1, MDA-MB-431 cells), 120 (MOLP-8, KMS-12-PE cells) or 168 (LAPC-4 cells) hours.
Subsequently, the fluorescence values were determined (CO values). For the data analysis, the CI
values were subtracted from the CO values and the results were compared between cells which had been treated with various dilutions of the substance or only with buffer solution. The IC50 values (substance concentration needed for 50% inhibition of cell proliferation) were calculated therefrom.
The substances were tested in the cell lines in Table 1, which represent the indications specified by way of example:
Cell line Source Indication MOLM-13 DSMZ acute myeloid leukaemia Bl6F10 ATCC melanoma (BRAE
wild-type) LOX IMVI NCI-60 melanoma (BRAF mutated) CHL-1 ATCC melanoma (BRAE
wild-type) MOLP-8 DSMZ multiple myeloma KMS-12-PE DSMZ multiple myeloma LAPC-4 ATCC prostate cancer MDA-MB-231 DSMZ mammary carcinoma 2. Results 2.1 Bindin2 assay Table 2 shows the results from the BRD4 (BD1) binding assay.
Table 2 IC 50 (BRD4) IC50 (BRD4) Example ( Example umol/l) (ttmol/l) 1 0.04 20-2 0.02 1-1 0.04 21 0.18 1-2 5.13 22 0.16 2 0.03 23 0.09 ..

IC50 (BRD4) 1050 (BRD4) Example Example (pmol/l) ()molt() 3 0.05 24 0.05 3-1 1.02 25 0.08 3-2 0.02 26 0.12 4 0.02 27 0.22 4-1 1.99 28. 0.62 4-2 0.02 29 0.04 5 0.05 29-1 3.45 5-1 0.11 29-2 0.03 6 0.04 30 0.04 7 0.02 30-1 0.06 7-1 0.63 30-2 11.75 7-2 0.02 31 0.05 8 0.03 32 0.05 8-1 0.02 33 0.07 9 0.04 33-1 0.06 9-1 5.66 33-2 3.64 9-2 0.02 34 0.72 10 0.07 35 0.15 11 0.05 35-1 19.16 12 0.02 35-2 0.09 12-1 5.42 36 0.21 12-2 0.01 36-1 0.07 13 0.03 36-2 3.05 13-1 0.03 37 0.08 14 0.02 37-1 0.06 14-1 4.73 38 0.22 14-2 0.01 38-1 3.37 15 0.05 38-2 0.11 16 0.03 39 0.30 _ 16-1 5.49 40 0.21 16-2 0.03 41 0.19 , 17 0.03 42 1.76 18 0.07 43 0.03 18-1 0.06 44 0.21 19 0.04 45 0.12 19-1 0.03 46 0.15 _ 20 0.03 47 0.05 20-1 1.71 48 0.02 _ IC50 (BRD4) IC50 (BRD4) Example Example ( mo1/1) ( mo1/1) 49 0.06 54 0.06 50 0.14 55 0.40 51 0.03 56 >10.0 52 0.09 57 9.68 53 0.04 2.2 Cell assays Table 3 shows the results from various cell proliferation assays.
