MX2008010119A

MX2008010119A - Novel azacycly-substituted arylthienopyrimidinones, process for their preparation and their use as medicaments

Info

Publication number: MX2008010119A
Application number: MXMX/A/2008/010119A
Authority: MX
Inventors: Stengelin Siegfried; Schwink Lothar; Gossel Matthias; Hessler Gerhard; Lennig Petra; Haack Torsten
Original assignee: Gossel Matthias; Haack Torsten; Hessler Gerhard; Lennig Petra; Sanofiaventis; Schwink Lothar; Stengelin Siegfried
Priority date: 2006-02-15
Filing date: 2008-08-07
Publication date: 2008-10-03

Abstract

The invention relates to azacyclyl-substituted arylthienopyrimidinones and their derivatives of formula (I), and their physiologically tolerated salts and physiologically functional derivatives, their preparation, medicaments comprising at least one azacyclyl-substituted arylthienopyrimidinone of the invention or its derivative, and the use of the azacyclyl-substituted aryithienopyrimidinones of the invention and their derivatives as MCH antagonists.

Description

NEW ARILTIENOPIRIMIDINONES REPLACED WITH AZACICLILO, PROCEDURE FOR ITS PREPARATION AND ITS USE AS MEDICINES The invention relates to azacyclyl or azacyclyl-substituted aryl-tienopyrimidinones and their derivatives, to their physiologically tolerated salts and physiologically functional derivatives, to their preparation, to medicaments comprising at least one azacyclyl-substituted arylthiopyrimidinone of the invention or its derivative, and to the use of the azacyclyl-substituted aryl-tienopyrimidinones of the invention and their derivatives as medicaments. In the prior art, compounds similar in structure to the azacyclic substituted arylthienopyrimidinones and their derivatives described in the present application and having a pharmacological effect have been described. Thus, for example, WO2005 / 042541 discloses 3- (4-aminophenyl) thienopyrimid-4-one derivatives as MCH R1 antagonists for the treatment of obesity, diabetes, depression and anxiety states. WO 03/033476 discloses bicyclic pyrimidone derivatives having an antagonistic effect of MCH R1 for the treatment of obesity, and WO 03/033480 discloses lactam derivatives suitable as MCH R1 antagonists. Other compounds that have an antagonistic effect of MCH for the treatment of obesity are described in the prior art (examples: WO2005047293, WO2004092181, WO2005103039, WO2004024702, WO2001021577, WO2003035624, WO2002089729, WO2002006245, WO2002002744, WO2002057233, WO2003045313, WO2003097047, WO2002010146, WO2003087044). The invention was based on the object of providing compounds that cause weight reduction in mammals and that are suitable for the prevention and treatment of obesity and diabetes and their various sequelae. Surprisingly, a number of compounds have been discovered that modulate the activity of MCH receptors. In particular, the compounds are distinguished by an antagonism of MCH1 R. Therefore, the invention relates to compounds of formula I, wherein the meanings are R1, R1 \ R1", RV" independently of each other H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (C6), O-alkoxy ( Ci-C4) -alkyl (CI-CA), S-alkyl (Ci-C6), alkyl (CrC6), alkenyl (C2-C6), cycloalkyl (C3-C8), O-cycloalkyl (C3-Ce), cycloalkenyl (C3-C8), alkynyl (C2-C6), alkylene (Co-Ce) -aryl, O-alkylene (C0-C8) -aryl, S-aryl, N (R3) (R4), S02-CH3, COOH , COO-alkyl (Ci-C6), CON (R5) (R6), N (R7) CO (R8), N (R9) SO2 (R10), CO (R1 1) or (C (R12) (R13)) X-0 (R14) preferably H, F, Cl, Br, OH, CF3 > N02, CN, OCF3, O-alkyl (Ci-C6), alkoxy (C4) -alkyl (C4), S-alkyl (Cr6), alkyl (C6), alkenyl (C2-C6), cycloalkyl (C3) -C8), O-cycloalkyl (C3-C8), alkynyl (C2-C6), O-alkylene (C0-C8) -aryl or CO-alkyl (C6); Particularly and preferably H, F, Cl, Br, CF3, CN, OCF3, O-alkyl (C6), alkoxy (Ci-C4) -alkyl (CrC4) or alkyl (Cr6); very particular and preferably H, F, Cl, O-alkyl (Ci-C6) or alkyl (CrC6); wherein preferably at least two, particularly and preferably at least three or all of the radicals R1, R1? R1 and R1 '"are H; R3, R4, R5, R6, R7, R9 