DE102005005813A1 - New thiazolo-indazole derivatives useful as PI3 kinase inhibitors, for treating e.g. cancer and other proliferative diseases, viral infections and inflammatory, autoimmune, skin and bone diseases - Google Patents

Abstract

Thiazolo[4,5-g]indazole derivatives (I) are new. Thiazolo[4,5-g]indazole derivatives (I) of formula (1) and their tautomers, isomers and acid addition salts are new: R 1> : NHRc, NHCORc, NHCOORc, NHCONRcRd or NHCOSRc; R 2> : 1-6C alkyl, 3-8C cycloalkyl, 3- to 8-membered heterocycloalkyl, 6-10C aryl or 5- to 10-membered heteroaryl, all optionally substituted with R 4>; R 3> : 6-10C aryl or 5- to 10-membered heteroaryl, all optionally substituted with Re and/or Rf; R 4> : Ra (optionally substituted with Rc and/or Rb) or Rb; Ra : 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl; Rb : =O, ORc, 1-3C haloalkoxy, OCF 3, =S, SRc, =NRc, =NORc, NRcRc, halo, CF 3, CN, NC, OCN, SCN, NO, NO 2, =N 2, N 3, SORc, SO 2Rc, SO 2ORc, SONRcRc, SO 2NRcRc, OSORc, OSO 2Rc, OSO 2ORc, OSO 2NRcRc, CORc, COORc, CONRcRc, CON(Rg)NRcRc, CON(Rg)ORc CN(Rg)NRcRc, OCORc, OCOORc, OCONRcRc, OCN(Rg)NRcRc, N(Rg)CORc, N(Rg)CSRc, N(Rg)SO 2Rc, N(Rg)SO 2NRcRc, N(SO 2Rc) 2, N(Rg)CORc, N(Rg)CONRcRc or N(Rg)CN(Rg)NRcRc; Rc : H or 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl, all optionally substituted with Rd and/or Re; Rd : H or 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl, all optionally substituted with Re and/or Rf; Re : =O, ORf, 1-3C haloalkoxy, OCF 3, =S, SRf, =NRf, =NORf, NRfRf, halo, CF 3, CN, NC, OCN, SCN, NO, NO 2, =N 2, N 3, SORf, SO 2Rf, SO 2ORf, SONRfRf, SO 2NRfRf, OSORf, OSO 2Rf, OSO 2ORf, OSO 2NRfRf, CORf, COORf, CONRfRf, CON(Rg)NRfRf, CON(Rg)ORf CN(Rg)NRfRf, OCORf, OCOORf, OCONRfRf, OCN(Rg)NRfRf, N(Rg)CORf, N(Rg)CSRf, N(Rg)SO 2Rf, N(Rg)SO 2NRfRf, N(SO 2Rf) 2, N(Rg)CORf, N(Rg)CONRfRf or N(Rg)CN(Rg)NRfRf; Rf : H or 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl, all optionally substituted with Rg; Rg : H, 1-6C alkyl, 3-8C cycloalkyl, 4-11C cycloalkylalkyl, 6-10C aryl, 7-16C arylalkyl, 2- to 6-membered heteroalkyl, 3- to 8-membered heterocycloalkyl, 4- to 14-membered heterocycloalkylalkyl, 5- to 10-membered heteroaryl or 6- to 16-membered heteroarylalkyl. Independent claims are also included for: (1) 4,5,6,7-tetrahydrobenzothiazol-7-one derivatives of formula (A); (2) pharmaceutical product comprising a compound (I) and at least one other cytostatic or cytotoxic agent. X : Me, OR 4> or SR 4>; Y : phenyl, 5- to 10-membered heteroaryl or COO; Ry : H, NO 2 or 1-6C alkyl. [Image] ACTIVITY : Cytostatic; Virucide; Anti-HIV; Antiinflammatory; Immunosuppressive; Antiarthritic; Neuroprotective; Nootropic; Nephrotropic; Antibacterial; Fungicide; Antiparasitic; Dermatological; Antipsoriatic; Osteopathic; Vasotropic. Various compounds (I), e.g. , had EC 50 values of less than 5 mu M against HCT116 human colon carcinoma cells. MECHANISM OF ACTION : PI3 kinase inhibitor.

Description

TECHNICAL TERRITORY

Phosphatidylinositol-3-kinases (PI3-kinases) are a subfamily of lipid kinases that catalyze the transfer of a phosphate moiety to the 3'-position of the inositol ring of phosphoinositides ( 1 ).

she play an important role in numerous cellular processes such as e.g. Cell growth and differentiation processes, the control of cytoskeletal changes and the regulation of intracellular transport processes (Vanhaesebroeck et al., Annu Rev Biochem. 2001; 70: 535-602). Due to their in vitro specificity for certain Phosphoinositide substrates can the PI3 kinases are divided into different classes. The members The receptor-regulated class I are heterodimeric enzymes that from a 110-120 kDa catalytic (p110) and a 50-101 kDa heavy non-catalytic subunit (p50, p55, p85, p101) are constructed. The highest conserved region in all PI3 kinases is the C-terminal Kinase domain. It has structural features also common in most known ones Protein kinases are found. These include e.g. also highly preserved Amino acids, the for the coordination of the ATP molecule (Walker et al., Nature, 1999 Nov 18, 402 (6759): 313-20).

Three of the four members of class I PI3 kinases constitutively associate with a 50-85 kDa adapter subunit, of which p85 is the prototype. The interaction occurs via the so-called p85 binding domain, which can be found on the catalytic subunits of the PI3 kinase α, β and δ. The three forms are grouped into Class IA because of this structural feature. The catalytic subunit of PI3 kinase γ, p110γ, instead associates with a 101 kDa regulatory protein called p101. It is - so far the only member - the class IB of the PI3 kinases. This structural classification into Class IA and IB also shows parallels in the functional properties of the corresponding PI3 kinase isoforms ( 2 ) Thus, the PI3 kinase α, β and δ are activated mainly by receptor tyrosine kinases (RTKs) or soluble tyrosine kinases. The p85 subunit serves as an adapter because it can recognize and bind the phosphorylated tyrosine residues of specific amino acid sequences (YxxM) with their SH2 domains. In contrast, PI3Kγ is primarily activated by Gβγ subunits released from heterotrimeric G proteins upon activation of heptahelical receptors. This different coupling to cell surface receptors in combination with a more or less restrictive expression inevitably results in very different tasks and functions of the 4 class I PI3 kinases in the intact organism (Wymann et al., Trends Pharmacol Sci. 2003 Jul; 7): 366-76).

Lots independent Findings speak for involvement of class IA PI3 kinases in uncontrolled cell growth and differentiation processes. Thus, the first demonstrated PI3-kinase activity was with the transforming activity of viral oncogenes, e.g. the middle T antigen of polyomaviruses, Src tyrosine kinases or activated growth factors (Workman, Biochem Soc Trans. 2004 Apr; 32 (Pt 2): 393-6). In many Tumors, e.g. Breast cancer, ovarian or pancreatic carcinoma one overactivity of act / PKB, which directly through the lipid products of class I PI3 kinases is activated and thus passes the signals into the cell. Furthermore has been recently found that the PIK3CA gene, which codes for p110α, in various types of tumors, such as colon, mammary or lung carcinomas a high frequency of mutations some of which are representative as activating mutations could be characterized (Samuels et al., Science. 2004 Apr 23; 304 (5670): 554).

The youngest Member of class IA PI3 kinases, the PI3Kδ, is expressed more restrictively as the PI3Kα and β. In so-called "knock-in" mice, in the catalytic subunit of PI3Kδ, p110δ, by an inactive mutant could be shown that this PI3K isoenzyme a specific role in signal transmission of B and T lymphocytes after antigen-receptor stimulation (Okkenhaug et al., Science. 2002 Aug; 297 (5583): 1031-4). These are mechanisms, first and foremost in autoimmune diseases, e.g. Crohn's disease or rheumatoid Arthritis play a role.

The PI3Kγ is activated almost exclusively by G _i -coupling heptahelical receptors. Thus, in Science could neutrophils from mice that express no PI3Kγ, no PI3, 4, 5-P ₃ formation are observed when these were stimulated with IL-8, fMLP, _LTB4 or C5a (Hirsch et al., 2000 Feb 11; 287 (5455): 1049-53). This shows that, at least in this cell type, PI3Kγ is the only PI3 kinase isoform that couples to these heptahelical receptors. In addition, isolated neutrophils and macrophages from the PI3Kγ-deficient mice showed greatly reduced chemotactic activity or oxygenase dikalproduktion against a whole series of chemokines and chemoattractors. Also reduced was the IgE-mediated activation of mast cells isolated from p110γ-deficient mice. As a responsible mechanism, a positive feedback mechanism is discussed in which the PI3Kγ is activated by G _i -coupling adenosine A ₃ receptors (Laffargue et al., Immunity 2002 Mar; 16 (3): 441-51).

In spite of this diminished ability on inflammatory mediators To respond are the p110γ-deficient Mice normal viable and reproducible and have the same life expectancy as identical wild-type ones Control animals. Leave it close, that the class IB PI3Kγ a central role in the activation of various inflammatory cells and therefore isoform-specific inhibitors an attractive possibility for anti-inflammatory therapy with comparatively low Side effects (Ward and Finan, Curr Opin Pharmacol. 2003 Aug; 3 (4): 426-34)

Next Despite its low expression, PI3Kγ seems to function in leukocytes in cardiomyocytes also has a role in the cardiovascular system to play. Thus showed p110γ-deficient Mice one increase myocardial contractility, which probably over an overproduction explained by cAMP (Crackower et al., Cell. 2002 Sep 20; 110 (6): 737-49). Just recently could be shown that the PI3Kγ also in the formation of the Cardiac hypertrophy is involved. Thus showed p110γ-deficient Mice in compared to an isoproterenol-induced heart failure model to the wild-type animals a significantly reduced hypertrophy and fibrosis (Oudit et al., Circulation, 2003 Oct 28; 108 (17): 2147-52).

task the present invention was to provide new compounds, due to their pharmaceutical efficacy as a PI3 kinase modulator for use in the therapeutic field for the treatment of inflammatory or allergic diseases. Examples are here inflammatory and respiratory allergic diseases, inflammatory diseases of the gastrointestinal tract Tract, rheumatoid arthritis, inflammatory and allergic skin diseases, inflammatory Eye diseases, diseases of the nasal mucosa, inflammatory or allergic disease states, involving autoimmune reactions or kidney inflammation called.

PI3 kinase Inhibitors for the treatment of inflammatory Diseases are known in the literature. Thus, WO 03/072557 discloses 5-phenylthiazole derivatives, WO 04/029055 shows fused azolpyrimidines and WO 04/007491 azolidinone-vinyl linked benzene derivatives. Farther are described by the two documents WO 04/052373 and WO 04/056820 Benzoxazine in benzoxazin-3-one derivatives disclosed.

SHORT DESCRIPTION THE DRAWINGS

1 : SIMPLIFIED ILLUSTRATION OF PI3-KINASE CATALYSED PHOSPHORYLATION OF PHOSPHOINOSITIDES.

phosphoinositide consist of a glycerol unit attached to all hydroxyl groups is substituted. Position 1 and 2 are with fatty acid residues (here by way of example: stearic acid and arachidonic acid), Position 3 with phosphoric acid esterifies the polar inositol head group is over the phosphoric acid ester linked at position 3. The enzyme class of PI3 kinases catalyzes the transfer of the terminal phosphate residue of adenosine triphosphate (ATP) to the 3 'position of the inositol ring. Depending on Substrate can be phosphatidylinositol-3-phosphate (PI3-P), PI3, 4-P2 or PI3, 4, 5-P3 are formed.

2 : CLASS I PI3 KINASEN RECEPTOR-ACTIVATED ACTIVATION.

The activation of class I PI3 kinases by extracellular stimuli is mediated by receptor tyrosine kinases, tyrosine kinase-associated receptors, and G protein-coupled receptors. Sensitivity to tyrosine kinases is due to SH2 domains of the p85 regulatory subunit of the PI3 kinase, α, β, and δ. The PI3 kinase γ is activated by heptahelical receptors mainly via Gβγ subunits. As a result of the activation, in both cases PI 3, 4, 5-P _{3 is} formed by 3'-phosphorylation of PI-4, 5-P _{2 of} the second messenger.

DETAILED DESCRIPTION OF THE INVENTION

mit der Maßgabe, dass die mit A gekennzeichnete, kreisförmige Linie ein aromatisches System bedeutet; worin
Y Kohlenstoff, Stickstoffatom, Schwefel; bevorzugt Kohlenstoff, Stickstoff;
Z Kohlenstoff, Stickstoffatom, Schwefel; bevorzugt Kohlenstoff, Stickstoff;
j 1, 2 oder 3;
k 0 oder 1;
R^a H, COR⁸, NR⁹R¹⁰, NO₂, OR⁸, SR¹¹, SOR¹¹, SO₂R¹¹, NHCO-C_1-6-Alkyl-NH₂, oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-6-Alkenyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkenyl, C_1-6-Haloalkyl, Aryl, C_7-11-Aralkyl, Spiro, Het, Heteroaryl und CH₂-O-Aryl, der gegebenenfalls substituiert sein kann;
R⁸ C_1-6-Alkyl, C_3-6-Cycloalkyl, NH₂, Hetaryl oder Aryl, gegebenenfalls substituiert mit einem oder mehreren Halogen oder C_1-4-Alkyl;
R⁹ H, COOR¹², CONR¹² oder C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren COOH, N(C_1-6-Alkyl)₂ oder Het, gegebenenfalls substituiert mit einem oder mehreren C_1-6-Alkyl; oder R⁹ bedeutet Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl;
R¹⁰ H, C_1-6-Alkyl, CO-C_1-6-Alkyl oder C_2-6-Alkinyl;
R¹¹ C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren N(C_1-4-Alkyl)₂;
R^b R⁴, OR⁴, -CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NR⁴R⁵, NR⁵COR⁴, NR⁵COOR⁴, NR⁵CONR⁴R⁵, NR⁵SOR⁴ oder NR⁵SO₂R⁴;
R⁴, R⁵ H, C_1-6-Alkyl, C_1-6-Haloalkyl, C_1-6-Alkylen-OH, C_2-6-Alkenyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, C_2-6-Alkinyl, gegebenenfalls substituiert mit Si(C_1-4-Alkyl)₃, oder R⁴ bedeutet ein Rest ausgewählt aus der Gruppe bestehend aus Aryl, Het, Hetaryl und gegebenenfalls substituiert mit C_1-4-Alkyl;
oder R⁴ und R⁵ bilden gemeinsam einen fünf-, sechs- oder siebengliedrigen Ring bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff, und Schwefel;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-6-Alkyl, C_2-6-Alkenyl oder C_2-6-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-6-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Surprisingly, it was found that the above-mentioned objects by Verbindun gen of formula 1 are solved. Accordingly, the present invention relates to compounds of formula 1,

with the proviso that the circular line marked A represents an aromatic system; wherein
Y is carbon, nitrogen, sulfur; preferably carbon, nitrogen;
Z is carbon, nitrogen, sulfur; preferably carbon, nitrogen;
j 1, 2 or 3;
k is 0 or 1;
R ^{a is} H, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , or a radical selected from the group consisting of C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, aryl, C _7-11 aralkyl, spiro, het, heteroaryl and CH ₂ -O-aryl which may be optionally substituted;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² , CONR ¹² or C _1-6 alkyl optionally substituted with one or more COOH, N (C _1-6 alkyl) ₂ or Het optionally substituted with one or more C _1-6 alkyl ; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-6 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ;
R ⁴ , R ^{5 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl -Aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted with Si (C _1-4 -alkyl) ₃ , or R ⁴ is a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ;
R ^{7.1 is} H, C _1-6 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
X Bindung oder C_1-4-Alkylen;
X' C_1-4-Alkylen, C_2-4-Alkenylen oder C_1-4-Alkinylen
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2, COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2. H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, C_1-6-Haloalkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1 CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂H, SO₂-C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C₂_₆-Alkenyl, C_2-6-Alkinyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, COC_1-4-Alkyl-Hetaryl, COC_2-4-Alkenyl-Hetaryl, COC_2-4-Alkinyl-Hetaryl; oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^a H, C_1-6-Alkyl, C_2-6-Alkenyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkenyl, C_1-6-Haloalkyl, COR⁸, NR⁹R¹⁰, NO₂, OR⁸, SR¹¹, SOR¹¹, SO₂R¹¹, NHCO-C_1-6-Alkyl-NH₂, Spiro oder ein Rest ausgewählt aus der Gruppe bestehend aus C_7-11-Aralkyl, CH₂-O-Aryl und Het der gegebenenfalls substituiert sein kann mit einem oder mehreren Halogen, C_1-6-Alkyl, CO-C_1-4-Haloalkyl, C_1-4-Alkyl-NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-6-Alkyl, C_3-6-Cycloalkyl, NH₂, Hetaryl oder Aryl, gegebenenfalls substituiert mit einem oder mehreren Halogen oder C_1-4-Alkyl;
R⁹ H, COOR¹², CONR¹² oder C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren COOH, N(C_1-6-Alkyl)₂ oder Het, gegebenenfalls substituiert mit einem oder mehreren C_1-6-Alkyl; oder R⁹ bedeutet Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl;
R¹⁰ H, C_1-6-Alkyl, CO-C_1-6-Alkyl oder C_2-6-Alkinyl;
R¹¹ C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren N(C_1-4-Alkyl)₂;
R¹² H, C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and heteroaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , Het or Hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
X 'is C _1-4 -alkylene, C _2-4 -alkenylene or C _1-4 -alkynylene
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 -alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 -cycloalkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2. H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _1-6 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ;
R ^3.3.1 C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ H, SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ - C _3-6 cycloalkyl and aryl;
R ^{3.3.1.1, 3.3.1.2} R and R ^3.3.1.3 a radical selected from the group consisting of C _1-6 alkyl, C ₂ _ ₆ alkenyl, C _2-6 alkynyl, C _7-11 aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, COC _1-4 Alkyl hetaryl, COC _2-4 alkenyl hetaryl, COC _2-4 alkynyl hetaryl; or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² , CONR ¹² or C _1-6 alkyl optionally substituted with one or more COOH, N (C _1-6 alkyl) ₂ or Het optionally substituted with one or more C _1-6 alkyl ; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-6 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} H, C _1-6 -alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2, COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2. H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, C_1-6-Haloalkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2; CONR^3.3.1.1R^3.3.1.2 COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂H, SO₂-C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl,
COC_1-4-Alkyl-Hetaryl, COC_2-4-Alkenyl-Hetaryl,
COC_2-4-Alkinyl-Hetaryl, oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^a H, C_1-6-Alkyl, C_2-6-Alkenyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkenyl, C_1-6-Haloalkyl, COR⁸, NR⁹R¹⁰, NO₂, OR⁸, SR¹¹, SOR¹¹, SO₂R¹¹, NHCO-C_1-6-Alkyl-NH₂, Spiro oder ein Rest ausgewählt aus der Gruppe bestehend aus C_7-11-Aralkyl, CH₂-O-Aryl und Het der gegebenenfalls substituiert sein kann mit einem oder mehreren Halogen, C_1-6-Alkyl, CO-C_1-4-Haloalkyl, C_1-4-Alkyl-NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-6-Alkyl, C_3-6-Cycloalkyl, NH₂, Hetaryl oder Aryl, gegebenenfalls substituiert mit einem oder mehreren Halogen oder C_1-4-Alkyl;
R⁹ H, COOR¹², CONR¹² oder C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren COOH, N(C_1-6-Alkyl)₂ oder Het, gegebenenfalls substituiert mit einem oder mehreren C_1-6-Alkyl; oder R⁹ bedeutet Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl;
R¹⁰ H, C_1-6-Alkyl, CO-C_1-6-Alkyl oder C_2-6-Alkinyl;
R¹¹ C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren N(C_1-4-Alkyl)₂;
R¹² H, C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 -alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 -cycloalkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2. H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _1-6 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ;
R ^3.3.1 C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 ; CONR ^3.3.1.1 R ^3.3.1.2 COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, halogen or Het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ H, SO ₂ -C _{1 -4} alkyl, SO ₂ C _7-11 aralkyl, CH ₂ -C _3-6 cycloalkyl and aryl;
R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl,
COC _1-4 -alkyl-hetaryl, COC _2-4 -alkenyl-hetaryl,
COC _2-4 alkynyl hetaryl, or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² , CONR ¹² or C _1-6 alkyl optionally substituted with one or more COOH, N (C _1-6 alkyl) ₂ or Het optionally substituted with one or more C _1-6 alkyl ; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-6 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} H, C _1-6 -alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2., COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, -NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
-C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2. H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_1-4-Haloalkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂H, SO₂-C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, COC_1-4-Alkyl-Hetaryl, COC_2-4-Alkenyl-Hetaryl, COC_2-4-Alkinyl-Hetaryl; oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen fünf-, sechs oder siebengliedrigen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^a H, C_1-6-Alkyl, C_2-6-Alkenyl, C_3-8-Cycloalkyl, C_3-8-Cycloalkenyl, C_1-6-Haloalkyl, COR⁸, NR⁹R¹⁰, NO₂, OR⁸, SR¹¹, SOR¹¹, SO₂R¹¹, NHCO-C_1-6-Alkyl-NH₂, Spiro oder ein Rest ausgewählt aus der Gruppe bestehend aus C_7-11-Aralkyl, CH₂-O-Aryl und Het der gegebenenfalls substituiert sein kann mit einem oder mehreren Halogen, C_1-6-Alkyl, CO-C_1-4-Haloalkyl, C_1-4-Alkyl-NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-6-Alkyl, C_3-6-Cycloalkyl, NH₂, Hetaryl oder Aryl, gegebenenfalls substituiert mit einem oder mehreren Halogen oder C_1-4-Alkyl;
R⁹ H, COOR¹² oder C_1-4-Alkyl, gegebenenfalls substituiert mit einem oder mehreren COOH, N(C_1-4-Alkyl)₂ oder Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl; oder R⁹ bedeutet Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl;
R¹⁰ H, C_1-6-Alkyl, CO-C_1-4-Alkyl oder C_2-6-Alkinyl;
R¹¹ C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren N(C_1-4-Alkyl)₂;
R¹² C_1-6-Alkyl;
R^b R⁴, OR⁴, -CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NR⁴R⁵, NR⁵COR⁴, NR⁵COOR⁴, NR⁵CONR⁴R⁵, NR⁵SOR⁴ oder NR⁵SO₂R⁴;
R⁴ H, C_1-6-Alkyl, C_1-6-Haloalkyl, C_1-6-Alkylen-OH, C_2-6-Alkenyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, C_2-6-Alkinyl, gegebenenfalls substituiert mit Si(C_1-4-Alkyl)₃, oder R⁴ bedeutet ein Rest ausgewählt aus der Gruppe bestehend aus Aryl, Het, Hetaryl und gegebenenfalls substituiert mit C_1-4-Alkyl;
R⁵ H oder C_1-6-Alkyl;
oder R⁴ und R⁵ bilden gemeinsam einen fünf-, sechs- oder siebengliedrigen Ring bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff, und Schwefel;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-4-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2. , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, -NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 cycloalkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2. H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _1-4 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ H, SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ - C _3-6 cycloalkyl and aryl;
R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, COC _1-4 Alkyl hetaryl, COC _2-4 alkenyl hetaryl, COC _2-4 alkynyl hetaryl; or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² or C _1-4 alkyl optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or Het optionally substituted with one or more C _1-4 alkyl; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-4 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} C _1-6 alkyl;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ;
R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted by Si (C _{1 -4-} alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl;
R ^{5 is} H or C _1-6 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ;
R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2, COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, -NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
-C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2. H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂H, SO₂-C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, COC_1-4-Alkyl-Hetaryl; oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen fünf-, sechs oder siebengliedrigen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^a H, C_1-6-Alkyl, C_2-6-Alkenyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, C_1-6-Haloalkyl, COR⁸, NR⁹R¹⁰, NO₂, OR⁸, SR¹¹, SOR¹¹, SO₂R¹¹, NHCO-C_1-6-Alkyl-NH₂, Spiro oder ein Rest ausgewählt aus der Gruppe bestehend aus C_7-11-Aralkyl, CH₂-O-Aryl und Het der gegebenenfalls substituiert sein kann mit einem oder mehreren Halogen, C_1-6-Alkyl, CO-C_1-4-Haloalkyl, C_1-4-Alkyl-NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-6-Alkyl, C_3-6-Cycloalkyl, NH₂, Hetaryl oder Aryl, gegebenenfalls substituiert mit einem oder mehreren Halogen oder C_1-4-Alkyl;
R⁹ H, COOR¹² oder C_1-4-Alkyl, gegebenenfalls substituiert mit einem oder mehreren COOH, N(C_1-4-Alkyl)₂ oder Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl; oder R⁹ bedeutet Het, gegebenenfalls substituiert mit einem oder mehreren C_1-4-Alkyl;
R¹⁰ H, C_1-6-Alkyl, CO-C_1-4-Alkyl oder C_2-6-Alkinyl;
R¹¹ C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren N(C_1-4-Alkyl)₂;
R¹² C_1-6-Alkyl;
R^b R⁴, OR⁴, -CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NR⁵COOR⁴, NR⁵CONR⁴R⁵ oder NR⁵SOR⁴;
R⁴ H, C_1-6-Alkyl, C_1-6-Haloalkyl, C_1-6-Alkylen-OH, C_2-6-Alkenyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, C_2-6-Alkinyl, gegebenenfalls substituiert mit Si(C_1-4-Alkyl)₃, oder R⁴ bedeutet ein Rest ausgewählt aus der Gruppe bestehend aus Aryl, Het, Hetaryl und gegebenenfalls substituiert mit C_1-4-Alkyl;
R⁵ H oder C_1-6-Alkyl;
oder R⁴ und R⁵ bilden gemeinsam einen fünf-, sechs- oder siebengliedrigen Ring bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff, und Schwefel;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_3-6-Cycloalkyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-4-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , Het or Hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe 2;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, -NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 cycloalkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2. H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl and aryl which may be optionally substituted by one or more radicals R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ H, SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ - C _3-6 cycloalkyl and aryl;
R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, COC _1-4 - alkyl hetaryl; or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² or C _1-4 alkyl optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or Het optionally substituted with one or more C _1-4 alkyl; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-4 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} C _1-6 alkyl;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ or NR ⁵ SOR ⁴ ;
R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, C _2-6 alkynyl optionally substituted with Si (C _1-4 alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted with C _1-4 alkyl;
R ^{5 is} H or C _1-6 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _3-6 -cycloalkyl, het, aryl, hetaryl, optionally substituted by one or more radicals R ^6.1 ;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, Het, optionally substituted by C _1-4 -alkyl or CONH ₂ ;
R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

R² C_1-4-Alkyl, C_1-4-Alkoxy oder Halogen;
R³ ein Rest ausgewählt aus der Gruppe bestehend aus

worin
n 0 oder 1;
m 0 oder 1;
o 2;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-4-Alkyl, C_2-4-Alkenyl, OH, C_1-4-Alkylen-OH, CH₂NEt₂, COMe, COOH, CONH₂, NH₂, Het, Hetaryl,

R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder zwei R^3.2.1
R^3.2.1 C_1-4-Alkyl, Cyclopentyl, OH, -NR^3.2.1.1R^3.2.1.2 oder

oder Het, gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, SO₂R^3.2.1.1,

R^3.2.1.1 H, Methyl oder Benzyl;
R^3.2.1.2 H, Methyl oder Benzyl; oder
-C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_2-4-Alkenyl, C_2-4-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-4-Haloalkyl, CN, OH, SO₂R^3.2.2.1, C_3-6-Cycloalkyl oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Cl, Methyl, CONR^3.2.2.1R^3.2.2.2, OH;
R^3.2.2.1 H oder Methyl;
R^3.2.2.2. H oder Methyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus

R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, SO₂H, SO₂-C_1-4-Alkyl, SO₂C_7-11-Aralkyl,

R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, COC-_1-4-Alkyl-Hetaryl;
R^a H, C_1-6-Alklyl, C_2-6-Alkenyl, C_3-6-Cycloalkyl, CF₃, COR⁸, NR⁹R¹⁰, NO₂, S(O)_nR¹¹, oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren Cl;
oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren CH₃, COCF₃, CH₂NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-4-Alkyl, C_3-6-Cycloalkyl, NH₂, Furanyl oder Phenyl, gegebenenfalls substituiert mit einem oder mehreren Chlor;
R⁹ H, COOR¹² oder Piperidino, gegebenenfalls substituiert mit einem oder mehreren CH₃, oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, der gegebenenfalls substituiert sein kann mit einem oder mehreren COOH, NMe₂ oder 4-Methylpiperazin;
R¹⁰ H, C_1-4-Alkyl, C_2-4-Alkinyl oder COCH₃;
R¹¹ C_1-4-Alkyl, gegebenenfalls substituiert mit einem oder mehreren NMe₂,
R¹² C_1-4-Alkyl;
R^b R⁴, CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NHCOOR⁴, NHCONR⁴R⁵ oder OH;
R⁴ H, C_1-4-Alkyl, C_1-4-Alkylen-OH, C_2-4-Alkinyl, C_1-6-Haloalkyl, Aryl, Het, Hetaryl,

R⁵ H oder C_1-4-Alkyl;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H, C_1-4-Alkyl, C_3-6-Cycloalkyl, C_7-11-Aralkyl, Aryl, gegebenenfalls substituiert mit SO₂CH₃;
R⁷ H, NR^7.1R^7.2, OR^7.1, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂, oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, C_1-4-Alkyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, C_1-4-Alkyl;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl and C _7-11 aralkyl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or hetaryl optionally substituted by one or more C _1-4 alkyl;
R ^{1 is} C _1-4 -alkyl, C _1-4 -haloalkyl, C _1-4 -alkylene-COOH, C _1-4 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SO ₂ R ^1.1 ;
R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} C _1-4 alkyl, C _1-4 alkoxy or halo;
R ^{3 is} a radical selected from the group consisting of

wherein
n is 0 or 1;
m is 0 or 1;
o 2;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-4 -alkyl, C _2-4 -alkenyl, OH, C _1-4 -alkylene-OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ , Het, hetaryl,

R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or two R ^3.2.1
R ^3.2.1 C _1-4 alkyl, cyclopentyl, OH, NR ^3.2.1.1 R ^3.2.1.2 or

or Het, optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl;
R ^3.2.1.2 H, methyl or benzyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _2-4 alkenyl, C _2-4 alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^3.2.2.1 , C _1-4 Haloalkyl, CN, OH, SO ₂ R ^3.2.2.1 , C _3-6 cycloalkyl or a radical selected from the group consisting of

or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH;
R ^3.2.2.1 H or methyl;
R ^3.2.2.2. H or methyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl and aryl which may be optionally substituted by one or more radicals R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or Het, optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ H, SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl,

R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 alkyl, C _7-11 aralkyl, C _1-4 alkyl hetaryl, COC _1-4 alkyl hetaryl;
R ^{a is} H, C _1-6 -alklyl, C _2-6 -alkenyl, C _3-6 -cycloalkyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , or a radical selected from the group consisting of

or a radical selected from the group consisting of

which may be optionally substituted with one or more Cl;
or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-4 alkyl, C _3-6 cycloalkyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro;
R ^{9 is} H, COOR ¹² or piperidino, optionally substituted by one or more CH ₃ , or a radical selected from the group consisting of C _1-4 -alkyl, which may optionally be substituted by one or more COOH, NMe ₂ or 4- methylpiperazine;
R ^{10 is} H, C _1-4 alkyl, C _2-4 alkynyl or COCH ₃ ;
R ^{11 is} C _1-4 -alkyl, optionally substituted by one or more NMe ₂ ,
R ^{12 is} C _1-4 alkyl;
R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH;
R ^{4 is} H, C _1-4 -alkyl, C _1-4 -alkylene-OH, C _2-4 -alkynyl, C _1-6 -haloalkyl, aryl, het, hetaryl,

R ^{5 is} H or C _1-4 alkyl;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H, C _1-4 alkyl, C _3-6 cycloalkyl, C _7-11 aralkyl, aryl optionally substituted with SO ₂ CH ₃ ;
R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.1 , SR ^7.2 , hetaryl, Het, optionally substituted by C _1-4 alkyl or CONH ₂ , or a radical selected from the group consisting of

R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-4 alkyl;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

R¹ Methyl, Ethyl, Propyl, Butyl, CF₃, CH₂COOH, Methoxy, F, Cl, Br, OH, CN, COR^1.1, OCF₃, NO₂ oder SO₂R^1.1;
R^1.1 OH, Methyl, NH₂, NHMe, NMe₂,

R² Methyl, Methoxy, F, Cl oder Br;
R³ ein Rest ausgewählt aus der Gruppe bestehend aus

worin
n 0 oder 1;
m 0 oder 1;
o 2;
R^3.1 ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren R^3.1.1;
R^3.1.1 Methyl, Ethyl, OH, CH₂OH, CH₂CH₂OH, CH₂NEt₂, COMe, COOH, CONH₂, NH₂,

R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, Ethyl, Cyclopentyl, OH, NH₂; oder
Cyclohexyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.1
R^3.2.1 -NR^3.2.1.1R^3.2.1.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, SO₂R^3.2.1.1,

R^3.2.1.1 H, Methyl oder Benzyl;
R^3.2.1.2 H, Methyl oder Benzyl; oder
-C_1-6-alkyl, gerade oder verzweigt, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C=CH₂, C≡CH, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, CF₃, CN, OH, SO₂R^3.2.2.1 oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Cl, Methyl, CONR^3.2.2.1R^3.2.2.2, OH;
R^3.2.2.1 H oder Methyl;
R^3.2.2.2. H oder Methyl; oder
Phenyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus

R^3.3 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, SO₂H, SO₂Me, SO₂CH₂Phenyl;

R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, COC_1-4-Alkyl-Hetaryl;
R^a H, Methyl, Ethyl, Propyl, Butyl, 3-Methyl-butyl, Propenyl, Cyclopropyl, Cyclohexyl, CF₃, COR⁸, NR⁹R¹⁰, NO₂, OR⁸, SR¹¹, SOR¹¹, SO₂R¹¹ oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren Cl,
oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren CH₃, COCF₃, CH₂NH₂ oder CH₂NHCOOR¹²;
R⁸ Methyl, Propyl, Cyclopropyl, NH₂, Furanyl oder Phenyl, gegebenenfalls substituiert mit einem oder mehreren Chlor;
R⁹ H, COOR¹² oder Piperidino, gegebenenfalls substituiert mit einem oder mehreren CH₃ oder ein Rest ausgewählt aus der Gruppe bestehend aus Methyl, Ethyl und Propyl, der gegebenenfalls substituiert sein kann mit einem oder mehreren COOH, NMe₂ oder 4-Methylpiperazin;
R¹⁰ H, Methyl, COCH₃, C≡CH oder CH₂C≡CH;
R¹¹ Ethyl oder Propyl, gegebenenfalls substituiert mit einem oder mehreren NMe₂,
R¹² Butyl
R^b R⁴, CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NHCOOR⁴, NHCONR⁴R⁵ oder OH;
R⁴ H, Methyl, Ethyl, 2-Hydroxyethyl, Propyl, C≡CH, CF₃, Phenyl,

R⁵ H, Methyl oder Ethyl;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, Methylen, Ethylen, Propylen oder Butinylen;
R⁶ H, C_1-4-Alkyl, Aryl, gegebenenfalls substituiert mit SO₂CH₃;
R⁷ H, NR^7.1R^7.2, OR^7.2, SR^7.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, Methyl, Ethyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, Methyl oder Ethyl;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} phenyl or benzyl, each optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, ethyl, propyl, butyl, CF ₃ , CH ₂ COOH, methoxy, F, Cl, Br, OH, CN, COR ^1.1 , OCF ₃ , NO ₂ or SO ₂ R ^1.1 ;
R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} methyl, methoxy, F, Cl or Br;
R ^{3 is} a radical selected from the group consisting of

wherein
n is 0 or 1;
m is 0 or 1;
o 2;
R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ;
R ^3.1.1 methyl, ethyl, OH, CH ₂ OH, CH ₂ CH ₂ OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ ,

R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, ethyl, cyclopentyl, OH, NH ₂ ; or
Cyclohexyl optionally substituted with one or two R ^3.2.1
R ^3.2.1 -NR ^3.2.1.1 R ^3.2.1.2 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl;
R ^3.2.1.2 H, methyl or benzyl; or
C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C = CH ₂ , C≡CH, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^3.2.2.1 , CF ₃ , CN, OH, SO ₂ R ^3.2.2.1 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH;
R ^3.2.2.1 H or methyl;
R ^3.2.2.2. H or methyl; or
Phenyl, which is optionally substituted with one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H, C _1-6 -alkyl, optionally substituted with one or more R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or Het which is optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ H, SO ₂ Me, SO ₂ CH ₂ phenyl;