Table 3 breast cancer leukaemia melanoma multiple myeloma prostate cancer Exa MOLM-13 B16-F10 LOX IMVI CHL-1 MOLP-8 ICMS-12-PE LAPC-4 MDA-MB-mple ICso ICso ICso IC50 1050 1050 ( mo1/1) ( mo1/1) ( mo1/1) ( mo1/1) ( mo1/1) ( mo1/1) ( mo1/1) IC50 (am o1/1) 1 0.15 0.43 0.06 0.06 1-1 0.12 0.33 0.07 0.08 1-2 >10.0 >10.0 >10.0 >10.0 2 0.14 ' 0.09 0.04 3 0.08 0.07 3-1 3.01 1.75 1.90 3-2 0.08 0.04 0.05 4 0.06 0.06 0.21 0.05 0.05 0.02 0.06 4-1 >10.0 7.34 5.60 4-2 0.02 0.02 0.01 _ _ Leukaemia Melanoma Multiple myeloma Exampl MOLM-13 B16-F10 CHL-1 MOLP-8 e IC 50 (nmoUl) IC 50 (Ftmol/l) 1050 (umoUl) IC 50 (Imola) 5 0.57 5-1 0.22 0.20 0.10 6 0.15 0.33 0.15 0.22 7 0.19 0.21 0.12 0.13 7-1 2.40 1.74 1.48 7-2 0.12 0.01 0.06 8 0.15 0.40 0.20 0.11 8-1 0.07 0.14 0.03 _ 9 0.28 0.18 0.16 9-1 3.37 1.80 1.67 9-2 0.15 0.09 0.07 10 0.85 1.45 0.29 0.69 11 0.49 0.75 0.28 0.49 12 0.15 0.36 0.10 0.11 12-1 >10.0 >10.0 >10.0 12-2 0.15 0.17 0.04 0.05 13 0.12 0.23 0.12 0.13 13-1 0.08 0.07 0.05 14 0.14 14-1 - >10.0 >10.0 >10.0 14-2 - 0.09 0.04 0.04 15 0.31 0.56 0.23 0.31 16 0.23 -, Exampl MOLM-13 B16-F10 CHL-1 e IC50 (amo1/1) 1050 (pmo1/1) 1050 (=61/1) 1050 (pmo1/1) 16-1 ' 8.72 5.34 8.47 16-2 0.10 0.08 0.05 0.07 ' 17 0.10 0.15 0.07 0.09 18 0.36 0.58 0.14 0.27 18-1 0.14 0.15 0.07 19 0.22 0.46 0.14 0.14 19-1 0.12 0.18 0.05 20 0.13 0.26 0.07 0.09 _ 20-1 8.94 >10.0 >10.0 >10.0 _ 20-2 0.08 0.08 0.03 21 0.21 0.27 0.15 22 0.33 0.39 0.16 _ 23 0.61 0.57 0.30 0.57 _ 24 0.10 0.26 0.07 0.06 ' 25 0.63 ' 26 0.65 0.73 0.30 ' 27 ' 1.00 1.08 0.55 ' 28 6.47 4.80 4.15 29 ' 0.24 0.60 0.23 0.22 ' 29-1 9.46 >10.0 6.90 >10.0 29-2 0.13 0.15 0.07 30 0.27 -30-1 0.20 0.29 0.12 30-2 ' >10.0 >10.0 >10.0 _ 31 0.05 0.07 0.06 32 0.50 0.45 0.33 33 ' 0.31 0.39 0.23 33-1 0.19 0.22 0.09 _ 33-2 7.53 9.93 8.57 =
34 2.78 3.14 1.71 , 35 0.36 0.43 0.15 _ Exampl MOLM-13 B16-F10 CHL-1 MOLP-8 e ICso ( mo1/0 1050 (innol/1) IC50 (ttmo1/1) IC50 (tunol/B
35-1 >10.0 >10.0 >10.0 35-2 0.19 0.18 0.08 36 0.55 0.44 0.38 36-1 0.24 0.21 0.18 36-2 >10.0 >10.0 >10.0 37 0.36 37-1 0.19 0.21 0.08 38 0.57 0.59 0.37 0.40 38-1 >10.0 9.87 9.70 38-2 0.18 0.09 39 0.37 0.36 0.18 40 0.46 0.47 0.23 0.32 41 0.38 0.43 0.36 42 1.42 0.50 0.99 43 0.06 0.12 0.03 0.04 44 0.10 45 0.23 Exampl e ICso (Amo1/1) ICso (iumo1/1) IC50 (Amo1/1) IC50 (Amon) 46 0.62 0.69 0.36
47 0.72 0.58 0.46
48 0.27 0.26 0.22 0.16
49 0.17 0.26 0.07 0.13
50 0.59 0.92 0.47
51 1.33 0.24 0.17
52 0.25 0.40 0.26
53 2.18 2.26 1.65
54 1.14 0.34 0.17
55 0.73 0.83 0.44 0.70
56 >10.0 >10.0 >10.0 >10.0
57 >10.0 >10.0

Claims (17)

Claims
1. Compounds of the general formula (I) in which X represents an oxygen or sulphur atom, R1a represents -OR6 or -NR7R8, R1b and R1c independently of one another represent hydrogen, halogen, hydroxy, cyano, nitro or represent a C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C30-cycloalkyl radical or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R2 represents a C1-C3-alkyl or trifluoromethyl or a C3- or C4-cycloalkyl radical, R3 represents C1-C3-alkyl-, C1-C3-alkoxy-, amino- or C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or C1-C6-alkylaminosulphonyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and a monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by C1-C3-alkyl, or represent C3-C10-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, C1-C6-alkoxy-, C6-alkoxy-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent phenyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylaminocarbonyl-, C1-C6-alkylaminosulphonyl-, C1-C6-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R6 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by C1-C6-alkylamino-, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the goup consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, Ci-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, or represents a benzyl radical, where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, and where the methylene group contained therein may optionally be substituted by a hydroxy group or one or two C1-C3-alkyl groups, represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by -NR9R10, or represents a -C(=O)R11 group, or represents a -S(=O)2R12 group, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-C12-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl-and C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl- or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-, R8 represents hydrogen or C1-C6-alkyl, R9 