independently of each other H or (C-i-C8) alkyl; or R3 and R4, R5 and R6 independently independently of each other together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-alkyl (? -? -? ß), oxygen and sulfur; R8, R10, R11 independently of each other H, (C-i-C8) alkyl or aryl; preferably, independently of each other H or (Ci-C8) alkyl; R12, R13 independently of each other H or (C-i-C8) alkyl, preferably independently of each other H; R 14 H, alkyl (C C 4) or aryl; preferably, independently of each other H or alkyl (CrCe); xO, 1, 2, 3, 4, 5 0 6; R2 H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (Ci-C6), O-alkoxy (CrC4) -alkyl (CrC4), S-alkyl (CrC6), alkyl (C Ce), alkenyl (C2-C6), cycloalkyl (C3-C8), O-cycloalkyl (C3-C8), cycloalkenyl (C3-C8), alkynyl (C2-C6), alkylene (Co-C8) -aryl , O-alkylene (C0-C8) -aryl, S-aryl, N (R15) (R16), S02-CH3, COOH, COO-alkyl (CrCe), CON (R17) (R18), N (R19) CO (R20), N (R21) S02 (R22), CO (R23) or (C (R24) (R25)) X-0 (R26); preferably H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (Ct-Ce), alkoxy (CrC4) -alkyl (CrC4), alkyl (CrC6), alkenyl (C2-C6) ) or alkynyl (C2-C6); particular and preferably H, F, Cl, Br, CF3, CN, OCF3, O-alkyl (d-C6), alkoxy (CrC4) -alkyl (CrC4) or alkyl (Ci-C6); very particular and preferably H, F, Cl, O-alkyl (Ci-C6) or alkyl (C6); in particular, very particular and preferably H; R15, R16, R17, R18, R19, R21 independently of each other H or alkyl (CrC8); or R15 and R16, R17 and R18 form independently of each other and optionally together with the nitrogen atom to which they are attached a ring of 5-6 members which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the group of NH, N-alkyl (C1-) C6), oxygen and sulfur; R 20, R 22, R 23 independently of each other H, (C Cs) alkyl or aryl; preferably, independently of each other H or alkyl (C-i-C8); R24, R25 independently of each other H or alkyl (C-i-Ce); R26 H, alkyl (CrC6) or aryl; preferably H or alkyl (C Ce); x '0, 1, 2, 3, 4, 5 0 6; R27 H or alkyl (CrC6), preferably H; X S, O or C (R30) = C (R30 '); preferably S, O; particular and preferably S; R30, R30 'independently of each other H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (CrC6), O-alkoxy (CC) -alkyl (C1-C4), S- alkyl (CrC6), alkyl (Ci-Ce), alkenyl (C2-C6), cycloalkyl (C3-C8), O-cycloalkyl (C3-Ce), cycloalkenyl (C3-C8), alkynyl (C2-C6) or aryl , optionally substituted with F, Cl, Br, O (C1-C6) alkyl or (C1-C6) alkyl; preferably H, F, Cl, Br, CF3, O-alkyl (C6), alkoxy (d-C4) -alkyl (C4) or alkyl (Cr6); particular and preferably H, F, Cl, O-alkyl (CrC6) or alkyl (C-i-Ce); very particular and preferably H; A link or linker having from 1 to 8 members, where the members are selected from the group consisting of O, S, SO2, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ') and cycloalkylene, preferably cyclopropylene and C = C, resulting in a chemically reasonable radical; preferably a bond or a linker having from 1 to 6 members, wherein the members are selected from the group consisting of O, SO2, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ') and C = C, resulting in a chemically reasonable radical; particularly and preferably a bond or linker having from 1 to 5 members, wherein the members are selected from the group consisting of O, SO2, N (R31), CO, C (R32) (R33) and C = C, resulting in a chemically reasonable radical; very particular and preferably a bond or linker having from 1 to 5 members, wherein the members are selected from the group consisting of O, SO2, N (R31), CO, C (R32) (R33) and C = C , resulting in a chemically reasonable radical, where the linker does not contain O-CO or CO-O groups; R31, R34, R34 'independently of each other H or alkyl (d-Cs); R32, R33 independently of each other H, alkyl (C C6), OH or O-alkyl (C C6); BH, N (R35) (R36), hydroxy-alkyl (C4), alkyl (Ci-Ce), alkoxy (CrC4) -alkyl (Ci-C4), alkenyl (C2-C8), alkynyl (C2-C8) , a mono-, bi-, tri- or spirocyclic ring of 3 to 10 members which may comprise from 0 to 4 