R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, COC _1-4 - alkyl hetaryl;
R ^{a is} H, methyl, ethyl, propyl, butyl, 3-methyl-butyl, propenyl, cyclopropyl, cyclohexyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ or a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more Cl,
or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} methyl, propyl, cyclopropyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro;
R ^{9 is} H, COOR ¹² or piperidino optionally substituted with one or more CH ₃ or a radical selected from the group consisting of methyl, ethyl and propyl, which may be optionally substituted with one or more COOH, NMe ₂ or 4-methylpiperazine;
R ^{10 is} H, methyl, COCH ₃ , C≡CH or CH ₂ C≡CH;
R ^{11 is} ethyl or propyl, optionally substituted by one or more NMe ₂ ,
R ¹² butyl
R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH;
R ^{4 is} H, methyl, ethyl, 2-hydroxyethyl, propyl, C 1 H ₃ , CF ₃ , phenyl,

R ^{5 is} H, methyl or ethyl;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, methylene, ethylene, propylene or butynylene;
R ^{6 is} H, C _1-4 alkyl, aryl, optionally substituted with SO ₂ CH ₃ ;
R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 or a radical selected from the group consisting of

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, methyl or ethyl;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2, COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2 H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, C_1-6-Haloalkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1 C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.3.1.1, SO₂C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, COC_1-4-Alkyl-Hetaryl, COC_2-4-Alkenyl-Hetaryl, COC_2-4-Alkinyl-Hetaryl; oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^b R⁴, OR⁴, -CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NR⁴R⁵, NR⁵COR⁴, NR⁵COOR⁴, NR⁵CONR⁴R⁵, NR⁵SOR⁴ oder NR⁵SO₂R⁴;
R⁴, R⁵ H, C_1-6-Alkyl, C_1-6-Haloalkyl, C_1-6-Alkylen-OH, C_2-6-Alkenyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, C_2-6-Alkinyl, gegebenenfalls substituiert mit Si(C_1-4-Alkyl)₃, oder R⁴ bedeutet ein Rest ausgewählt aus der Gruppe bestehend aus Aryl, Het, Hetaryl und gegebenenfalls substituiert mit C_1-4-Alkyl;
oder R⁴ und R⁵ bilden gemeinsam einen fünf-, sechs- oder siebengliedrigen Ring bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-6-Alkyl, C_2-6-Alkenyl oder C_2-6-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-6-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring, given if substituted with a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 -alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 -cycloalkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2 H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _1-6 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ;
R ^3.3.1 C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, halogen or Het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.3.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ -C _3-6 -cycloalkyl and aryl;
R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, COC _1-4 Alkyl hetaryl, COC _2-4 alkenyl hetaryl, COC _2-4 alkynyl hetaryl; or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ;
R ⁴ , R ^{5 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl -Aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted with Si (C _1-4 -alkyl) ₃ , or R ⁴ is a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ;
R ^{7.1 is} H, C _1-6 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2, COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, -NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
-C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2. H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_1-4-Haloalkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2 CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, SO₂C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, COC_1-4-Alkyl-Hetaryl, COC_2-4-Alkenyl-Hetaryl, COC_2-4-Alkinyl-Hetaryl; oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen fünf-, sechs oder siebengliedrigen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^b R⁴, OR⁴, -CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NR⁴R⁵, NR⁵COR⁴, NR⁵COOR⁴, NR⁵CONR⁴R⁵, NR⁵SOR⁴ oder NR⁵SO₂R⁴;
R⁴ H, C_1-6-Alkyl, C_1-6-Haloalkyl, C_1-6-Alkylen-OH, C_2-6-Alkenyl, C_7-11-Aralkyl, C_2-4-Alkenyl-Aryl, C_2-4-Alkinyl-Aryl, C_1-4-Alkyl-Hetaryl, C_2-4-Alkenyl-Hetaryl, C_2-4-Alkinyl-Hetaryl, C_2-6-Alkinyl, gegebenenfalls substituiert mit Si(C_1-4-Alkyl)₃, oder R⁴ bedeutet ein Rest ausgewählt aus der Gruppe bestehend aus Aryl, Het, Hetaryl und gegebenenfalls substituiert mit C_1-4-Alkyl;
R⁵ H oder C_1-6-Alkyl;
oder R⁴ und R⁵ bilden gemeinsam einen fünf-, sechs- oder siebengliedrigen Ring bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-4-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, -NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 cycloalkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2. H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _1-4 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, halogen or Het, optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ -C _3-6 -cycloalkyl and aryl;
R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, COC _1-4 Alkyl hetaryl, COC _2-4 alkenyl hetaryl, COC _2-4 alkynyl hetaryl; or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ;
R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted by Si (C _{1 -4-} alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl;
R ^{5 is} H or C _1-6 alkyl;
or R ⁴ and R ⁵ together form a five-, six- or seven-membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, stick fabric and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ;
R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-6-Alkyl, C_2-6-Alkenyl, OH, C_1-4-Alkylen-OH, C_1-4-Alkylen-NR^3.1.1.1R^3.1.1.2,, COR^3.1.1.1, COOR^3.1.1.1, CONR^3.1.1.1R^3.1.1.2, NR^3.1.1.1R^3.1.1.2, Het, Hetaryl, NHCOR^3.1.1.1
R^3.1.1.1 ein Rest ausgewählt aus der Gruppe bestehend aus H, C_1-4-Alkyl, Aryl und C_7-11-Aralkyl; gegebenenfalls substituiert mit einem Rest ausgewählt aus der Gruppe Halogen, OH und CN;
R^3.1.1.2 H, C_1-4-Alkyl;
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder mehreren R^3.2.1
R^3.2.1 C_1-6-Alkyl, C_3-6-Cycloalkyl, OH, -NR^3.2.1.1R^3.2.1.2, NHCOR^3.2.1.3 oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, CH₂-C_3-6-Cycloalkyl und Aryl;
R^3.2.1.1 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 H, C_1-4-Alkyl oder C_7-11-Aralkyl;
R^3.2.1.2 Aryl, C_7-11-Aralkyl; oder
-C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_1-6-Alkyl, C_2-6-Alkenyl, C_2-6-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-6-Haloalkyl, CN, OR^3.2.2.1, SO₂R^3.2.2.1, C_3-6-Cycloalkyl, CO-Het, C_2-4-Alkinyl-Hetaryl, Guanidin oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Halogen, C_1-6-Alkyl, CONR^3.2.2.1R^3.2.2.2, OH, Imidazolidinon;
R^3.2.2.1 H oder C_1-6-Alkyl, Aryl, C_7-11-Aralkyl
R^3.2.2.2. H oder C_1-6-Alkyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus NH-C_1-6-alkyl-N(C_1-6-alkyl)₂ oder Het, wobei Het gegebenenfalls substituiert mit einem Rest C_1-6-Alkyl sein kann;
R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, SO₂C_1-4-Alkyl, SO₂C_7-11-Aralkyl, CH₂-C_3-6-Cycloalkyl und Aryl;;
R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, COC_1-4-Alkyl-Hetaryl; oder
zwei der Gruppen R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 bilden gemeinsam einen fünf-, sechs oder siebengliedrigen Ring, bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^b R⁴, OR⁴, -CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NR⁵COOR⁴, NR⁵CONR⁴R⁵ oder NR⁵SOR⁴;
R⁴ H, C_1-6-Alkyl, C_1-6-Haloalkyl, C_1-6-Alkylen-OH, C_2-6-Alkenyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, C_2-6-Alkinyl, gegebenenfalls substituiert mit Si(C_1-4-Alkyl)₃, oder R⁴ bedeutet ein Rest ausgewählt aus der Gruppe bestehend aus Aryl, Het, Hetaryl und gegebenenfalls substituiert mit C_1-4-Alkyl;
R⁵ H oder C_1-6-Alkyl;
oder R⁴ und R⁵ bilden gemeinsam einen fünf-, sechs- oder siebengliedrigen Ring bestehend aus Kohlenstoffatomen und gegebenenfalls einem Heteroatom ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_3-6-Cycloalkyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.1, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-4-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl,
R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2,, COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1
R ^{3.1.1.1 is} a radical selected from the group consisting of H, C _1-4 -alkyl, aryl and C _7-11 -aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN;
R ^3.1.1.2 H, C _1-4 alkyl;
R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1
R ^3.2.1 C _1-6 -alkyl, C _3-6 -cycloalkyl, OH, -NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , CH ₂ -C _3-6 cyclo alkyl and aryl;
R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl;
R ^3.2.1.2 aryl, C _7-11 aralkyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone;
R ^3.2.2.1 H or C _1-6 alkyl, aryl, C _7-11 aralkyl
R ^3.2.2.2. H or C _1-6 alkyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, wherein Het may optionally be substituted by a radical C _1-6 -alkyl;
R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl and aryl which may be optionally substituted by one or more radicals R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ -C _3-6 -cycloalkyl and aryl;
R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, COC _1-4 - alkyl hetaryl; or
two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ or NR ⁵ SOR ⁴ ;
R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, C _2-6 alkynyl optionally substituted with Si (C _1-4 alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted with C _1-4 alkyl;
R ^{5 is} H or C _1-6 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _3-6 -cycloalkyl, het, aryl, hetaryl, optionally substituted by one or more radicals R ^6.1 ;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.1 , SR ^7.2 , hetaryl, het, optionally substituted by C _1-4 -alkyl or CONH ₂ ;
R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

R² C_1-4-Alkyl, C_1-4-Alkoxy oder Halogen;
R³ ein Rest ausgewählt aus der Gruppe bestehend aus

worin
n 0 oder 1;
m 0 oder 1;
o 2;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 C_1-4-Alkyl, C_2-4-Alkenyl, OH, C_1-4-Alkylen-OH, CH₂NEt₂, COMe, COOH, CONH₂, NH₂, Het, Hetaryl,

R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus C_3-6-Cycloalkyl, Het, Hetaryl und Spiro der gegebenenfalls substituiert ist mit einem oder zwei R^3.2.1
R^3.2.1 C_1-4-Alkyl, Cyclopentyl, OH, -NR^3.2.1.1R^3.2.1.2 oder

oder Het, gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, SO₂R^3.2.1.1,

R^3.2.1.1 H, Methyl oder Benzyl;
R^3.2.1.2 H, Methyl oder Benzyl; oder
-C_1-6-alkyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C_2-4-Alkenyl, C_2-4-Alkinyl, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, C_1-4-Haloalkyl, CN, OH, SO₂R^3.2.2.1, C_3-6-Cycloalkyl oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus Het, Hetaryl und Aryl, der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Cl, Methyl, CONR^3.2.2.1R^3.2.2.2, OH;
R^3.2.2.1 H oder Methyl;
R^3.2.2.2. H oder Methyl; oder
Aryl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus

R^3.3 H oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-6-Alkyl und Aryl, der gegebenenfalls substituiert sein kann mit einem oder mehreren Resten R^3.3.1;
R^3.3.1 C_5-6-Cycloalkyl, C_5-6-Cycloalkenyl, OR^3.3.1.1, NR^3.3.1.1R^3.3.1.2, CONR^3.3.1.1R^3.3.1.2, COOR^3.3.1.1, NR^3.3.1.1COR^3.3.1.2, SOR^3.3.1.1, SO₂R^3.3.1.1, C(NR^3.3.1.1R^3.3.1.2)NR^3.3.1.3, NR^3.3.1.1CONR^3.3.1.2R^3.3.1.3, OH, CN, Halogen oder Het, gegebenenfalls substituiert mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, SO₂R^3.2.1.1, SO₂C_1-4-Alkyl, SO₂C_7-11-Aralkyl,

R^3.3.1.1, R^3.3.1.2 und R^3.3.1.3 ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, C_7-11-Aralkyl, C_1-4-Alkyl-Hetaryl, COC_1-4-Alkyl-Hetaryl;
R^b R⁴, CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NHCOOR⁴, NHCONR⁴R⁵ oder OH;
R⁴ H, C_1-4-Alkyl, C_1-4-Alkylen-OH, C_2-4-Alkinyl, C_1-6-Haloalkyl, Aryl, Het, Hetaryl,

R⁵ H oder C_1-4-Alkyl;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H, C_1-4-Alkyl, C_3-6-Cycloalkyl, C_7-11-Aralkyl, Aryl, gegebenenfalls substituiert mit SO₂CH₃;
R⁷ H, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂, oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, C_1-4-Alkyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, C_1-4-Alkyl;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} a radical selected from the group consisting of aryl and C _7-11 aralkyl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or hetaryl optionally substituted by one or more C _1-4 alkyl;
R ^{1 is} C _1-4 -alkyl, C _1-4 -haloalkyl, C _1-4 -alkylene-COOH, C _1-4 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SO ₂ R ^1.1 ;
R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} C _1-4 alkyl, C _1-4 alkoxy or halo;
R ^{3 is} a radical selected from the group consisting of

wherein
n is 0 or 1;
m is 0 or 1;
o 2;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 C _1-4 -alkyl, C _2-4 -alkenyl, OH, C _1-4 -alkylene-OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ , Het, hetaryl,

R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or two R ^3.2.1
R ^3.2.1 C _1-4 alkyl, cyclopentyl, OH, NR ^3.2.1.1 R ^3.2.1.2 or

or Het, optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl;
R ^3.2.1.2 H, methyl or benzyl; or
C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C _2-4 alkenyl, C _2-4 alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^3.2.2.1 , C _1-4 Haloalkyl, CN, OH, SO ₂ R ^3.2.2.1 , C _3-6 cycloalkyl or a radical selected from the group consisting of

or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH;
R ^3.2.2.1 H or methyl;
R ^3.2.2.2. H or methyl; or
Aryl which is optionally substituted by one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl and aryl which may be optionally substituted by one or more radicals R ^3.3.1 ;
R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl,

R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, COC _1-4 - alkyl hetaryl;
R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH;
R ^{4 is} H, C _1-4 -alkyl, C _1-4 -alkylene-OH, C _2-4 -alkynyl, C _1-6 -haloalkyl, aryl, het, hetaryl,

R ^{5 is} H or C _1-4 alkyl;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H, C _1-4 alkyl, C _3-6 cycloalkyl, C _7-11 aralkyl, aryl optionally substituted with SO ₂ CH ₃ ;
R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, Het, optionally substituted by C _1-4 alkyl or CONH ₂ , or a radical selected from the group consisting of

R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-4 alkyl;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

R¹ Methyl, Ethyl, Propyl, Butyl, CF₃, CH₂COOH, Methoxy, F, Cl, Br, OH, CN, COR^1.1, OCF₃, NO₂ oder SO₂R^1.1;
R^1.1 OH, Methyl, NH₂, NHMe, NMe₂,

R² Methyl, Methoxy, F, Cl oder Br;
R³ ein Rest ausgewählt aus der Gruppe bestehend aus

worin
n 0 oder 1;
m 0 oder 1;
o 2;
R^3.1 ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren R^3.1.1;
R^3.1.1 Methyl, Ethyl, OH, CH₂OH, CH₂CH₂OH, CH₂NEt₂, COMe, COOH, CONH₂, NH₂,

R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, Ethyl, Cyclopentyl, OH, NH₂; oder
Cyclohexyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.1
R^3.2.1 -NR^3.2.1.1R^3.2.1.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, SO₂R^3.2.1.1,

R^3.2.1.1 H, Methyl oder Benzyl;
R^3.2.1.2 H, Methyl oder Benzyl; oder
-C_1-6-alkyl, gerade oder verzweigt, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C=CH₂, C≡CH, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, NHCOR^3.2.2.1, CF₃, CN, OH, SO₂R^3.2.2.1 oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Cl, Methyl, CONR^3.2.2.1R^3.2.2.2, OH;
R^3.2.2.1 H oder Methyl;
R^3.2.2.2. H oder Methyl; oder
Phenyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus

R^3.3 H, Methyl oder Ethyl;
R^b R⁴, CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NHCOOR⁴, NHCONR⁴R⁵ oder OH;
R⁴ H, Methyl, Ethyl, 2-Hydroxyethyl, Propyl, C≡CH, CF₃, Phenyl,

R⁵ H, Methyl oder Ethyl;
R^c NH₂ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, Methylen, Ethylen, Propylen oder Butinylen;
R⁶ H, Phenyl, gegebenenfalls substituiert mit SO₂CH₃;
R⁷ H, NR^7.1R^7.2, OR^7.1, SR^7.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, Methyl, Ethyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, Methyl oder Ethyl;
R^7.1.1 NMe₂ oder 1-Imidazolyl
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} phenyl or benzyl, each optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, ethyl, propyl, butyl, CF ₃ , CH ₂ COOH, methoxy, F, Cl, Br, OH, CN, COR ^1.1 , OCF ₃ , NO ₂ or SO ₂ R ^1.1 ;
R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} methyl, methoxy, F, Cl or Br;
R ^{3 is} a radical selected from the group consisting of

wherein
n is 0 or 1;
m is 0 or 1;
o 2;
R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ;
R ^3.1.1 methyl, ethyl, OH, CH ₂ OH, CH ₂ CH ₂ OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ ,

R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, ethyl, cyclopentyl, OH, NH ₂ ; or
Cyclohexyl optionally substituted with one or two R ^3.2.1
R ^3.2.1 -NR ^3.2.1.1 R ^3.2.1.2 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl;
R ^3.2.1.2 H, methyl or benzyl; or
C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C = CH ₂ , C≡CH, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^3.2.2.1 , CF ₃ , CN, OH, SO ₂ R ^3.2.2.1 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH;
R ^3.2.2.1 H or methyl;
R ^3.2.2.2. H or methyl; or
Phenyl, which is optionally substituted with one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H, methyl or ethyl;
R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH;
R ^{4 is} H, methyl, ethyl, 2-hydroxyethyl, propyl, C 1 H ₃ , CF ₃ , phenyl,

R ^{5 is} H, methyl or ethyl;
R ^{c is} NH ₂ or a radical selected from the group consisting of

wherein
B bond, methylene, ethylene, propylene or butynylene;
R ^{6 is} H, phenyl optionally substituted with SO ₂ CH ₃ ;
R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.1 , SR ^7.2 or a radical selected from the group consisting of

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, methyl or ethyl;
R ^7.1.1 NMe ₂ or 1-imidazolyl
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
B Methylen, Propylen;
R⁷ H, NR^7.1R^7.2 oder 1-Imidazolyl;
R^7.1 H oder Methyl;
R^7.2 H oder Methyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^c a remainder

wherein
B is methylene, propylene;
R ⁷ H, NR ^7.1 R ^7.2 or 1-imidazolyl;
R ^{7.1 is} H or methyl;
R ^{7.2 is} H or methyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting from R ¹ and R ³ ;
R ^{1 is} methyl, ethyl, propyl, CF ₃ , methoxy, F, Cl or Br;
R ^{3 is} a remainder

and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ and R ³ ;
R ^{1 is} methyl, ethyl, propyl, CF ₃ , methoxy, F, Cl or Br;
R ^{3 is} a remainder

and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin R^a, R^b und R^c die oben genannte Bedeutung haben, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred of the above-mentioned compounds of formula 1 are the compounds of formula 1.1; wherein

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

R¹ Methyl, Ethyl, Propyl, CF₃, CH₂COOH, Methoxy, F, Cl, Br, CN, COR^1.1 oder SO₂R^1.1;
R^1.1 OH, Methyl, NH₂, NHMe, NMe₂ oder

R² Methyl, F, Cl oder Br;
R³ ein Rest ausgewählt aus der Gruppe bestehend aus

worin
n 0 oder 1;
m 0 oder 1;
o 2;
R^3.1 ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren R^3.1.1;
R^3.1.1 Methyl, OH, CH₂OH, CH₂CH₂OH, CH₂NEt₂, COMe, COOH, CONH₂,

R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe bestehend aus Methyl, Ethyl, Cyclopentyl, OH, NH₂; oder
Cyclohexyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.1
R^3.2.1 -NR^3.2.1.1R^3.2.1.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einer oder mehreren Methylgruppen
R^3.2.1.1 H oder Methyl;
R^3.2.1.2 H oder Methyl; oder
-C_1-6-alkyl, gerade oder verzweigt, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 C=CH₂, C≡CH, COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2.2, NR^3.2.2.1R^3.2.2.2, CN, OH oder ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Methyl, CONR^3.2.2.1R^3.2.2.2, OH;
R^3.2.2.1 H oder Methyl;
R^3.2.2.2. H oder Methyl; oder
Phenyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.3
R^3.2.3 ein Rest ausgewählt aus der Gruppe bestehend aus

R^3.3 H, Methyl oder Ethyl;
R^b R⁴, CH₂OCH₃, COR⁴, COOH, COOCH₃ CONR⁴R⁵, NH₂, NHCOOR⁴ oder OH;
R⁴ H, Methyl, Propyl, C≡CH, Phenyl,

R⁵ H oder Methyl;
R^c ein Rest

worin
B Methylen, Propylen;
R⁷ H, NR^7.1R^7.2 oder 1-Imidazolyl;
R^7.1 H oder Methyl;
R^7.2 H oder Methyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.1; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, ethyl, propyl, CF ₃ , CH ₂ COOH, methoxy, F, Cl, Br, CN, COR ^1.1 or SO ₂ R ^1.1 ;
R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ or

R ^{2 is} methyl, F, Cl or Br;
R ^{3 is} a radical selected from the group consisting of

wherein
n is 0 or 1;
m is 0 or 1;
o 2;
R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ;
R ^3.1.1 methyl, OH, CH ₂ OH, CH ₂ CH ₂ OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ ,

R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, ethyl, cyclopentyl, OH, NH ₂ ; or
Cyclohexyl optionally substituted with one or two R ^3.2.1
R ^3.2.1 -NR ^3.2.1.1 R ^3.2.1.2 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more methyl groups
R ^3.2.1.1 H or methyl;
R ^3.2.1.2 H or methyl; or
C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 C = CH ₂ , C≡CH, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , CN, OH or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH;
R ^3.2.2.1 H or methyl;
R ^3.2.2.2. H or methyl; or
Phenyl, which is optionally substituted with one or two R ^3.2.3
R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H, methyl or ethyl;
R ^b R ⁴ , CH ₂ OCH ₃ , COR ⁴ , COOH, COOCH ₃ CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ or OH;
R ^{4 is} H, methyl, propyl, C≡CH, phenyl,

R ^{5 is} H or methyl;
R ^c a remainder

wherein
B is methylene, propylene;
R ⁷ H, NR ^7.1 R ^7.2 or 1-imidazolyl;
R ^{7.1 is} H or methyl;
R ^{7.2 is} H or methyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

R¹ Methyl, CF₃, Methoxy, F, Cl, Br, COR^1.1 oder SO₂R^1.1;
R^1.1 OH, NH₂, NHMe oder NMe₂;
R² Cl;
R³ ein Rest ausgewählt aus der Gruppe bestehend aus

worin
n 0 oder 1;
m 0 oder 1;
R^3.1 ein Rest ausgewählt aus der Gruppe bestehend aus

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren R^3.1.1;
R^3.1.1 OH, CONH₂ oder 4-Pyridinyl,
R^3.2 ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einer oder mehreren Methylgruppen; oder
Cyclohexyl, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.1
R^3.2.1 ein Rest ausgewählt aus der Gruppe bestehend aus

-C_1-6-alkyl, gerade oder verzweigt, das gegebenenfalls substituiert ist mit einem oder zwei R^3.2.2;
R^3.2.2 COOR^3.2.2.1, CONR^3.2.2.1R^3.2.2, 4-Pyrdinyl oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert ist mit einem oder mehreren Resten ausgewählt aus der Gruppe Methyl;
R^3.2.2.1 H oder Methyl;
R^3.2.2. H oder Methyl; oder
R^3.3 H, Methyl oder Ethyl;
R^b R⁴, CH₂OCH₃ oder OH;
R⁴ H, C≡CH,

R^c ein Rest

worin
B Methylen, Propylen;
R⁷ H oder NR^7.1R^7.2;
R^7.1 H oder Methyl;
R^7.2 H oder Methyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Most preferred are the above compounds of formula 1.1; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, CF ₃ , methoxy, F, Cl, Br, COR ^1.1 or SO ₂ R ^1.1 ;
R ^{1.1 is} OH, NH ₂ , NHMe or NMe ₂ ;
R ² Cl;
R ^{3 is} a radical selected from the group consisting of

wherein
n is 0 or 1;
m is 0 or 1;
R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ;
R ^3.1.1 OH, CONH ₂ or 4-pyridinyl,
R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more methyl groups; or
Cyclohexyl optionally substituted with one or two R ^3.2.1
R ^{3.2.1 is} a radical selected from the group consisting of

C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ;
R ^3.2.2 COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2 , 4-pyridinyl or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group methyl;
R ^3.2.2.1 H or methyl;
R ^3.2.2. H or methyl; or
R ^{3.3 is} H, methyl or ethyl;
R ^b R ⁴ , CH ₂ OCH ₃ or OH;
R ⁴ H, C≡CH,

R ^c a remainder

wherein
B is methylene, propylene;
R ⁷ H or NR ^7.1 R ^7.2 ;
R ^{7.1 is} H or methyl;
R ^{7.2 is} H or methyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin R^a, R^b und R^c die oben genannte Bedeutung haben, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred of the above-mentioned compounds of formula 1 are the compounds of formula 1.2; wherein

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 NR^3.1.1.1R^3.1.1.2;
R^3.1.1.1 H, C_1-4-Alkyl;
R^3.1.1.2 H, C_1-4-Alkyl;
bedeutet, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.2; wherein R ^b and R ^{c have} the abovementioned meaning and
R ^{a is} aryl optionally substituted with one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ² are independently C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, halogen, COR ^1.1, SO ₂ R ^1.1,
R ^1.1 C _1-6 -alkyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 NR ^3.1.1.1 R ^3.1.1.2 ;
R ^3.1.1.1 H, C _1-4 alkyl;
R ^3.1.1.2 H, C _1-4 alkyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
X Bindung oder Methylen, Ethylen, Propylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 NR^3.1.1.1R^3.1.1.2;
R^3.1.1.1 H, Methyl Ethyl, Propyl;
R^3.1.1.2 H, Methyl Ethyl, Propyl;
R^b R⁴;
R⁴ H;
R^c NHR⁶ oder ein Rest

worin
B Bindung, Methylen, Ethylen oder Propylen;
R⁶ H;
R⁷ H oder NR^7.1R^7.2,

R^7.1 H, Methyl, Ethyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, Methyl oder Ethyl;
R^7.1.1 NMe₂ oder 1-Imidazolyl
bedeutet, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of formula 12; wherein
R ^{a is} phenyl optionally substituted with one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ;
R ¹ and R ² are independently C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, halogen, COR ^1.1, SO ₂ R ^1.1,
R ^1.1 methyl ethyl, propyl, NR ^1.1.1 R ^1.1.2
R ^1.1.1 H, methyl ethyl, propyl;
R ^1.1.2 H, methyl ethyl, propyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or methylene, ethylene, propylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 NR ^3.1.1.1 R ^3.1.1.2 ;
R ^3.1.1.1 H, methyl ethyl, propyl;
R ^3.1.1.2 H, methyl ethyl, propyl;
R ^b R ⁴ ;
R ⁴ H;
R ^c NHR ⁶ or a remainder

wherein
B bond, methylene, ethylene or propylene;
R ⁶ H;
R ⁷ H or NR ^7.1 R ^7.2 ,

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, methyl or ethyl;
R ^7.1.1 NMe ₂ or 1-imidazolyl
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
B Bindung, Methylen, Ethylen oder Propylen;
R⁶ H;
R⁷ H oder NR^7.1R^7.2,

R^7.1 H, Methyl, Ethyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, Methyl oder Ethyl;
R^7.1.1 NMe₂ oder 1-Imidazolyl
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.2; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ and R ² ;
R ^{1 is} methyl, ethyl, propyl, CF ₃ , F, Cl, COR ^1.1 or SO ₂ R ^1.1 ;
R ^1.1 methyl;
R ^{2 is} methyl, F or Cl;
R ^b R ⁴ ;
R ⁴ H;
R ^c NHR ⁶ or a remainder

wherein
B bond, methylene, ethylene or propylene;
R ⁶ H;
R ⁷ H or NR ^7.1 R ^7.2 ,

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, methyl or ethyl;
R ^7.1.1 NMe ₂ or 1-imidazolyl
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
B Bindung, Methylen oder Propylen;
R⁷ H oder NR^7.1R^7.2,
R^7.1 H oder Methyl;
R^7.2 Methyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Most preferred are the above compounds of formula 1.2; wherein
R ^{a is} phenyl optionally substituted with R ¹ ;
R ^{1 is} methyl, F, Cl, Br or COR ^1.1 ;
R ^1.1 methyl;
R ^b R ⁴ ;
R ⁴ H;
R ^c a remainder

wherein
B bond, methylene or propylene;
R ⁷ H or NR ^7.1 R ^7.2 ,
R ^{7.1 is} H or methyl;
R ^7.2 methyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin R^a, R^b und R^c die oben genannte Bedeutung haben, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred of the above-mentioned compounds of the formula 1 are the compounds of the formula 1.3; wherein

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 NR^3.1.1.1R^3.1.1.2;
R^3.1.1.1 H, C_1-4-Alkyl;
R^3.1.1.2 H, C_1-4-Alkyl;
bedeutet, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.3; wherein R ^b and R ^{c have} the abovementioned meaning and
R ^{a is} aryl optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ , or hetaryl;
R ¹ and R ^{2 are} independently C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, halogen, COR ^1.1 ;
R ^1.1 OH, C _1-6 -alkyl, NR ^1.1.1 R ^1.1.2
R ^{1.1.1 is} H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ;
R ^1.1.2 H, C _1-6 -alkyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 NR ^3.1.1.1 R ^3.1.1.2 ;
R ^3.1.1.1 H, C _1-4 alkyl;
R ^3.1.1.2 H, C _1-4 alkyl;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
X Bindung oder C_1-4-alkylen;
R^3a ein Rest, gleich oder verschieden, ausgewählt aus der Gruppe bestehend aus R^3.1, R^3.2 und R^3.3;
R^3.1 Spiro oder Het, wobei Het gegebenenfalls substituiert mit einem oder mehreren R^3.1.1 sein kann;
R^3.1.1 NR^3.1.1.1R^3.1.1.2;
R^3.1.1.1 H, Methyl Ethyl, Propyl;
R^3.1.1.2 H, Methyl Ethyl, Propyl;
R^b R⁴ oder OH;
R⁴ H;
R^c NHR⁶ oder ein Rest

worin
B Bindung, Methylen, Ethylen oder Propylen;
R⁶ H;
R⁷ H, NR^7.1R^7.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, Methyl oder (CH₂)₂R^7.1.1;
R^7.2 H, Methyl oder Ethyl;
R^7.1.1 NMe₂;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.3; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ , pyrazolyl or pyridinyl;
R ¹ and R ² are independently C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkoxy, halogen, COR ^1.1,
R ^1.1 methyl ethyl, propyl, NR ^1.1.1 R ^1.1.2
R ^1.1.1 H, methyl ethyl, propyl;
R ^1.1.2 H, methyl ethyl, propyl;
or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl;
R ^{3 is} a radical selected from the group consisting of

wherein
X bond or C _1-4 alkylene;
R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ;
R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ;
R ^3.1.1 NR ^3.1.1.1 R ^3.1.1.2 ;
R ^3.1.1.1 H, methyl ethyl, propyl;
R ^3.1.1.2 H, methyl ethyl, propyl;
R ^{b is} R ⁴ or OH;
R ⁴ H;
R ^c NHR ⁶ or a remainder

wherein
B bond, methylene, ethylene or propylene;
R ⁶ H;
R ⁷ H, NR ^7.1 R ^7.2 or a radical selected from the group consisting of

R ^7.1 H, methyl or (CH ₂ ) ₂ R ^7.1.1 ;
R ^{7.2 is} H, methyl or ethyl;
R ^7.1.1 NMe ₂ ;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

R¹ Methyl, Methoxy, Cl, OH oder COR^1.1;
R^1.1 NH₂, NHMe oder NMe₂;
R² Methoxy oder Cl;
R^b R⁴ oder OH;
R⁴ H;
R^c NHR⁶ oder ein Rest

worin
B Bindung, Methylen, Ethylen oder Propylen;
R⁶ H;
R⁷ H, NR^7.1R^7.2 oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, Methyl oder (CH₂)₂R^7.1.1;
R^7.2 H, Methyl oder Ethyl;
R^7.1.1 NMe₂;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.3; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of and R ² ; or

R ^{1 is} methyl, methoxy, Cl, OH or COR ^1.1 ;
R ^1.1 NH ₂ , NHMe or NMe ₂ ;
R ^{2 is} methoxy or Cl;
R ^{b is} R ⁴ or OH;
R ⁴ H;
R ^c NHR ⁶ or a remainder

wherein
B bond, methylene, ethylene or propylene;
R ⁶ H;
R ⁷ H, NR ^7.1 R ^7.2 or a radical selected from the group consisting of

R ^7.1 H, methyl or (CH ₂ ) ₂ R ^7.1.1 ;
R ^{7.2 is} H, methyl or ethyl;
R ^7.1.1 NMe ₂ ;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
B Methylen;
R⁶ H;
R⁷ H;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Most preferred are the above compounds of formula 1.3; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or
R ^{1 is} Cl or COR ^1.1 ;
R ^1.1 NH ₂ ;
R ² Cl;
R ^{b is} R ⁴ or OH;
R ⁴ H;
R ^c NHR ⁶ or a remainder

wherein
B methylene;
R ⁶ H;
R ⁷ H;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin R^a, R^b und R^c die oben genannte Bedeutung haben, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred of the above-mentioned compounds of the formula 1 are the abovementioned compounds of the formula 1.4; wherein

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
m 0;
R^3.2 ein Rest

der gegebenenfalls substituiert ist mit einem Rest ausgewählt aus der Gruppe bestehend aus Methyl und Cyclopentyl;
Cyclohexyl, das gegebenenfalls substituiert ist mit einem R^3.2.1
R^3.2.1 ein Rest

R^3.3 H;
R^b R⁴;
R⁴ ein Rest ausgewählt aus der Gruppe bestehend aus

R^c ein Rest

worin
B Methylen;
R⁷ H;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Particularly preferred are the abovementioned compounds of the formula 1.4; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ and R ³ ; or
R ^{1 is} methyl, F, Cl or Br;
R ^{3 is} a radical selected from the group consisting of

wherein
m 0;
R ^3.2 a remainder

which is optionally substituted by a radical selected from the group consisting of methyl and cyclopentyl;
Cyclohexyl which is optionally substituted with an R ^3.2.1
R ^3.2.1 a remainder

R ^3.3 H;
R ^b R ⁴ ;
R ^{4 is} a radical selected from the group consisting of

R ^c a remainder

wherein
B methylene;
R ⁷ H;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
m 0;
R^3.2 ein Rest

der gegebenenfalls substituiert ist mit Methyl; oder
Cyclohexyl, das gegebenenfalls substituiert ist mit einem R^3.2.1
R^3.2.1 ein Rest

R^3.3 H;
R^b R⁴;
R⁴ ein Rest

R^c ein Rest

worin
B Methylen;
R⁷ H;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Most preferred are the above compounds of formula 1.4; wherein
R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ and R ³ ; or
R ¹ Cl;
R ^{3 is} a radical selected from the group consisting of

wherein
m 0;
R ^3.2 a remainder

which is optionally substituted with methyl; or
Cyclohexyl which is optionally substituted with an R ^3.2.1
R ^3.2.1 a remainder