and R10 independently of one another represent hydrogen or C1-C6-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 3 to 8 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- or C3-C7-cycloalkyl-, R11 represents C3-C7-cycloalkyl- or C1-C6-alkyl- monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-C12-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- and C3-C7-cycloalkyl-, or represents a mono- or bicyclic aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, and represents C1-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, carboxy, cyano, C1-C6-alkoxy-, -NR9R10, phenyl, a monocyclic heteroaryl radical having 5 or 6 ring atoms or a monocyclic heterocyclyl radical having 3 to 8 ring atoms, where phenyl and the monocyclic heteroaryl radical having or 6 ring atoms for their part may be mono- to trisubstituted by identical or different substituents from the group consisting of halogen, cyano, C1-C3-alkyl, trifluoromethyl, C1-C3-alkoxy- and trifluoromethoxy-, and where the monocyclic heterocyclyl radical for its part may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- and C3-C7-cycloalkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C10-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, C1-C3-alkoxy- and -NR9R10, or represents a monocyclic heterocyclyl radical having 3 to 8 ring atoms, a bridged C6-C12-heterocycloalkyl radical, a C5-C12-heterospirocycloalkyl radical or a C6-C12-heterobicycloalkyl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, phenyl-C1-C3-alkyl- and C3-C7-cycloalkyl-, or represents an aryl or heteroaryl radical, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, hydroxy, cyano, C1-C3-alkyl, fluoro-C1-C3-alkyl, hydroxy-C1-C3-alkyl, C1-C3-alkoxy-, C1-C3-alkylamino-, amino-C1-C3-alkyl-, C1-C3-alkylaminocarbonyl-, C1-C3-alkylaminosulphonyl-, C1-C3-alkylcarbonylamino-, C1-C3-alkylsulphonylamino-, C1-C3-alkylcarbonyl-, C1-C3-alkylsulphonyl- and trifluoromethoxy-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
2. Compounds of the general formula I according to Claim 1, in which X represents an oxygen atom, R1a represents -OR6 or -NR7R8, R1b and R1c independently of one another represent hydrogen, halogen, hydroxy, cyano, or represent a C1-C3-alkyl-, C1-C3-alkoxy-, fluoro-C1-C3-alkyl- or fluoro-C1-C3-alkoxy- radical, R2 represents methyl- or ethyl-, R3 represents C1-C3-alkyl-, C1-C3-alkoxy-, amino- or C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, nitro, amino, aminocarbonyl-, fluorine, chlorine, bromine, or represent C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkylamino-, C1-C6-alkylcarbonylamino-, C1-C6-alkylaminocarbonyl- or C1-C6-alkylaminosulphonyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, carboxy, hydroxy-C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino- or amino-C1-C6-alkyl-, a monocyclic heterocyclyl radical having 3 to 8 ring atoms and monocyclic heteroaryl radical having 5 or 6 ring atoms where the monocyclic heterocyclyl and heteroaryl radicals mentioned may for their part optionally be monosubstituted by C1-C3-alkyl-, or represent monocyclic heteroaryl- having 5 or 6 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, nitro, carboxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, or represent monocyclic heterocyclyl- having 3 to 8 ring atoms which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of halogen, amino, hydroxy, cyano, oxo, carboxy, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-alkoxy-C1-C6-alkyl-, C1-C6-alkylamino-, amino-C1-C6-alkyl-, C1-C6-alkylamino-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, halo-C1-C6-alkyl-, halo-C1-C6-alkoxy-, C3-C10-cycloalkyl- and a monocyclic heterocyclyl radical having 3 to 8 ring atoms, R6 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by C1-C3-alkylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C4-alkoxycarbonyl-, benzyl- or C3-C7-cycloalkyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-, or represents a benzyl radical, where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-, R7 represents C3-C7-cycloalkyl- or C2-C6-alkyl- monosubstituted by -NR9R10, or represents a -C(=O)R11 group, or represents a -S(=O)2R12 group, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, benzyl- or C1-C4-alkoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-, R8 represents hydrogen or C1-C3-alkyl, R9 and R10 independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, benzyl- or