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system may be further substituted with one or more of the following substituents: F, Cl, Br, CF3, N02, CN, alkyl (CrC6), O-alkyl (d-C8), alkoxy (Ci-C4) -alkyl (C4), hydroxy-alkyl (C4) ), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (C C6), N (R42) (R43), S02CH3, SCF3 or S-alkyl ( C C6); preferably H, hydroxy (Ci-C4) alkyl, (Ci-C8) alkyl, (Ci-C4) alkoxy-alkyl (CrC), (C2-C8) alkenyl, (C2-C8) alkynyl, a mono-, bi- or spirocyclic of 3 to 10 members which can comprise from 0 to 4 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system can be further substituted with F, Cl, Br, CF3, N02, CN, alkyl (d-Ce), O-alkyl (Ci-C8), alkoxy (C4) -alkyl (C4), hydroxy-alkyl (Ci-C4), oxo, CO (R37), CON (R38) (R39) ), hydroxy, COO (R40), N (R41) COalkyl (CrC6), N (R42) (R43) or S02CH3; particular and preferably H, alkyl (CrC8), alkoxy (CrC4) -alkyl (C4), a mono-, bi- or spirocyclic ring of 3 to 10 members which may comprise from 0 to 3 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system can be further substituted with F, Cl, Br, CF3, NO2, CN, (C1-C6) alkyl, O-alkyl (CrC8), alkoxy (Ci-C4) -alkyl (C1-C4), hydroxy (C1-C4) alkyl, oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (C C6), N (R42) ) (R43) or S02CH3; very particular and preferably H, alkyl (CrC8), alkoxy (C1-C4) -alkyl (C1-C4), a mono-, bi- or spirocyclic ring of 3 to 10 members which may comprise from 0 to 3 heteroatoms selected from the group consisting of group of oxygen, nitrogen and sulfur, where the ring system can be further substituted with F, Cl, Br, CF3, N02, CN, alkyl (d-C6), O-alkyl (Ci-C8), alkoxy (Ci- C4) -alkyl (CrC4), hydroxy-alkyl (d-C4), oxo, CO (R37), hydroxy, N (R41) COalkyl (d-Ce), N (R42) (R43) or S02CH3; R35, R36, R37, R38, R39, R40, R41, R42, R43 independently of each other H or alkyl (C-i-Cs); or R38 and R39, R42 and R43 independently independently of each other together with the nitrogen atom to which they are attached are a 5-6 membered ring which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-alkyl (CrC6), oxygen and sulfur; where R35, R36, R37, R38, R39, R40, R41, R42, R43 are preferably independently of each other H or alkyl (C-i-Ca); Q structure of mono-, bi-, tri- or spirocyclic, saturated or partially unsaturated rings, having a nitrogen atom and 0-3 additional heteroatoms selected from the group of N, O and S, where the rings of the structure can be spiro-bound, condensed or linked, and wherein the ring system may be substituted with one or more of the following substituents: F, OH, CF3, CN, OCF3, oxo, O-alkyl (Ci-C8), alkoxy ( CrC4) -alkyl (C4), alkyl (d-Ce), alkenyl (C2-C6), alkynyl (C2-C6), CO (R44), (C (R45) (R46)) 0-R47 and CO ( C (R45) (R46)) p-R48, where Q comprises in total at least two N atoms; Q is preferably linked to the group by a nitrogen atom of the group Q ring; R44 H or alkyl (Ci-C8); R 45, R46 independently of each other H, alkyl (C-i-Ce), OH, (C 3 -C 8) cycloalkyl or (C 1 -C 4) alkoxy-C 4 alkyl; preferably H or (C1-C6) alkyl; particular and preferably H; or, p independently of each other 0, 1, 2, 3, 4, 5 or 6; preferably 0, 1, 2, 3 0 4; R47, R48 independently of each other OH, F, O-alkyl (Ci-C8), CON (R49) (R50), N (R51) CO (R52), N (R53) (R54), CO2 (R55), SO2Me , CN, a ring system of 3-10 members having from 0 to 3 heteroatoms selected from the group of N, O and S, which may be substituted with one or more of the following substituents: F, Cl, Br, CF3 , alkyl (CrC8), O-alkyl (Ci-C8), alkoxy (C4) -alkyl (Ci-C4), CO (R56), oxo and OH; R49, R50, R51, R52, R55, R56 independently of each other H or (Ci-C8) alkyl; or R49 and R50 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH, N-alkyl group Ce), oxygen and sulfur; R53, R54 independently of each other H, (Ci-C8) alkyl, (Ci-C4) alkoxy (C1-C4) alkyl, (C3-C8) alkenyl, (C3-C8) alkynyl, CO (R57), (C) (R58) (R59)) q-R60, CO (C (R61) (R62)) r-R63 or CO-Oalkyl (CrC8); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, comprises from 0 to 3 additional heteroatoms