R ^3.3 H;
R ^b R ⁴ ;
R ⁴ a remainder

R ^c a remainder

wherein
B methylene;
R ⁷ H;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

worin
B Bindung, C_1-6-Alkyl, C_2-6-Alkenyl oder C_2-6-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-6-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Also preferred are the above compounds of formula 1; wherein
R ^a is H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C ₃ _ ₈ cycloalkenyl, C _1-6 haloalkyl, COR ^8, NR ⁹ R ^10, NO _2, OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² , CONR ¹² or C _1-6 alkyl optionally substituted with one or more COOH, N (C _1-6 alkyl) ₂ or Het optionally substituted with one or more C _1-6 alkyl ; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-6 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} H, C _1-6 -alkyl;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ;
R ⁴ , R ^{5 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl -Aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted with Si (C _1-4 -alkyl) ₃ , or R ⁴ is a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ;
R ^{7.1 is} H, C _1-6 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, C_3-6-Cycloalkenyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_2-4-Alkenyl, C_2-4-Alkinyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-4-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² or C _1-4 alkyl optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or Het optionally substituted with one or more C _1-4 alkyl; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-4 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} C _1-6 alkyl;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ;
R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl _; C _2-6 alkynyl optionally substituted with Si (C _1-4 alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted with C _1-4 alkyl;
R ^{5 is} H or C _1-6 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ;
R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H oder ein Rest ausgewählt aus der Gruppe C_1-4-Alkyl, C_3-6-Cycloalkyl, Het, Aryl, Hetaryl gegebenenfalls substituiert mit einem oder mehreren Resten R^6.1;
R^6.1 Halogen, CF₃, OH, CN, OMe, SO₂(C_1-4-Alkyl);
R⁷ H, C_1-4-Alkyl, C_3-6-Cycloalkyl, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂;
R^7.1 H, C_1-4-Alkyl, (CH₂)_2-4R^7.1.1 oder COOButyl;
R^7.2 H, C_1-6-Alkyl, gegebenenfalls substituiert mit einem oder mehreren OH;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl;
R ^{9 is} H, COOR ¹² or C _1-4 alkyl optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or Het optionally substituted with one or more C _1-4 alkyl; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl;
R ^{10 is} H, C _1-6 -alkyl, CO-C _1-4 -alkyl or C _2-6 -alkynyl;
R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ;
R ^{12 is} C _1-6 alkyl;
R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ or NR ⁵ SOR ⁴ ;
R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, C _2-6 alkynyl optionally substituted with Si (C _1-4 alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted with C _1-4 alkyl;
R ^{5 is} H or C _1-6 alkyl;
or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _3-6 -cycloalkyl, het, aryl, hetaryl, optionally substituted by one or more radicals R ^6.1 ;
R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl);
R ^{7 is} H, C _1-4 -alkyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, Het, optionally substituted by C _1-4 -alkyl or CONH ₂ ;
R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren Cl;
oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren CH₃, COCF₃, CH₂NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-4-Alkyl, C_3-6-Cycloalkyl, NH₂, Furanyl oder Phenyl, gegebenenfalls substituiert mit einem oder mehreren Chlor;
R⁹ H, COOR¹² oder Piperidino, gegebenenfalls substituiert mit einem oder mehreren CH₃, oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, der gegebenenfalls substituiert sein kann mit einem oder mehreren COOH, NMe₂ oder 4-Methylpiperazin;
R¹⁰ H, C_1-4-Alkyl, C_2-4-Alkinyl oder COCH₃;
R¹¹ C_1-4-Alkyl, gegebenenfalls substituiert mit einem oder mehreren NMe₂,
R¹² C_1-4-Alkyl;
R^b R⁴, CH₂OR⁴, COR⁴, COOR⁴, CONR⁴R⁵, NH₂, NHCOOR⁴, NHCONR⁴R⁵ oder OH;
R⁴ H, C_1-4-Alkyl, C_1-4-Alkylen-OH, C_2-4-Alkinyl, C_1-6-Haloalkyl, Aryl, Het, Hetaryl,

R⁵ H oder C_1-4-Alkyl;
R^c NHR⁶ oder ein Rest ausgewählt aus der Gruppe bestehend aus

worin
B Bindung, C_1-4-Alkyl oder C_2-4-Alkinyl;
R⁶ H, C_1-4-Alkyl, C_3-6-Cycloalkyl, C_7-11-Aralkyl, Aryl, gegebenenfalls substituiert mit SO₂CH₃;
R⁷ H, NR^7.1R^7.2, OR^7.2, SR^7.2, Hetaryl, Het, gegebenenfalls substituiert mit C_1-4-Alkyl oder CONH₂, oder ein Rest ausgewählt aus der Gruppe bestehend aus

R^7.1 H, C_1-4-Alkyl, (CH₂)₂R^7.1.1 oder COOButyl;
R^7.2 H, C_1-4-Alkyl;
R^7.1.1 NR^7.1.1.1R^7.1.1.2, Het oder 1-Imidazolyl, 2-(N-Ethylpyrollidin);
R^7.1.1.1 H oder C_1-6-Alkyl;
R^7.1.1.2 H oder C_1-6-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Preference is given to the abovementioned compounds of the formula 1; wherein
R ^{a is} H, C _1-6 -alklyl, C _2-6 -alkenyl, C _3-6 -cycloalkyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , or a radical selected from consisting of the group

or a radical selected from the group consisting of

which may be optionally substituted with one or more Cl;
or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-4 alkyl, C _3-6 cycloalkyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro;
R ^{9 is} H, COOR ¹² or piperidino, optionally substituted by one or more CH ₃ , or a radical selected from the group consisting of C _1-4 -alkyl, which may optionally be substituted by one or more COOH, NMe ₂ or 4- methylpiperazine;
R ^{10 is} H, C _1-4 alkyl, C _2-4 alkynyl or COCH ₃ ;
R ^{11 is} C _1-4 -alkyl, optionally substituted by one or more NMe ₂ ,
R ^{12 is} C _1-4 alkyl;
R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH;
R ^{4 is} H, C _1-4 -alkyl, C _1-4 -alkylene-OH, C _2-4 -alkynyl, C _1-6 -haloalkyl, aryl, het, hetaryl,

R ^{5 is} H or C _1-4 alkyl;
R ^c NHR ⁶ or a radical selected from the group consisting of

wherein
B bond, C _1-4 alkyl or C _2-4 alkynyl;
R ^{6 is} H, C _1-4 alkyl, C _3-6 cycloalkyl, C _7-11 aralkyl, aryl optionally substituted with SO ₂ CH ₃ ;
R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, Het, optionally substituted by C _1-4 alkyl or CONH ₂ , or a radical selected from the group consisting of

R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl;
R ^{7.2 is} H, C _1-4 alkyl;
R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine);
R ^7.1.1.1 H or C _1-6 alkyl;
R ^7.1.1.2 H or C _1-6 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} H, C _1-6 -alklyl, C _2-6 -alkenyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , spiro, NHCO-C _1-6 -alkyl-NH ₂ or a radical selected from the group consisting of C _7-11 -aralkyl and CH ₂ O-aryl, which may optionally be substituted by one or more Cl; or a group selected from the group consisting of Het which may be optionally substituted with one or more C _1-4 alkyl, COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-4 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl, aryl, optionally substituted with one or more chlorine;
R ^{9 is} H, COOR ¹² or Het optionally substituted with one or more C _1-4 alkyl, or a radical selected from the group consisting of C _1-4 alkyl which may be optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or 4-methylpiperazine;
R ^{10 is} H, C _1-4 alkyl, C _2-4 alkynyl or COCH ₃ ;
R ^{11 is} C _1-4 -alkyl, optionally substituted with one or more N (C _1-4 -alkyl) ₂ ,
R ^{12 is} C _1-4 alkyl;
n is 0 or 2;
R ^{b is} H, OH or COOEt;
R ^{c is} NH ₂ or NHCOR ¹³ ;
R ^{13 is} C _1-4 -alkyl, or NR ^13.1 R ^13.2 ,
R ^{13.1 is} H or C _1-4 alkyl;
R ^{13.2 is} H or C _1-4 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren Cl;
oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren CH₃, COCF₃, CH₂NH₂ oder CH₂NHCOOR¹²;
R⁸ C_1-4-Alkyl, C_3-6-Cycloalkyl, NH₂, Furanyl oder Phenyl, gegebenenfalls substituiert mit einem oder mehreren Chlor;
R⁹ H, COOR¹² oder Piperidino, gegebenenfalls substituiert mit einem oder mehreren CH₃, oder ein Rest ausgewählt aus der Gruppe bestehend aus C_1-4-Alkyl, der gegebenenfalls substituiert sein kann mit einem oder mehreren COOH, NMe₂ oder 4-Methylpiperazin;
R¹⁰ H, C_1-4-Alkyl, C_2-4-Alkinyl oder COCH₃;
R¹¹ C_1-4-Alkyl, gegebenenfalls substituiert mit einem oder mehreren NMe₂,
R¹² C_1-4-Alkyl;
R^b H, OH oder COOEt;
R^c NH₂ oder NHCOR¹³;
R¹³ C_1-4-Alkyl, oder NR^13.1R^13.2,
R^13.1 H oder C_1-4-Alkyl;
R^13.2 H oder C_1-4-Alkyl;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} H, C _1-6 -alklyl, C _2-6 -alkenyl, C _3-6 -cycloalkyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , or a radical selected from the group consisting of

or a radical selected from the group consisting of

which may be optionally substituted with one or more Cl;
or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} C _1-4 alkyl, C _3-6 cycloalkyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro;
R ^{9 is} H, COOR ¹² or piperidino, optionally substituted by one or more CH ₃ , or a radical selected from the group consisting of C _1-4 -alkyl, which may optionally be substituted by one or more COOH, NMe ₂ or 4- methylpiperazine;
R ^{10 is} H, C _1-4 alkyl, C _2-4 alkynyl or COCH ₃ ;
R ^{11 is} C _1-4 -alkyl, optionally substituted by one or more NMe ₂ ,
R ^{12 is} C _1-4 alkyl;
R ^{b is} H, OH or COOEt;
R ^{c is} NH ₂ or NHCOR ¹³ ;
R ^{13 is} C _1-4 -alkyl, or NR ^13.1 R ^13.2 ,
R ^{13.1 is} H or C _1-4 alkyl;
R ^{13.2 is} H or C _1-4 alkyl;
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren Cl;
oder ein Rest ausgewählt aus der Gruppe bestehend aus

der gegebenenfalls substituiert sein kann mit einem oder mehreren CH₃, COCF₃, CH₂NH₂ oder CH₂NHCOOR¹²;
R⁸ Methyl, Propyl, Cyclopropyl, NH₂, Furanyl oder Phenyl, gegebenenfalls substituiert mit einem oder mehreren Chlor;
R⁹ H, COOR¹² oder Piperidino, gegebenenfalls substituiert mit einem oder mehreren CH₃, oder ein Rest ausgewählt aus der Gruppe bestehend aus Methyl, Ethyl und Propyl, der gegebenenfalls substituiert sein kann mit einem oder mehreren COOH, NMe₂ oder 4-Methylpiperazin;
R¹⁰ H, Methyl, COCH₃, C≡CH oder CH₂C≡CH;
R¹¹ Ethyl oder Propyl, gegebenenfalls substituiert mit einem oder mehreren NMe₂,
R¹² Butyl
R^b H, OH oder COOEt;
R^c NH₂ oder NHCOR¹³;
R¹³ Methyl oder NR^13.1R^13.2,
R^13.1 H oder Methyl;
R^13.2 H oder Methyl.
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon, mit der Maßgabe, dass R^a nicht H oder Me sein kann, wenn Y = Stickstoff; Z = Stickstoff; j = 2; k = 0; R^b = H und R^c = NHCONH-Et bedeutet.Particularly preferred are the abovementioned compounds of the formula 1; wherein
R ^{a is} H, methyl, ethyl, propyl, butyl, 3-methyl-butyl, propenyl, cyclopropyl, cyclohexyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , or a radical consisting of the group

or a radical selected from the group consisting of

which may be optionally substituted with one or more Cl;
or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ;
R ^{8 is} methyl, propyl, cyclopropyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro;
R ^{9 is} H, COOR ¹² or piperidino, optionally substituted with one or more CH ₃ , or a radical selected from the group consisting of methyl, ethyl and propyl, which may be optionally substituted with one or more COOH, NMe ₂ or 4-methylpiperazine ;
R ^{10 is} H, methyl, COCH ₃ , C≡CH or CH ₂ C≡CH;
R ^{11 is} ethyl or propyl, optionally substituted by one or more NMe ₂ ,
R ¹² butyl
R ^{b is} H, OH or COOEt;
R ^{c is} NH ₂ or NHCOR ¹³ ;
R ^{13 is} methyl or NR ^13.1 R ^13.2 ,
R ^{13.1 is} H or methyl;
R ^{13.2 is} H or methyl.
as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et.

R⁸ Furanyl;
R⁹ Methyl;
R¹⁰ Methyl;
R¹¹ Ethyl;
n 0;
R^b H oder OH;
R^c NH₂ oder NHCOCH₃;
bedeuten, sowie pharmakologisch verträgliche Salz, Diastereomere, Enantiomere, Racemate, Hydrate oder Solvate davon.Most preferred are the above compounds of formula 1; wherein
R ^{a is} Propyl, COR ⁸ , NR ⁹ R ¹⁰ , S (O) _n R ¹¹ and

R ⁸ furanyl;
R ^{9 is} methyl;
R ^{10 is} methyl;
R ¹¹ ethyl;
n 0;
R ^{b is} H or OH;
R ^{c is} NH ₂ or NHCOCH ₃ ;
and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof.

USED TERMS AND DEFINITIONS

The term "C _1-6 -alkyl" (including those which are part of other groups) is understood to mean branched and unbranched alkyl groups having 1 to 6 carbon atoms and branched and unbranched alkyl groups having 1 to 10 by the term "C _1-4 -alkyl" 4 carbon atoms understood. Preferred are alkyl groups having 1 to 4 carbon atoms. Examples include: methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl or hexyl. Optionally, the abbreviations Me, Et, n-Pr, i-Pr, n-Bu, i-Bu, t-Bu, etc. are also used for the abovementioned groups. Unless otherwise specified, the definitions of propyl, butyl, pentyl and hexyl include all conceivable isomeric forms of the respective radicals. For example, propyl includes n-propyl and iso-propyl, butyl includes iso-butyl, sec-butyl and tert-butyl, etc.

The term "C _1-6 -alkylene" (including those which are part of other radicals) are to be understood as meaning branched and unbranched alkylene groups having 1 to 6 carbon atoms and branched and unbranched alkylene groups having 1 to 10 by the term "C _1-4 -alkylene" 4 carbon atoms understood. Preferred are alkylene groups having 1 to 4 carbon atoms. Examples include: methylene, ethylene, propylene, 1-methylethylene, butylene, 1-methylpropylene, 1,1-dimethylethylene, 1,2-dimethylethylene, pentylene, 1,1-dimethylpropylene, 2,2, -dimethylpropylene, 1, 2-dimethylpropylene, 1,3-dimethylpropylene or hexylene. Unless otherwise stated, the definitions propylene, butylene, pentylene and hexylene include all conceivable isomeric forms of the respective radicals of the same carbon number. For example, propyl also includes 1-methylethylene and butylene includes 1-methylpropylene, 1,1-dimethylethylene, 1,2-dimethylethylene.

The term "C _2-6 alkenyl" (including those which are part of other radicals) are branched and unbranched alkenyl groups having 2 to 6 carbon atoms and the term "C _2-4 alkenyl" branched and unbranched alkenyl groups having 2 to 4 Carbon atoms understood, as far as they have at least one double bond. Preferred are alkenyl groups having 2 to 4 carbon atoms. Examples include: ethenyl or vinyl, propenyl, butenyl, pentenyl, or hexenyl. Unless otherwise described, the definitions propenyl, butenyl, pentenyl and hexenyl include all conceivable isomeric forms of the respective radicals. For example, propenyl includes 1-propenyl and 2-propenyl, butenyl includes 1-, 2- and 3-butenyl, 1-methyl-1-propenyl, 1-methyl-2-propenyl, etc.

The term "C _2-6 alkenylene" (including those which are part of other radicals) is understood as meaning branched and unbranched alkenylene groups having 2 to 6 carbon atoms and branched and unbranched alkylene groups having 2 to 6 under the term "C _2-4 alkenylene" 4 carbon atoms understood. Alkenylene groups having 2 to 4 carbon atoms are preferred. Examples include: ethenylene, propenylene, 1-methylethenylene, butenylene, 1-methylpropenylene, 1,1-dimethylethenylene, 1,2-dimethylethenylene, pentenylene, 1,1-dimethylpropenylene, 2,2-dimethylpropenylene, 1,2- Dimethylpropenylene, 1,3-dimethylpropenylene or hexenylene. Unless otherwise stated, the definitions propenylene, butenylene, pentenylene and hexenylene include all conceivable isomeric forms of the respective radicals of equal carbon number. For example, propenyl also includes 1-methylethenylene and butenylene includes 1-methylpropenylene, 1,1-dimethylethenylene, 1,2-dimethylethenylene.

The term "C _2-6 -alkynyl" (including those which are part of other radicals) are branched and unbranched alkynyl groups having 2 to 6 carbon atoms and the term "C _2-4 -alkynyl" branched and unbranched alkynyl groups having 2 to 4 Carbon atoms understood as far as they have at least one triple bond. Preferred are alkynyl groups having 2 to 4 carbon atoms. Examples include: ethynyl, propynyl, butynyl, pentynyl, or hexynyl. Unless otherwise stated, the definitions of propynyl, butynyl, pentynyl and hexynyl include all conceivable isomeric forms of the respective radicals. For example, propynyl includes 1-propynyl and 2-propynyl, butinyl includes 1-, 2- and 3-butynyl, 1-methyl-1-propynyl, 1-methyl-2-propynyl, etc.

The term "C _2-6 -alkynylene" (even if they are part of other groups) are branched and unbranched alkynylene groups having 2 to 6 carbon atoms and the term "C _2-4 -alkynylene" branched and unbranched alkylene groups having 2 to 4 carbon atoms understood. Alkynylene groups having 2 to 4 carbon atoms are preferred. Examples include: ethynylene, propynylene, 1-methylethynylene, butynylene, 1-methylpropynylene, 1,1-dimethylethynylene, 1,2-dimethylethynylene, pentynylene, 1,1-dimethylpropynylene, 2,2-dimethylpropynylene, 1,2- Dimethylpropynylene, 1,3-dimethylpropynylene or hexynylene. Unless otherwise stated, the definitions propynylene, butynylene, pentynylene and hexynylene include all conceivable isomeric forms of the respective radicals of the same carbon number. For example, propynyl also includes 1-methylethynylene and butynylene includes 1-methylpropynylene, 1,1-dimethylethynylene, 1,2-dimethylethynylene.

The term "C _1-6 -alkoxy" (even if they are part of other radicals) are branched and unbranched alkoxy groups having 1 to 6 carbon atoms and the term "C _1-4 alkoxy" branched and unbranched alkoxy groups with 1 to 4 carbon atoms understood. Preferred are alkoxy groups having 1 to 4 carbon atoms. Examples include: methoxy, ethoxy, propoxy, butoxy or pentoxy. If appropriate, the abbreviations OMe, OEt, OPr, etc. are also used for the abovementioned groups. Unless otherwise stated, the definitions of propoxy, butoxy and pentoxy include all conceivable isomeric forms of the respective radicals. For example, propoxy includes n-propoxy and iso-propoxy, butoxy includes iso-butoxy, seobutoxy and tert-butoxy, etc.

The term "C _3-8 -cycloalkyl" (even if they are part of other radicals) are cyclic alkyl groups having 3 to 8 carbon atoms, by the term "C _3-6 -cycloalkyl" cyclic alkyl groups having 3 to 8 carbon atoms and lower the term "C _5-6 cycloalkyl" means cyclic alkyl groups having 5 to 6 carbon atoms. Examples include: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

The term "C _3-6 -cycloalkenyl" (including those which are part of other groups) means cyclic alkyl groups having 5 or 6 carbon atoms which contain one or two double bonds. Examples include: cyclopentenyl, cyclopentadienyl, cyclohexenyl or cyclohexadienyl.

The term "C _1-6 haloalkyl" (including those which are part of other radicals) is understood as meaning branched and unbranched alkyl groups having 1 to 6 carbon atoms in which one or more hydrogen atoms are selected from the group consisting of fluorine, chlorine or bromine by a halogen atom. preferably fluorine and chlorine, particularly preferably fluorine are exchanged. The term "C _1-4 -haloalkyl" means correspondingly branched and unbranched alkyl groups having 1 to 4 carbon atoms, in which one or more hydrogen atoms have been exchanged analogously as described above. Preferably, C _1-4 haloalkyl. For example:
CH ₂ F, CHF ₂ , CF ₃ ,

The term "C _7-11 -aralkyl" (including those which are part of other groups) means branched and unbranched alkyl groups having 1 to 4 carbon atoms which are substituted by an aromatic ring system having 6 carbon atoms.

For example be for this called: benzyl, 1- or 2-phenylethyl. Unless otherwise stated, can the aromatics are substituted with one or more radicals selected from the group consisting of methyl, ethyl, iso-propyl, tert-butyl, Hydroxy, fluorine, chlorine, bromine and iodine.

Under the term "aryl" (as far as they are Are part of other radicals) are aromatic ring systems with 6 or 10 carbon atoms understood. For example: Phenyl or naphthyl, more preferably aryl, is phenyl.

The term heterocyclic rings ("Het") is understood as meaning five-, six- or seven-membered, saturated or unsaturated heterocyclic rings or 5-10-membered, bicyclic hetero rings, the one, two or three heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen The ring may be linked to the molecule via a carbon atom or, if present, via a nitrogen atom. As examples of five-, six- or seven-membered, saturated or unsaturated heterocyclic rings, mention is made:

So far not mentioned otherwise, For example, a heterocyclic ring may be provided with a keto group. As an example are called.

As an example of 5-10 membered bicyclic hetero rings are mentioned pyrrolizine, indole, indolizine, isoindole, indazole, purine, quinoline, isoquinoline, benzimidazole, benzofuran, benzopyran, benzothiazole, benzothiazole, benzoisothiazole, pyridopyrimidine, pteridine, pyrimidopyrimidine,

Although the term comprises heterocyclic rings ("hetaryl"), the term heterocyclic aromatics defines five- or six-membered heterocyclic aromatics or 5-10-membered bicyclic hetaryl rings the one, two or three heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, can contain and contain as many conjugated double bonds that an aromatic system is formed. The ring may be linked to the molecule via a carbon atom or, if present, via a nitrogen atom. As examples of five- or six-membered heterocyclic aromatic compounds, there are mentioned:

When example for 5-10 membered bicyclic hetaryl rings are called pyrrolizine, Indole, indolizine, isoindole, indazole, purine, quinoline, isoquinoline, Benzimidazole, benzofuran, benzopyran, benzothiazole, benzothiazole, Benzoisothiazole, pyridopyrimidine, pteridine, pyrimidopyrimidine.

The term heterocyclic spiro rings ("spiro") is understood to mean 5-10 membered spirocyclic rings which may optionally contain one, two or three heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, in which case the ring may have a carbon atom or, if present be linked to the molecule via a nitrogen atom. Unless otherwise stated, a spirocyclic ring may be provided with a keto group. As examples are mentioned:

• • Gerade oder verzweigte Kohlenstoffketten, gegebenenfalls unterbrochen durch Heteroatome, gegebenenfalls substituiert mit Ringen, Heteroatomen oder anderen gängigen funktionellen Gruppen.
• • Aromatische oder nicht-aromatische Ringsysteme bestehend aus Kohlenstoffatomen und gegebenenfalls Heteroatomen, die wiederum substituiert sein können mit funktionellen Gruppen.
• • Mehrere aromatische oder nicht-aromatische Ringsysteme bestehend aus Kohlenstoffatomen und gegebenenfalls Heteroatomen, die durch eine oder mehrere Kohlenstoffketten, gegebenenfalls unterbrochen durch Heteroatome, gegebenenfalls substituiert mit Heteroatomen oder anderen gängigen funktionellen Gruppen verknüpft sein können.

In the context of the invention, the term "optionally substituted" is understood to mean the abovementioned group which is optionally substituted by a lower-molecular radical. Low-molecular radicals are understood to be chemically meaningful groups consisting of 1-200 atoms. Preferably, such groups have no negative effect on the pharmacological activity of the compounds. For example, the groups may include:

• • Straight or branched carbon chains, optionally interrupted by heteroatoms optionally substituted with rings, heteroatoms or other common functional groups.
• Aromatic or non-aromatic ring systems consisting of carbon atoms and optionally heteroatoms, which in turn may be substituted with functional groups.
• A plurality of aromatic or non-aromatic ring systems consisting of carbon atoms and optionally heteroatoms, which may be linked by one or more carbon chains, optionally interrupted by heteroatoms, optionally substituted by heteroatoms or other common functional groups.

SYNTHESIS OF REAGENTS

Imidazol-1-yl- [1- (2-trimethylsilanyl-ethoxymethyl) -1H-imidazol-4-yl] -methanone

A Suspension of 1.5 g (63 mmol) of sodium hydride (60% suspension in mineral oil) in 80 ml of DMF is added portionwise with 8 g (63 mmol) of imidazole-4-carboxylic acid methyl ester added and the resulting solution 1 Hour stirred. The reaction mixture is at 5 ° C chilled and 12 ml (70 mmol) of [2- (trimethylsilyl) ethoxy] methyl chloride. After 12 hours, the suspension is mixed with 100 ml of water and with ethyl acetate extracted. The combined organic phases are washed with sodium chloride solution, dried and concentrated. Yield: 16 g

16 g (62 mmol) of the intermediate described above is dissolved in 20 ml Dissolved dioxane and 66 ml of 2 N sodium hydroxide solution and 1.5 hours under reflux cooked. The reaction mixture is acidified with 2N hydrochloric acid and the precipitated solid is filtered off with suction, with water and diethyl ether washed and dried. Yield: 13 g

13 g (55 mmol) of the above-described intermediate are dissolved in 150 submitted dichloromethane and with 22.4 g (138 mmol) of carbonyldiimidazole added. The reaction mixture is left at room temperature for 1 hour touched and then half-saturated Sodium chloride solution washed. The organic phase is dried and evaporated to dryness. Yield: 15 g

Imidazol-1-YL (1-methyl-1H-imidazol-4-yl) -methanone

39.5 g (0.31 mol) of 1-methyl-1H-imidazole-4-carboxylic acid are dissolved in 400 ml of dichloromethane submitted and 115.6 g (0.71 mol) of carbonyldiimidazole added. The Suspension is stirred for 3 hours at room temperature, then with saturated Sodium chloride solution extracted. The water phase is extracted with dichloromethane, the dried combined organic phases and evaporated to dryness. Yield: 60.6 g

1-imidazol-1-YL-2-METHYL-PROPANE-1-ON

12.0 g (0.18 mol) of imidazole are introduced at 0 ° C in 200 ml of chloroform and then treated with 10.8 ml (0.10 mol) of isobutyl chloride. It will Stirred for 1 hour at room temperature. Subsequently the reaction mixture is washed with water, the organic phase dried and evaporated to dryness. Yield: 10.7 g

(R) -imidazole-1-yl- (tetrahydrofuran-2-yl) -methanone

21.8 g (32 mmol) of imidazole are placed in 400 ml of chloroform and on Cooled to 0 ° C. 21.3 g (15.0 mol) of (R) -tetrahydrofuran-2-carbonyl chloride are added dropwise, then stirred for 1.5 hours at room temperature. After cooling down again 0 ° C is the reaction mixture with semisaturated Sodium chloride solution extracted. The organic phase is dried and dried evaporated. Yield: 24.0 g

(S) -imidazole-1-yl- (tetrahydrofuran-2-yl) -methanone

21.8 g (32.0 mmol) of imidazole are placed in 400 ml of chloroform and at 0 ° C cooled. 21.5 g (15.0 mmol) of (S) -tetrahydrofuran-2-carbonyl chloride added dropwise, then stirred for 1.5 hours at room temperature. To re-cooling at 0 ° C the reaction mixture is extracted with half-saturated sodium chloride solution. The organic phase is dried and evaporated to dryness. Yield: 23.5 g

1-imidazol-1-YL-2-METHOXY-ethanone

Analogous for the procedure described above, from 14.9 g (219 mmol) of imidazole and 10 ml (109 mmol) of methoxyacetic acid chloride 5.6 g of the desired Received product.

1-imidazol-1-yl-3-trimethylsilanyl-propinone

0.5 g (3.5 mmol) of 3-trimethylsilylpropionic acid are dissolved in 10 ml of THF and washed with 1.7 g (10.6 mmol) of carbonyldiimidazole are added. The reaction mixture will over Stirred at room temperature overnight and subsequently filtered. The filtrate is diluted with diethyl ether and Washed twice with cold water. The organic phase is over magnesium sulfate dried and concentrated. Yield: 0.4 g

(4-HYDRAZINO-PHENYL) ACETIC ACID HYDROCHLORIDE

15.1 g (10.0 mmol) of 4-aminophenylacetic acid are dissolved in a solution Provided 10.6 g (10.0 mmol) of sodium carbonate in 100 ml of water. It gets to 0 ° C cooled, then added 6.9 g (10.0 mmol) of sodium nitrite in 50 ml of water. This mixture is under cooling to 100 ml conc. hydrochloric acid dropped, then stirred for 0.1 hours. 45.1 g (20.0 mmol) of tin (II) chloride in 40 ml conc. hydrochloric acid be under vigorous Added dropwise, it falls a precipitate. The reaction mixture is left at room temperature for 1 hour touched, then sucked off. The precipitate is washed with water and dried. Yield: 22.0 g

3-Chloro-5-hydrazino-PHENOL

2.1 g (14.3 mmol) of 3-amino-5-chloro-phenol are concentrated in 20 ml of conc. Hydrochloric acid and Dissolve 20 ml of water and at 0 ° C cooled. 1.0 g (15.0 mmol) of sodium nitrite in 4 ml of water are added. Subsequently becomes a solution from 12.1 g (53.5 mmol) of tin (II) chloride in 16 ml of hydrochloric acid slow at -5 ° C dropwise. It is stirred for 1 hour at 0 ° C, then with sodium bicarbonate adjusted to pH 7. The precipitate is sucked off and washed with water. The filtrate is extracted with diethyl ether. The organic phase is dried and evaporated to dryness. The residue is stirred with hexane. Yield: 1.2 g

2-Chloro-4-hydrazino-PHENOL

Analogous to the method described above are from 2.2 g (15 mmol) of 4-amino-2-chlorophenol 2.3 g of hydrazine obtained.

3-Chloro-4-hydrazino-benzoic acid methyl ester

3.0 g (16.0 mmol) of methyl 4-amino-3-chlorobenzoate are in 15 ml conc. hydrochloric acid suspended and cooled to -10 ° C. First becomes a solution from 1.1 g (16.0 mmol) of sodium nitrite in 15 ml of water, then a solution of 16.1 g (71.0 mmol) of stannous chloride in 13.5 ml of hydrochloric acid. One Precipitation falls out. The reaction mixture is basic with 3 molar sodium hydroxide solution put, then sucked off. The precipitate is mixed with dichloromethane and water extracted, the organic phase dried, with charcoal added and evaporated to dryness. The residue is chromatographed cleaned. Yield: 1.4 g (mp: 120 ° C.)

3-Chloro-4-hydrazino-benzoic acid

4.0 g (20.0 mmol) of methyl 3-chloro-4-hydrazino-benzoate are presented and 75 ml of 3 molar sodium hydroxide solution was added. It will be 16 hours Room temperature stirred. Subsequently the reaction mixture is adjusted to pH 6 with glacial acetic acid and the sucked out precipitated solid. This is stirred in diethyl ether. Yield: 2.4 g

(4- bromo-2-trifluoromethyl-phenyl) -hydrazine

A Suspension of 25.6 g (0.11 mol) of 4-bromo-2- (trifluoromethyl) -aniline in 125 ml conc. hydrochloric acid is cooled to -10 ° C and a solution from 7.7 g (0.11 mol) of sodium nitrite in 125 ml of water is added. The reaction mixture is stirred for 3 hours at -10 to -5 ° C, then a solution of 103 g (0.46 mol) of tin (II) chloride dihydrate in 125 ml of conc. Hydrochloric acid added dropwise. It is stirred for 1 hour at -5 ° C. The failed one Precipitate is filtered off with suction and washed with water. The aqueous mother liquor is extracted with petroleum ether, then basic with sodium hydroxide posed. The resulting precipitate is washed with diethyl ether extracted. The organic phase is dried and dried evaporated. Yield: 12.9 g

2,2,2-trifluoro-1- (4-hydrazino-piperidine-1-yl) ethanone trifluoroacetate

100 g (0.65 mol) of 4-piperdinone hydrate hydrochloride and 274.6 ml (1.97 mol) of triethylamine are introduced into 1000 ml of dichloromethane and then at 0 ° C cooled. 182.1 ml (1.31 mol) of trifluoroacetic anhydride become slow added and stirred for 0.5 hours. The reaction mixture is washed with water and sodium bicarbonate solution, the organic Dried phase and evaporated to dryness. The residue is stirred with methyl tert-butyl ether, the precipitate is filtered off with suction, washed and dried. Yield: 106.0 g

106.0 g (0.54 mol) of 1- (2,2,2-trifluoro-acetyl) -piperidin-4-one are dissolved in Dissolved 1000 ml of ethanol and with 71.8 g (0.54 mol) hydrazoic acid tert-butyl ester. The reaction mixture is stirred for 3.5 hours at room temperature, then to Dry evaporated. Yield: 172.0 g

172.0 g (0.56 mol) of N '- [1- (2,2,2-trifluoro-acetyl) -piperidin-4-ylidene] -hydrazine-carboxylic acid tert-butyl ester dissolved in 2000 ml of methanol. 17.0 g of palladium on carbon (10%) are added and at 1 bar Hydrogen hydrogenated. After completion of the hydrogen uptake, the catalyst is removed by suction and the mother liquor evaporated. The residue crystallizes overnight. Yield: 168.0 g

5.0 g (16.1 mmol) of N '- [1- (2,2,2-trifluoro-acetyl) -piperidin-4-yl] -hydrazine-carboxylic acid-tert butyl ester are dissolved in 50 ml of dichloromethane and treated with 6.0 ml (77.9 mmol) trifluoroacetic added. It is stirred for 5 hours at room temperature, then the reaction mixture evaporated. Yield: 6.70 g

4- (4-methyl-piperazin-1-yl) -phenylamine

18.1 g (0.18 mol) of 1-methylpiperazine, 25.5 g (0.18 mol) of 1-fluoro-4-nitrobenzene and 50 g (0.36 mol) of potassium carbonate in 200 ml of dimethylformamide submitted and 15 hours at 130 ° C. touched. After cooling 300 ml of water are added, this precipitates out. The aqueous Phase with the precipitate is cooled, then aspirated and with Washed water. The precipitate is recrystallized from ethanol. Yield: 23.2 g

10.0 g (45 mmol) of 1-methyl-4- (4-nitro-phenyl) -piperazine are dissolved in 250 ml of ethanol, then with 2 g Palladium / carbon (10%) and hydrogenated at 5 bar hydrogen for 2 hours. The reaction mixture is then filtered off with suction, the filtrate is evaporated. The residue is recrystallized from cyclohexane. Yield: 7.7 g

4- (1-METHYL-PIPERIDIN-4-YL) -phenylamine

125 g (0.78 mol) of 4-phenylpiperidine are dissolved in 1300 ml of dichloromethane and washed with Added 149 ml (0.85 mol) of diisopropylethylamine. The reaction mixture is cooled to -5 ° C, then become within 2 hours 120 ml (0.85 mol) of trifluoroacetic anhydride dropwise. Subsequently is left for 1 hour under ice-cooling and stirred for 16 hours at room temperature. There are 400 ml of water added, the phases separated. The organic phase is mixed with water washed, dried and evaporated to dryness. Yield: 193 G

80 g (0.31 mol) 2,2,2-trifluoro-1- (4-phenyl-piperidin-1-yl) -ethanone are dissolved in 400 ml of glacial acetic acid and 200 ml of acetic anhydride and on Cooled to 0 ° C. 1.6 Sodium nitrite is added, then 52 ml (1.24 mol) of fuming nitric acid dropwise. The reaction mixture is allowed to stand at room temperature for 16 hours touched. Subsequently the reaction mixture is poured onto 1200 ml of ice water and washed with 8 N sodium hydroxide solution adjusted to pH 8 (temp. <20 ° C). After addition of dichloromethane, the phases are separated, the aqueous phase with Extracted dichloromethane. The combined organic phases become washed with 0.1 N sodium hydroxide solution and water, dried and dried evaporated. The product is recrystallized from cyclohexane / ethyl acetate. Yield: 47 g

20 g (66.2 mmol) 2,2,2-trifluoro-1- [4- (4-nitro-phenyl) -piperidin-1-yl] -ethanone and 32 g (23.2 mmol) of potassium carbonate are placed in 400 ml of methanol and stirred for 48 hours at room temperature. Subsequently, will the reaction mixture evaporated, the residue with water and dichloromethane extracted. The organic phase is dried and dried evaporated. The hydrochloride is precipitated. Yield: 15 g

6.0 g (24.7 mmol) of 4- (4-nitrophenyl) -piperidine hydrochloride are dissolved in Submitted to 300 ml of tetrahydrofuran and successively with 11 ml (61.8 mmol) Diisopropylethylamine, 5 ml (49.4 mmol) formaldehyde (37% in water) and 13 g (61.8 mmol) of sodium triacetoxyborohydride were added. The reaction mixture is stirred for 16 hours at room temperature, then poured onto water and evaporated. The watery Residue is basified with 2N sodium hydroxide solution and with dichloromethane extracted. The combined organic phases are dried and evaporated to dryness. Yield: 4.5 g

4.3 g (19.5 mmol) of 1-methyl-4- (4-nitro-phenyl) -piperidine are in a Mixture of 60 ml of ethanol and 60 ml of THF dissolved with 2 g of palladium / carbon (10%) and hydrogenated at 1 bar hydrogen. Subsequently, will the reaction mixture is filtered off with suction and the filtrate is evaporated. Yield: 3.5 g

4- (1-cyclopropylmethyl-piperidin-4-yl) -phenylamine

6.0 g (24.7 mmol) of the previously described intermediate 4- (4-nitro-phenyl) -piperidine hydrochloride are presented in 300 ml of tetrahydrofuran and successively with 11 ml (61.8 mmol) of diisopropylethylamine, 3.7 ml (49.4 mmol) of cyclopropanecarboxaldehyde and 13 g (61.8 mmol) of sodium triacetoxyborohydride were added. The reaction mixture is stirred for 3 hours at room temperature, then poured into water and evaporated. The watery Residue is extracted with dichloromethane, the organic phase dried and evaporated to dryness. The aqueous phase is washed with 2N sodium hydroxide solution made basic, then extracted with dichloromethane. The organic Phase is dried and evaporated to dryness. Yield: 5.6 G

3.3 g (12.5 mmol) of 1-cyclopropylmethyl-4- (4-nitro-phenyl) -piperidine dissolved in a mixture of 40 ml of ethanol and 40 ml of THF, with 1.3 g of palladium / carbon (10%) and hydrogenated at 1 bar hydrogen. Subsequently, will the reaction mixture is filtered off with suction and the filtrate is evaporated. Yield: 2.7 g

1,1-DIMETHYL-2-DIMETHYLAMINO-1-YL-ETHYLAMINE AND 1,1-DIMETHYL-2-PIPERIDIN-1-YL-ETHYLAMINE

The Compounds were prepared according to the following references: a) S. Schuetz et al. Arzneimittel-Forschung 1971, 21, 739-763 b) V.M. Belikov et al. Tetrahedron 1970, 26, 1199-1216. c) E.B. butler and McMillan J. Amer. Chem. Soc. 1950, 72, 2978.