C1-C4-alkoxycarbonyl-, represents C3-C7-cycloalkyl- or C1-C6-alkyl- monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, phenyl-C1-C3-alkyl- or C1-C4-alkoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of C1-C3-alkyl-, halogen and C1-C3-alkoxy-, and R12 represents C1-C6-alkyl- which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, C1-C3-alkoxy- and -NR9R10, or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl- which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, cyano, C1-C3-alkyl-, C1-C3-alkoxy- and -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C12-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by oxo, C1-C3-alkyl-, C1-C3-alkylcarbonyl-, C1-C3-alkoxycarbonyl- and phenyl-C1-C3-alkyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of halogen, C1-C3-alkyl- and C1-C3-alkoxy-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
3. Compounds of the general formula (I) according to Claims 1 and 2, in which X represents an oxygen atom, - 191 ¨
R1a represents -OR6 or -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, R1b represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R1c represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R6 represents C2-C4-alkyl- monosubstituted by C1-C3-alkylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl radical which may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy-and ethoxy-, or represents a benzyl radical where the phenyl radical contained therein may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy- and ethoxy-, R7 represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9R10, or represents a -C(=O)R11 group, or represents a -S(=O)2R12 goup, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine, R8 represents hydrogen or C1-C3-alkyl, R9 and R10 independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, represents C1-C4-alkyl monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and R12 represents C1-C3-alkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, methyl-, ethyl-, methoxy-, ethoxy- and N,N-dimethylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono-or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
4. Compounds of the general formula (I) according to any of Claims 1 to 3 in which X represents an oxygen atom, R1a represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, R1b represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R1c represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, represents a -C(=O)R11 group, R8 represents hydrogen or C1-C3-alkyl, R9 and R10 independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and R11 represents CI-CI-alkyl monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
5. Compounds of the general formula (I) according to any of Claims 1 to 3 in which X represents an oxygen atom, R1a represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, R1b represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R1c represents hydrogen, represents methyl-, R3 represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, represents a -S(=O)2R12 group, R8 represents hydrogen or C1-C3-alkyl-, and R12 represents C1-C3-alkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, methyl-, ethyl-, methoxy-, ethoxy- and N,N-dimethylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
6. Compounds of the general formula (I) according to any of Claims 1 to 3 in which X represents an oxygen atom, R1a represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, R1b represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R1c represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, R7 represents a -S(=O)2R12 group, R8 represents hydrogen or C1-C3-alkyl-, and Ri2 represents C1-C3-alkyl-, or represents fluoro-C1-C3-alkyl-, or represents C3-C7-cycloalkyl which may optionally be mono- or polysubstituted by identical or different substituents from the group consisting of fluorine, hydroxy, oxo, methyl-, ethyl-, methoxy-, ethoxy- and N,N-dimethylamino-, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl-, benzyl- or tert-butoxycarbonyl-, or represents a phenyl or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine or bromine, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