selected from the group of N, O and S and may be additionally substituted with one or more than the following substituents: F, Cl, Br, CF3, O-alkyl (CrC8), alkyl (Ci-C6), CO (R64), oxo, OH, alkoxy (Ci-C4) -alkyl (C1-C4) , hydroxy (C4) alkyl, CON (R65) (R66), N (R67) CO (R68), N (R69) (R70), CO2 (R71) and SO2alkyl (CrC6); R53 is preferably: H, alkyl (CrC8), (C (R58) (R59)) q-R60, (C4) alkoxy-alkyl (CC), (C3-C8) alkenyl, (C3-C8) alkynyl, CO -alkyl (Ci-C8), CO-Oalkyl (C8) or CO (C (R61) (R62)) rN (R76) (R77); R54 is preferably: alkyl (Ci-C8), (C (R58) (R59)) q-R60, alkoxy (Ci-C4) -alkyl (Ci-C4), alkenyl (C3-C8) or alkynyl (C3-C8) ); or R53 and R54 preferably together with the nitrogen atom to which they are attached are a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, may comprise from 0 to 3 additional heteroatoms selected from the oxygen, nitrogen and sulfur group, where the heterocyclic ring system can be further substituted with F, Cl, Br, CF3, alkyl (CrCe), O-alkyl (d-Cs), alkoxy (Ci-C4) -alkyl (C C4), hydroxy-alkyl (CrC4), oxo, CO (R64), CON (R65) (R66), hydroxy, COO (R71), N (R67) COalkyl (C C6), N (R69) (R70) ) or SO2alkyl (CrCe); R53, R54 are very particular and preferably: alkyl (CrC8), (C (R58) (R59)) q-R60 or (C4) alkoxy-alkyl (C4); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, can comprise from 0 to 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system can be further substituted with F, Cl, Br, CF3, alkyl (Ci-C6), O-alkyl (Ci-C8), alkoxy (d-C4) -alkyl ( C C4), hydroxyalkyl (C C4), oxo, CO (R64), hydroxy, N (R67) COalkyl (Ci-C6) or S02alkyl (d-C6); R58, R59 independently of each other H, (C1-C6) alkyl or OH; R57, R61, R62, R64, R65, R66, R67, R68, R69, R70, R71 independently of each other H or alkyl (Ci-Ce); or R69 and R70 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, may also comprise 0-1 additional heteroatoms of the group of NH, N-alkyl (C1-) C6), oxygen and sulfur; q, r independently of each other 0, 1, 2, 3, 4, 5 or 6; R60, R63 independently of each other OH, F, O-alkyl (Ci-C6), CN, COO (R78), N (R74) COalkyl (C C6), N (R76) (R77), CON (R72) (R73) ), SO2alkyl (C C6), a 3-12 member mono-, bi- or spirocyclic ring that can comprising one or more heteroatoms of the group of N, O and S, and the 3-12 membered ring may comprise additional substituents such as F, Cl, Br, OH, CF3, N02, CN, OCF3, oxo, O-alkyl ( Ci-C6), alkoxy (Ci-C4) -alkyl (d-C4), S-alkyl (CrC6), alkyl (C6), alkenyl (C2-CQ), cycloalkyl (C3-C8), O-cycloalkyl ( C3-C8), cycloalkenyl (C3-Ce), O-cycloalkenyl (C3-C8), alkynyl (C2-C6), N (R76) (R77), COO (R78), S02alkyl (C6) and COOH; preferably OH, F, O-alkyl (Ci-C6), N (R74) COalkyl (C Ce), S02alkyl (Ci-C6), a mono-, bi- or spirocyclic ring of 3-12 members which may comprise one or more heteroatoms of the N, O and S group, and the 3-12 membered ring may comprise additional substituents such as F, Cl, Br, OH, CF3, N02, CN, OCF3, oxo, O-alkyl (Ci-C6) ), alkoxy (Ci-C4) -alkyl (Ci-C4), (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, N (R76) (R77) and S02alkyl (Ci-C6) ); R72, R73, R74, R76, R77, R78 independently of each other H or alkyl (C-pCe); or R72 and R73, R76 and R77 independently optionally independently together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-C 1 -C 6 alkyl, oxygen and sulfur; if Q is a structure of monocyclic rings, saturated, from 6 to 7 members, which has a nitrogen atom and a nitrogen atom additional, where group Q is attached to the group by a nitrogen atom of the group Q ring; B is a non-aromatic ring, where the additional meanings for B have the meanings mentioned above for B; in case Q is a saturated, monocyclic, 5- to 7-membered ring structure, having a nitrogen atom and no additional heteroatom, where the ring structure is substituted with a substituent (C (R45) (R46)) 0-R47, where R47 is N (R53) (R54), and group Q is linked to the group by a nitrogen atom of the ring of group Q; B is not an unsubstituted phenyl ring. The compounds of formula I are distinguished by showing