Further Amines were modified in to the literature described above Way made as follows.

1,1-dimethyl-2-morpholin-1-yl-ethylamine

8.7 ml of morpholine and 9.3 ml of 2-nitropropane are placed under ice-cooling, 7.5 ml of formaldehyde (37% in water) and 4 ml of a 0.5 mol / L NaON solution. are slowly added dropwise (<10 ° C). After that is 1 h at 25 ° C and 1 h at 50 ° C touched. The solution is treated with water and ether and the aqueous phase extracted 3x with ether. The combined organic phases are dried over sodium sulfate and with hydrochloric acid in dioxane (4 mol / L), the resulting precipitate is aspirated. Yield: 21.7 g of colorless powder

5 g of white Powders are dissolved in 80 ml of methanol and added with the addition of 2 g RaNi with hydrogen at 35 ° C and 50 psi for Treated for 40 minutes. This gives 3.6 g of 1,1-dimethyl-2-morpholin-1-yl-ethylamine.

Analogous For this purpose, the following amine is prepared:

1,1-dimethyl-N-methylpiperazin-1-yl-ethylamine

1.3 DIMORPHOLIN-2-AMINO-PROPANE

5 g 1.3 dimorpholine-2-nitropropane are dissolved in 80 ml of methanol and Add 2 g RaNi with hydrogen at 30 ° C and 50 psi for 5.5 h treated. This gives 4.2 g of 1,3 dimorpholine-2-amino-propane.

TRANS-N, N-dibenzyl-cyclohexane-1,4-diamine

33 g (112 mmol) of 4-dibenzylcyclohexanone are dissolved in 300 ml of methanol, with 17.4 g (250 mmol) of hydroxylamine hydrochloride added and 4 h at Stirred 60 ° C. The solvent is concentrated in vacuo, with 500 ml of water and 50 g of potassium carbonate added and extracted twice with 300 ml of dichloromethane. The organic Phase is dried, concentrated in vacuo, the residue crystallized from petroleum ether, dissolved in 1.5 L of ethanol and on Heated to 70 ° C. It 166 g of sodium are added in portions and until the dissolution of the Sodium under reflux cooked. The solvent is stripped off in vacuo, the residue with 100 ml of water and extracted twice with 400 ml of ether. The org. Phase is washed with water, dried, in vacuo narrowed and over a column isolate the trans isomer (about 1.5 L of silica gel, about 2 L of ethyl acetate 80 / methanol 20 + 2% conc. Ammonia). Yield: 12.6 g

TRANS-N, N-DIMETHYL-CYCLOHEXANE-1,4-DIAMIN (DIMETHANSULFONATE)

4 g (13.6 mmol) of trans-N, N-dibenzyl-cyclohexane-1,4-diamine are in 8.1 g (100 mmol) of formalin solution (37% in water) and 20 ml (43.4 mmol) of formic acid and 2 hours under reflux touched. The Reaction mixture is added to ice-water and treated with conc. ammonia added. It is extracted with ethyl acetate. The organic phase is washed with water, dried and evaporated to dryness. The residue is crystallized from acetone and methanesulfonic acid. Yield: 6 g (mp 203-204 ° C

6 g (11.7 mmol) of trans-N, N-dibenzyl-N ', N'-dimethyl-cyclohexane-1,4-diamine dimethanesulfonate are initially charged in 120 ml of methanol, 1.2 g of palladium / carbon (10%) are added and then hydrogenated at 50 psi and 20 ° C. The reaction mixture will over Drained diatomaceous earth, the mother liquor evaporated. The residue will be crystallized from acetone. Yield: 3.5 g

CIS AND TRANS 4 MORPHOLINO CYCLOHEXYLAMINE

3.9 g (30 mmol) of 4-dibenzylcyclohexanone are dissolved in 100 ml of dichloromethane solved and 3.9 g (45 mmol) of morpholine and 9.5 g (45 mmol) of sodium triacetoxyborohydride Stirred for 12 h at RT. Subsequently is added with water and potassium carbonate, the organic phase separated, dried and the solvent removed in vacuo. Of the Residue will over a silica gel column Purified (about 20 ml of silica gel, about 500 ml of ethyl acetate 90 / methanol 10 + 1% conc. Ammonia). The suitable fractions are in vacuo concentrated. Yield: 6.6 g of cis isomer and 2 g of trans isomer.

Alternatively, the trans-dibenzyl-4-morpholino-cyclohexylamine can be prepared by the following route:
6.8 g (23 mmol) of trans-N, N-dibenzyl-cyclohexane-1,4-diamine are dissolved in 90 ml of DMF and treated with 5 ml (42 mmol) of 2,2'-dichloroethyl ether and 5 g of potassium carbonate for 8 h at 100 ° C stirred. After cooling, 30 ml of water are added, precipitated crystals are filtered off with suction and purified over a short column (about 20 ml of silica gel, about 100 ml of ethyl acetate). The residue is extracted from methanol and conc. HCl crystallized as dihydrochloride. Yield: 7.3 g

7.2 g (16.4 mmol) of trans-dibenzyl-4-morpholino-cyclohexylamine are dissolved in 100 ml of methanol and hydrogenated at 1.4 g Pd / C (10%) at 30-50 ° C. The solvent is removed in vacuo and the residue from ethanol and conc. HCl crystallizes. Yield: 3.9 g (mp 312 ° C)

The cis isomer can be represented analogously.

CIS AND TRANS-4-PIPERIDINO CYCLOHEXYLAMINE

2.0 g (6.8 mmol) trans-1Amino-4-dibenzylaminocyclohexane (see example previously) are dissolved in 50 ml of DMF and with 1.6 g (7 mmol) of 1,5-dibromopentane and 2 g of potassium carbonate 48 Stirred at RT. It is cooled mixed with water, extracted twice with 100 ml of dichloromethane each time, dried and the solvent deducted in vacuo. The residue will over a column Purified (about 100 ml of silica gel, about 500 ml of ethyl acetate 80 / methanol 20 +1% conc. Ammonia). The suitable fractions are in vacuo concentrated and crystallized from petroleum ether. Yield: 1.2 g

1.7 g (4.8 mmol) of trans-dibenzyl-4-piperidino-cyclohexylamine are dissolved in Dissolved 35 ml of methanol and 350 mg Pd / C (10%) at 20 ° C hydrogenated. The solvent is stripped off in vacuo and the residue from ethanol and conc. HCl crystallizes. Yield: 1.1 g

The cis isomer can be represented analogously.

CIS AND TRANS-4- (4-PHENYL-PIPERAZINE-1-YL) -CYCLOHEXYLAMINE

4.1 g (25.3 mmol) of 4-dibenzylcyclohexanone are dissolved in 50 ml of dichloromethane solved and 7.4 g (25.3 mmol) of N-phenylpiperazine and 7.4 g (35 mmol) Sodium triacetoxyborohydride stirred for 12 h at RT. Subsequently, will treated with water and potassium carbonate, the organic phase separated, dried and the solvent deducted in vacuo. The residue will over a silica gel column purified (ethyl acetate 80 / methanol 20 + 0.5% concentrated ammonia). Yield: 1.7 g of cis isomer and 0.27 g of trans isomer.

270 mg (0.61 mmol) of trans -dibenzyl- [4- (4-phenyl-piperazin-1-yl) -cyclohexyl] -amine are dissolved in 5 ml of methanol and 40 mg Pd / C (10%) at 20-30 ° C hydrogenated. The solvent is stripped off in vacuo and the residue from ethanol and conc. HCl crystallizes. Yield: 110 mg

The cis isomer can be represented analogously.

CIS-4- (4-cyclopropylmethyl-piperazin-1-yl) -cyclohexylamine

9.8 g (33.4 mmol) of 4-dibenzylcyclohexanone are dissolved in 100 ml of dichloromethane solved and with 5.6 g (40 mmol) of N-cyclopropylmethylpiperazine and 8.5 g (40 mmol) sodium triacetoxyborohydride for 12 h at RT. Subsequently, will treated with water and potassium carbonate, the organic phase separated, dried and the solvent deducted in vacuo. The residue will over a silica gel column cleaned (about 50 ml of silica gel, about 3 L ethyl acetate 95 / methanol 5 + 0.25% conc. Ammonia). The suitable fractions are in vacuo concentrated. Yield: 8.5 g cis isomer and 2.2 trans isomer.

8.5 g (20 mmol) of cis -dibenzyl- [4- (4-cyclopropylmethyl-piperazin-1-yl) -cyclohexyl] -amine are dissolved in 170 ml of methanol and 1.7 g Pd / C (10%) at 30-50 ° C hydrogenated. The solvent is stripped off in vacuo and the residue from ethanol and conc. HCl crystallizes. Yield: 4.4 g

4- (4,4-DIMETHYL-PIPERIDIN-1-yl) -cyclohexylamine

8.8 g (30 mmol) of 4-dibenzylamino-cyclohexanone, 6.7 g (45 mmol) of 4,4-dimethyl-piperidine hydrochloride and 9.5 g (45 mmol) of sodium triacetoxyborohydride are dissolved in 100 ml of dichloromethane Stirred for 16 hours at room temperature. It will be 200 ml of water and 20 g of potassium carbonate added, the organic phase separated and evaporated to dryness. The residue is chromatographed cleaned. Yield: 0.7 g of cis isomer (Mp .: 125-126 ° C) and 0.4 trans isomer.

0.7 g (1.8 mmol) cis-dibenzyl- [4- (4,4-dimethyl-piperidin-1-yl) -cyclohexyl] -amine are initially charged in 14 ml of methanol, 0.14 g of palladium / carbon (10%) added and at 50 psi and 20 ° C hydrogenated. Subsequently the catalyst is filtered off with suction, the mother liquor is evaporated. Yield: 0.3 g

CIS AND TRANS-4-PYRROLIDIN-1-YL-CYCLOHEXYLAMINE (HYDROCHLORIDE)

0.8 g (21 mmol) of lithium aluminum hydride are dissolved in 50 ml of tetrahydrofuran submitted and 6.2 g (20 mmol) of 4-dibenzylamino-cyclohexanonoxim (representation see above) added dropwise in 62 ml of tetrahydrofuran. Subsequently, the reaction mixture 3 hours under reflux touched. After cooling 0.8 ml of water and 2.4 ml of 15% sodium hydroxide solution are added dropwise. Of the Precipitated precipitate is filtered off with suction and with tetrahydrofuran washed. The mother liquor is evaporated to dryness. Yield: 4.9 g (cis / trans mixture)

2.9 g (10 mmol) cis / trans-N, N-dibenzyl-cyclohexane-1,4-diamine, 2.4 g (11 mmol)) 1,4-dibromobutane and 2.7 g of potassium carbonate are introduced into 70 ml of dimethylformamide and stirred for 48 hours at room temperature. Subsequently, will the reaction mixture was evaporated, the residue extracted with water and dichloromethane. The organic phase is washed with water, dried and added to Dry evaporated. The residue is purified by chromatography, corresponding fractions are combined, evaporated and crystallized from petroleum ether. Yield: 0.8 g cis isomer (mp. 81-82 ° C) and 0.9 g trans isomer (122-124 ° C).

2.2 g (6.1 mmol) trans-dibenzyl- (4-pyrrolidin-1-yl-cyclohexyl) -amine are presented in 40 ml of methanol and 0.4 g of palladium / carbon (10%) added. It is hydrogenated at 5 bar and 20 ° C. Subsequently, will the catalyst is filtered off with suction, the mother liquor with conc. Hydrochloric acid added and evaporated. The residue is stirred with acetone. Yield: 1.20 g

Analogous the cis-isomer can be prepared.

Trans-4- (4-methanesulfonyl-piperazin-1-yl) -cyclohexylamine

14 g (47 mmol) 4-dibenzylamino-cyclohexanone, 8.5 g (51 mmol) 1-methanesulfonyl-piperazine and 17.5 g (78 mmol) Sodium triacetoxyborohydride are dissolved in 250 ml of dichloromethane Stirred for 4 hours at room temperature. Subsequently The reaction mixture is washed with 200 ml of water and 20 g of potassium carbonate added. The organic phase is separated off, dried and added to Dry evaporated. The residue is purified by chromatography. Yield: 4.8 g of trans isomer

4.8 g (11 mmol) trans -dibenzyl- [4- (4-methanesulfonyl-piperazin-1-yl) -cyclohexyl] -amine are dissolved in 100 ml of methanol and 2 g of palladium / carbon (10%). It will be at 50 psi and Hydrogenated at 50 ° C. Subsequently the catalyst is filtered off with suction, the mother liquor is evaporated. Of the Precipitated precipitate is filtered off with suction and washed with diethyl ether. Yield: 2.4 g

CIS AND TRANS-4- (2,6-DIMETHYL-MORPHOLIN-4-YL) -CYCLOHEXYLAMINE DIHYDROCHLORIDE

9 g (31 mmol) 4-dibenzylamino-cyclohexanone, 7.5 g (65 mmol) of cis-2,6-dimethylmorpholine and 9.5 g (45 mmol) sodium triacetoxyborohydride are dissolved in 100 ml Dichloromethane stirred for 2 hours at room temperature. Then be 200 ml of water was added and made basic with potassium carbonate. The organic phase is separated, dried and dried evaporated. The residue is purified by chromatography. Appropriate factions will be combined and evaporated, then the hydrochloride is precipitated. Yield: 10 g of cis isomer (mp: 304-305 ° C) and 3.5 g trans isomer (334-335 ° C).

9.8 g (21 mmol) of cis-dibenzyl- [4- (2,6-dimethyl-morpholin-4-yl) -cyclohexyl] -amine-dihydrochloride are prepared in Submitted to 150 ml of methanol and 2 g of palladium / carbon (10%) was added. It will be at 50 psi and 50 ° C hydrogenated. Subsequently the catalyst is filtered off with suction, the mother liquor is evaporated. Of the precipitate is filtered off with suction and washed with diethyl ether. Yield: 5.5 g

Analogous the trans isomer can be prepared.

CIS AND TRANS 4- (4-METHYL-PIPERAZINE-1YL) -CYCLOHEXYLAMINE

14.7 g (50 mmol) of 4-dibenzylamino-cyclohexanone, 15.8 g (100 mmol) of piperazine-N-carboxylic acid ethyl ester and 10.6 g (50 mmol) of sodium triacetoxyborohydride are dissolved in 200 ml of dichloromethane Stirred for 16 hours at room temperature. Subsequently, will the reaction mixture with 200 ml of water and 20 g of potassium carbonate. The organic phase is separated and evaporated to dryness. The residue is purified by chromatography. Yield: 12 g of cis isomer (m.p. 143-144 ° C) and 4 g of trans isomer (281-282 ° C).

12 g (27.5 mmol) ethyl cis-4- (4-dibenzylamino-cyclohexyl) -piperazine-1-carboxylate in 50 ml of water and 50 ml of conc. Hydrochloric acid, then 72 hours under reflux touched. Subsequently, will the reaction mixture was evaporated, the residue with 200 ml of water and 20 g of potassium carbonate and extracted with dichloromethane. The organic phase is separated, dried and evaporated to dryness. The residue is crystallized from ethyl acetate. Yield: 8.6 g (mp: 100-101 ° C) 4 g (11 mmol) of cis-dibenzyl- (4-piperazin-1-yl-cyclohexyl) -amine are in 5 ml (16.7 mmol) formalin solution (37% in water) and 10 ml (22 mmol) of formic acid, then 2 hours under reflux touched. The reaction mixture is poured onto ice-water and treated with conc. ammonia added. It is extracted with diethyl ether. The organic phase is washed with water, dried and evaporated to dryness. The residue is stirred with petroleum ether, sucked off and dried. Yield: 4.10 g (mp: 93-94 ° C)

4.1 g (11 mmol) cis -dibenzyl- [4- (4-methylpiperazin-1-yl) cyclohexyl] amine are initially charged in 80 ml of methanol, 0.8 g of palladium / carbon (10%) and then hydrogenated at 50 psi and 20 ° C. The reaction mixture will over Drained diatomaceous earth, the mother liquor evaporated. Yield: 1.90 G

The Trans isomer can be prepared analogously.

SYNTHESIS OF INTERCONNECTIONS

INTERMEDIATE 1. N- (7-OXO-4,5,6,7-TETRAHYDRO BENZOTHIAZOL-2-YL) ACETAMIDE

112 g (1.0 mol) of 1,3-cyclohexanedione are suspended in 700 ml of ice water and 51.6 ml (1.0 mol) Bromine added dropwise at 0 ° C within 45 minutes. The suspension is left for 3.5 hours at max. 10 ° C stirred. It is then filtered off with suction and the solid is stirred in 800 ml of water, filtered off, washed with 3 L of water and dried. The resulting solid is recrystallized from ethanol. Yield: 37 g Z2a (mp. 159-160 ° C)

15.5 g (0.2 mol) of thiourea are dissolved in 200 ml of ethanol at room temperature submitted. 37.1 g (0.2 mol) of Z2a are added in portions to this suspension given, then rinsed with 60 ml of ethanol. The gradually arising solution will reflux for 2 hours touched and subsequently evaporated. The residue is extracted with water and diethyl ether, the water phase with sodium basic. The resulting solid is filtered off with suction, washed with water, then stirred with methanol and evaporated to dryness. Yield: 22 g Z3a (mp. 265-268 ° C) 230 ml (2.4 mol) acetic anhydride are initially charged at room temperature, 22 g (0.13 mol) of Z3a was added and stirred under reflux for 3 hours. The Suspension is partly in solution. After cooling by means of Ice / saline, the solid is filtered off with suction, 2x in 150 ml of acetone boiled, filtered off with suction and dried. Yield: 25 g Z4a (mp. 268-272 ° C)

INTERMEDIATE 2. N- (6-FORMYL-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-2-YL) ACETAMIDE

20 g (0.37 mol) of sodium methylate are suspended in 50 ml of dimethylformamide, a suspension of 21 g (0.1 mol) of intermediate compound 1 in 100 ml Dimethylformamide added dropwise. It is stirred for 15 minutes, then at 0 ° C cooled. A mixture of 29.9 ml (0.37 mol) of ethyl formate and 60 ml of benzene is added dropwise and the reaction mixture with another 100 ml of benzene diluted. Gradually come in mind Precipitate and stir at 0 ° C for 3.5 hours. The Suspension is hydrolyzed with 370 ml of 1 molar hydrochloric acid, thereby precipitated solid is sucked off. The two phases of the mother liquor are separated, the water phase extracted with dichloromethane. The resulting organic phase is dried and dried evaporated. The solid and the residue from the extraction are recrystallized from acetonitrile. Yield: 20 g Z5a

INTERMEDIATE 3. N- (6-DIMETHYLAMINOMETHYLENE-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL) ACETAMIDE

30 g (0.13 mol) of intermediate 2 are dissolved in 750 ml of dichloromethane suspended and under ice-cooling with 1 ml of glacial acetic acid and 30 ml of dimethylamine (33% solution in THF). The reaction mixture is left overnight at room temperature touched, concentrated and extracted the remaining solid with cyclohexane. Yield: 33g Z5b

INTERMEDIATE 4. N- [6- (FURAN-2-CARBONYL) -7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 2 are prepared from 2 g (10 mmol) Intermediate 1, 1.6 g (30 mmol) of sodium methylate and 3.8 g (30 mmol) 2-furoic acid methyl ester 1.7 g of product Z5c obtained. (Mp .: 255-256 ° C)

INTERMEDIATE 5. N- (6-BENZOYL-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-2-YL) ACETAMIDE

Analogous for preparation of Intermediate 2 are prepared from 10 g (50 mmol) Intermediate 1, 7.8 g (140 mmol) of sodium methylate and 17.9 ml (140 mmol) of methyl benzoate 3.6 g product Z5d obtained.

INTERMEDIATE 6. N- [6- (FURAN-3-CARBONYL) -7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 2 are prepared from 7.5 g (40 mmol) Intermediate 1, 7.7 g (110 mmol) of sodium methylate and 15.1 ml (110 mmol) of furan-3-carboxylic acid ethyl ester 4.8 g product Z5e obtained.

INTERMEDIATE 7. (2-ACETYLAMINO-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-6-YL) -OXO-ACETIC ACID METHYL ETHER

Analogously to the preparation of intermediate compound 2, from 40 g (190 mmol) of intermediate compound 1, 38 g (0.7 mol) of sodium methylate and 84 g (0.7 mol) of dimethyloxalate 52 g of product Z5f ^Me are obtained.

INTERMEDIATE B. (2-ACETYLAMINO-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-6-YL) -OXO-ACETIC ACID ETHYL ESTER

Analogously to the preparation of intermediate 2, from 73 g (348 mmol) of intermediate compound 1, 54 g (1 mol) of sodium methylate and 152 g (1 mol) of diethyl oxalate 78 g of product Z5f ^Et are obtained.

INTERMEDIATE 9. N- [7-OXO-6- (PYRIDINE-3-CARBONYL) -4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] ACETAMIDE

Analogous for the preparation of intermediate compound 2 are prepared from 4 g (19 mmol) Intermediate 1, 3.9 g (57 mmol) of sodium ethylate and 7.9 g (57 mmol) nicotinic acid methyl ester 3.1 g of product Z5g.

INTERMEDIATE 10. N- (6-ACETYL-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-2-YL) ACETAMIDE

1 g (4.8 mmol) Intermediate 1 are dissolved in 20 ml of THF, cooled to -20 ° C and with 12 ml (12 mmol) of a 1N solution of lithium hexamethyldisilazide in hexane. After 45 minutes be at -20 ° C 0.8 g (7.2 mmol) of 1-imidazol-1-yl-ethanone added and the reaction mixture slowly warmed to room temperature. After one hour at this temperature is with 2 N hydrochloric acid Adjusted pH of 6 and extracted with ethyl acetate. The Combined organic phases are dried and concentrated. Yield: 1.2 g Z5h

INTERMEDIATE 11. N- [6- (1-METHYL-1H-IMIDAZOLE-4-CARBONYL) -7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 10 are prepared from 50 g (0.24 mol) Intermediate 1, 714 ml (0.71 mol) LiHMDS (1 M in THF) and 55 g (0.31 mol) of imidazol-1-yl- (1-methyl-1H-imidazol-4-yl) -methanone 57 g of product Z5i obtained.

INTERMEDIATE 12. N- (6-ISOBUTYRYL-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-2-YL) ACETAMIDE

Analogous for the preparation of intermediate compound 10 are prepared from 4.8 g (23 mmol) Intermediate 1, 71 ml (71 mmol) LiHMDS (1 M in hexane) and 6.3 g (46 mmol) of 1-imidazol-1-yl-2-methyl-propan-1-one 4.4 g of product Z5j.

INTERMEDIATE 13. N- [6- (2-METHOXY-ACETYL) -7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 10 are prepared from 4.2 g (20 mmol) Intermediate 1, 60 ml (60 mmol) LiHMDS (1 M in hexane) and 5.6 g (40 mmol) of 1-imidazol-1-yl-2-methoxy-ethanone Receive 1.8 g of product Z5k.

INTERMEDIATE 14. (R) -N- [7-OXO-6- (TETRAHYDRO-FURAN-2-CARBONYL) -4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 10 are prepared from 10 g (48 mmol) Intermediate 1, 145 ml (145 mmol) LiHMDS (1 M in hexane) and 23.5 g (52 mmol) of (R) -imidazol-1-yl (tetrahydrofuran-2-yl) -methanone 1 g product Z5l received.

INTERMEDIATE 15. (S) -N- [7-OXO-6- (TETRAHYDRO-FURAN-2-CARBONYL) -4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 10 are prepared from 19.4 g (92 mmol) Intermediate 1, 277 ml (277 mmol) LiHMDS (1 M in hexane) and 23.5 g (141 mmol) of (S) -imidazol-1-yl (tetrahydrofuran-2-yl) -methanone 3.1 g product Z5m obtained.

INTERMEDIATE 16. N- [7-OXO-6- (3-TRIMETHYLSILANYL-PROPYNOYL) -4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

Analogous for the preparation of intermediate compound 10 are prepared from 1.1 g (5.7 mmol) Intermediate 1, 17.5 ml (17.5 mmol) LiHMDS (1 M in hexane) and 4.6 g (8.4 mmol) of 1-imidazol-1-yl-3-trimethylsilanyl-propynone 1.1 g of product Z5n.

INTERMEDIATE 17. N- {7-OXO-6- [1- (2-TRIMETHYLSILANYL-ETHOXY-METHYL) -1H-IMIDAZOLE-4-CARBONYL] -4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL} -ACETAMIDE

A solution of 125 ml (0.125 mol) of LHMDS (lithium hexamethyldisilazide) in 100 mL Tetrahydrofuran is treated at -20 ° C with 10.5 g (50 mmol) of intermediate compound 1 and stirred for 0.75 hours. 15.6 g (53 mmol) imidazol-1-yl [1- (2-trimethylsilanylethoxymethyl) -1H-imidazol-4-yl] -methanone are added dissolved in 80 ml of tetrahydrofuran. The resulting Suspension is stirred for 16 hours at room temperature. Subsequently, will with 2N hydrochloric acid hydrolyzed and extracted with methyl tert-butyl ether. The organic Phase is dried and evaporated to dryness. The residue is purified by chromatography. Yield: 1.5 g

INTERMEDIATE 18. 2-ACETYLAMINO-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOLE-6-CARBOXYLIC ACID ETHYLENE:

4.0 g (19 mmol) of intermediate 1 are initially charged in 120 ml of tetrahydrofuran and cooled to -50 ° C. 80 ml (60 mmol) of a 1 molar solution of lithium bis (trimethylsilylamide) in tetrahydrofuran are added and stirred at -30 ° C to -50 ° C for 5 hours. Subsequently, the reaction mixture with 6.5 ml (80 mmol) of ethyl chloroformate, then stirred for 1 hour. There are 50 ml of water added acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The organic phase is dried and evaporated to dryness. The residue is purified by chromatography, combined appropriate fractions and evaporated. The crude product is triturated with diethyl ether and filtered with suction. Yield: 2.3 g Z5o

INTERMEDIATE 19. N- [7-OXO-6- (2,2,2-TRIFLUORO-ACETYL) -4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL] -ACETAMIDE

140 g (1.25 mol) of 1,3-cyclohexanedione are dissolved in 625 ml of chloroform, then Added 145 ml (2.49 mol) of ethanol and 3.4 g (18 mmol) of p-toluenesulfonic acid. The reaction mixture is stirred under reflux for 72 hours, the resulting Water is separated by means of a water separator. Subsequently, will evaporated and the residue mixed with diethyl ether, dried and evaporated to dryness. The residue is purified by distillation. Yield: 166 g

4.6 g (0.115 mol) of sodium hydride are suspended in 250 ml of diethyl ether and at 40 ° C heated. Then a solution from 17 ml (0.14 mol) of ethyl trifluoroacetate and 10 g (71 mmol) of the above-described intermediate in 50 ml of diethyl ether dropwise. It is stirred under reflux for 24 hours. After cooling to Room temperature, 150 ml of water are added and 0.1 hour at Room temperature stirred. The Phases are separated, the organic phase extracted with 5% sodium hydroxide solution. The combined basic water phases are acidified and extracted with ethyl acetate. The ethyl acetate phases are dried and evaporated to dryness. The crude product is chromatographed cleaned. Yield: 4.1 g

0.4 g (1.7 mmol) of the above-described intermediate are dissolved in 10 ml of dioxane and 10 ml of water, at 10 ° C chilled and then treated with 0.3 g (1.9 mmol) of N-bromosuccinimide. It will Stirred for 1 hour at room temperature and subsequently 0.13 g (1.7 mmol) of thiourea was added. It will take 0.5 hours at room temperature and 3 hours at 80 ° C touched. After cooling The reaction mixture is made basic and with dichloromethane extracted. The organic phase is dried and dried evaporated. Yield: 0.2 g

0.2 g (0.76 mmol) of the above-described intermediate are dissolved in 10 ml (0.1 mol) acetic anhydride suspended and then at 100 ° C heated. It is stirred for 3 hours at 100 ° C and 16 hours at room temperature. Subsequently, will the reaction mixture is evaporated, the residue is treated with glacial acetic acid and evaporated. Yield: 0.3 g Z5p

INTERMEDIATE 20. 1-PHENYL-4,5-DIHYDRO-4H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YLAMINE

650 ml of 37% hydrochloric acid are presented in 650 ml of water and 99 g (0.27 mol) of N- (1-phenyl-4,5-dihydro-1H-pyrazolo [3 ', 4': 3,4] benzo [1,2-d] thiazol-7-yl) -acetamide (prepared analogously to Example 1) dissolved therein. The solution is refluxed for 2 hours touched. After cooling to room temperature, carefully basified with sodium hydroxide solution (pH 10-11). The precipitate is sucked off and washed with Stirred methanol. Yield: 66 g (mp. 307-308 ° C)

INTERMEDIATE 21. N- (6-BROM-7-OXO-4,5,6,7-TETRAHYDRO-BENZOTHIAZOL-2-YL) ACETAMIDE

A solution of 2 g (9.5 mmol) of intermediate compound 1 in 60 ml of glacial acetic acid is added Room temperature with a solution of 1.5 g (9.5 mmol) of bromine in 10 ml of glacial acetic acid. The reaction mixture gets slow to 75 ° C heated with a rapid discoloration occurs. It is evaporated to dryness, the residue dissolved in methanol and the Product precipitated by addition of water. Yield: 2.2 g (m.p. 180-182 ° C)

INTERMEDIATE 22. N- (5-FORMYL-6-OXO-4,5,6,6A-TETRAHYDRO-3AH-CYCLOPENTATHIAZOL-2-YL) ACETAMIDE

100 g (0.36 mol) 2-bromo-cyclopentane-1,3-dione (see M. Vanderwalle et al., Bull. Soc. Chim. Belg. 1966, 75, 648-654) are in 370 ml Dissolved dimethylformamide and added with 43 g (0.36 mol) of N-acetylthiourea. It will 3 hours at 75 ° C touched, then at 50 ° C 15 g of activated carbon added. After filtration through diatomaceous earth, the filtrate at 10 ° C chilled and mixed with 1200 ml of water. The failed precipitation is Stirred for 16 hours at room temperature, filtered off with suction and dried. Yield: 20.4 g Z4b (mp 270-272 ° C)

27.6 g (0.51 mol) of sodium methylate are suspended in 50 ml of dimethylformamide and at room temperature, a suspension of 20.0 g (0.10 mol) Z4b in 350 ml of dimethylformamide within 0.25 hours in portions dropwise. The reaction mixture is left at room temperature for 1 hour touched, then on 60 ° C internal temperature heated. It becomes a solution from 41 ml (0.51 mol) of ethyl formate added dropwise in 40 ml of benzene and stirred for 2 hours. After cooling to 5 ° C 100 ml of half-concentrated hydrochloric acid added and diluted to 3000 ml with water. It's falling a precipitate, this is sucked off. The filtrate is with Dichloromethane extracted, the organic phase dried and to Dry evaporated. The residue is stirred with dichloromethane / diethyl ether 1: 5, filtered off with suction and dried. Yield: 12.3 g Z5q

INTERMEDIATE 23. N- (7-FORMYL-8-OXO-5,6,7,8-TETRAHYDRO-4H-CYCLOHEPTATHIAZOL-2-YL) ACETAMIDE

A solution of 7.4 g (90 mmol) of sodium acetate and 9.9 g (79 mmol) of 1,3-cycloheptadiene in 300 ml of glacial acetic acid at 15 ° C with 12.6 g (79 mmol) of bromine and stirred for 30 min. Then be 6.0 g (79 mmol) of thiourea were added and the suspension 5 hours under reflux cooked. The acetic acid is removed in vacuo and the residue in saturated Saline solution added. insoluble Ingredients are sucked off and the aqueous phase with Ether extracted and then made alkaline with ammonia. The failed one The solid is filtered off with suction and dried. Yield: 3.7 g Z3b

3.7 g (20 mmol) of compound Z3b are dissolved in 50 ml of acetic anhydride Heated under reflux for 1 hour. Of the after cooling precipitated solid is filtered off with suction and stirred with ether. Yield: 2.4g Z4c

1.7 g (31 mmol) of sodium methylate are suspended in 20 ml of DMF and treated portionwise with 2.4 g (11 mmol) of the compound Z4c. After 30 minutes, cooled to -5 ° C, a solution of 2.5 ml (31 mmol) Ethyl formate in 10 ml of benzene was added dropwise and stirred at room temperature overnight. It is treated with 70 ml of 1 N hydrochloric acid, the precipitate was filtered off with suction and washed with water. Yield: 2 g Z5r

SYNTHESIS OF COMPOUNDS THE FORMULA 1

EXAMPLE 1 N- (1-P-TOLYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) ACETAMIDE

0.5 g (2 mmol) of intermediate 2 are presented in 7.5 ml of glacial acetic acid, with 0.32 g (2 mmol) of p-tolylhydrazine hydrochloride and 3.5 Hours at 60 ° C heated. The precipitated after the addition of 20 ml of water precipitate is filtered off and recrystallized from acetonitrile with addition of activated carbon. Yield: 0.32 g (mp .: 240-242 ° C)

Example 2: N- [1- (5-fluoro-2-methyl-phenyl) -4,5-dihydro-1H-pyrazolo [3 ', 4': 3,4] benzo [1,2-D] thiazole 7-yl] -acetamide

8.8 mg (0.05 mmol) of 5-fluoro-2-methyl-phenylhydrazine hydrochloride presented in 2.5 ml of ethanol and with 13.3 mg (0.05 mmol) of intermediate compound 3, solved in 2.5 ml of ethanol. The reaction mixture is overnight to 50 ° C heated concentrated and the residue purified by RP-HPLC. Yield: 13.3 mg

EXAMPLE 3: 7-ACETYLAMINO-4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-1-CARBOXYLIC AMID

14 g (59 mmol) Intermediate 2 and 6.7 g (60 mmol) semicarbazide are suspended in 130 ml of water and refluxed for 1 hour heated. The solid is filtered off with suction and purified by chromatography. Yield: 5.6 g (mp .: 265-270 ° C)

EXAMPLE 4: 1- (4-NITRO-PHENYL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YLAMINE

Analogous to Example 1 are from 15 g (63 mmol) of intermediate 2 and 9.8 g (64 mmol) of 4-nitrophenylhydrazine 14 g of product (mp. 300-310 ° C).

7 g (20 mmol) of this intermediate are described as for Intermediate 20 saponified with 90 ml of half-concentrated hydrochloric acid. 5.2 g are obtained Product (mp .: 273-278 ° C).