7. Compounds of the general formula (I) according to any of Claims 1 to 3 in which X represents an oxygen atom, represents -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, R1b represents hydrogen, fluorine, chlorine, bromine, cyano, methyl-, methoxy- or trifluoromethyl-, R1c represents hydrogen, R2 represents methyl-, R3 represents C1-C3-alkylamino-, R4 and R5 independently of one another represent hydrogen, hydroxy, cyano, fluorine, chlorine, bromine, C1-C3-alkoxy-, fluoro-C1-C3-alkoxy-, represents C3-C7-cycloalkyl- or C2-C4-alkyl- monosubstituted by -NR9R10, or represents a monocyclic heterocyclyl radical having 4 to 7 ring atoms or a bridged C6-C10-heterocycloalkyl radical, where the radicals mentioned may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, or represents phenyl- or a monocyclic heteroaryl radical having 5 or 6 ring atoms, where the radicals mentioned may optionally be mono-or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine, bromine, methoxy and ethoxy-, or represents fluoro-C1-C3-alkyl or C1-C3-alkyl monosubstituted by a phenyl or a monocyclic heteroaryl radical, where the phenyl and heteroaryl radicals mentioned may be mono- or disubstituted by identical or different substituents from the group consisting of methyl-, ethyl-, fluorine, chlorine and bromine, R8 represents hydrogen or C1-C3-alkyl-, and R9 and R10 independently of one another represent hydrogen or C1-C3-alkyl-, or together with the nitrogen atom to which they are attached represent a monocyclic heterocyclyl radical having 4 to 7 ring atoms which may optionally be monosubstituted by methyl-, ethyl-, acetyl- or tert-butoxycarbonyl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
8. Compounds of the general formula (I) according to any of Claims 1 to 3 in which X represents an oxygen atom, R1a represents -OR6 or -NR7R8 and is located in the meta- or para-position with respect to the benzodiazepine, R1b represents hydrogen or fluorine, R1c represents hydrogen, R2 represents methyl-, R3 represents methylamino-, R4 and R5 independently of one another represent hydrogen, chlorine, methoxy or trifluoromethoxy, R6 represents N, N-dimethylaminoethyl-, or represents a monosubstituted monocyclic heterocyclyl radical selected from or represents a phenyl radical which may optionally be substituted by a fluorine atom, or represents a benzyl radical, R7 represents N,N-dimethylaminoethyl- or N, N-dimethylaminopropyl-, or represents a -C(=O)R11 group, or represents a -S(=O)2R12 group, or represents a radical selected from or represents fluorophenyl-, pyridyl-, fluoropyridyl-, dimethyloxazolyl-, methylpyrazolyl-, methoxyoxadiazolyl-, pyridazinyl- or methylimidazolyl-, R8 represents hydrogen or methyl, and R11 represents -CH2-NH(CH3), -CH2-N(CH3)2, methylpiperidinyl-, methylpyrrolyl-, thiadiazolyl-, or represents a radical selected from where "*" in each case indicates the point of attachment to the remainder of the molecule, R12 represents methyl-, trifluoromethyl-, phenyl-, benzyl-, cyclopropyl-, tetrahydropyran-4-yl or pyrid-3-yl-, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
9. Compounds of the general formula (I) according to any of Claims 1 to 8:
- (~)-7,8-dimethoxy-N,4-dimethyl -1- {4-[(1-methylpiperidin-4-yl)amino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-di methyl-1-{4(1-methylpiperidin-4-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methylpiperidin-4-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[methyl(pyridin-3-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-{4-[(2-fluorophenyl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-{4-[(2-fluorophenyl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-{4-[(2-fluorophenyl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-{4-[(3,5-dimethylisoxazol-4-yl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-{4-[(3,5-dimethylisoxazol-4-yl)amino)phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-{4-[(3,5-dimethylisoxazol-4-yl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-(4-{[2-(dimethylamino)ethyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-(4-{[2-(dimethylamino)ethyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-{4-[(4-fluorophenyl)methylamino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-(1-methyl-1H-pyrazol-5-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methyl-1H-pyrazol-5-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methyl-1H-pyrazol-5-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-[4-(1-azabicyclo[2.2.2]oct-3-ylamino)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-[4-(1-azabicyclo[2.2.2]oct-3-ylamino)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