EXAMPLE 5: N- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -FORMAMID

A Mixture of 0.25 g (0.9 mmol) of intermediate 20 in 8 ml of formic acid phenyl ester is 4 hours at 60 ° C touched. After cooling At room temperature, the precipitate is filtered off with suction and with little Washed acetone. The crude product is made from acetonitrile with addition recrystallized from charcoal. Yield: 0.11 g (mp. 273-277 ° C)

EXAMPLE 6: (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -CARBAMOYLIC ACID METHYL ETERER

00:50 g (1.9 mmol) of intermediate 20 are suspended in 10 ml of pyridine and at 50 ° C heated. 0.6 ml (7.6 mmol) of ethyl chloroformate become slow added and the reaction mixture then stirred at 50 ° C for 48 hours. in the During this time are still twice each 0.6 ml of ethyl chloroformate added. It is stirred for a further 72 hours at room temperature. The The suspension is filtered, the filtrate is mixed with 130 ml of water. The precipitate is filtered off with suction, washed and dried. The Crude product is recrystallized from methanol. Yield: 0.15 g (Mp .: 283-287 ° C)

EXAMPLE 7 4-DIMETHYLAMINO-N- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -BUTYRAMID

In a lockable pressure tubes 0.9 g (4.8 mmol) of freshly prepared 4- (dimethylamino) butyric acid chloride hydrochloride suspended in 30 ml of tetrahydrofuran and heated to 50 ° C. There are 0.6 ml of triethylamine, then, in portions, 0.5 g (1.9 mmol) of intermediate 20 was added. The reaction mixture is stirred at 70 ° C for 71 hours. After cooling to Room temperature, the precipitate is filtered off with suction, washed and in saturated sodium bicarbonate and chloroform. The organic phase is mixed with water washed, dried and evaporated to dryness. The crude product is recrystallized from acetonitrile with the addition of activated carbon. Yield: 0.2 g (mp. 165-166 ° C)

EXAMPLE 8: (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -THIOCARBAMOYLIC ACID S-ETHYL SAMPLE

2.7 g (9.9 mmol) of intermediate 20 are initially charged in 70 ml of pyridine and at 50 ° C heated. 1.6 ml (15 mmol) of ethyl thiochlorofomate are added to this suspension given. The resulting solution is 2 hours at 50 ° C touched. After cooling Room temperature becomes the solution in 700 ml of water, the precipitate sucked off, washed and dried. Yield: 2.2 g

EXAMPLE 9: (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) UREA

In a lockable pressure tubes become a suspension of 0.5 g (1.4 mmol) of the example given in FIG 8 described compound in 9 ml of ethanol and 7 ml (14 mmol) 2 given molar ethanolic ammonia solution. The tube is closed and the reaction mixture a total of 24 hours at 80 ° C touched. After a reaction time of 5 hours, a further 3 ml (6 mmol) of the ammonia solution are added. After cooling at room temperature, the precipitate is sucked off, washed and dried. The crude product is from isopropanol under Addition of activated carbon recrystallized. Yield: 0.16 g (mp. 321-325 ° C)

EXAMPLE 10: 3-METHANESULFONYL-PHENYL) - (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) - AMIN

A Mixture of 0.5 g (2 mmol) intermediate 20, 0.5 g (2 mmol) 1-bromo-3-methansulfonylbenzol, 0.13 g (0.4 mmol) of tri-tert-butylphosphine tetrafluoroborate, 0.2 g (0.2 mmol) tris (dibenzylideneacetone) dipalladium (0) and 0.2 g (2 mmol) of sodium carbonate in 10 ml of DMF is stirred at 90 ° C. for 48 hours. The Reaction mixture is mixed with dichloromethane and water and the watery Phase extracted with dichloromethane. The combined organic phases are dried, concentrated and the remaining residue by column cleaned. Yield: 25 mg

EXAMPLE 11: 1-TERT-BUTYL-3- {4- [3- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] thiazol-7-yl) -ureido] -but-2-ynyl} -urea

A solution of 0.4 g (1.5 mmol) of intermediate 20 in 0.5 ml of pyridine, 3 ml of dichloromethane and 0.5 ml of THF is mixed with 0.4 g (2 mmol) of 4-nitrophenyl chloroformate added and stirred for 2 hours at room temperature. Subsequently, will the reaction mixture with 0.5 g (2.7 mmol) (4-amino-but-2-ynyl) -carbamoylic acid tert-butyl ester and 1 ml of pyridine and stirred for a further 24 hours. After addition of dichloromethane and water becomes the watery Phase extracted with dichloromethane. The combined organic phases are concentrated and the residue residue purified by column chromatography. Yield: 0.2 g (mp .: 196 ° C)

EXAMPLE 12: 1- (4-AMINO-BUT-2-YNYL) -3- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2- d] thiazole-7-yl) -urea

0.1 g (0.2 mmol) of the compound obtained in Example 11 are dissolved in 0.5 ml of trifluoroacetic acid and 2 ml of dichloromethane and overnight at room temperature touched. The reaction mixture is concentrated, the residue taken up in acetone and the product is precipitated by the addition of ethereal hydrochloric acid. Yield: 0.1 g (mp .: 232 ° C)

EXAMPLE 13: 2 - [(1-ETHYL-PYRROLIDIN-2-YLMETHYL) -AMINO] -N- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [ 1,2-d] thiazole-7-yl) -acetamide

0.8 g (6.2 mmol) bromoacetic acid are dissolved in 20 ml of DMF, with 4.9 g of N-cyclohexylcarbodiimide-N'-methyl-polystyrene HL (1.9 mmol / g) and stirred for 30 minutes at room temperature. Subsequently, will a solution of 0.83 g (3.1 mmol) of intermediate 20 was added and overnight touched. The polymer is filtered off with suction and washed with DMF. The filtrate is concentrated and the residue in ethyl acetate / diisopropyl ether rubbed. Yield: 1 g

6 mg (0.048 mmol) of C- (1-ethyl-pyrrolidin-2-yl) -methylamine are dissolved in 0.4 ml of DMF dissolved and treated with 0.02 ml (0.12 mmol) of triethylamine, dissolved in 0.1 ml of DMF. Subsequently 16 mg (0.04 mmol) of a solution the bromide intermediate described above in 0.5 ml of DMF. The reaction mixture is over Night stirred and then concentrated. Yield: 4 mg.

EXAMPLE 14: 2-AMINO-N- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMtD

26 mg of the bromide intermediate obtained in the first part of Example 13 are in 3 ml of 33% aq Ammonia solution suspended and over Stirred at room temperature overnight. The reaction mixture is extracted with dichloromethane and the Concentrated concentrated organic phases. The residue is purified by RP-HPLC cleaned. Yield: 8 mg

EXAMPLE 15: 2-HYDROXY-N- (1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMIDE

26 mg of the bromide intermediate obtained in the first part of Example 13 are suspended in 2 ml of water and 1 ml of DMF and 48 hours at 100 ° C stirred. The Reaction mixture is purified by RP-HPLC. Yield: 9 mg

EXAMPLE 16: N- {1- [4- (MORPHOLIN-4-CARBONYL) -PHENYL] -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] thiazol-7-yl} -acetamide

A solution of 3.5 mg (0.01 mmol) of 4- (7-acetylamino-4,5-dihydro-pyrazolo [3 ', 4': 3,4] benzo [1,2-d] thiazol-1-yl) benzoic acid (prepared analogously to Example 1) in 0.5 ml of DMF with 4 .mu.L (0.03 mmol) of triethylamine and 4 mg (0.01 mmol) of O-pentafluorophenyl-1,1,3,3-tetramethyluronium hexafluorophosphate (PFTU) and stirred for 15 minutes. To this mixture is a solution of 1 mg (0.01 mmol) of morpholine in 0.5 ml of DMF and 12 hours shaken at room temperature. Subsequently 3 mg of polyamine resin HL (0.01 mmol, 200-400 mesh) are added and shaken for another 8 hours. The resin is filtered off and the filtrate in vacuo to dryness evaporated.

EXAMPLE 17: N- {1- [4- (4-AMINO-PIPERIDIN-1-CARBONYL) -PHENYL] -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1, 2-d] thiazole-7-yl} -acetamide

A solution from 0.3 g (0.85 mmol)) of 4- (7-acetylamino-4,5-dihydro-pyrazolo (3 ', 4': 3,4] benzo [1,2-d] thiazol-1-yl) -benzoic acid ( produced analogously to Example 1), 0.32 g (1.00 mmol) of TBTU and 0.75 ml (4.38 g) mmol) of diisopropylethylamine in 25 ml of dichloromethane is added 15 minutes stirred at room temperature and then 0.17 g (0.86 mmol) of 4-N-Boc-aminopiperidine. After 2.5 hours, the reaction mixture is poured onto 25 ml of 5% potassium carbonate solution. The organic phase is dried and concentrated. The residue is treated with ethyl acetate / ether rubbed. Yield: 0.43 mg (mp .: 230 ° C)

00:40 g (0.75 mmol) of the compound described above are dissolved in 10 ml ethereal hydrochloric acid suspended and stirred for 72 hours at room temperature. Of the The solid is filtered off with suction and washed with ether. Yield: 0.35 mg (mp .: 269-270 ° C)

EXAMPLE 18: N- {1- [4- (7-ACETYLAMINO-4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4) BENZO (1,2-D] THIAZOL-1-YL) -BENZOYL ] -piperidin-4-yl} -2-phenylacetamide

A solution from 12 mg (0.09 mmol) phenylacetic acid, 33 mg (0.09 mmol) TBTU and 80 μL (0.47 mmol) of diisopropylethylamine in 2 ml of dichloromethane is added 15 minutes stirred at room temperature and then with 40 mg (0.09 mmol) of those described in Example 17 Compounded. After 2.5 hours, the reaction mixture to 5% potassium carbonate solution cast. The organic phase is dried and concentrated. Of the Residue is with ethyl acetate rubbed. Yield: 34 mg (mp: 271-272 ° C)

EXAMPLE 19: N- [1- (4-METHYLSULFAMOYL-PHENYL) -4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL] -ACETAMIDE

3.0 g (7.7 mmol) of 4- (7-acetylamino-4,5-dihydro-pyrazolo [3 ', 4': 3,4] benzo [1,2-d] thiazol-1-yl) benzenesulfonic acid (prepared analogously to Example 1) are initially charged in 180 ml of phosphorus oxychloride, under cooling 1.6 g (7.7 mmol) of phosphorus pentachloride are added. The suspension is 3 hours at 90 ° C and stirred for 16 hours at room temperature, then on Cooled to 5 ° C. Within of 0.75 hours, the reaction solution is dropped on ice, then extracted with chloroform. The organic phase is dried and evaporated to dryness. Yield: 1.3 g

In a pressure reaction vessel 0.15 g (0.37 mmol) of the sulfonic acid chloride described above and 2 ml (4.0 mmol) of methylamine (2 M in THF), then Stirred for 1 hour at room temperature. The solution is evaporated, the residue crystallized from ethanol. The crude product is recrystallized from methanol. Yield: 0.02 g (mp .:> 260 ° C)

EXAMPLE 20: N- (1-CYCLOHEX-2-ENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMIDE

EXAMPLE 21: N- (2-CYCLOHEX-2-ENYL-4,5-DIHYDRO-2H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMIDE

4.0 g (16.8 mmol) of intermediate 2 are suspended in 50 ml of glacial acetic acid and with 1.6 g (16.8 mol) of hydrazine acetate. It will be 3.5 Hours at 60 ° C touched and subsequently 150 ml of water added. The resulting precipitate is sucked off, washed and dried. Yield: 2.8 g (mp. 261-264 ° C)

0.2 g (0.85 mmol) of the intermediate described above are in 2 ml of dimethylacetamide dissolved and with 0.1 g (2.5 mmol) of sodium hydroxide (mortared). It will be 0.5 Stirred hours at room temperature. Subsequently 12 mg (0.035 mmol) of tetrabutylammonium hydrogen sulfate and 0.09 ml (0.9 mmol) of 3-bromocyclohexene added. It will be 3 hours Stirred at 120 ° C. The The reaction mixture is evaporated, the residue with water and dichloromethane extracted. The combined organic phases are dried and evaporated to dryness. The crude product is chromatographed cleaned. Yield: 0.020 g (mp .: 247-249 ° C, Example 21); Yield: 0.060 g (mp. 213-214 ° C, Example 20)

EXAMPLE 22: N- (1-BENZOYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMIDE

EXAMPLE 23: N- (2-BENZOYL-4,5-DIHYDRO-2H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) ACETAMIDE

0.2 g (0.85 mmol) of the intermediate described in Example 20/21 are suspended in 2 ml of benzene and 0.25 ml (1.80 mmol) of triethylamine and 0.18 ml (1.55 mmol) of benzoyl chloride. The reaction mixture is 2 hours at 75 ° C touched. Subsequently the suspension is filtered off with suction, the precipitate with ethyl acetate and water washed. Yield: 0.12 g (mp. 266-267 ° C, example 23) The mother liquor is evaporated and the residue purified by chromatography. Yield: 7 mg (Example 22)

EXAMPLE 24: N- [1- (2-CHLORO-PHENYL) -3-FURAN-2-YL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2- d] thiazole-7-yl] -acetamide

EXAMPLE 25: N- [2- (2-CHLORO-PHENYL) -3-FURAN-2-YL-4,5-DIHYDRO-2H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2- d] thiazole-7-yl] -acetamide

220 mg (0.7 mmol) intermediate 4 are presented in 3 ml of glacial acetic acid and 179 mg (0.7 mmol) of 2-chloro-phenylhydrazine hydrochloride was added. The suspension is over Night at 50 ° C heated then mixed with 20 ml of water and the resulting precipitate aspirated. The solid is purified by column chromatography (eluent: dichloromethane / methanol 98: 2). Yield: 120 mg (yellow solid, mp. 265-266 ° C, example 24); 38 mg (mp .:> 300 ° C, example 25)

EXAMPLE 26: 4- (7-ACETYLAMINO-3-FURAN-2-YL-4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4) BENZO (1,2-D] THIAZOL-1-YL) -3-chloro-N- (1-methyl-piperidin-4-yl) -benzamide

Analogous to Example 1 receives from 3.3 g (11 mmol) of intermediate 4 and 2.1 g (11 mmol) of methyl 3-chloro-4-hydrazino-benzoate a mixture of the two possible ones Pyrazole isomers by column chromatography be separated. Yield: 0.6 g isomer A; 0.7 g isomer B

0.7 g (1.5 mmol) of isomer B described above are dissolved in 8 ml of dioxane solved and with a solution of 0.1 g (4.4 mmol) of lithium hydroxide in 1 ml of water. To 1.5 hours, the reaction mixture is acidic with 2 N hydrochloric acid placed and the precipitated solid is sucked off. The product is stirred with ether. Yield: 0.5 g

40 mg (0.09 mmol) of the previously described acid, 33 mg (0.09 mmol) HATU and 46 μL Diisopropylethylamine are dissolved in 3 ml of DMF and stirred for 10 minutes. Subsequently, will with a solution of 10 mg (0.09 mmol) of methylaminopiperidine in 2 ml of DMF and the mixture stirred for 2 hours. The reaction mixture is diluted with 15 ml of 5% potassium hydrogen carbonate solution and extracted with dichloromethane. The combined organic phases become washed with water, dried and concentrated. The crude product is by column cleaned. Yield: 24 mg

EXAMPLE 27: N- [1- (2-CHLORO-PHENYL) -3-FURAN-3-YL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2- d] thiazole-7-yl] -acetamide

EXAMPLE 28: N- [2- (2-CHLORO-PHENYL) -3-FURAN-3-YL-4,5-DIHYDRO-2H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2- d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 0.5 g (1.2 mmol) of intermediate 6 and 0.2 g (1.2 mmol) of 2-chloro-phenylhydrazine hydrochloride by column chromatography Purification 102 mg (mp 265-266 ° C, Example 27); 12 mg (mp.> 300 ° C, example 28).

EXAMPLE 29: N- [1- (2-CHLORO-PHENYL) -3-ISOPROPYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-yl] -acetamide

Analogous to Example 1 are from 0.2 g (0.7 mmol) of intermediate 13 and 0.13 g (0.7 mmol) of 2-chloro-phenylhydrazine hydrochloride 0.22 g Product received.

EXAMPLE 30: 4- (7-ACETYLAMINO-3-METHOXYMETHYL-4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-1-YL) -3-CHLORO -N- (1-methylpiperidin-4-yl) -benzamide

Analogous to Example 1 receives from 0.9 g (3.2 mmol) of intermediate 13 and 0.7 g (3.2 mmol) of methyl 3-chloro-4-hydrazino-benzoate 1.2 g of product, its ester function hydrolyzed with 0.2 g (8.4 mmol) of lithium hydroxide analogously to Example 26 becomes.

Then be 50 mg of the resulting acid with methylaminopiperidine as described in Example 26 of an amide coupling subjected.

EXAMPLE 31: 7-ACETYLAMINO-1- (2-CHLORO-PHENYL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-3-CARBOXYLIC ACID METHYL ESTER

Analogous Example 1 are prepared from 1.0 g (3.4 mmol) of intermediate 7 and 0.6 g (3.4 mmol) of 2-chloro-phenylhydrazine hydrochloride 0.8 g of product obtained (mp 294-297 ° C).

EXAMPLE 32: 7-ACETYLAMINO-1- (2-CHLORO-PHENYL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-3-CARBOXYLIC ACID

24 g (1 mol) of the compound described in Example 31 are dissolved in Submitted to 250 ml of dioxane and a solution of 4 g (10 mmol) of lithium hydroxide in 35 ml of water. It will be 16 hours at room temperature touched. Subsequently becomes the solution slightly acidified and the dioxane evaporated. The suspension will diluted with water, then sucked off. The precipitate is dried. Yield: 23 g

EXAMPLE 33: 7-ACETYLAMINO-1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-3-CARBOXYLIC ACID

Analogous to Example 1 are from 30 g (0.1 mol) of intermediate compound 7 and 10.3 ml (0.1 mol) of phenylhydrazine 27 g of product (mp. 298-300 ° C).

From 0.1 g (0.3 mmol) of this is suspended in 12 ml of methanol / water (1: 1) and treated with 0.4 ml of 10% potassium hydroxide solution. After 1.5 hours the reaction mixture is concentrated and the solution with dilute hydrochloric acid acid posed. The resulting precipitate is recrystallized from acetonitrile. Yield: 0.1 g (mp .:> 300 ° C)

EXAMPLE 34: N- [3-AMINO-1- (2-CHLOROPHENYL) -4,5-DIHYDRO-1H-PYRAZOLE [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-7 YL] -acetamide

0.1 g (0.26 mmol) of the compound described in Example 32, 0.06 ml (0.27 mmol) of diphenyl ester phosphoric acid (DPPA) and 0.04 ml (0.29 mmol) of triethylamine are introduced into 5 ml of dimethylacetamide places and stirred for 2 hours at 50 ° C. There are added 0.05 g (0.29 mmol) of p-toluenesulfonic acid and 0.10 ml of water and stirred at 50 ° C for 16 hours. Subsequently, the reaction mixture is purified by chromatography, corresponding fractions combined and evaporated. The residue is crystallized from ethyl acetate / petroleum ether. Yield: 0.02 g

EXAMPLE 35: N- (3-AMINO-1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMIDE

Analogous Example 34 is prepared from 1.5 g of the acid described in Example 33, 1 ml (4.6 mmol) DPPA and 0.6 ml (4.4 mmol) triethylamine in 20 ml dimethylacetamide and subsequently Reaction with 2 g of p-toluenesulfonic acid and 10 ml of water 0.5 g Product received.

EXAMPLE 36: N- [1- (2-CHLOROPHENYL) -3- (3-ISOPROPYL-UREIDO) -4,5-DIHYDRO-1H-PYRAZOLE [3 ', 4': 3,4] BENZO [1,2- d] thiazole-7-yl] -acetamide

1.0 g (3.1 mmol) of the compound described in Example 35 and 1.0 ml (12.1 mmol) of pyridine are dissolved in 10 ml of dichloromethane and 2 ml of tetrahydrofuran suspended and with a solution from 0.8 g (4.0 mmol) of 4-nitrophenyl chloroformate in 5 ml of dichloromethane. It is stirred for 0.5 hours at room temperature. 1.8 ml of this solution is added with 0.05 ml (0.53 mmol) of isopropylamine. It will be 16 Stirred hours at room temperature, subsequently extracted with dichloromethane and water. The organic phase is dried and evaporated to dryness. The residue is chromatographed cleaned, corresponding fractions combined and evaporated. Of the Residue is dissolved in water, with sodium bicarbonate solution basified and sucked out precipitated crystals. Yield: 0.010 g

EXAMPLE 37: N- [1- (2-CHLORO-PHENYL) -3- (3-METHYL-UREIDO) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1, 2-d] thiazole-7-yl] -acetamide

Analogous Example 36 became the desired product by using methylamine receive.

EXAMPLE 38: [7-ACETYLAMINO-1- (2-CHLOROPHENYL) -4,5-DIHYDRO-1H-PYRAZOLE [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-73-YL] CARBAMIC ACID ISOPROPYLESTER

10 g (25 mmol) of the compound described in Example 32, 6.0 ml (27 mmol) phosphoric acid diphenyl ester azide (DPPA) and 4.0 ml (29 mmol) of triethylamine are dissolved in 80 ml of dimethylacetamide submitted and 2 hours at 50 ° C. touched. 9 ml of this solution are mixed with 2 ml of isopropanol and stirred at 50 ° C for 48 hours. Subsequently, will diluted with dichloromethane, then with potassium bisulfate solution and sodium bicarbonate solution washed. The organic phase is dried and dried evaporated. The residue is dissolved in dichloromethane and shaken with 0.3 g of anhydride scavenging resin (MP Anhydride Resin) for 3 hours. After that the resin is filtered off with suction, washed with dichloromethane and the organic Phase evaporated. The residue is purified by chromatography, corresponding fractions combined and evaporated. Yield: 0.09 (mp .: 196 ° C)

EXAMPLE 39: N- [1- (2-CHLORO-PHENYL) -3- (MORPHOLIN-4-CARBONYL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1, 2-d] thiazole-7-yl] -acetamide

0.1 g (0.26 mmol) of the compound described in Example 32 in 5 ml of dichloromethane and 0.1 g (0.28 mmol) of HATU (o-7-azabenzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate) added. Subsequently is treated with 0.09 ml (0.53 mmol) of diisopropylethylamine and 0.03 ml (0.28 mmol) morpholine. The reaction mixture is allowed to stand for 4 hours Room temperature stirred, subsequently extracted with dichloromethane and water. The organic phase becomes dried and evaporated to dryness. The residue is chromatographed cleaned. Appropriate fractions are combined, evaporated, dissolved in water and with sodium bicarbonate solution basic. The precipitated solid is filtered off with suction and dried. Yield: 0.02 g

EXAMPLE 40: 7-ACETYLAMINO-1-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-3-CARBOXYLIC ACID (2-HYDROXY-ETHYL ) -methyl

00:09 g (0.25 mmol) of the compound described in Example 33 presented in 5 ml of dimethylformamide, 0.1 ml (0.75 mmol) of triethylamine and 0.1 g (0.25 mmol) of dimethylamino-pentafluorophenyloxymethylene) -dimethylammonium hexafluorophosphate added. It is stirred for 0.1 hours at room temperature, then 0.02 g (0.25 mmol) 2-methylaminoethanol added. The reaction mixture is allowed to stand at room temperature for 16 hours and 24 hours at 70 ° C touched. Subsequently is evaporated, the residue purified by chromatography. Appropriate fractions are combined and freeze-dried. Yield: 0.04 g

EXAMPLE 41: 7-ACETYLAMINO-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE-3-CARBOXYLIC ACID ETHYL ESTER

Analogous to Example 1 are prepared from 10 g (32 mmol) of intermediate 8 and 1.7 g (33 mmol) of hydrazine hydrate 6.4 g of product.

EXAMPLE 42: N- [1- (2-CHLORO-PHENYL) -3- (1-METHYL-1H-IMIDAZOLE-4-YL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3, 4] benzo [1,2-d] thiazole-7-yl] -acetamide

EXAMPLE 43: N- [2- (2-CHLORO-PHENYL) -3- (1-METHYL-1H-IMIDAZOLE-4-YL) -4,5-DIHYDRO-2H-PYRAZOLO (3 ', 4': 3, 4] benzo [1,2-d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 0.25 g (0.8 mmol) of intermediate 11 and 0.14 g (0.8 mmol) of 2-chloro-phenylhydrazine hydrochloride by column chromatography Purification 100 mg (mp> 300 ° C, example 42) and 4 mg (Example 43).

EXAMPLE 44: N- [1- (2-CHLORO-PHENYL) -3-ISOPROPYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-yl] -acetamide

Analogous to Example 1 are from 0.25 g (0.9 mmol) of intermediate 12 and 0.16 g (0.9 mmol) of 2-chloro-phenylhydrazine hydrochloride by column chromatography Cleaning 0.2 g product obtained.

EXAMPLE 45: 4- (7-ACETYLAMINO-3-ISOPROPYL-4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-1-YL) -3-CHLORO -N- (1-methylpiperidin-4-yl) -benzamide

Analogous to Example 1 receives from 3.25 g (10.7 mmol) of intermediate 12 and 2.14 g (10.7 mmol) 3-chloro-4-hydrazinbenzoesäuremethylester 0.68 g of product, its ester function with 0.1 g of lithium hydroxide is saponified analogously to Example 26. Subsequently, 40 mg of the obtained Acid with Methylaminopiperidine as described in Example 26 of an amide coupling subjected.

EXAMPLE 46: N- [1- (2-CHLORO-PHENYL) -3-METHYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-yl] -acetamide

Analogous to Example 1, from 0.25 g (1.0 mmol) of intermediate 10 and 0.18 g (1.0 mmol) of 2-chloro-phenylhydrazine hydrochloride 0.16 g Product received.

EXAMPLE 47: N- [1- (2-CHLORO-PHENYL) -3-PYRIDIN-3-YL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3, 4] BENZO [1,2- d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 0.1 g (0.3 mmol) of intermediate 9 and 0.06 g (0.3 mmol) of 2-chloro-phenylhydrazine hydrochloride by column chromatography Purification 0.06 g product obtained.

EXAMPLE 48: N- [1- (2-CHLORO-PHENYL) -3-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-yl] -acetamide

Analogous to Example 1 are from 0.3 g (1.0 mmol) of intermediate 5 and 0.18 g (1.0 mmol) of 2-chloro-phenylhydrazine hydrochloride 0.2 g of product obtained (mp .: 232-234 ° C).

EXAMPLE 49: N- [1- (2-CHLORO-PHENYL) -3-PHENYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-YL] -4-dIMETHYLAMINO butyloamide

A Mixture of 0.5 g (1.2 mmol) of the compound obtained in Example 48 in 5 ml of water and 5 ml of hydrochloric acid will reflux for 2 hours cooked. The after cooling the solution precipitated solid is filtered off with suction and dried. Yield: 0.4 g (mp .: 182-185 ° C)

0.1 g of the above-described intermediate are dissolved in 5 ml of dichloromethane suspended, treated with 0.16 ml (1.2 mmol) of triethylamine and 15 Stirred minutes at room temperature, being a solution arises. This gets to 40 ° C heated and 0.17 g (0.9 mmol) of 4-dimethylamino-butanoic acid chloride. The reaction mixture is 3 hours at 40 ° C touched and subsequently with 5% sodium carbonate solution and Washed water. The organic phase is dried, concentrated and the residue recrystallized from isopropanol. Yield: 11 mg (mp 290-291 ° C)

EXAMPLE 50: N- [3- (1H-IMIDAZOLE-4-YL) -1- (2-TRIFLUOROMETHYL-PHENYL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [ 1,2-d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 1.36 g (3.1 mmol) of intermediate 17 and 0.55 g (3.1 mmol) of 2-trifluoromethyl-phenylhydrazine 1.26 g of intermediate receive. Of this, 75 mg (0.13 mmol) in 0.65 ml (0.65 mmol) Tetrabutylammonium fluoride solution (1 M in THF) and boiled under reflux for 5.5 hours. The solution will be with 5 ml of pH 7 buffer solution diluted, diluted with 10 ml of water and extracted with ethyl acetate. The organic phase is washed with buffer solution, dried and evaporated to dryness. The residue is chromatographed cleaned, appropriate fraction with diethyl ether. Yield: 5 mg (mp .:> 300 ° C)

EXAMPLE 51 N- [1- (2-CHLORO-PHENYL) -3- (1H-IMIDAZOLE-4-YL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [ 1,2-d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 0.6 g (1.4 mmol) of intermediate 17 and 0.3 g (1.4 mmol) of 2-chlorophenylhydrazine hydrochloride 0.5 g of intermediate receive. This is mixed with 1.7 ml (1.7 mmol) of tetrabutylammonium fluoride solution (1 M in THF), as described in Example 50, into the desired product. Yield: 35 mg (mp .: 287-288 ° C)

EXAMPLE 52: (R) -N- [1- (2-CHLORO-PHENYL) -3- (TETRAHYDRO-FURAN-2-YL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3, 4] benzo [1,2-d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 0.25 g (0.8 mmol) of intermediate 14 and 0.15 g (0.8 mmol) of 2-chloro-phenylhydrazine hydrochloride by column chromatography Purification 0.23 g product obtained.

EXAMPLE 53: (R) -4- [7-ACETYLAMINO-3- (TETRAHYDRO-FURAN-2-YL) -4,5-DIHYDRO-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2- d] thiazole-1-yl] -3-chloro-N-pyridin-4-ylmethyl-benzamide

Analogous to Example 1 receives from 1.25 g (4.1 mmol) of intermediate 14 and 0.82 g (4.1 mmol) of methyl 3-chloro-4-hydrazinobenzoate 1.16 g of product, its ester function is saponified with 0.2 g of lithium hydroxide analogously to Example 26. Then be 50 mg of the resulting acid with 4-picolylamine as described in Example 26 of an amide coupling subjected.

EXAMPLE 54: (S) -N- [1- (2-CHLORO-PHENYL) -3- (TETRAHYDRO-FURAN-2-YL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3, 4] benzo [1,2-d] thiazole-7-yl] -acetamide

Analogous to Example 1 are from 0.1 g (0.3 mmol) of intermediate 15 and 0.05 g (0.3 mmol) of 2-chloro-phenylhydrazine hydrochloride by column chromatography Purification 0.08 g product obtained.

EXAMPLE 55: N- [1- (2-CHLORO-PHENYL) -3-TRIMETHYLSILANYLETHINYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-yl] -acetamide

Analogous to Example 1 are from 0.1 g (0.3 mmol) of intermediate compound 16 and 0.06 g (0.3 mmol) of 2-chlorophenylhydrazine hydrochloride by column chromatography Purification 0.02 g product obtained.

EXAMPLE 56: N- (3-ETHINYL-1- (2-TRIFLUOROMETHYL-PHENYL) -4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOLE 7-yl] -acetamide

Analogously to Example 1, 0.05 g of product are obtained from 0.3 g (0.9 mmol) of intermediate compound 16 and 0.16 g (0.9 mmol) of 2- (trifluoromethyl) phenylhydrazine after purification by column chromatography. From this 0.04 g are placed in 5 ml of THF and mixed with 0.1 ml (0.1 mmol) of tetrabutylammonium fluoride solution (1 M in THF). It is stirred for 0.5 hours at room temperature and then water was added. The aqueous phase is extracted with ethyl acetate, the organic phase is washed with water and 1 N hydrochloric acid. The organic phase is dried and evaporated to dryness. The residue is purified by chromatography. Yield: 0.012 g

EXAMPLE 57: N- (1-PHENYL-3-TRIFLUOROMETHYL-4,5-DIHYDRO-1H-PYRAZOLO [3 ', 4': 3,4] BENZO [1,2-D] THIAZOL-7-YL) -ACETAMIDE

Analogous to Example 1 are from 0.3 g (1.0 mmol) of intermediate 19 and 0.15 g (1.0 mmol) phenylhydrazine hydrochloride 0.04 g product receive.

EXAMPLE 58: N- [4- (4-CHLORO-PHENYL) -4,7-DIHYDRO-3-THIA-1,4,5-TRIAZA-CYCLOPENTA [A] PENTALENE-2-YL] -ACETAMIDE

00:50 g (1.56 mmol) of intermediate 22 are suspended in 8 ml of glacial acetic acid, with 0.34 g (1.88 mmol) of 4-Chlorphenylhydrazin hydrochloride. It will take 1.5 hours at 60 ° C touched, then cooled to room temperature. After adding 50 ml of water drops a precipitate. This is stirred for 0.1 hours at 5 ° C, filtered with suction and recrystallized from methanol. Yield: 0.19 g (mp. 296-305 ° C)

EXAMPLE 59: 4-PHENYL-4,7-DIHYDRO-3-THIA-1,4,5-TRIAZA-CYCLOPENTA [A] PENTALENE-2-YL-AMINE

2.9 g (8.71 mmol) N- (4-phenyl-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta [a] pentalen-2-yl) -acetamide (mfd analogous to Example 58 from intermediate compound 22) are dissolved in 20 ml Water and 20 ml of 32% hydrochloric acid suspended and stirred under reflux for 2 hours. After cooling to Room temperature is extracted with diethyl ether and the water phase basic. The resulting precipitate becomes 0.25 hours at 5 ° C touched, sucked off and dried. The crude product is dissolved in 150 ml of tetrahydrofuran suspended and concentrated with 5 ml. Hydrochloric acid, then 16 hours at 60 ° C touched.

To cooling at 5 ° C the precipitate is filtered off with suction and dried. Yield: 1.8 g

EXAMPLE 60) 4-O-TOLYL-3A, 4,7,7A-TETRAHYDRO-3-THIA-1,4,5-TRIAZA-CYCLOPENTA [A] PENTALENE-2-YLAMINE

Analogous Example 59 is prepared from 140 mg (0.5 mmol) of N- (4-o-tolyl-4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta [a] pentalen-2-yl) -acetamide (prepared analogously to Example 58) in 1 ml of water and 1 ml of hydrochloric acid by column chromatography Purification 14 mg product.

EXAMPLE 61: 4-DIMETHYLAMINO-N- (4-PHENYL-4,7-DIHYDRO-3-THIA-1,4,5-TRIAZA-CYCLOPENTA [A] PENTALENE-2-YL) BUTANIC ACID AMID

0.5 g (1.72 mmol) of the compound described in Example 59 suspended in 25 ml of dichloromethane, with 0.8 ml (6.02 mmol) of triethylamine offset and to the reflux heated. 0.8 g (4.30 mmol) of 4-dimethylamine-butyric acid chloride hydrochloride are added dropwise in 5 ml of dichloromethane within 0.1 hours and the reaction mixture stirred for 16 hours under reflux. After cooling to Room temperature, the precipitate is filtered off and the filtrate with 5% sodium bicarbonate solution and water washed. The organic phase is dried and added to Dry evaporated. The residue is triturated with diethyl ether and filtered with suction. Yield: 0.2 g (m.p .: 218-222 ° C)

EXAMPLE 62) N- [4- (2-CHLORO-PHENYL) -4,7-DIHYDRO-3-THIA-1,4,5-TRIAZA-CYCLOPENTA [A] PENTALENE-2-YL] -4-DIMETHYLAMINO BUTANIC ACID AMID

Analogous Example 59 is prepared from 3.9 g (11.7 mmol) of 4- (2-chlorophenyl) -4,7-dihydro-3-thia-1,4,5-triaza-cyclopenta [a] pentalen-2-ylamine (prepared analogously to Example 58) 2.5 g of a compound obtained, from the 0.7 g (1.7 mmol) corresponding to Example 61 to 0.2 g of product be reacted (mp .: 167-170 ° C).

EXAMPLE 63 PIPERIDINE-1-CARBOXYLIC ACID (4-PHENYL-4,7-DIHYDRO-3-THIA-1,4,5-TRIAZA-CYCLOPENTA [A] PENTALENE-2-YL) AMID

A Suspension of 2.3 g (8 mol) of the compound obtained in Example 59 in 60 ml of pyridine is heated to 50 ° C heated, then treated with 1.6 ml (10 mmol) Ethylchlorthioformiat. The reaction mixture is stirred for 12 hours at 70 ° C, then in Stirred 600 ml of water. The resulting precipitate is filtered off with suction and with water and ether washed. Yield: 2.3 g (mp .: 142-145 ° C)

In a lockable Pressure tubes 0.3 g (0.7 mmol) of the previously described compound in FIG. 8 ml of ethanol, treated with 1 ml (10.5 mmol) of piperidine and stirred under reflux for 16 hours. To cooling down at room temperature, the reaction mixture is evaporated. The crude product will over Silica gel filtered. The residue is triturated with 20 ml of water and 5 drops of acetonitrile, filtered with suction and dried. Yield: 0.07 g (mp .: 120-125 ° C)

EXAMPLE 64: N- (8- (4-HYDROXY-PHENYL) -4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2-YL] -ACETAMIDE

2.7 g (11.3 mmol) Intermediate 2 and 1.7 g (12.6 mmol) 4-hydroxybenzamidine are suspended in 6 ml of pyridine and heated at 100 ° C for 2 hours. The Reaction mixture is mixed with ether and the precipitate Stirred with methanol. Yield: 2.1 g

EXAMPLE 65: 4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLINE-2,8-DIAMINE

10 g (42 mmol) Intermediate 2, 4 g (42 mmol) guanidine hydrochloride and 2.2 g (21 mmol) of sodium carbonate in 30 ml of amyl alcohol suspended and heated under reflux for 1 hour on a water separator. The Reaction mixture is concentrated, the residue several times with xylene distilled off and then purified by chromatography. The product is taken up in methanol and with methanolic hydrochloric acid precipitated as hydrochloride. Yield: 1.2 g (mp .: 293-300 ° C)

EXAMPLE 66: N- (8-ACETYLAMINO-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2-YL) ACETAMIDE

0.5 g (1.7 mmol) of the compound described in Example 65 and 0.4 g (4.6 mmol) of sodium acetate are dissolved in 15 ml of acetic anhydride suspended and 2 hours at 100 ° C touched. It is at 5 ° C cooled, the resulting solid was filtered off with suction and washed with water. The Crude product is stirred with methanol. Yield: 0.4 g (mp .:> 310 ° C)

EXAMPLE 67: N- (6-OXO-8-PHENYL-4,5,6,7-TETRAHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL) -ACETAMIDE

In a glass pressure tube Add 0.1 g (0.35 mmol) of intermediate 18 and 0.1 g (0.83 mmol) of benzamidine presented in 1 ml of pyridine and heated to 160 ° C for 4 hours. The solvent is evaporated, the residue gets hot Stirred ethanol and sucked off. Yield: 14 mg

EXAMPLE 68: N- (8-ETHYLSULFANYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL) ACETAMIDE

10.0 g (42 mmol) Intermediate 2 and 14.6 g (80 mmol) of ethylisothiourea hydrobromide are suspended in 20 ml of pyridine and then stirred at 110 ° C for 3 hours. To cooling down At room temperature, the reaction mixture with a little methanol triturated, filtered off with suction and dried. Yield: 10.2 g

EXAMPLE 69: N- (8-ETHANSULFONYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL) ACETAMIDE

10.6 g (34.6 mmol) of the compound prepared under Example 68 dissolved in 100 ml of dichloromethane, 17.0 g (75.9 mmol) of m-chloroperbenzoic acid were added and then 24 hours stirred at room temperature. The reaction mixture is diluted with dichloromethane and extracted with sodium carbonate solution. The organic phase is washed with water, dried and added to Dry evaporated. Yield: 8.8 g

EXAMPLE 70: [1- (2-ACETYLAMINO-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-8YL) -PIPERIDIN-3-YLMETHYL] -carbamic Acid-TERT-BUTY-ETER

0.2 g (0.6 mmol) of the compound prepared under Example 69 and 0.25 g (1.2 mmol) of piperidin-3-ylmethyl-carbamic acid tert-butyl ester presented in 2 ml of N-methyl-pyrrolidine and refluxed for 24 hours touched. Subsequently The reaction mixture is washed with dilute potassium carbonate solution and Dichloromethane is added and extracted. The organic phase becomes washed with water, dried and evaporated to dryness. Of the Residue is purified by chromatography. Yield: 0.03 g (mp. 250-255 ° C)

EXAMPLE 71: 8-PHENYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLINE-2-YLAMINE

9.0 g (28 mmol) N- (8-phenyl-4,5-dihydro-thiazolo [4,5-h] quinazolin-2-yl) -acetamide (prepared analogously to Example 64) are semiconcentrated in 130 ml hydrochloric acid 2 hours under reflux heated. After cooling the reaction mixture is made basic, the precipitate precipitated sucked off and dried. Yield: 7.3 g

EXAMPLE 72: N * 8 *, N * 8 * -DIMETHYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLINE-2,8-DIAMINE

Analogous to example 71 from 0.20 g (0.7 mmol) of N- (8-dimethylamino-4,5-dihydro-thiazolo [4,5-h] quinazolin-2-yl) -acetamide (obtained analogously to Example 58) 0.14 g of product can be obtained (Mp .: 292-295 ° C)

EXAMPLE 73: N- (8-PHENYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL) PROPIONIC ACID AMID

0.3 g (1.1 mmol) of the compound obtained in Example 71 are dissolved in 15 ml of dichloromethane, with 0.4 ml (2.5 mmol) of triethylamine offset and to the slight reflux heated. 0.2 ml (2.3 mmol) of propionic acid chloride are added and 5 hours under reflux touched. After cooling to room temperature, the reaction solution with sodium bicarbonate and water, dried and evaporated to dryness. Of the Residue is stirred with diethyl ether and sucked off. Yield: 0.2 g (mp. 274-275 ° C)

EXAMPLE 74: 4-DIMETHYLAMINO-N- (8-PHENYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2-YL) BUTTERIC ACID AMID

Analogous Example 73 are prepared from 0.15 g (0.5 mmol) of that obtained in Example 71 Compound, 1 ml of triethylamine and 0.2 g (1.3 mmol) of 4-dimethylamine-butyric acid hydrochloride 0.03 g product obtained.

EXAMPLE 75: N- (8-PHENYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2-YL) -FORMAMID

In a glass pressure tube 0.2 g (0.71 mmol) of the compound described in Example 71 and 2.5 ml (22.7 mmol) phenyl formate submitted and 16 hours at 80 ° C. touched. Subsequently, will the reaction mixture was evaporated and the residue with diethyl ether / ethanol rubbed. Yield: 0.17g (mp. 304-306 ° C)

EXAMPLE 76: MORPHOLIN-4-CARBOXYLIC ACID (8-PHENYL-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2-YL) AMID

2.5 g (8.9 mmol) of the compound obtained in Example 71 are dissolved in Submitted to 50 ml of pyridine and heated to 50 ° C. 1.5 ml (13.8 mmol) Ethyl chlorothiol formate are added and stirred at 50 ° C for 20 hours. To cooling down At room temperature, the reaction solution is added to water and extracted with dichloromethane. The organic phase is dried and evaporated to dryness. The residue is treated with diethyl ether crystallized. Yield: 1.0 g

In a glass pressure tube 0.2 g (0.54 mmol) of the intermediate described above and 0.1 submitted g (1.15 mmol) morpholine in 5 ml of ethanol and then 16 Hours at 80 ° C touched. After cooling At room temperature, the precipitate is filtered off with suction and dried. Yield: 0.14 g (mp 165-168 ° C)

EXAMPLE 77: 4- (2-ACETYLAMINO-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-8YL) -N, N-DIMETHYL BENZAMIDE

1.0 g (3.8 mmol) of intermediate 2 and 0.8 g (3.1 mmol) of carbamimidoyl-benzoic acid methanesulfonate are presented in 5 ml of pyridine and heated to 180 ° C for 5 hours. After cooling At room temperature, the reaction mixture is stirred with ethanol and aspirated. Yield: 0.6 g

0.1 g (0.27 mmol) of the previously prepared compound and 0.1 g of O- (1H-benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate (TBTU) are placed in 2 ml of dimethylformamide, with 0.2 ml of diisopropylethylamine mixed and stirred for 0.5 hours at room temperature. There are 0.2 ml (4.0 mmol) dimethylamine (2 M in THF) was added and a further 16 hours stirred at room temperature. The resulting suspension is dissolved with dimethylformamide, then purified by RP-HPLC. Appropriate fractions are combined and freeze-dried. Yield: 0.04 g (mp .:> 300 ° C.)

EXAMPLE 78: N- [8- (2-OXO-PYRROLIDIN-1-YL) -4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2-YL] -ACETAMIDE

In a glass pressure tube 2.0 g (8.4 mmol) of intermediate 2 and 2.4 g (16.8 mmol) of 4-guanidine-butyric acid in 30 ml of pyridine and then heated to 190 ° C for 20 hours. The reaction mixture is evaporated, the residue boiled up with methanol and insoluble Components filtered off. From the mother liquor is the crude product precipitated as hydrochloride, sucked off and dried. The solid is purified by column chromatography. Yield: 0.02 g (mp .:> 160 ° C.)

EXAMPLE 79: N- [8- (3-AMINOMETHYL-PIPERIDIN-1YL) -4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL] -ACETAMIDE

0.05 g (0.1 mmol) of the compound described under Example 70 are dissolved in 5 ml of ethereal salt acid dissolved and stirred for 16 hours at room temperature. The resulting solid is filtered off with suction, washed with diethyl ether and dried. Yield: 0.035 g

EXAMPLE 80: N- {8- [3- (ISOPROPYLAMINO-METHYL) -PIPERIDIN-1YL] -4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL} -ACETAMIDE

0.2 g (0.5 mmol) of the compound obtained in Example 79, 0.05 ml (0.6 mmol) of acetone and 0.02 g (0.5 mol) of sodium borohydride are dissolved in methanol solved and 0.5 hours at 40 ° C touched. There are again the same amounts of acetone and sodium borohydride added and stirred for a further 16 hours at room temperature. Subsequently, will the reaction mixture was evaporated, the residue with dichloromethane and Extracted water. The organic phase is dried and added to Dry evaporated. The crude product is triturated with diethyl ether and sucked off. Yield: 0.040 g

EXAMPLE 81: N- {8- [ACETYL- (2-DIMETHYLAMINO-ETHYL) -AMINO] -4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL} -ACETAMIDE

0.4 g (1.2 mmol) of the compound obtained in Example 69 and 0.4 ml (4.5 mmol) N * 1 *, N * 1 * -dimethylethane-1,2-diamine are dissolved in 5 ml N-methylpyrollidine presented and stirred at 90 ° C for 48 hours. The Reaction mixture is extracted with dichloromethane and 10% potassium carbonate solution. The organic phase is dried and evaporated to dryness. Yield: 0.08 g

00:08 g (0.28 mmol) of the compound described above are dissolved in 5 ml (49 mmol) acetic anhydride solved and 1 hour at 140 ° C touched. The reaction mixture is evaporated, the residue is stirred with acetonitrile and aspirated. Yield: 0.07 g

EXAMPLE 82: (2-ACETYLAMINO-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLINE-8YL) PROP-2-INYL-CARBAMIC ACID TERT BUTYL ETER

0.34 g (2.2 mmol) of tert-butyl prop-2-ynylcarbamate are initially charged in 3 ml of tetrahydrofuran and cooled to -30 ° C. 2.3 ml (4.4 mmol) of 2 M isopropylmethylmagnesium chloride solution in tetrahydrofuran are slowly added dropwise and stirred for 0.5 hours. Thereafter, a solution of 0.34 g (1.0 mmol) of the compound described in Example 69 in 4 ml of tetrahydrofuran at -10 ° C is added and it is stirred for 4 hours, being warmed to room temperature. The reaction mixture is extracted with water and dichloromethane, the organic phase dried and evaporated to dryness. The residue is triturated with diethyl ether. Yield: 0.18 g

EXAMPLE 83: N- (8-PROP-2-INYLAMINO-4,5-DIHYDRO-THIAZOLO [4,5-H] CHINAZOLIN-2YL) ACETAMIDE

00:05 g (0.13 mmol) of the compound obtained in Example 82 are dissolved in 5 ml of ethereal hydrochloric acid solved and stirred for 16 hours at room temperature. The resulting solid is filtered off, triturated with diethyl ether / acetone 9: 1 and again aspirated. Yield: 0.03g

EXAMPLE 84: N- [1- (4-METHOXY-PHENYL) -1,4,5,6-TETRAHYDRO-9-THIA-1,2,7-TRIAZA-CYCLOPENTA [E] AZULEN-8-YL] -ACETAMIDE

A solution of 0.25 g (1 mmol) of intermediate 23 and 0.18 mg (1 mmol) of 4-methoxyphenylhydrazine hydrochloride in 5 ml of glacial acetic acid is 2 h at 60 ° C. heated. It is mixed with water and extracted three times with ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The residue will be first by column chromatography (Eluent: dichloromethane / methanol 95: 5), then purified by RP-HPLC. Yield: 0.07 g

EXAMPLE 85: N- (8-NITRO-4,5-DIHYDRO-3H-1Λ * 4 * -NAPHTHO [2,1-D] THIAZOL-2-YL) ACETAMIDE

0.8 g (10.0 mmol) of sodium acetate and 1.9 g (9.40 mmol) of 7-nitro-3,4-dihydro-1H-naphthalene-2-one (prepared according to D.E. Nichols et al., J. Med. Chem. 1989, 32, 2128-2134) in 40 ml of acetic acid and dissolved Cooled to 15 ° C. It 0.5 g (3.19 mmol) of bromine are added and the mixture is stirred for 0.1 hours until the bromine completely has reacted. Thereafter, 0.8 g (10.5 mmol) of thiourea are added. The reaction mixture is heated for 0.25 hours to 60 ° C, then filtered with suction and washed. The crystals are recrystallized from ethanol. Yield: 0.75 g (mp .: 247-248 ° C)

0.75 g (3.0 mmol) of the compound described above are dissolved in 5 ml (49 mmol) of acetic anhydride and 0.1 hours under reflux touched. After cooling At room temperature, the resulting precipitate is removed by suction, washed with ethyl acetate and diethyl ether and dried. Yield: 0.8 g (mp .:> 315 ° C)

EXAMPLE 86: N- (8-ACETYLAMINO-4,5-DIHYDRO-3H-1Λ * 4 * -NAPHTHO [2,1-D] THIAZOL-2-YL) ACETAMIDE

0.5 g (1.7 mmol) of the compound described in Example 85 in 10 ml of acetic acid suspended and mixed with 2 g of iron powder. The reaction mixture gets to 70 ° C heated and stirred for 0.1 hours. Subsequently is filtered off with suction and the mother liquor is evaporated. The residue Water is added, the precipitate is filtered off with suction, washed and dried. Yield: 0.4 g

0.1 g (0.4 mmol) of the previously described compound, 0.1 g (1.0 mmol) acetic anhydride and 0.1 ml of triethylamine are introduced into 5 ml of dichloromethane and Stirred for 1 hour at room temperature. Subsequently the reaction mixture is washed with 2 N hydrochloric acid and 2 N sodium hydroxide solution. The organic phase is dried and evaporated to dryness. The residue is crystallized from ethyl acetate. Yield: 0.07 g (mp: 181-183 ° C)

EXAMPLE 87: N- (2-ACETYLAMINO-4,5-DINYDRO-NAPHTHO [2,1-D] THIAZOL-8-YL) ISOBUTTERIC ACID AMID

Analogous to Example 86 from 0.1 g (0.4 mmol) of the intermediate described there, 0.045 g (0.4 mmol) isobutyric acid chloride and 0.1 ml of triethylamine in 5 ml of dichloromethane 0.075 g of product be (m .: 272-274 ° C)

EXAMPLE 88: N- (8-ISOPROPYLAMINO-4,5-DIHYDRO-3H-1Λ * 4 * -NAPHTHO [2,1-D] THIAZOL-2-YL) ACETAMIDE

00:15 g (0.58 mmol) of the intermediate described in Example 86, 1.0 g (17.2 mmol) of acetone and 0.4 g of sodium triacetoxyborohydride placed in 10 ml of dichloromethane and stirred for 4 hours at room temperature. The Reaction mixture is mixed with 50 ml of water and 2 g of potassium carbonate, the organic phase separated, dried and evaporated to dryness. The residue is purified by chromatography, then crystallized from diethyl ether. Yield: 0.11 g (mp 183-184 ° C)

Below are exemplified compounds that can be represented by one of the synthetic routes shown above. All melting points (m _p ) are given in ° C. In order to determine the inhibitory activity of the compounds on the PI3Kγ, an in vitro kinase assay was established based on the transfer of the terminal γ-phosphate of ATP to phosphatidylinositol-4,5-bisphosphate (PIP ₂ ). As enzyme activity, the Gβ ₁ γ ₂ -His stimulated PI3Kγ was used. The expression and purification of Gβ ₁ γ ₂ -His and p101-GST / p110γ from Sf9 cells (spodoptera frugiperda 9) has been previously (Maier et al., J. Biol. Chem. 1999 (274) 29311-29317).

The kinase assay was performed in white 384-well flat-bottomed plates. Each well contained 5 μl of the compound to be tested in assay buffer (40 mM Hepes, pH 7.5, 100 mM NaCl, 1 mM EGTA, 1 mM β-glycerophosphate, 1 mM DTT, 7 mM MgCl ₂ and 0.1 BSA 6% DMSO) was dissolved. For this purpose, in each case 15 μl lipid vesicles containing 10 ng PI3Kγ and 31.5 ng Gβ ₁ γ ₂ -His were added. The lipid vesicles in turn were generated by PIP ₂ (0.35μg / well), phosphatidylethanolamine (3.75μg / well), phosphatidylserine (3.5μg / well), sphingomyelin (0.35μg / well) and phosphatidylcholine (1.6μg / well) by sonication in Lipid buffer (assay buffer without DMSO) were suspended. Following the addition of the lipid vesicles, the reaction was terminated by adding 10 μl of reaction buffer (40 mM Hepes, pH 7.5, 100 mM NaCl, 1 mM EGTA, 1 mM β-glycerophosphate, 1 mM DTT, 7 mM MgCl ₂ and 0.1% BSA; 1 μM ATP and 0.2 μCi [γ- ³³ P] ATP). The reaction mixture was incubated for 1 h and then by adding a suspension of 0.12 mg LEADseeker beads (Amersham Biosciences) in stop buffer (40 mM Hepes, pH 7.5, 100 mM NaCl, 1 mM EGTA, 12 mM EDTA, 1 mM β-glycerophosphate, 1 mM DTT). After centrifugation at 500 × g for 1 minute, the plates were read using a LEADseeker instrument and analyzed. All compounds shown have an IC ₅₀ value below 800 nM in the test.

EXAMPLES A

EXAMPLES B

EXAMPLES C

EXAMPLES D

EXAMPLES E

EXAMPLES F

EXAMPLES G

EXAMPLES H

INDICATIONS

As was found, the compounds of formula 1 are characterized diverse applications in the therapeutic field. To emphasize are such applications, for which the Compounds of the invention of the formula due to its pharmaceutical activity as a PI3 kinase Modulator may preferably be used.

Generally expressed these are diseases whose pathology involves activity of PI3 kinases is, in particular inflammatory and allergic diseases. In particular, be inflammatory and respiratory allergic diseases, inflammatory diseases of the gastrointestinal tract Tract, inflammatory Musculoskeletal disorders, inflammatory and allergic skin diseases, inflammatory Eye diseases, diseases of the nasal mucosa, inflammatory or allergic disease states involved in autoimmune reactions or kidney inflammation called. The treatment can be symptomatic, adaptive, curative or preventive respectively.

• • Gewebezerstörung
• • der Entzündung der Atemwege
• • der bronchialen Hyperreaktivität
• • des Umbauprozesses der Lunge infolge der Entzündung
• • der Verschlechterung der Krankheit (Progression)

bewirken. Besonders bevorzugt sind die erfindungsgemäßen Verbindungen zur Herstellung eines Medikaments zur Behandlung von Chronischer Bronchitis, akuter Bronchitis, Bronchitis aufgrund bakterieller oder viraler Infektion oder Pilzen oder Helminthen, allergischer Bronchitis, toxischer Bronchitis, chronisch obstruktiver Bronchitis (COPD), Asthma (intrinsisch oder allergisch), pediatrischem Asthma, Bronchiektasien, allergischer Alveolitis, allergischer oder nicht-allergischer Rhinitis, chronischer Sinusitis, zystischer Fibrose oder Mukoviszidose, alpha-1-Antitrypsin-Mangel, Husten, Lungenemphysem, interstitieller Lungenerkrankungen wie z.B. Lungenfibrose, Asbestose und Silikose und Alveolitis; hyperreaktiver Atemwege, Nasenpolypen, Lungenödemen wie z.B. toxischem Lungenödem und ARDS/IRDS, Pneumonitis aufgrund unterschiedlicher Genese wie Strahlen-induziert oder durch Aspiration oder infektiöse, Kollagenosen wie Lupus eryth, systemische Sklerodermie, Sarkoidose oder M. Boeck.Preferred respiratory diseases mentioned here would be chronic and / or obstructive respiratory diseases. The compounds of formula 1 according to the invention can, due to their pharmacological properties, a reduction of

• • tissue destruction
• • the inflammation of the respiratory tract
• • bronchial hyperreactivity
• • Lung remodeling process as a result of inflammation
• • the worsening of the disease (progression)

cause. Particularly preferred compounds of the invention are for the manufacture of a medicament for the treatment of chronic bronchitis, acute bronchitis, bronchitis due to bacterial or viral infection or fungi or helminths, allergic bronchitis, toxic bronchitis, chronic obstructive bronchitis (COPD), asthma (intrinsic or allergic), pediatric asthma, bronchiectasis, allergic alveolitis, allergic or non-allergic rhinitis, chronic sinusitis, cystic fibrosis or cystic fibrosis, alpha-1-antitrypsin deficiency, cough, pulmonary emphysema, interstitial lung diseases such as pulmonary fibrosis, asbestosis and silicosis and alveolitis; hyperreactive airways, nasal polyps, pulmonary edema such as toxic pulmonary edema and ARDS / IRDS, pneumonitis due to different causes such as radiation-induced or by aspiration or infectious, collagenoses such as lupus eryth, systemic scleroderma, sarcoidosis or M. boeck.

Also suitable compounds of the formula 1 for the treatment of diseases the skin, e.g. Psoriasis, contact dermatitis, atopic dermatitis, Alopecia areata (circular hair loss), erythema exudative multiforme (Stevens-Johnson syndrome), Dermatitis herpetiformis, scleroderma, vitiligo, hives (urticaria), Lupus erythematosus, follicular and areal Pyoderma, endogenous and exogenous acne, acne rosacea and others inflammatory or allergic or proliferative skin diseases.

Furthermore, the compounds of formula 1 are suitable for therapeutic use in inflammatory or allergic disease states in which autoimmune reactions are involved, such as ent inflammatory bowel disease, eg Crohn's disease or ulcerative colitis; Arthritic diseases such as rheumatoid or psoriatic arthritis, osteoarthritis, rheumatoid spondylitis and other arthritic conditions or multiple sclerosis.

• • Entzündungen am Auge, wie z.B. Bindehautentzündung (Konjunktivitis) verschiedener Arten, wie z.B. durch Infektionen mit Pilzen oder Bakterien, allergische Konjunktivitis, Reizkonjunktivitis, durch Medikamenten induzierten Konjunktivitis, Keratitis, Uveitis
• • Krankheiten der Naseschleimhaut, wie z.B. allergische Rhinitis/Sinusitis oder Nasenpolypen
• • Entzündliche oder allergische Krankheitszustände, wie z.B. systemische Lupus erythematodes, chronische Hepatitis, Nierenentzündungen, wie Glomerulonephritis, interstitielle Nephritis oder idiopathisches nephrotisches Syndrom.

Also to be mentioned are the following general inflammatory or allergic diseases which can be treated by medicaments containing compounds of the formula 1:

• O Inflammation on the eye, such as conjunctivitis of various species, such as infections with fungi or bacteria, allergic conjunctivitis, irritant conjunctivitis, drug-induced conjunctivitis, keratitis, uveitis
• • diseases of the nasal mucosa, such as allergic rhinitis / sinusitis or nasal polyps
• • Inflammatory or allergic conditions, such as systemic lupus erythematosus, chronic hepatitis, nephritis, such as glomerulonephritis, interstitial nephritis or idiopathic nephrotic syndrome.

When other diseases due to the pharmacological efficacy containing the compounds of formula 1 with a medicament selbige can be treated be toxic or septic shock syndromes, atherosclerosis, otitis media, (otitis media), hypertrophy of the heart, heart failure, stroke, Ischemia-reperfusion damage or neurodegenerative diseases such as Parkinson's disease or Called Alzheimer's.

COMBINATIONS

• • Betamimetika mit Corticosteroiden, PDE4-Inhibitoren, EGFR-Hemmern oder LTD4-Antagonisten,
• • Anticholinergika mit Betamimetika, Corticosteroiden, PDE4-Inhibitoren, EGFR-Hemmern oder LTD4-Antagonisten,
• • Corticosteroiden mit PDE4-Inhibitoren, EGFR-Hemmern oder LTD4-Antagonisten
• • PDE4-inhibitoren mit EGFR-Hemmern oder LTD4-Antagonisten
• • EGFR-Hemmern mit LTD4-Antagonisten.

The compounds of the formula 1 can be used alone or in combination with other active compounds of the formula 1 according to the invention. Optionally, the compounds of formula 1 can also be used in combination with other pharmacologically active ingredients. Preference is given here to those active substances which are selected, for example, from the group consisting of betamimetics, anticholinergics, corticosteroids, PDE4 inhibitors, LTD4 antagonists, EGFR inhibitors, dopamine agonists, H1-antihistamines, PAF antagonists and PI3-kinase Inhibitors or two or three combinations thereof, such as combinations of

• • betamimetics with corticosteroids, PDE4 inhibitors, EGFR inhibitors or LTD4 antagonists,
• Anticholinergics with betamimetics, corticosteroids, PDE4 inhibitors, EGFR inhibitors or LTD4 antagonists,
• • Corticosteroids with PDE4 inhibitors, EGFR inhibitors or LTD4 antagonists
• • PDE4 inhibitors with EGFR inhibitors or LTD4 antagonists
• EGFR inhibitors with LTD4 antagonists.

Also the combinations of three active ingredients each one of the above Classes of compounds is part of the invention.

Preferred betamimetics for this purpose are compounds selected from the group consisting of albuterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, arformoterol, zinterol, hexoprenaline, ibuterol, isoetharines, isoprenalines, levosalbutamol, mabuterol, meluadrine , Metaproterenol, Orciprenaline, Pirbuterol, Procaterol, Reproterol, Rimiterol, Ritodrine, Salmeterol, Salmefamol, Soterenol, Sulphoneterol, Tiaramide, Terbutaline, Tolubuterol, CHF-1035, HOKU-81, KUL-1248, 3- (4- {6- [ 2-Hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) -ethylamino] -hexyloxy} -butyl) -benzylsulfonamide, 5- [2- (5,6-diethylindan-2-ylamino) -1- hydroxyethyl] -8-hydroxy-1H-quinolin-2-one, 4-hydroxy-7- [2 - {[2 - {[3- (2-phenylethoxy) propyl] sulphonyl} ethyl] amino} ethyl] -2 (3H) -benzothiazolone, 1- (2-fluoro-4-hydroxyphenyl) -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol, 1- [3- (4-methoxybenzyl amino) -4-hydroxyphenyl] -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] etha nol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-N, N-dimethylaminophenyl) -2-methyl-2-propylamino ] ethanol, 1- (2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-methoxyphenyl) -2-methyl-2-propylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-n-butyloxyphenyl) -2-methyl-2-propylamino] ethanol, 1 - [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- {4- [3- (4-methoxyphenyl) -1,2,4-triazol-3-yl ] -2-methyl-2-butylamino} ethanol, 5-hydroxy-8- (1-hydroxy-2-isopropylaminobutyl) -2H-1,4-benzoxazine-3- (4H) -one, 1- (4-amino 3-chloro-5-trifluoromethylphenyl) -2-tert-butylamino) ethanol, 6-hydroxy-8- {1-hydroxy-2- [2- (4-methoxyphenyl) -1,1-dimethyl-ethylamino ] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- (2- (4-phenoxy-acetic acid ethyl ester) -1,1-dimethyl-ethylamino ] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxyacetic acid) -1,1-dimethyl-ethylamino ] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 8- {2- [1,1-dimethyl-2- (2,4,6-trimethylphenyl) ethylamino] -1-hydroxy ethyl} - 6-hydroxy-4H-benzo [1,4] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- [2- (4-hydroxyphenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-one, 6-hydroxy-8- {1-hydro xy-2- [2- (4-isopropyl-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 8- {2- [2- (4 Ethyl-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxyethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 8- {2- [2- (4 -Ethoxy-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxyethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 4- (4- {2- [2 -hydroxy-2- (6-hydroxy-3-oxo-3,4-dihydro-2H-benzo [1,4] oxazin-8-yl) ethylamino] -2-methyl-propyl} -phenoxy) -butyric acid, 8- {2- [2- (3,4-difluoro-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3- on and 1- (4-ethoxycarbonylamino-3-cyano-5-fluorophenyl) -2- (tert-butylamino) ethanol, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates.

Prefers the betamimetics are selected from the group consisting of bambuterol, bitolterol, carbuterol, Clenbuterol, Fenoterol, Formoterol, Hexoprenaline, Ibuterol, Pirbuterol, Procaterol, Reproterol, Salmeterol, Sulphone terol, Terbutaline, Tolubuterol, 3- (4- {6- [2-Hydroxy-2- (4-hydroxy-3-hydroxymethyl-phenyl) -ethylamino] -hexyloxy} -butyl) -benzenesulfoneamide, 5- [2- (5,6-diethyl-indan-2-ylamino) -1-hydroxy-ethyl] -8-hydroxy-1H-quinolin-2-one, 4-hydroxy-7- [2 - {[2 - {[3- (2-phenylethoxy) propyl] sulphonyl} ethyl] -amino} ethyl] -2 (3H) -benzothiazolone, 1- (2-fluoro-4-hydroxyphenyl) -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol, 1- [3- (4-methoxybenzyl-amino) -4-hydroxyphenyl] -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-N, N-dimethylaminophenyl) -2-methyl-2-propylaminojethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-methoxyphenyl) -2-methyl-2-propylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- [3- (4-n-butyloxyphenyl) -2-methyl-2-propylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- {4- [3- (4-methoxyphenyl) -1,2,4-triazol-3- yl] -2-methyl-2-butylamino} ethanol, 5-hydroxy-8- (1-hydroxy-2-isopropylaminobutyl) -2H-1,4-benzoxazine-3- (4H) -one, 1- (4-amino-3-chloro-5-trifluoromethylphenyl) -2- tert-butylamino) ethanol, 6-hydroxy-8- {1-hydroxy-2- [2- (4-methoxyphenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4 ] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- (2- (4-phenoxy-acetic acid ethyl ester) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4 ] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxy-acetic acid) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 8- {2- [1,1-dimethyl-2- (2,4,6-trimethylphenyl) -ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3- on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-hydroxy-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-isopropyl-phenyl) -1,1dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 8- {2- [2- (4-ethyl-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 8- {2- [2- (4-ethoxy-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 4- (4- {2- [2-hydroxy-2- (6-hydroxy-3-oxo-3,4-dihydro-2H-benzo [1,4] oxazin-8-yl) ethylamino] -2 methyl-propyl} -phenoxy) -butyric acid, 8- {2- [2- (3,4-difluoro-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H- benzo [1,4] oxazin-3-one and 1- (4-ethoxycarbonylamino-3-cyano-5-fluorophenyl) -2- (tert-butylamino) ethanol, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable Acid addition salts, solvates or hydrates.

Particularly preferred betamimetics are selected from the group consisting of fenoterol, formoterol, salmeterol, 3- (4- {6- [2-hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) -ethylamino] -hexyloxy} -butyl ) -benzenesulfoneamide, 5- [2- (5,6-diethyl-indan-2-ylamino) -1-hydroxy-ethyl] -8-hydroxy-1H-quinolin-2-one, 1- [3- (4- Methoxybenzylamino) -4-hydroxyphenyl] -2- [4- (1-benzimidazolyl) -2-methyl-2-butylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4- benzoxazin-8-yl] -2- [3- (4-N, N-dimethylaminophenyl) -2-methyl-2-propylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4 benzoxazin-8-yl] -2- [3- (4-methoxyphenyl) -2-methyl-2-propylamino] ethanol, 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazine 8-yl] -2- [3- (4-n-butyloxyphenyl) -2-methyl-2-propylamino] ethanol, 6-hydroxy-8- {1-hydroxy-2- [2- (4-methoxyphenyl ) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxy-acetic acid, ethyl ester ) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxyacetic acid ) -1,1-di methyl ethylamino] ethyl} -4 H -benzo [1,4] oxazin-3-one, 8- {2- [1,1-dimethyl-2- (2,4,6-trimethylphenyl) ethylamino] -1 -hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one,
6-hydroxy-8- {1-hydroxy-2- [2- (4-hydroxy-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-isopropyl-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 8- {2- [2- (4-ethylphenyl) -1,1-dimethylethylamino] -1-hydroxyethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 8- {2- [2- (4-ethoxyphenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 4- (2- {4- [2-hydroxy-2- (6-hydroxy-3-oxo 3,4-dihydro-2H-benzo [1,4] oxazin-8-yl) ethylamino] -2-methyl- propyl} phenoxy) butyric acid, 8- {2- [2- (3,4-difluoro-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo 1,4] oxazin-3-one and 1- [2H-5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl] -2- {4- [3- (4-methoxyphenyl) - 1,2,4-triazol-3-yl] -2-methyl-2-butylamino} ethanol, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates or hydrates.

From According to the invention, these betamimetics are particularly preferably formoterol, Salmeterol, 3- (4- {6- [2-hydroxy-2- (4-hydroxy-3-hydroxymethylphenyl) -ethylamino] -hexyloxy} -butyl) -benzenesulfoneamide, 6-hydroxy-8- {1-hydroxy-2- [2- (4-methoxy-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxy-acetate) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-phenoxy-acetic acid) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 8- {2- [1,1-dimethyl-2- (2,4,6-trimethylphenyl) -ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3- on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-hydroxy-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4H-benzo [1,4] oxazin-3-on, 6-hydroxy-8- {1-hydroxy-2- [2- (4-isopropyl-phenyl) -1,1-dimethyl-ethylamino] -ethyl} -4 H -benzo [1,4] oxazin-3-one, 8- {2- [2- (4-ethyl-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo (1,4] oxazin-3-one, 8- {2- [2- (4-ethoxy-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H-benzo [1,4] oxazin-3-one, 4- (4- {2- [2-hydroxy-2- (6-hydroxy-3-oxo-3,4-dihydro-2H-benzo [1,4] oxazin-8-yl) ethylamino] -2 methyl-propyl} -phenoxy) -butyric acid, 8- {2- [2- (3,4-difluoro-phenyl) -1,1-dimethyl-ethylamino] -1-hydroxy-ethyl} -6-hydroxy-4H- benzo [1,4] oxazin-3-one and 5- [2- (5,6-diethyl-indan-2-ylamino) -1-hydroxy-ethyl] -8-hydroxy-1H-quinolin-2-one, optionally in the form of their racemates, enantiomers, diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, Solvates or hydrates.

According to the invention preferred are the acid addition salts the betamimetics selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, Hydrosulfate, hydrophosphate, hydromethanesulfonate, hydronitrate, hydromaleate, Hydroacetate, hydrobenzoate, hydrocitrate, hydrofumarate, hydrotartrate, Hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulfonate, preferably hydrochloride, hydrobromide, hydrosulfate, hydrophosphate, Hydrofumarate and hydromethanesulfonate understood. From the above mentioned acid addition salts are the salts of hydrochloric acid, methanesulfonic acid, the benzoic acid and the acetic acid particularly according to the invention prefers.

When Anticholinergics are preferably compounds for Application that are selected from the group consisting of tiotropium salts, oxitropium salts, Flutropium salts, ipratropium salts, glycopyrronium salts, trospium salts 2,2-diphenylpropionate-methobromide, 2-fluoro-2,2-diphenylacetic acid copopper ester methobromide, 2-fluoro-2,2-diphenylacetic acid tropol ester methobromide, 2,2-diphenylpropionic acid co-ester methobromide, 3,3 ', 4,4'-Tetrafluorbenzilsäuretropenolester methobromide, 3,3 ', 4,4'-Tetrafluorbenzilsäurescopinester methobromide, 4,4'-difluorobenzilate methobromide, 4,4'-Difluorobenzilic acid copoprene methobromide, 3,3'-difluorobenzilic acid-tropol ester methobromide, 3,3'-Difluorbenzilsäurescopinester methobromide, 9-hydroxy-fluorene-9-carbonsäuretropenolester -Methobromide, 9-fluoro-fluorene-9-carboxylic acid tropol ester -methobromide, 9-hydroxy-fluorene-9-carbonsäurescopinester -Methobromide, 9-fluoro-fluoren-9-carboxylic acid copoprene methobromide, 9-methyl-fluorene-9-carbonsäuretropenolester Methobromide, 9-methyl-fluorene-9-carboxylic acid copolinester Methobromide, Benzylcyclopropyltropinester Methobromid, 2,2-Diphenylpropionsäurecyclopropyltropinester Methobromide, 9-hydroxy-xanthene-9-carboxylic acid cyclopropyltropine ester methobromide, 9-methyl-fluorene-9-carbonsäurecyclopropyltropinester methobromide, 9-methyl-xanthene-9-carbonsäurecyclopropyltropinester Methobromide, 9-hydroxyfluorene-9-carboxylic acid cyclopropyltropine ester methobromide, 4,4'-Difluorbenzilsäuremethylestercyclopropyltropinester -Methobromide, 9-hydroxy-xanthene-9-carboxylic acid tropol ester -methobromide, 9-hydroxy-xanthene-9-carbonsäurescopinester Methobromide, 9-methyl-xanthene-9-carboxylic acid tropol ester -methobromide, 9-methyl-xanthene-9-carboxylic acid copolinester -Methobromide, 9-ethyl-xanthene-9-carboxylic acid tropol ester, methobromide, 9-difluoromethyl-xanthene-9-carbonsäuretropenolester -Methobromid. 9-hydroxymethyl-xanthene-9-carboxylic acid copo-ester -methobromide, optionally in the form of their solvates or hydrates.

In the cations mentioned above are tiotropium, Oxitropium, Flutropium, Ipratropium, Glycopyrronium and Trospium the pharmacologically active ingredients. As anions, the above mentioned salts preferably contain chloride, bromide, iodide, sulfate, Phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, Tartrate, oxalate, succinate, benzoate or p-toluenesulfonate, wherein Chloride, bromide, iodide, sulfate, methanesulfonate or p-toluenesulfonate are preferred as counterions. Of all the salts are the chlorides, Bromides, iodide and methanesulfonate particularly preferred.

From Of particular importance is the tiotropium bromide. In the case of tiotropium bromide contain the drug combinations according to the invention this is preferably in the form of the crystalline tiotropium bromide monohydrate, which is known from WO 02/30928. Will the tiotropium bromide in the drug combinations according to the invention used in anhydrous form, so preferably the anhydrous crystalline tiotropium bromide for use, which is known from WO 03/000265 is known.