-1-{4-[(4-methoxy-1,2,5-oxadiazol-3-yl)amino]phenyl}-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-1-{4-[(4-methoxy-1,2,5-oxadiazol-3-yl)amino]phenyl}-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-1-{4-[(4-methoxy-1,2,5-oxadiazol-3-yl)amino]phenyl}-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-[4-(pyridazin-4-ylamino)phenyl]-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-[4-(pyridazin-3-ylamino)phenyl]-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[methyl(1-methyl-1H-imidazol-2-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-dimethyl-1-{4-[methyl(1-methyl-1H-imidazol-2-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-{4-[methyl(1-methyl-1H-imidazol-2-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methyl-1H-pyrazol-3-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methyl-1H-pyrazol-3-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-{4-[(2-fluoropyridin-3-yl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-{4-[(2-fluoropyridin-3-yl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-{4-[(2-fluoropyridin-3-yl)amino]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-{4-[(3-fluoropyridin-4-yl)amino]phenyl } -7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-14-[(3-fluoropyridin-2-yl)amino]phenyl } -7, 8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3 -benzodiazepine-3 -carboxamide, - (4R)-1- { 4-[(3-fluoropyridin-2-yl)amino]phenyl } -7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3 -benzodiazepine-3-carboxamide, - (4S)-1- {4-[(3-fluoropyridin-2-yl)amino]phenyl } -7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7, 8-dimethoxy-N,4-dimethyl-1-(4- { [2,2,2-trifluor-1-(1 -methyl- 1H-pyrrol-2-yl)ethyl]amino} phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-(4- { [2-(dimethylamino)ethyl]methylamino} phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-(4- { [2-(dimethylamino)ethyl]methylamino} phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1-(4- { [2-(4-methylpiperazin-1-yl)ethyl]
amino } phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-(4 -{ [2-(4-methylpiperazin-1-yl)ethyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3 -carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1-{4-[methyl( 1 -methylpiperidin-4-yl)amino]phenyl } -4,5 -dihydro-3H-2,3 -benzodiazepine-3-carboxamide, - (4R)-7, 8-dimethoxy-N,4-dimethyl-1- {4-[methyl( 1 -methylpiperidin-4-yl)amino]phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7, 8-dimethoxy-N,4-dimethyl-1- { 4- [methyl( 1-methylpiperidin-4-yl)amino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3 -carboxamide, - ( )-tert-butyl 4-[{4-[7,8-dimethoxy -4-methyl-3-(methylcarbamoyl)-4,5-dihydro-3H-2,3-benzodiazepin-1-yl]phenyl}methylamino]piperidine-1-carboxylate, - ( )-7,8-dimethoxy-N,4-dimethyl- 1- {4-[( 1-methylazetidin-3-yl)amino]phenyl} -4,5-dihydro-3H-2,3 -benzodiazepine-3 -carboxamide, - ( )-1-{ 4-[( 1 -acetylazetidin-3 -yl)amino]phenyl } -7, 8-dimethoxy -N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{3-[methyl(pyridin-3-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{3-[(1-methylpiperidin-4-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-(3-{[3-(dimethylamino)propyl]methylamino}-4-fluorophenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-(3-{[2-(dimethylamino)ethyl]methylamino}-4-fluorophenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-(4-{[(dimethylamino)acetyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-(4-[(dimethylamino)acetyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (45)-1-(4-{[(dimethylamino)acetyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[(1-methylpiperidin-4-yl)carbonyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[(1-methylpiperidin-4-yl)carbonyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[(1-methylpiperidin-4-yl)carbonyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(piperidin-4-ylcarbonyl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(morpholin-4-ylacetyl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-(4-{[(1-benzylpiperi din-4yl)carbonyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-1-(4-1[(1-benzylpiperidin-4-yl)carbonyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-(4-{[(1-benzylpiperidin-4-yl)carbonyl]amino}phenyl)-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-(4-{methyl[(methylamino)acetyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[(4-methyIpiperazin-1-yl)acetyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-(4-{[(4-methylpiperazin-1-yl)acetyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-tert-butyl 