Preferred corticosteroids here are compounds which have been selected are selected from the group consisting of prednisolone, prednisone, butixocortepionate, flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, dexamethasone, betamethasone, deflazacort, RPR-106541, NS-126, 6,9-difluoro-17- [(2-furanylcarbonyl) oxy] -11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothionic acid (S) -fluoromethyl ester and 6,9-difluoro-11-hydroxy-16- methyl 3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothionic acid (S) - (2-oxo-tetrahydrofuran-3S-yl) ester, optionally in the form of their racemates, enantiomers or diastereomers, and optionally in the form of their salts and derivatives, their solvates and / or hydrates.

Especially Preferably, the steroid is selected from the group consisting of flunisolide, beclomethasone, triamcinolone, Budesonide, fluticasone, mometasone, ciclesonide, rofleponide, dexamethasone, NS-126, 6,9-difluoro-17 - ((2-furanylcarbonyl) oxy] -11-hydroxy-16-methyl-3-oxo-androsta-1,4 -diene-17-carbothionic acid (S) -fluoromethyl ester and 6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothioic acid (S) - (2-oxo-tetrahydrofuran-3S-yl ) ester, optionally in the form of their racemates, enantiomers or diastereomers and optionally in the form of their salts and derivatives, their solvates and / or hydrates.

Especially Preferably, the steroid is selected from the group consisting of budesonide, fluticasone, mometasone, ciclesonide and 6,9-difluoro-17 - [(2-furanylcarbonyl) oxy] -11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothionic acid (S) -fluoromethyl ester, optionally in the form of their racemates, enantiomers or diastereomers and optionally in the form of their salts and derivatives, their solvates and / or Hydrates.

each Reference to steroids concludes a reference to their possibly existing salts or Derivatives, hydrates or solvates. Examples of possible Salts and derivatives of steroids may be: alkali salts, such as For example, sodium or potassium salts, sulfobenzoates, phosphates, Isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, Pivalate or furoate.

When PDE4 inhibitors preferably lead to compounds here Application that are selected from the group consisting of enprofylline, theophylline, roflumilast, Ariflo (Cilomilast), Tofimilast, Pumafentrin, Lirimilast, Arofylline, Atizoram, D-4396 (Sch-351591), AW D-12-281 (GW-842470), NCS-613, CDP-840, D-4418, PD-168787, T-440, T-2585, V-11294A, CI-1018, CDC-801, CDC-3052, D-22888, YM-58997, Z-15370, N- (3,5-dichloro-1-oxopyridin-4-yl) -4-difluoromethoxy-3- cyclopropylmethoxybenzamide, (-) p - [(4aR *, 10bS *) - 9-ethoxy-1,2,3,4,4a, 10b-hexahydro-8-methoxy-2-methyl-benzo [s] [1,6 ] naphthyridin-6-yl] -N, N-diisopropylbenzamide, (R) - (+) - 1- (4-Bromobenzyl) -4 - [(3-cyclopentyloxy) -4-methoxyphenyl] -2-pyrrolidone, 3- (cyclopentyloxy-4-methoxyphenyl) -1- (4-N '- [N-2-cyano-S-methylisothioureido] benzyl) -2-pyrrolidone, cis [4-cyano-4- (3-cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid], 2-carbomethoxy 4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-one, cis [4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-ol], (R) - (+) - ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-ylidene] acetate, (S) - (-) - ethyl [4- (3-cyclopentyloxy-4-methoxyphenyl) pyrrolidin-2-ylidene] acetate, 9-cyclopentyl-5,6-dihydro-7-ethyl-3- (2-thienyl) -9H-pyrazolo [3,4-c] -1,2,4-triazolo [4,3-a] pyridine and 9-cyclopentyl-5,6-dihydro-7-ethyl-3- (tert -butyl) -9H-pyrazolo [3,4-c] -1,2,4-triazolo [4,3-a] pyridine, optionally in the form of their racemates, enantiomers or diastereomers and optionally in the form of their pharmacologically acceptable Acid addition salts, Solvates and / or hydrates.

Especially Preferably, the PDE4 inhibitor is selected from the group consisting from Enprofylline, Roflumilast, Ariflo (Cilomilast), Arofylline, Atizoram, AWD-12-281 (GW-842470), T-440, T-2585, PD-168787, V-11294A, CI-1018, CDC-801, D-22888, YM-58997, Z-15370, N- (3,5-Dichloro-1-oxopyridin-4-yl) -4-difluoromethoxy-3-cyclopropylmethoxybenzamide, Cis (4-cyano-4- (3 cyclopentyloxy-4-methoxyphenyl) cyclohexane-1-carboxylic acid], 2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-one, cis [4-cyano-4- (3 cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-ol], 9-cyclopentyl-5,6-dihydro-7-ethyl-3- (2-thienyl) -9H-pyrazolo [3,4-c] -1,2,4-triazolo [4,3-a] pyridine and 9-cyclopentyl-5,6-dihydro-7-ethyl-3- (tert -butyl) -9H-pyrazolo [3,4-c] -1,2,4-triazolo [4,3-a] pyridine, possibly in the form of their racemates, enantiomers or diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates and / or hydrates.

More preferably, the PDE4 inhibitor is selected from the group consisting of roflumilast, ariflo (cilomilast), arofylline, AWD-12-281 (GW-842470), 2-carbomethoxy-4-cyano-4- (3-cyclopropylmethoxy-4- difluoromethoxyphenyl) cyclohexan-1-one, cis [4-cyano-4- (3-cyclopropylmethoxy-4-difluoromethoxyphenyl) cyclohexan-1-ol], Atizoram, Z-15370, 9-cyclopentyl-5,6-dihydro-7- ethyl 3- (2-thienyl) -9H-pyrazolo [3,4-c] -1,2,4-triazolo [4,3-a] pyridine and 9-cyclopentyl-5,6-dihydro-7-ethyl -3- (tert-butyl) -9H-pyrazolo [3,4-c] -1,2,4-triazolo [4,3-a] pyridine optionally in the form of their racemates, enantiomers or diastereomers and optionally in the form of their pharmacologically acceptable acid addition salts, solvates and / or hydrates.

Under Acid addition salts with pharmacologically acceptable acids for their formation the o.g. PDE4 inhibitors optionally in the For example, salts are selected from the group consisting hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, Hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, Hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, Hydrobenzoate and hydro-p-toluenesulfonate, preferably hydrochloride, Hydrobromide, hydrosulfate, hydrophosphate, hydrofumarate and hydromethanesulfonate Understood.

When LTD4 antagonists are preferably compounds for Application that are selected from the group consisting of Montelukast, Pranlukast, Zafirlukast, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078, VUF-K-8707, L-733321, 1 - (((R) - (3- (2- (6,7-Difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl) thio) methylcyclopropane-acetic acid, 1 - (((1 (R) -3 (3- (2- (2,3-dichloro thieno [3,2-b] pyridin-5-yl) - (E) -ethenyl) phenyl) -3- (2- (1-hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclopropaneacetic acid and [2 - [[2- (4-tert-butyl-2-thiazolyl) -5-benzofuranyl] oxymethyl] phenyl] acetic acid optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form of their pharmacologically acceptable acid addition salts and optionally in the form of their salts and derivatives, their solvates and / or hydrates.

Prefers the LTD4 antagonist is selected from the group consisting of Montelukast, Pranlukast, Zafirlukast, MCC-847 (ZD-3523), MN-001, MEN-91507 (LM-1507), VUF-5078, VUF-K-8707 and L-733321, optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form of their pharmacologically acceptable Acid addition salts and optionally in the form of their salts and derivatives, their solvates and / or hydrates.

Especially Preferably, the LTD4 antagonist is selected from the group consisting from Montelukast, Pranlukast, Zafirlukast, MCC-847 (ZD-3523), MN-001 and MEN-91507 (LM-1507) optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form of their pharmacologically acceptable Acid addition salts and optionally in the form of their salts and derivatives, their solvates and / or hydrates.

Under Acid addition salts with pharmacologically acceptable acids The LTD4 antagonists may be capable of forming them For example, salts are selected from the group consisting of hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, Hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, Hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, Hydrobenzoate and hydro-p-toluenesulfonate, preferably hydrochloride, Hydrobromide, hydrosulfate, hydrophosphate, hydrofumarate and hydromethanesulfonate Understood. Among salts or derivatives for their formation the LTD4 antagonists where appropriate, are understood, for example : Alkali salts, such as sodium or potassium salts, alkaline earth salts, Sulfobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, Palmitate, pivalate or furoate.

Compounds which are preferably selected from the group consisting of 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl) -1] are preferably used as EGFR inhibitors. oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-diethylamino) -1- oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxyquinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1- oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - {[4- (morpholin-4-yl) - 1-oxo-2-buten-1-yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - {[4 - ((R) -6 -methyl-2-oxomorpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxyquinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino ] -6 - {[4 - ((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7 - [(S) - (tetrahydrofuran-3-yl) oxy] quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6 - {[4 - ((R) -2-methoxymethyl-6-oxo-morpholine] 4-yl) -1-oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy-china zoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2 - ((S) -6-methyl-2-oxo-morpholin-4-yl) -ethoxy] -7-methoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N- (2-methoxyethyl) -N-methyl-amino] -1-oxo-2-butene 1-yl} amino) -7-cyclopropylmethoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-butene] 1-yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - {[4- (N, N-bis (2-methoxy-ethyl) -amino) -1-oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy-quinazoline, -4 - [(R) - (1-phenyl-ethyl) amino] -6 - ({4- [N- (2-methoxy-ethyl) -N-ethyl-amino] -1-oxo-2-buten-1 -yl} amino) -7-cyclopropylmethoxy quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - ({4- [N- (2-methoxyethyl) -N-methyl- amino] -1-oxo-2-buten-1-yl} amino) -7-cyclopropylmethoxy quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - ({4- [N- (tetrahydropyran-4-yl) - N -methyl-amino] -1-oxo-2-buten-1-yl} amino) -7-cyclopropylmethoxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) -amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7 - ((R) -tetrahydrofuran-3-yloxy) quinazoline, 4 - [( 3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7 - ((S) -tetrahydrofuran-3 -yloxy) quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2 -but-1-yl} -amino) -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) -amino] -6 - {[4- (N-cyclopropyl-N-methyl-amino) -1 -oxo-2-buten-1-yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1 oxo-2-buten-1-yl] amino} -7 - [(R) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo -2-buten-1-yl] amino} -7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-ethynylphenyl) amino] -6,7-bis- (2-methoxyethoxy) quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -7- [3- (morpholin-4-yl) -propyloxy] -6 - [(vinylcarbonyl) amino] - quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6- (4-hydroxy-phenyl) -7H-pyrrolo [2,3-d] pyrimidine, 3-cyano-4 - [(3 -chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7-ethoxy-quinoline, 4 - {[3 -Chloro- 4- (3-fluoro-benzyloxy) -phenyl] -amino} -6- (5 - {[(2-methanesulfonyl-ethyl) -amino] -methyl} -furan-2-yl) -quinazoline, 4 - [(R ) - (1-phenyl-ethyl) amino] -6 - {[4 - ((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7-methoxyquinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N, N-bis (2-methoxy ethyl) amino] oxo-2--1-buten-1-y l} amino) -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-ethynylphenyl) amino] -6 - {[4- (5,5-dimethyl-2-oxo) morpholin-4-yl) -1-oxo-2-buten-1-yl-amino) quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2-dimethyl 6-oxo-morpholin-4-yl) -ethoxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (2- (2,2-dimethyl- 6-oxo-morpholin-4-yl) -ethoxy] -7 - [(R) - (tetrahydrofuran-2-yl) -methoxy] quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] - 7- [2- (2,2-dimethyl-6-oxomorpholin-4-yl) -ethoxy] -6 - [(S) - (tetrahydrofuran-2-yl) -methoxy] -quinazoline, 4 - [(3 -Chloro-4-fluoro-phenyl) -amino] -6- {2- [4- (2-oxomorpholin-4-yl) -piperidin-1-yl] -ethoxy} -7-methoxy-quinazoline, 4- ((3-chloro-4-fluoro-phenyl) -amino] -6- [1- (tert -butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-) fluorophenyl) amino] -6- (trans-4-aminocyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6- (trans 4-methanesulfonylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyr an-3-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methylpiperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(morpholin-4-yl) -carbonyl] -piperidin-4-yl-oxy} -7-methoxy-quinazoline, 4- [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - ((methoxymethyl) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4- fluorophenyl) amino] -6- (piperidin-3-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [1- (2-acetylamino] ethyl) -piperidin-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7-ethoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - ((S) -tetrahydrofuran-3-yloxy) -7-hydroxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methoxyethoxy) quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6- {trans-4- [ (dimethylamino) sulfonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {trans-4 - [(morpholin-4-yl ) carbonylamino] cyclohexane-1-yloxy} -7-me thoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6- {trans-4 - [(morpholin-4-yl) sulfonylamino] cyclohexan-1-yloxy} -7-methoxy quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7- (2-acetylamino-ethoxy) quinazoline, 4 - [(3-chloro-4 fluorophenyl) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methanesulfonylamino-ethoxy) -quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- { 1 - [(piperidin-1-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-aminocarbonylmethyl- piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(tetrahydropyran-4-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [( morpholin-4-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis -4- {N - [(morpholin-4-yl) sulfonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl ) amino] -6- (trans-4-ethane sulfonylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-ethoxy- quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7- (2-methoxy-ethoxy) -quinazoline, 4 - [(3 chloro-4-fluoro-phenyl) amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7- (2-metho xyethoxy) quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4-acetylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [( 3-ethynylphenyl) amino] -6- [1- (tert -butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline, 4 - ((3-ethynylphenyl) amino] -6- ( tetrahydropyran-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(piperidin-1-yl) -carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxyquinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(4- methyl-piperazin-1-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {cis-4 - [(morpholin-4-yl) carbonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [2- (2-oxopyrrolidin-1-yl) ethyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(morpholin-4-yl) carbonyl] piperidin-4-yloxy} -7- (2-methoxyethoxy) quinazoline, 4 - [(3-ethynylphenyl) amino] -6- (1-acetyl -piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3 Ethynylphenyl) amino] -6- (1-methylpiperidin-4-yloxy) -7-methoxyquinazoline, 4 - [(3-ethynylphenyl) amino] -6- (1-methanesulfonylpiperidine) 4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methylpiperidin-4-yloxy) -7 (2-methoxy-ethoxy) quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-isopropyloxycarbonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4- fluorophenyl) amino] -6- (cis-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {cis -4- [N- (2-methoxy-acetyl) -N-methyl-amino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-ethynyl-phenyl) -amino] -6- ( piperidin-4-yloxy) -7-methoxyquinazoline, 4 - [(3-ethynylphenyl) amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7-methoxy- quinazoline, 4 - [(3-ethynylphenyl) amino] -6- {1 - [(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3 Chloro-4-fluoro-phenyl) amino] -6- {1 - [(cis-2,6-dimethyl-morpholin-4-yl) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4- [(3-chloro-4-fluoro-phenyl ) amino] -6- {1 - [(2-methyl-morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl ) amino] -6- {1 - [(S, S) - (2-oxa-5-aza-bicyclo [2.2.1] hept-5-yl) carbonyl] piperidin-4-yloxy} -7-methoxy quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(N-methyl-N-2-methoxyethyl-amino) -carbonyl] -piperidin-4-yloxy} -7 -methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-ethyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro 4-fluoro-phenyl) amino] -6- {1 - [(2-methoxyethyl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- {1 - [(3-methoxy-propyl-amino) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] - 6- [cis -4- (N-methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6 [cis-4- (N-acetyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-f Luoro-phenyl) amino] -6- [trans-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro -phenyl) amino] -6- (trans-4-dimethylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans- 4- {N - [(morpholin-4-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- [2- (2,2-dimethyl-6-oxomorpholin-4-yl) ethoxy] -7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4- [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino ] -6- (1-cyano-piperidin-4-yloxy) -7-methoxy-quinazoline, cetuximab, trastuzumab, ABX-EGF and Mab ICR-62, optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form of their pharmacological compatible acid addition salts, their solvates and / or hydrates.

Preferred EGFR inhibitors are selected from the group consisting of 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl) -1-oxo-2-butene-1. yl] amino} -7-cyclopropylmethoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-diethylamino) -1-oxo-2-butene-1] yl] amino} -7-cyclopropylmethoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-butene-1] yl] amino} -7-cyclopropylmethoxyquinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - {(4- (morpholin-4-yl) -1-oxo-2-butene 1-yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - {[4 - ((R) -6-methyl-2-oxo-morpholine 4-yl) -1-oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - {[4- ((R) -6-methyl-2-oxomorpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7 - [(S) - (tetrahydrofuran-3-yl) oxy ] -quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6 - {[4 - ((R) -2-methoxymethyl-6-oxo-morpholin-4-yl) -1-oxo -2-buten-1-yl] -amino} -7-cyclopropylmethoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2 - ((S) -6-m ethyl 2-oxomorpholin-4-yl) ethoxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- (N- (2-methoxy -ethyl) -N-methylamino] -1-oxo-2-buten-1-yl} amino) -7-cyclopropylmethoxyquinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6- { [4- (N, N -dimethylamino) -1-oxo-2-buten-1-yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - {(4- (N, N-bis (2-methoxyethyl) amino) -1-oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxyquinazoline, 4 - [(R) - (1-phenyl-ethyl) amino] -6 - ({4- [N- (2-methoxy-ethyl) -N-ethyl-amino] -1-oxo-2-buten-1-yl} amino) - 7-cycl poly (methoxy) quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - ({4- [N- (2-methoxyethyl) -N-methylamino] -1-oxo-2 -but-1-yl} -amino) -7-cyclopropylmethoxy-quinazoline, 4 - [(R) - (1-phenyl-ethyl) -amino] -6 - ({4- [N- (tetrahydropyran-4-yl) - N -methyl-amino] -1-oxo-2-buten-1-yl} -amino) -7-cyclopropyl-methoxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) -amino] -6 - {[4- (4-yl) N, N -dimethylamino) -1-oxo-2-buten-1-yl] amino} -7 - ((R) -tetrahydrofuran-3-yloxy) quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7 - ((S) -tetrahydrofuran-3-yloxy) quinazoline, 4- [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-buten-1-yl} amino ) -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N-cyclopropyl-N-methylamino) -1-oxo-2-butene-1 -yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-butene-1 -yl] amino} -7 - [(R) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N dimethylamino) 1-oxo-2-buten-1-yl] amino} -7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-ethynylphenyl) amino] -6, 7-bis (2-methoxyethoxy) quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -7- [3- (morpholin-4-yl) -propyloxy] -6 - [(vinylcarbonyl ) amino] quinazoline, 4 - [(R) - (1-phenylethyl) amino] -6- (4-hydroxy-phenyl) -7H-pyrrolo [2,3-d] pyrimidine, 3-cyano-4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7-ethoxy-quinoline, 4 - {[3-Chloro-4- (3-fluoro-benzyloxy) -phenyl] -amino} -6- (5 - {[(2-methanesulfonyl-ethyl) -amino] -methyl} -furan-2-yl) -quinazoline, 4 - [(R) - (1-phenyl-ethyl) amino] -6 - {[4 - ((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo-2-butene 1-yl] amino} -7-methoxyquinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl) -1-oxo-2-butene] 1-yl] amino} -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N, N-bis-) (2-methoxyethyl) amino] -1-oxo-2-buten-1-yl} amino) -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-ethynylphenyl ) amino] -6 - {[4- (5,5-dimethyl-2-oxo -morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2, 2-dimethyl-6-oxomorpholin-4-yl) -ethoxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2 -dimethyl-6-oxo-morpholin-4-yl) -ethoxy] -7 - [(R) - (tetrahydrofuran-2-yl) -methoxy] -quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -7- [2- (2,2-dimethyl-6-oxomorpholin-4-yl) -ethoxy] -6 - ((S) - (tetrahydrofuran-2-yl) -methoxy] -quinazoline, 4- [(3-chloro-4-fluoro-phenyl) amino] -6- {2- [4- (2-oxo-morpholin-4-yl) piperidin-1-yl] -ethoxy} -7-methoxy-quinazoline , 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- (1- (tert-butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro 4-fluoro-phenyl) -amino] -6- (trans-4-amino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - (trans-4-methanesulfonylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-3-yloxy) -7- methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methyl-piperidin-4-yloxy) -7-methoxy y-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(morpholin-4-yl) -carbonyl] -piperidin-4-yl-oxy} -7-methoxy quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(methoxymethyl) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3 Chloro-4-fluoro-phenyl) amino] -6- (piperidin-3-yloxy) -7-methoxyquinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [1- ( 2-acetylamino-ethyl) -piperidin-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7-ethoxy quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - ((S) -tetrahydrofuran-3-yloxy) -7-hydroxy-quinazoline, 4 - [(3-chloro-4-) fluorophenyl) amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methoxy-ethoxy) quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino-6-one {trans- 4 - [(dimethylamino) sulfonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {trans-4 - [(morpholine) 4-yl) carbonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {trans-4 - [(morpholine-4- yl) sulfonylamino] -cyclohexan-1 -yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7- (2-acetylamino-ethoxy) -quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7- (2-methanesulfonylamino-ethoxy) -quinazoline, 4 - [(3-chloro-4-fluoro) phenyl) amino] -6- {1- [(piperidin-1-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-aminocarbonylmethyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [( tetrahydropyran-4-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis -4- {N - [(morpholin-4-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl ) amino] -6- (cis-4- {N - [(morpholin-4-yl) sulfonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3 -Chloro-4-fluoro-phenyl) amino] -6- (trans-4-ethanesulfonylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6- (1-methansulfony 1-piperidin-4-yloxy) -7-ethoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7- (2 -methoxy-ethoxy) quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7- (2- methoxyethoxy) quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (cis-4-acetylamino-cyclohexan-1-yloxy) -7-metho xy-quinazoline, 4 - [(3-ethynylphenyl) amino] -6- [1- (tert -butyloxycarbonyl) -piperidin-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-ethynyl) phenyl) amino] -6- (tetrahydropyran-4-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [( piperidin-1-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis -4- {N - [(4-methylpiperazin-1-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4 -fluorophenyl) amino] -6- {cis-4 - ((morpholin-4-yl) carbonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro -phenyl) -amino] -6- {1- [2- (2-oxo-pyrrolidin-1-yl) -ethyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro -phenyl) -amino] -6- {1 - [(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7- (2-methoxy-ethoxy) -quinazoline, 4 - [(3-ethynylphenyl ) amino] -6- (1-acetyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-ethynyl-phenyl) -amino] -6- (1-methylpiperidin-4-yloxy) 7-methoxyquinazoline, 4 - [(3-ethynylphenyl) amino] - 6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methyl-piperidin-4-yloxy) -7 (2-methoxy-ethoxy) -quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-isopropyloxycarbonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro) phenyl) amino] -6- {cis-4- [N- (2-methoxy-acetyl) -N-methylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-ethynyl -phenyl) amino] -6- (piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-ethynylphenyl) amino] -6- [1- (2-methoxy-acetyl) -piperidine 4-yloxy] -7-methoxy-quinazoline, 4 - [(3-ethynylphenyl) amino] -6- {1 - [(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amin] -6- {1 - [(cis-2,6-dimethyl-morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - ((3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(2-methyl-morpholin-4-yl) -carbonyl] -piperidin-4-yloxy} 7-methoxy-quinazoline, 4 - [(3-chloro-4-f luor-phenyl) amino] -6- {1 - [(S, S) - (2-oxa-5-aza-bicyclo [2.2.1] hept-5-yl) carbonyl] piperidin-4-yloxy} - 7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(N-methyl-N-2-methoxyethyl-amino) -carbonyl] -piperidin-4-yloxy } -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-ethyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3 -Chloro-4-fluoro-phenyl) -amino] -6- {1 - [(2-methoxyethyl) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro -phenyl) -amino] -6- {1 - [(3-methoxy-propyl-amino) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- [cis-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino ] -6- [cis-4- (N-acetyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [trans-4- (N- methanesulfonyl-N-methyl-amino) -cyclohexane-1-yloxy] -7-methoxy-quinazoline , 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-dimethylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4- fluorophenyl) amino] -6- (trans-4- {N - [(morpholin-4-yl) carbonyl] -N-methylamino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4- [(3-chloro-4-fluoro-phenyl) amino] -6- [2- (2,2-dimethyl-6-oxo-morpholin-4-yl) -ethoxy] -7 - [(S) - (tetrahydrofuran -2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4- [ (3-chloro-4-fluoro-phenyl) -amino] -6- (1-cyano-piperidin-4-yloxy) -7-methoxy-quinazoline, and cetuximab, optionally in the form of their racemates, enantiomers or diastereomers, optionally in the form their pharmacologically acceptable acid addition salts, their solvates and / or hydrates.

Particularly preferred for the purposes of the present invention are those EGFR inhibitors which are selected from the group consisting of 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl ) -1-oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxyquinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - {(4- (morpholine-4 -yl) -1-oxo-2-buten-1-yl] amino} -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - {[4 - (( R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7 - [(S) - (tetrahydrofuran-3-yl) oxy] - quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2 - ((S) -6-methyl-2-oxo-morpholin-4-yl) -ethoxy] -7-methoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino) -6 - ({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-butene 1-yl} amino) -7-cyclopropylmethoxyquinazoline, 4 - [(R) - (1-phenylethyl) amino] -6 - ({4- [N- (tetrahydropyran-4-yl) -N-methyl -amino] -1-oxo-2-buten-1-yl} amino) -7-cyclopropylmethoxy quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - ({4- [N- ( 2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-buten-1-yl} ami no) -7-cyclopentyloxy-quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7 - [(R) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-ethynylphenyl) amino] -6,7-bis (2-methoxyethoxy) quinazoline , 4 - [(R) - (1-phenylethyl) amino] -6- (4-hydroxy-phenyl) -7H-pyrrolo [2,3-d] pyrimidine, 3-cyano-4 - [(3 chloro-4-fluorophenyl) amino] -6 - {[4- (N, N-dimethylamino) -1-oxo-2-buten-1-yl] amino} -7-ethoxy-quinoline, 4 - [(R) - (1-phenyl-ethyl) -amino] -6 - {[4 - ((R) -6-methyl-2-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl] -amino } -7-methoxyquinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] -amino } -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-ethynylphenyl) amino] -6 - {[4- (5,5-dimethyl-2-oxo-morpho lin-4-yl) -1-oxo-2-buten-1-yl] amino} quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {2- [4- ( 2-oxomorpholin-4-yl) -piperidin-1-yl] -ethoxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4 -amino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-methanesulfonyl-amino-cyclohexan-1-yloxy) -7 -methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-3-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro) phenyl) amino] -6- {1 - [(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (piperidin-3-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [1- (2-acetylamino-ethyl) -piperidine-4 -yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-4-yloxy) -7-ethoxy-quinazoline, 4 - [(3-chloro 4-fluoro-phenyl) amino] -6- {trans-4 - [(morpholin-4-yl) carbonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4 fluoro-phenyl) amino] -6- {1 - [(piperidin-1-yl) carbonyl] -pi peridin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (cis-4- {N - [(morpholin-4-yl) -carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-ethanesulfonyl-amino-cyclohexane-1 -yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7- (2-methoxy-ethoxy) quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [1- (2-methoxy-acetyl) -piperidin-4-yloxy] -7- (2-methoxy-ethoxy) - quinazoline, 4 - [(3-ethynylphenyl) amino] -6- (tetrahydropyran-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (Cis-4- {N - [(piperidin-1-yl) carbonyl] -N-methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - ((3-chloro-4-fluoro -phenyl) amino] -6- {cis-4 - [(morpholin-4-yl) carbonylamino] -cyclohexan-1-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl ) amino] -6- {1- [2- (2-oxopyrrolidin-1-yl) -ethyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-ethynyl-phenyl) -amino] - 6- (1-acetyl-piperidin-4-yloxy) -7-methoxy-c hinazoline, 4 - [(3-ethynylphenyl) amino] -1- (1-methylpiperidin-4-yloxy) -7-methoxyquinazoline, 4 - [(3-ethynylphenyl) amino] -6- ( 1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methyl-piperidin-4-yloxy) -7 ( 2-methoxyethoxy) quinazoline, 4 - [(3-ethynylphenyl) amino] -6- {1 - [(morpholin-4-yl) carbonyl] piperidin-4-yloxy} -7-methoxyquinazoline , 4 - [(3-Chloro-4-fluoro-phenyl) -amino] -6- {1 - [(N-methyl-N-2-methoxyethyl-amino) -carbonyl] -piperidin-4-yloxy} -7-methoxy quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-ethyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-) fluorophenyl) amino) -6- [cis-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro -phenyl) -amino] -6- [cis-4- (N-acetyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro phenyl) amino] -6- (trans-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [trans-4 - (N-methanesulfonyl-N-methyl-amino) -cy clohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-dimethylamino-cyclohexan-1-yloxy) -7-methoxy- quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4- {N - [(morpholin-4-yl) -carbonyl] -N-methyl-amino} -cyclohexane-1 -yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2-dimethyl-6-oxo-morpholin-4-yl) - ethoxy] -7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidine-4- yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-cyano-piperidin-4-yloxy) -7-methoxy-quinazoline, and 4- [ (3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(2-methoxyethyl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, optionally in the form of their racemates, enantiomers or diastereomers optionally in the form of their pharmacologically acceptable acid addition salts, their solvates and / or hydrates.

Particularly preferred according to the invention as EGFR inhibitor are those compounds which are selected from the group consisting of 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {[4- (morpholin-4-yl) -1- oxo-2-buten-1-yl] amino} -7-cyclopropylmethoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6 - {[4 - ((R) -6-methyl 2-oxo-morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7 - [(S) - (tetrahydrofuran-3-yl) oxy] -quinazoline, 4 - [( 3-chloro-4-fluoro-phenyl) amino] -6- [2 - ((S) -6-methyl-2-oxo-morpholin-4-yl) -ethoxy] -7-methoxy-quinazoline, 4- [ (3-chloro-4-fluorophenyl) amino] -6 - ({4- [N- (2-methoxy-ethyl) -N-methyl-amino] -1-oxo-2-buten-1-yl} amino) 7-cyclopropylmethoxy quinazoline, 4 - [(3-ethynylphenyl) amino] -6,7-bis (2-methoxyethoxy) quinazoline, 4 - [(3-chloro-4-fluorophenyl) amino] -6 - {(4- (morpholin-4-yl) -1-oxo-2-buten-1-yl] amino} -7 - [(tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3 Ethynylphenyl) amino] -6 - {[4- (5,5-dimethyl-2-oxomorpholin-4-yl) -1-oxo-2-buten-1-yl] amino} quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (trans-4-methanesulfonyl amino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (tetrahydropyran-3-yloxy) -7-methoxy-quinazoline, 4- [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(morpholin-4-yl) -carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3 Chloro-4-fluoro-phenyl) -amino] -6- {1- [2- (2-oxo-pyrrolidin-1-yl) -ethyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3 Ethynyl-phenyl) amino-6- (1-acetyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-ethynyl-phenyl) -amino] -6- (1-methylpiperidine-4-) yloxy) -7-methoxy-quinazoline, 4 - [(3-ethynylphenyl) amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline, 4 - [(3-ethynyl- phenyl) amino] -6- {1 - [(morpholin-4-yl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- {1 - [(2-methoxyethyl) carbonyl] -piperidin-4-yloxy} -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -iamine no) -6- [cis-4- (N-methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino ] -6- [cis-4- (N-acetyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-methylamino-cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [trans-4- (N- methanesulfonyl-N-methyl-amino) -cyclohexan-1-yloxy] -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4-dimethylamino-cyclohexane 1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (trans-4- {N - [(morpholin-4-yl) -carbonyl] -N -methyl-amino} -cyclohexan-1-yloxy) -7-methoxy-quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- [2- (2,2-dimethyl-6- oxo-morpholin-4-yl) -ethoxy] -7 - [(S) - (tetrahydrofuran-2-yl) methoxy] quinazoline, 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-methanesulfonyl-piperidin-4-yloxy) -7-methoxy-quinazoline and 4 - [(3-chloro-4-fluoro-phenyl) -amino] -6- (1-cyano-piperidin-4-yloxy) -7 -methoxy-quinazoline, optionally in the form of their R acemates, enantiomers or diastereomers, optionally in the form of their pharmacologically acceptable acid addition salts, their solvates and / or hydrates.

Under Acid addition salts with pharmacologically acceptable acids to whose formation the EGFR inhibitors may be able to For example, salts selected from the group consisting hydrochloride, hydrobromide, hydroiodide, hydrosulfate, hydrophosphate, Hydromethanesulfonate, hydronitrate, hydromaleate, hydroacetate, hydrobenzoate, Hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, Hydrobenzoate and hydro-p-toluenesulfonate, preferably hydrochloride, Hydrobromide, hydrosulfate, hydrophosphate, hydrofumarate and hydromethanesulfonate Understood.

When Dopamine agonists in this case prefer connections to Application that selected are from the group consisting of bromocriptine, cabergoline, alpha-dihydroergocryptine, Lisuride, pergolide, pramipexole, roxindole, ropinirole, talipexole, terguride and Viozan. A reference to the aforementioned dopamine agonists includes in the context of the present invention, a reference to their optionally existing pharmacologically acceptable acid addition salts and optionally their hydrates. Among the physiologically acceptable acid addition salts available from the aforementioned dopamine agonists can be formed For example, pharmaceutically acceptable salts understood, the selected from the salts of hydrochloric acid, hydrobromic, Sulfuric acid, Phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid and maleic are.

When H1-antihistamines are preferably compounds for Application that are selected from the group consisting of epinastine, cetirizine, azelastine, fexofenadine, Levocabastine, loratadine, mizolastine, ketotifen, emedastine, dimetinden, Clemastine, Bamipin, Cexchlorpheniramine, Pheniramine, Doxylamine, Chlorphenoxamine, Dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratidine and Meclozin. A reference to the aforementioned H1 antihistamines includes in the context of the present invention, a reference to their optionally existing pharmacologically acceptable acid addition salts.

When PAF antagonists preferably reach compounds here Application that are selected from the group consisting of 4- (2-chlorophenyl) -9-methyl-2- [3 (4-morpholinyl) -3-propanone-1-yl] -6H-thieno [3,2-f] - [1 , 2,4] triazolo [4,3-a] [1,4] diazepine, 6- (2-chlorophenyl) -8,9-dihydro-1-methyl-8 - [(4-morpholinyl) carbonyl] -4H , 7H-cyclo-penta [4,5] thieno [3,2-f] [1,2,4] triazolo [4,3-a) (1,4] diazepin.

FORMULATIONS

The compounds according to the invention can be administered orally, transdermally, by inhalation, parenterally or sublingually. The compounds of the invention are present as active ingredients in conventional dosage forms, for example in compositions consisting essentially of an inert pharmaceutical carrier and an effective dose of the active ingredient, such as tablets, dragees, capsules, wafers, powders, solutions, suspensions, emulsions , Syrups, suppositories, transdermal systems etc. An effective dose of the compounds according to the invention is between 0.1 and 5000, preferably between 1 and 500, more preferably between 5-300 mg / dose when administered orally, for intravenous, subcutaneous or intramuscular administration 0.001 and 50, preferably between 0.1 and 10 mg / dose. According to the invention, solutions suitable for inhalation are those which contain 0.01 to 1.0, preferably 0.1 to 0.5% of active ingredient. For inhalative administration, the use of powders, ethanolic or aqueous solutions is preferred. Likewise, it is possible to use the compounds according to the invention as an infusion solution, preferably in a physiological saline solution or nutrient salt solution enforce.

The Compounds of the invention can alone or in combination with other active compounds according to the invention, optionally also in combination with other pharmacological active substances, are used. Suitable application forms For example, tablets, capsules, suppositories, solutions, juices, emulsions or dispersible Powder. Corresponding tablets, for example, by mixing the active ingredient (s) with known excipients, for example inert diluents, such as calcium carbonate, calcium phosphate or lactose, disintegrants, like cornstarch or alginic acid, Binders, such as starch or gelatin, lubricants, such as magnesium stearate or talc, and / or Means for achieving the depot effect, such as carboxymethylcellulose, Cellulose acetate phthalate, or polyvinyl acetate. The Tablets can also consist of several layers.

Corresponding can Dragees by coating of cores produced analogously to the tablets with usually used in dragee coatings Agents, such as Kollidon or shellac, gum arabic, Talc, titanium dioxide or sugar. To achieve a depot effect or to avoid incompatibilities the core also consist of several layers. Likewise also the dragee cover To obtain a depot effect consist of several layers using the excipients mentioned above for the tablets can be.

Juices of active ingredients according to the invention or combinations of active substances may additionally contain a sweetener, such as saccharin, cyclamate, glycerine or sugar as well as a taste-improving agent, e.g. Flavorings such as vanillin or orange extract. she can Furthermore Suspending adjuvants or thickening agents, such as sodium carboxymethylcellulose, Wetting agents, for example condensation products of fatty alcohols with ethylene oxide, or protective agents such as p-hydroxybenzoates.