4-({4-[7,8-dimethoxy-4-methyl-3-(methylcarbamoyl)-4,5-dihydro-3H-2,3-benzodiazepin-1-yl]phenyl}carbamoyl)piperidine-1-carboxylate, - (4S)-tert-butyl 4-({4-[7,8-dimethoxy-4-methyl-3-(methylcarbamoyl)-4,5-dihydro-3H-2,3-benzodiazepin-1-yl]phenyl}carbamoyl)piperidine-1-carboxylate, - (4R)-tert-butyl 4-({4-[7,8-dimethoxy-4-methyl-3-(methylcarbamoyl)-4,5-dihydro-3H-2,3-benzodiazepin-1-yl]phenyl}carbamoyl)piperidine-1-carboxylate, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methylpiperidin-4-yl)oxy]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methylpiperidin-4-yl)oxy]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4R)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (45)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-7,8-dimethoxy-N,4-dimethyl-1-{4-[(1-methylazetidin-3-yl)oxy]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1-(4-phenoxyphenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-[4-(4-fluorophenoxy)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-8-chloro-1-{4-[(2-fluoropyridin-3-yl)amino]phenyl } -N,4-dimethyl-7-(trifluoromethoxy)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1-{4-{methyl(1-methylpiperidin-4-yl)amino]phenyl} -8-(trifluoromethoxy)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-8-methoxy-N,4-dimethyl-1-(4-{ [(1-methyl-1H-pyrrol-2-yl)carbonyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-8-methoxy-N,4-dimethyl-1- {4- [(1,2,3-thiadiazol-4-ylcarbonyl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1-(4-{ [(dimethylamino)acetyl] amino} phenyl)-8-methoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1- {4-[(methylsulphonyl)amino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1-{4- [(pyridin-3-ylsulphonyl)amino]
phenyl } -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (4S)-7,8-dimethoxy-N,4-dimethyl-1- {4-[(tetrahydro-2/1-pyran-4-ylsulphonyl)amino]phenyl -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1- {4- [methyl(methyl sulphonyl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1-{4-[(phenylsulphonyl)amino]phenyl} -4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-1- {4-[(benzylsulphonyl)amino]phenyl -7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - ( )-7,8-dimethoxy-N,4-dimethyl-1-(4-{
[(trifluoromethyl)sulphonyl]amino}phenyl)-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1- { 4-[(cyclopropylsulphonyl)amino] phenyl} -7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-144-(benzyloxy)phenyl1-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, - (~)-1- { 4-[(N,N-dimethylglycyl)(methyl)amino] phenyl 1 -4-ethyl -7,8-dimethoxy-N-methyl-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide and - (~)-4-isopropyl-7,8-dimethoxy-N-methyl-1-{4-[methyl(1-methyl-1H-imidazol-2-yl)amino]phenyl}-4,5-dihydro-3H-2,3-benzodiazepine-3-carboxamide, and their polymorphs, enantiomers, diastereomers, racemates, tautomers, solvates, physiologically acceptable salts and solvates of these salts.
10. Compounds according to any of Claims 1 to 9 for prophylaxis and/or treatment of hyperproliferative disorders, benign hyperplasias, inflammatoryl)isorders, autoimmune disorders, sepsis, viral infections, vascular disorders, atherosclerotic disorders and neurodegenerative disorders.
11. Compound according to any of Claims 1 to 9 for prophylaxis and/or treatment of neoplastic disorders.
12. Compound according to any of Claims 1 to 9 in male fertility control.
13. Compound according to any of Claims 1 to 9 for prophylaxis and/or treatment of leukaemias, prostate carcinomas, mammary carcinomas, melanomas or multiple myelomas.
14. Use of a compound of the general formula (I) according to any of Claims 1 to 9 for preparing a medicament.
15. Use of a compound of the formula (I) according to any of Claims 1 to 9 for prophylaxis and/or treatment of disorders of humans or other mammals.
16. Compound of the formula (I) according to any of Claims 1 to 9 in combination with a further active ingredient.
17. Pharmaceutical formulation comprising a compound of the formula (I) according to any of Claims 1 to 9.
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TW200902024A (en) * 2007-04-02 2009-01-16 Teva Pharma Novel 2,3-benzodiazepine derivatives and their use as antipsychotic agents

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