Become injection solutions in usual Way, e.g. with the addition of preservatives, such as p-hydroxybenzoates, or stabilizers such as alkali salts of ethylenediaminetetraacetic acid and filled into injection bottles or ampoules.

The one or more active substances or combinations of active substances containing capsules For example, be prepared by using the active ingredients inert carriers, like lactose or sorbitol, mixed and encapsulated in gelatine capsules.

suitable suppository can be, for example, by mixing with designated Carriers, such as neutral fats or polyethylene glycol or its derivatives.

A therapeutically effective daily dose is between 1 and 2000 mg, preferably 10-500 mg per adult

The following examples illustrate the present invention without, however, limiting its scope: Pharmaceutical Formulation Examples A) tablets per tablet active substance 100 mg lactose 140 mg corn starch 240 mg polyvinylpyrrolidone 15 mg magnesium stearate 5 mg 500 mg

The finely ground active substance, lactose and part of the corn starch are mixed together. The mixture is screened, then moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet granulated and dried. The granules, the remainder of the corn starch and the magnesium stearate are sieved and mixed together. The mixture is compressed into tablets of suitable shape and size. B) tablets per tablet active substance 80 mg corn starch 190 mg lactose 55 mg Microcrystalline cellulose 35 mg polyvinylpyrrolidone 15 mg Sodium carboxymethyl starch 23 mg magnesium stearate 2 mg 400 mg

The finely ground active ingredient, a portion of the corn starch, lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixed together, the mixture is sieved and processed with the remainder of the corn starch and water to a granulate which is dried and sieved. To this is added the sodium carboxymethyl starch and the magnesium stearate, mixed and pressed the mixture into tablets of suitable size. C) Dragées per dragée active substance 5 mg corn starch 41.5 mg lactose 30 mg polyvinylpyrrolidone 3 mg magnesium stearate 0.5 mg 80 mg

The active ingredient, corn starch, lactose and polyvinylpyrrolidone are mixed well and moistened with water. The moist mass is forced through a sieve with 1 mm mesh size, dried at about 45 ° C and then strikes the granules through the same sieve. After admixing magnesium stearate, curved tablet cores having a diameter of 6 mm are pressed on a tableting machine. The dragee cores thus produced are coated in a known manner with a layer consisting essentially of sugar and talc. The finished dragees are polished with wax. D) capsules per capsule active substance 50 mg corn starch 268.5 mg magnesium stearate 1.5 mg 320 mg

Substance and cornstarch are mixed and moistened with water. The moist mass is sieved and dried. The dry granules are sieved and mixed with magnesium stearate. The final mixture is filled into hard gelatine capsules size 1. E) Ampoule solution active substance 50 mg sodium chloride 50 mg Aqua pro inj. 5 ml

The active ingredient is dissolved at its own pH or optionally at pH 5.5 to 6.5 in water and treated with sodium chloride as isotonic. The resulting solution is filtered pyrogen-free and the filtrate filled under aseptic conditions in ampoules, which are then sterilized and sealed. The vials contain 5 mg, 25 mg and 50 mg active ingredient. F) Suppositories active substance 50 mg Adeps solidus 1650 mg 1700 mg

The hard fat is melted. At 40 ° C., the ground active substance is dispersed homogeneously. It is cooled to 38 ° C and poured into slightly pre-cooled suppository molds G) oral suspension active substance 50 mg hydroxyethyl 50 mg sorbic acid 5 mg Sorbitol (70%) 600 mg glycerin 200 mg Aroma 15 mg Water ad 5 ml

distilled Water gets to 70 ° C heated. Herein is stirring Hydroxyethyl cellulose dissolved. To Addition of sorbitol solution and glycerol is cooled to room temperature.

At room temperature, sorbic acid, flavor and substance are added. To vent the suspension is evacuated with stirring.
and 50 mg of active ingredient.

Claims (36)

Compounds of the formula 1;

with the proviso that the circular line marked A represents an aromatic system; wherein Y is carbon, nitrogen, sulfur; Z is carbon, nitrogen, sulfur; j 1, 2 or 3; k is 0 or 1; R ^{a is} H, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , or a radical selected from the group consisting of C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, aryl, C _7-11 aralkyl, spiro, het, hetaryl and CH ₂ -O-aryl which may be optionally substituted; R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl; R ^{9 is} H, COOR ¹² , CONR ¹² or C _1-6 alkyl optionally substituted with one or more COOH, N (C _1-6 alkyl) ₂ or Het optionally substituted with one or more C _1-6 alkyl ; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl; R ^{10 is} H, C _1-6 -alkyl, CO-C _1-6 -alkyl or C _2-6 -alkynyl; R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ; R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ; R ⁴ , R ^{5 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl -Aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted with Si (C _1-4 -alkyl) ₃ , or R ⁴ is a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl; or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; R ^c NHR ⁶ or a radical selected from the group consisting of

wherein B is B, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl; R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more radicals R ^6.1. ; R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl); R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ; R ^{7.1 is} H, C _1-6 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl; R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH; R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine); R ^7.1.1.1 H or C _1-6 alkyl; R ^7.1.1.2 H or C _1-6 alkyl; as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of formula 1 according to claim 1; wherein R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl, R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2 R ^1.1.1 H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ; R ^1.1.2 H, C _1-6 -alkyl; or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl; R ^{3 is} a radical selected from the group consisting of

wherein X is bond or C _1-4 alkylene; X 'is C _1-4 -alkylene, C _2-4 -alkenylene or C _1-4 -alkynylene R ^{3a is} a radical, identical or different, selected from the group consisting of R ^3.1 , R ^3.2 and R ^3.3 ; R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ; R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1 R ^3.1.1.1 a radical selected from the group consisting of H, C _1-4 Alkyl, aryl and C _7-11 aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN; R ^3.1.1.2 H, C _1-4 alkyl; R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1 R ^3.2.1 C _1-6 -alkyl, C _3-6 - Cycloalkyl, OH, NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , CH ₂ - C _3-6 cycloalkyl and aryl; R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl; R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl; R ^3.2.1.2 aryl, C _7-11 aralkyl; or C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ; R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2. 2.1} , C _1-6 -haloalkyl, CN, OR ^3.2.2.1 , SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from among A group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 OH, imidazolidinone; R ^3.2.2.1 H or C _1-6 -alkyl, aryl, C _7-11 -aralkyl R ^3.2.2.2. H or C _1-6 alkyl; or aryl which is optionally substituted by one or two R ^3.2.3 R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, where Het may optionally be substituted with a radical C _1-6 alkyl; R ^{3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _1-6 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ; R ^3.3.1 C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 OH, CN, halogen or Het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.3.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ -C _3-6 -cycloalkyl and aryl; R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, COC _1-4 Alkyl hetaryl, COC _2-4 alkenyl hetaryl, COC _2-4 alkynyl hetaryl; or two of the groups R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ; R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl; R ^{9 is} H, COOR ¹² , CONR ¹² or C _1-6 alkyl optionally substituted with one or more COOH, N (C _1-6 alkyl) ₂ or Het optionally substituted with one or more C _1-6 alkyl ; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl; R ^{10 is} H, C _1-6 -alkyl, CO-C _1-6 -alkyl or C _2-6 -alkynyl; R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ; R ^{12 is} H, C _1-6 -alkyl; as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of formula 1 according to one of claims 1 or 2; wherein R ^{a is} a radical selected from the group consisting of aryl, C _7-11 aralkyl and hetaryl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; R ¹ and R ^{2 are} independently C _1-6 alkyl, C _2-6 alkenyl C _2-6 alkynyl, C _3-6 cycloalkyl, C _3-6 cycloalkenyl, C _1-6 haloalkyl, C _{1 -6-} alkylene-COOH, C _1-6 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SR ^1.1 , SOR ^1.1 , SO ₂ R ^1.1 , het or hetaryl, R ^1.1 OH, C _1-6 -alkyl, C _2-6 -alkenyl C _2-6 -alkynyl, NR ^1.1.1 R ^1.1.2 R ^1.1.1 H, C _1-6 -alkyl, optionally substituted by a radical selected from the group consisting of NH ₂ , NHMe, NMe ₂ ; R ^1.1.2 H, C _1-6 -alkyl; or R ^1.1.1 and R ^1.1.2 together form a five- or six-membered heterocyclic ring which may optionally be substituted by a radical selected from the group consisting of methyl, ethyl, propyl; R ^{3 is} a radical selected from the group consisting of

wherein X is bond or C _1-4 alkylene; R ^3a is a residue, the same or different, selected from the group consisting of R ^3.1, R ^3.3 and R ^3.3; R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ; R ^3.1.1 C _1-6 -alkyl, C _2-6 -alkenyl, OH, C _1-4 -alkylene-OH, C _1-4 -alkylene-NR ^3.1.1.1 R ^3.1.1.2 , COR ^3.1.1.1 , COOR ^3.1.1.1 , CONR ^3.1.1.1 R ^3.1.1.2 , NR ^3.1.1.1 R ^3.1.1.2 , Het, hetaryl, NHCOR ^3.1.1.1 R ^3.1.1.1 a radical selected from the group consisting of N, C _1-4 Alkyl, aryl and C _7-11 aralkyl; optionally substituted with a radical selected from the group consisting of halogen, OH and CN; R ^3.1.1.2 H, C _1-4 alkyl; R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or more R ^3.2.1 R ^3.2.1 C _1-6 -alkyl, C _3-6 - Cycloalkyl, OH, -NR ^3.2.1.1 R ^3.2.1.2 , NHCOR ^3.2.1.3 or Het, optionally substituted by one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 CH ₂ - C _3-6 cycloalkyl and aryl; R ^3.2.1.1 H, C _1-4 alkyl or C _7-11 aralkyl; R ^3.2.1.2 H, C _1-4 alkyl or C _7-11 aralkyl; R ^3.2.1.2 aryl, C _7-11 aralkyl; or C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ; R ^3.2.2 C _1-6 -alkyl, C _2-6 -alkenyl, C _2-6 -alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^{3.2 .2.1} , C _1-4 -haloalkyl, CN, OR ^3.2.2.1 SO ₂ R ^3.2.2.1 , C _3-6 -cycloalkyl, CO-Het, C _2-4 -alkynyl-hetaryl, guanidine or a radical selected from among A group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group consisting of halogen, C _1-6 -alkyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH, imidazolidinone; R ^3.2.2.1 H or C _1-6 -alkyl, aryl, C _7-11 -aralkyl R ^3.2.2.2. H or C _1-6 alkyl; or aryl which is optionally substituted by one or two R ^3.2.3 R ^{3.2.3 is} a radical selected from the group consisting of NH-C _1-6 -alkyl-N (C _1-6 -alkyl) ₂ or Het, where Het may optionally be substituted with a radical C _1-6 alkyl; R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _1-4 -haloalkyl and aryl which may be optionally substituted with one or more several residues R ^3.3.1 ; R ^3.3.1 C _5-6 cycloalkyl, C _5-6 cycloalkenyl, OR ^{3.3.1.1, 3.3.1.1} NR R ^3.3.1.2, CONR ^{3.3.1.1 3.3.1.2} R, COOR ^{3.3.1.1, 3.3.1.1} NR COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 OH, CN, halogen or Het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.3.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl, CH ₂ -C _3-6 -cycloalkyl and aryl; R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, COC _1-4 Alkyl hetaryl, COC _2-4 alkenyl hetaryl, COC _2-4 alkynyl hetaryl; or two of R ^3.3.1.1 , R ^3.3.1.2 and R ^3.3.1.3 together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; R ^{a is} H, C _1-6 alkyl, C _2-6 alkenyl, C _3-8 cycloalkyl, C _3-8 cycloalkenyl, C _1-6 haloalkyl, COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ , NHCO-C _1-6 -alkyl-NH ₂ , spiro or a radical selected from the group consisting of C _7-11 -aralkyl, CH ₂ -O-aryl and Het which may optionally be substituted with one or more halo, C _1-6 alkyl, CO-C _1-4 haloalkyl, C _1-4 alkyl-NH ₂ or CH ₂ NHCOOR ¹² ; R ^{8 is} C _1-6 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl or aryl optionally substituted with one or more halo or C _1-4 alkyl; R ^{9 is} H, COOR ¹² or C _1-4 alkyl optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or Het optionally substituted with one or more C _1-4 alkyl; or R ⁹ is het optionally substituted with one or more C _1-4 alkyl; R ^{10 is} H, C _1-6 -alkyl, CO-C _1-4 -alkyl or C _2-6 -alkynyl; R ^{11 is} C _1-6 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ ; R ^{12 is} C _1-6 alkyl; R ^b R ⁴ , OR ⁴ , -CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NR ⁴ R ⁵ , NR ⁵ COR ⁴ , NR ⁵ COOR ⁴ , NR ⁵ CONR ⁴ R ⁵ , NR ⁵ SOR ⁴ or NR ⁵ SO ₂ R ⁴ ; R ^{4 is} H, C _1-6 -alkyl, C _1-6 -haloalkyl, C _1-6 -alkylene-OH, C _2-6 -alkenyl, C _7-11 -aralkyl, C _2-4 -alkenyl-aryl, C _2-4 -alkynyl-aryl, C _1-4 -alkyl-hetaryl, C _2-4 -alkenyl-hetaryl, C _2-4 -alkynyl-hetaryl, C _2-6 -alkynyl, optionally substituted by Si (C _{1 -4-} alkyl) ₃ , or R ^{4 represents} a radical selected from the group consisting of aryl, het, hetaryl and optionally substituted by C _1-4 alkyl; R ^{5 is} H or C _1-6 alkyl; or R ⁴ and R ⁵ together form a five, six or seven membered ring consisting of carbon atoms and optionally a heteroatom selected from the group consisting of oxygen, nitrogen and sulfur; R ^c NHR ⁶ or a radical selected from the group consisting of

wherein B is B, C _1-4 alkyl or C _2-4 alkynyl; R ^{6 is} H or a radical selected from the group consisting of C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, het, aryl, hetaryl optionally substituted with one or more R ^6.1 radicals; R ^6.1 halogen, CF ₃ , OH, CN, OMe, SO ₂ (C _1-4 alkyl); R ^{7 is} H, C _1-4 -alkyl, C _2-4 -alkenyl, C _2-4 -alkynyl, C _3-6 -cycloalkyl, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, het, optionally substituted with C _1-4 alkyl or CONH ₂ ; R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) _2-4 R ^7.1.1 or COOButyl; R ^{7.2 is} H, C _1-6 -alkyl, optionally substituted with one or more OH; R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine); R ^7.1.1.1 H or C _1-6 alkyl; R ^7.1.1.2 H or C _1-6 alkyl; as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of formula 1 according to any one of claims 1 to 3; wherein R ^{a is} a radical selected from the group consisting of aryl and C _7-11 aralkyl, which may optionally be substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or hetaryl optionally substituted by one or more C _1-4 alkyl; R ^{1 is} C _1-4 -alkyl, C _1-4 -haloalkyl, C _1-4 -alkylene-COOH, C _1-4 -alkoxy, halogen, OH, CN, COR ^1.1 , OC _1-4 -haloalkyl, NO ₂ or SO ₂ R ^1.1 ; R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} C _1-4 alkyl, C _1-4 alkoxy or halo; R ^{3 is} a radical selected from the group consisting of

wherein n is 0 or 1; m is 0 or 1; o 2; R ^{3.1 is} spiro or het, where Het may be optionally substituted with one or more R ^3.1.1 ; R ^3.1.1 C _1-4 -alkyl, C _2-4 -alkenyl, OH, C _1-4 -alkylene-OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ , Het, hetaryl,

R ^{3.2 is} a radical selected from the group consisting of C _3-6 -cycloalkyl, het, hetaryl and spiro which is optionally substituted by one or two R ^3.2.1 R ^3.2.1 C _1-4 -alkyl, cyclopentyl, OH, - NR ^3.2.1.1 R ^3.2.1.2 or

or Het, optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl; R ^3.2.1.2 H, methyl or benzyl; or C _1-6 alkyl optionally substituted with one or two R ^3.2.2 ; R ^3.2.2 C _2-4 alkenyl, C _2-4 alkynyl, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^3.2.2.1 , C _1-4 Haloalkyl, CN, OH, SO ₂ R ^3.2.2.1 , C _3-6 cycloalkyl or a radical selected from the group consisting of

or a radical selected from the group consisting of het, hetaryl and aryl which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH; R ^3.2.2.1 H or methyl; R ^3.2.2.2. H or methyl; or aryl which is optionally substituted by one or two R ^3.2.3 R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H or a radical selected from the group consisting of C _1-6 -alkyl and aryl which may be optionally substituted by one or more radicals R ^3.3.1 ; R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or het optionally substituted with one or more radicals selected from the group consisting of C _1-4 alkyl, SO ₂ R ^3.2.1.1 , SO ₂ C _1-4 alkyl, SO ₂ C _7-11 aralkyl,

R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, COC _1-4 - alkyl hetaryl; R ^{a is} H, C _1-6 -alklyl, C _2-6 -alkenyl, C _3-6 -cycloalkyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , or a radical selected from the group consisting of

or a radical selected from the group consisting of

which may be optionally substituted with one or more Cl; or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ; R ^{8 is} C _1-4 alkyl, C _3-6 cycloalkyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro; R ^{9 is} H, COOR ¹² or piperidino, optionally substituted by one or more CH ₃ , or a radical selected from the group consisting of C _1-4 -alkyl, which may optionally be substituted by one or more COOH, NMe ₂ or 4- methylpiperazine; R ^{10 is} H, C _1-4 alkyl, C _2-4 alkynyl or COCH ₃ ; R ^{11 is} C _1-4 alkyl optionally substituted with one or more NMe ₂ , R ^{12 is} C _1-4 alkyl; R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH; R ^{4 is} H, C _1-4 -alkyl, C _1-4 -alkylene-OH, C _2-4 -alkynyl, C _1-6 -haloalkyl, aryl, het, hetaryl,

R ^{5 is} H or C _1-4 alkyl; R ^c NHR ⁶ or a radical selected from the group consisting of

wherein B is B, C _1-4 alkyl or C _2-4 alkynyl; R ^{6 is} H, C _1-4 alkyl, C _3-6 cycloalkyl, C _7-11 aralkyl, aryl optionally substituted with SO ₂ CH ₃ ; R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 , hetaryl, Het, optionally substituted by C _1-4 alkyl or CONH ₂ , or a radical selected from the group consisting of

R is ^7.1 H, C _1-4 alkyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl; R ^{7.2 is} H, C _1-4 alkyl; R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine); R ^7.1.1.1 H or C _1-6 alkyl; R ^7.1.1.2 H or C _1-6 alkyl; as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of formula 1 according to any one of claims 1 to 4; wherein R ^{a is} phenyl or benzyl, each optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, ethyl, propyl, butyl, CF ₃ , CH ₂ COOH, methoxy, F, Cl, Br, OH, CN, COR ^1.1 , OCF ₃ , NO ₂ or SO ₂ R ^1.1 ; R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} methyl, methoxy, F, Cl or Br; R ^{3 is} a radical selected from the group consisting of

wherein n is 0 or 1; m is 0 or 1; o 2; R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ; R ^3.1.1 methyl, ethyl, OH, CH ₂ OH, CH ₂ CH ₂ OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ ,

R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, ethyl, cyclopentyl, OH, NH ₂ ; or cyclohexyl which is optionally substituted with one or two R ^{3.2.1, 3.2.1} -NR R ^{3.2.1.1 3.2.1.2} R or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl; R ^3.2.1.2 H, methyl or benzyl; or C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ; R ^3.2.2 C = CH ₂ , C≡CH, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , NHCOR ^3.2.2.1 , CF ₃ , CN, OH, SO ₂ R ^3.2.2.1 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH; R ^3.2.2.1 H or methyl; R ^3.2.2.2. H or methyl; or phenyl which is optionally substituted by one or two R ^3.2.3 R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H, C _1-6 -alkyl, optionally substituted with one or more R ^3.3.1 ; R ^3.3.1 C _5-6 -cycloalkyl, C _5-6 -cycloalkenyl, OR ^3.3.1.1 , NR ^3.3.1.1 R ^3.3.1.2 , CONR ^3.3.1.1 R ^3.3.1.2 , COOR ^3.3.1.1 , NR ^3.3.1.1 COR ^3.3.1.2 , SOR ^3.3.1.1 , SO ₂ R ^3.3.1.1 , C (NR ^3.3.1.1 R ^3.3.1.2 ) NR ^3.3.1.3 , NR ^3.3.1.1 CONR ^3.3.1.2 R ^3.3.1.3 , OH, CN, Halogen or Het which is optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ H, SO ₂ CH ₃ , SO ₂ CH ₂ phenyl,

R ^3.3.1.1 , R ^3.3.1.2 and R ^{3.3.1.3 is} a radical selected from the group consisting of C _1-4 -alkyl, C _7-11 -aralkyl, C _1-4 -alkyl-hetaryl, COC _1-4 - alkyl hetaryl; R ^{a is} H, methyl, ethyl, propyl, butyl, 3-methyl-butyl, propenyl, cyclopropyl, cyclohexyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , OR ⁸ , SR ¹¹ , SOR ¹¹ , SO ₂ R ¹¹ or a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more Cl, or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ; R ^{8 is} methyl, propyl, cyclopropyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro; R ^{9 is} H, COOR ¹² or piperidino, optionally substituted with one or more CH ₃ , or a radical selected from the group consisting of methyl, ethyl and propyl, which may be optionally substituted with one or more COOH, NMe ₂ or 4-methylpiperazine ; R ^{10 is} H, methyl, COCH ₃ , C≡CH or CH ₂ C≡CH; R ^{11 is} ethyl or propyl, optionally substituted with one or more NMe ₂ , R ¹² butyl R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH; R ^{4 is} H, methyl, ethyl, 2-hydroxyethyl, propyl, C 1 H ₃ , CF ₃ , phenyl,

R ^{5 is} H, methyl or ethyl; R ^c NHR ⁶ or a radical selected from the group consisting of

wherein B is bond, methylene, ethylene, propylene or butynylene; R ^{6 is} H, C _1-4 alkyl, aryl, optionally substituted with SO ₂ CH ₃ ; R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 or a radical selected from the group consisting of

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl; R ^{7.2 is} H, methyl or ethyl; R ^7.1.1 NR ^7.1.1.1 R ^7.1.1.2 , Het or 1-imidazolyl, 2- (N-ethylpyrollidine); R ^7.1.1.1 H or C _1-6 alkyl; R ^7.1.1.2 H or C _1-6 alkyl; as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of formula 1 according to any one of claims 1 to 5; wherein R ^{a is} phenyl or benzyl, each optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, ethyl, propyl, butyl, CF ₃ , CH ₂ COOH, methoxy, F, Cl, Br, OH, CN, COR ^1.1 , OCF ₃ , NO ₂ or SO ₂ R ^1.1 ; R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ ,

R ^{2 is} methyl, methoxy, F, Cl or Br; R ^{3 is} a radical selected from the group consisting of

wherein n is 0 or 1; m is 0 or 1; o 2; R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ; R ^3.1.1 methyl, ethyl, OH, CH ₂ OH, CH ₂ CH ₂ OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ , NH ₂ ,

R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, ethyl, cyclopentyl, OH, NH ₂ ; or cyclohexyl which is optionally substituted by one or two R ^3.2.1 R ^3.2.1 -NR ^3.2.1.1 R ^3.2.1.2 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, SO ₂ R ^3.2.1.1 ,

R ^3.2.1.1 H, methyl or benzyl; R ^3.2.1.2 H, methyl or benzyl; or C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ; R ^3.2.2 C = CH ₂ , C≡CH, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2 , NR ^3.2.2.1 R ^3.2.2 , NHCOR ^3.2.2.1 , CF ₃ , CN, OH, SO ₂ R ^3.2.2.1 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group Cl, methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH; R ^3.2.2.1 H or methyl; R ^3.2.2.2. H or methyl; or phenyl which is optionally substituted by one or two R ^3.2.3 R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H, methyl or ethyl; R ^b R ⁴ , CH ₂ OR ⁴ , COR ⁴ , COOR ⁴ , CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ , NHCONR ⁴ R ⁵ or OH; R ^{4 is} H, methyl, ethyl, 2-hydroxyethyl, propyl, C 1 H ₃ , CF ₃ , phenyl,

R ^{5 is} H, methyl or ethyl; R ^{c is} NH ₂ or a radical selected from the group consisting of

wherein B is bond, methylene, ethylene, propylene or butynylene; R ^{6 is} H, phenyl optionally substituted with SO ₂ CH ₃ ; R ⁷ H, NR ^7.1 R ^7.2 , OR ^7.2 , SR ^7.2 or a radical selected from the group consisting of

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl; R ^{7.2 is} H, methyl or ethyl; R ^7.1.1 mean NMe ₂ or 1-imidazolyl, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1 according to any one of claims 1 to 6; wherein R ^{c is} a radical

wherein B is methylene, propylene; R ⁷ H, NR ^7.1 R ^7.2 or 1-imidazolyl; R ^{7.1 is} H or methyl; R ^{7.2 is} H or methyl; and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1 according to any one of claims 1 to 7; wherein R ^{a is} phenyl optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1 according to any one of claims 1 to 8; wherein R ^{a is} phenyl optionally substituted with one or more radicals selected from the group consisting of R ¹ and R ³ ; R ^{1 is} methyl, ethyl, propyl, CF ₃ , methoxy, F, Cl or Br; R ^{3 is} a remainder

and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1 according to any one of claims 1 to 9; wherein R ^{a is} phenyl optionally substituted with one or more radicals selected from the group consisting of R ¹ and R ³ ; R ^{1 is} methyl, ethyl, propyl, CF ₃ , methoxy, F, Cl or Br; R ^{3 is} a remainder

and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of the formula 1.1 according to one of claims 1 to 10;

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of the formula 1.1 according to one of claims 1 to 11; R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ , R ² and R ³ ; or

R ^{1 is} methyl, ethyl, propyl, CF ₃ , CH ₂ COOH, methoxy, F, Cl, Br, CN, COR ^1.1 or SO ₂ R ^1.1 ; R ^1.1 OH, methyl, NH ₂ , NHMe, NMe ₂ or

R ^{2 is} methyl, F, Cl or Br; R ^{3 is} a radical selected from the group consisting of

wherein n is 0 or 1; m is 0 or 1; o 2; R ^{3.1 is} a radical selected from the group consisting of

or a radical selected from the group consisting of

which may optionally be substituted by one or more R ^3.1.1 ; R ^3.1.1 methyl, OH, CH ₂ OH, CH ₂ CH ₂ OH, CH ₂ NEt ₂ , COMe, COOH, CONH ₂ ,

R ^{3.2 is} a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, ethyl, cyclopentyl, OH, NH ₂ ; or cyclohexyl which is optionally substituted by one or two R ^3.2.1 R ^3.2.1 -NR ^3.2.1.1 R ^3.2.1.2 or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more methyl groups R ^3.2.1.1 H or methyl; R ^3.2.1.2 H or methyl; or C _1-6 alkyl, straight or branched, which is optionally substituted with one or two R ^3.2.2 ; R ^3.2.2 C = CH ₂ , C≡CH, COOR ^3.2.2.1 , CONR ^3.2.2.1 R ^3.2.2.2 , NR ^3.2.2.1 R ^3.2.2.2 , CN, OH or a radical selected from the group consisting of

or a radical selected from the group consisting of

which is optionally substituted by one or more radicals selected from the group consisting of methyl, CONR ^3.2.2.1 R ^3.2.2.2 , OH; R ^3.2.2.1 H or methyl; R ^3.2.2.2. H or methyl; or phenyl which is optionally substituted by one or two R ^3.2.3 R ^{3.2.3 is} a radical selected from the group consisting of

R ^{3.3 is} H, methyl or ethyl; R ^b R ⁴ , CH ₂ OCH ₃ , COR ⁴ , COOH, COOCH ₃ CONR ⁴ R ⁵ , NH ₂ , NHCOOR ⁴ or OH; R ^{4 is} H, methyl, propyl, C≡CH, phenyl,

R ^{5 is} H or methyl; R ^c a remainder

wherein B is methylene, propylene; R ⁷ H, NR ^7.1 R ^7.2 or 1-imidazolyl; R ^{7.1 is} H or methyl; R ^{7.2 is} H or methyl; and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1.2 according to any one of claims 1 to 10;

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1.2 according to any one of claims 1 to 10 and 13; R ^{a is} phenyl, optionally substituted by one or more radicals selected from the group consisting of R ¹ and R ² ; R ^{1 is} methyl, ethyl, propyl, CF ₃ , F, Cl, COR ^1.1 or SO ₂ R ^1.1 ; R ^1.1 methyl; R ^{2 is} methyl, F or Cl; R ^b R ⁴ ; R ⁴ H; R ^c NHR ⁶ or a remainder

wherein B is bond, methylene, ethylene or propylene; R ⁶ H; R ⁷ H or NR ^7.1 R ^7.2 ,

R ^{7.1 is} H, methyl, ethyl, (CH ₂ ) ₂ R ^7.1.1 or COOButyl; R ^{7.2 is} H, methyl or ethyl; R ^7.1.1 mean NMe ₂ or 1-imidazolyl, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of the formula 1.3 according to one of claims 1 to 10;

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of the formula 1.3 according to one of claims 1 to 10 and 15; wherein R ^{a is} phenyl optionally substituted by one or more radicals selected from the group consisting of R ¹ and R ² ; or

R ^{1 is} methyl, methoxy, Cl, OH or COR ^1.1 ; R ^1.1 NH ₂ , NHMe or NMe ₂ ; R ^{2 is} methoxy or Cl; R ^{b is} R ⁴ or OH; R ⁴ H; R ^c NHR ⁶ or a remainder

wherein B is bond, methylene, ethylene or propylene; R ⁶ H; R ⁷ H, NR ^7.1 R ^7.2 or a radical selected from the group consisting of

R ^7.1 H, methyl or (CH ₂ ) ₂ R ^7.1.1 ; R ^{7.2 is} H, methyl or ethyl; R ^7.1.1 NMe ₂ ; and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of the formula 1.4 according to one of claims 1 to 10; wherein

wherein R ^a , R ^b and R ^{c have} the abovementioned meaning, as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of the formula 1.4 according to one of claims 1 to 10, 17; wherein R ^{a is} phenyl optionally substituted with one or more radicals selected from the group consisting of R ¹ and R ³ ; or R ^{1 is} methyl, F, Cl or Br; R ^{3 is} a radical selected from the group consisting of

wherein m is 0; R ^3.2 a remainder

which is optionally substituted by a radical selected from the group consisting of methyl and cyclopentyl; Cyclohexyl which is optionally substituted with a R ^3.2.1 R ^{3.2.1 is} a radical

R ^3.3 H; R ^b R ⁴ ; R ^{4 is} a radical selected from the group consisting of

R ^c a remainder

wherein B is methylene; R ⁷ H; and pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof. Compounds of formula 1 according to any one of claims 1 to 5; wherein R ^{a is} H, C _1-6 -alklyl, C _2-6 -alkenyl, C _3-6 -cycloalkyl, C _3-6 -cycloalkenyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O ) _n R ¹¹ , spiro, NHCO-C _1-6 -alkyl-NH ₂ or a radical selected from the group consisting of C _7-11 -aralkyl and CH ₂ O-aryl, which may optionally be substituted by one or more Cl ; or a group selected from the group consisting of Het which may be optionally substituted with one or more C _1-4 alkyl, COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ; R ^{8 is} C _1-4 alkyl, C _3-6 cycloalkyl, NH ₂ , hetaryl, aryl, optionally substituted with one or more chlorine; R ^{9 is} H, COOR ¹² or Het optionally substituted with one or more C _1-4 alkyl, or a radical selected from the group consisting of C _1-4 alkyl which may be optionally substituted with one or more COOH, N (C _1-4 alkyl) ₂ or 4-methylpiperazine; R ^{10 is} H, C _1-4 alkyl, C _2-4 alkynyl or COCH ₃ ; R ^{11 is} C _1-4 alkyl optionally substituted with one or more N (C _1-4 alkyl) ₂ , R ¹² C _1-4 alkyl; n is 0 or 2; R ^{b is} H, OH or COOEt; R ^{c is} NH ₂ or NHCOR ¹³ ; R ^{13 is} C _1-4 -alkyl, or NR ^13.1 R ^13.2 , R ^{13.1 is} H or C _1-4 -alkyl; R ^{13.2 is} H or C _1-4 alkyl; as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of formula 1 according to any one of claims 1 to 5 and 19; wherein R ^{a is} H, methyl, ethyl, propyl, butyl, 3-methyl-butyl, propenyl, cyclopropyl, cyclohexyl, CF ₃ , COR ⁸ , NR ⁹ R ¹⁰ , NO ₂ , S (O) _n R ¹¹ , or a radical selected from the group consisting of

or a radical selected from the group consisting of

which may be optionally substituted with one or more Cl; or a radical selected from the group consisting of

which may optionally be substituted with one or more CH ₃ , COCF ₃ , CH ₂ NH ₂ or CH ₂ NHCOOR ¹² ; R ^{8 is} methyl, propyl, cyclopropyl, NH ₂ , furanyl or phenyl optionally substituted with one or more chloro; R ^{9 is} H, COOR ¹² or piperidino, optionally substituted with one or more CH ₃ , or a radical selected from the group consisting of methyl, ethyl and propyl, which may be optionally substituted with one or more COOH, NMe ₂ or 4-methylpiperazine ; R ^{10 is} H, methyl, COCH ₃ , C≡CH or CH ₂ C≡CH; R ^{11 is} ethyl or propyl, optionally substituted with one or more NMe ₂ , R ¹² butyl R ^b H, OH or COOEt; R ^{c is} NH ₂ or NHCOR ¹³ ; R ^{13 is} methyl or NR ^13.1 R ^13.2 , R ^{13.1 is} H or methyl; R ^{13.2 is} H or methyl. as well as pharmacologically acceptable salt, diastereomers, enantiomers, racemates, hydrates or solvates thereof, with the proviso that R ^a can not be H or Me when Y = nitrogen; Z = nitrogen; j = 2; k = 0; R ^b = H and R ^c = NHCONH-Et. Compounds of the formula 1 according to one of claims 1 to 20 as a medicine. Use of the compounds of the formula 1 according to one the claims 1 to 21 for the manufacture of a medicament for the treatment of Diseases in whose pathology an activity of PI3-kinases is involved, in which therapeutically effective doses of the compounds of the formula 1 can develop a therapeutic benefit. Use according to claim 22, characterized that it is inflammatory and respiratory allergic diseases. Use according to claim 22 or 23, characterized that it is a disease that is selected from the group consisting of chronic bronchitis, acute bronchitis, Bronchitis due to bacterial or viral infection or fungi or helminths, allergic bronchitis, toxic bronchitis, chronic obstructive bronchitis (COPD), asthma (intrinsic or allergic), pediatric asthma, bronchiectasis, allergic Alveolitis, allergic or non-allergic rhinitis, chronic Sinusitis, cystic fibrosis or cystic fibrosis, alpha-1-antitrypsin deficiency, Cough, pulmonary emphysema, interstitial lung disease, alveolitis, hyperreactive airways, nasal polyps, pulmonary edema, pneumonitis due different genesis such as radiation-induced or by aspiration or infectious, Collagenoses such as lupus eryth, systemic scleroderma, sarcoidosis and M. Boeck. Use according to claim 22, characterized that it is inflammatory and allergic diseases of the skin. Use according to claim 22 or 25, characterized that it is a disease that is selected from the group consisting of psoriasis, contact dermatitis, atopic Dermatitis, alopecia areata (circular hair loss), erythema exudative multiforme (Stevens-Johnson syndrome), dermatitis herpetiformis, Scleroderma, vitiligo, hives (urticaria), lupus erythematosus, follicular and areal Pyoderma, endogenous and exogenous acne, acne rosacea and others inflammatory and allergic or proliferative skin diseases. Use according to claim 22, characterized that it is inflammation on the eye. Use according to claim 22 or 27, characterized in that it is a disease selected from the group consisting of conjunctivitis (conjunctivitis) of various types, for example by infections with fungi or bacteria, allergic conjunctivitis, irritant conjunctivitis, drug-induced conjunctivitis, keratitis and uveitis. Use according to claim 22, characterized that it is diseases of the nasal mucosa. Use according to claim 22 or 29, characterized that it is a disease that is selected from the group consisting of allergic rhinitis, allergic Sinusitis and nasal polyps. Use according to claim 22, characterized that it is inflammatory or allergic disease states which involves autoimmune reactions involved. Use according to claim 22 or 31, characterized that it is a disease that is selected from the group consisting of Crohn's disease, ulcerative colitis, systemic Lupus erythematosus, chronic hepatitis, multiple sclerosis, rheumatoid Arthritis, psoriatic arthritis, osteoarthritis, rheumatoid Spondylitis. Use according to claim 22, characterized that it is kidney inflammation is. Use according to claim 22 or 33, characterized that it is a disease that is selected from the group consisting of glomerulonephritis, interstitial Nephritis and idiopathic nephrotic syndrome. Pharmaceutical formulations characterized by the content of one or more compounds of the formula 1 one of the claims 1 to 20. Inhalable pharmaceutical formulation, characterized by a content of a compound of formula 1 according to one claims 1 to 20.