an improved solubility compared to compounds of similar structure in aqueous media while exhibiting high activity. The preferred compounds of the invention are distinguished in particular by the low blocking of the hERG channel. Preferred compounds of the invention further show improved metabolic stability compared to prior art compounds. The alkyl, alkenyl and alkynyl radicals of the substituents R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R27 R28, R28 'R29, R29' R30, R30 'R31, R32, R33, R34, R34 R35, R36, R37, R38, R39, R40, R41, R42, R43, R43 ', R44, R45, R46, R47, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R61, R63, R64, R65, R66, R67 , R68, R69, R70, R71, R72, R73, R74, R76, R77 and R78 may be straight or branched chain and / or may be optionally substituted with substituents such as (C1-C4) alkoxy or halogen. This also applies when the alkyl, alkenyl and alkynyl radicals are part of another group, for example, part of an alkoxy group (such as (d-C4) alkoxy (C1-C4) alkyl). Suitable halogens are fluorine, chlorine, bromine and iodine, preferably fluorine, chlorine and bromine, particularly and preferably fluorine. Examples of alkyl groups are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl and octyl. These include the n-isomers of these radicals and branched isomers such as isopropyl, isobutyl, isopentyl, sec-butyl, tere-butyl, neopentyl, 3,3-dimethylbutyl, etc. Unless otherwise indicated, the term alkyl further includes alkyl radicals which are unsubstituted or optionally substituted with one or more additional radicals, for example with 1, 2, 3 or 4 identical or different radicals such as (CrC 4) alkoxy or halogen Examples of alkyl groups substituted with halogen are fluorinated alkyl groups such as CF3, CHF2, CH2F, 3-fluoroprop-1-yl, 2,2,1, 1-tetrafluoroethyl. In addition, it is also possible that the additional substituents are in any desired position of the alkyl radical. Unless otherwise indicated, the alkyl radicals are preferably unsubstituted. The term "cycloalkyl" refers, in the context of the present application, to cycloalkyl and cycloalkylalkyl (alkyl which in turn is substituted with cycloalkyl), wherein the cycloalkyl group has at least 3 carbon atoms. Examples of cycloalkyl radicals are: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl; cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl. Polycyclic ring systems are also possible where appropriate, such as decalinyl, norbornyl, bornyanium or adamantanyl. The cycloalkyl radicals can be unsubstituted or optionally substituted with one or more additional radicals as indicated above by way of example for the alkyl radicals. Unless otherwise indicated, the cycloalkyl radicals are preferably unsubstituted. Examples of alkenyl and alkynyl groups are: vinyl, 1-propenyl, 2-propenyl (allyl), 2-butenyl, 2-methyl-2-propenyl, 3-methyl-2-butenyl, ethynyl, 2-propynyl (propargyl), 2-butynyl or 3-butynyl. The term "cycloalkenyl" refers, in the context of the present application, to cycloalkenyl radicals and cycloalkenylalkyl radicals (alkyl that is substituted by cycloalkenyl), which comprise at least three carbon atoms. Examples of cycloalkenyl groups are cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl. Alkenyl radicals and cycloalkenyl radicals may have from one to three conjugated or unconjugated double bonds (ie, also alk-dienyl and alk-trienyl radicals), preferably a double bond in a straight or branched chain. The same applies to the triple bonds for alkynyl radicals. The alkenyl and alkynyl radicals can be unsubstituted or optionally substituted with one or more additional radicals as indicated above by way of example for the alkyl radicals. Unless otherwise indicated, the alkenyl and alkynyl radicals are preferably unsubstituted. The term "aryl" refers in the present invention to radicals that are obtained from aromatic, monocyclic or bicyclic compounds, which do not comprise heteroatoms in the ring. When the term "aryl" refers to systems that are not monocyclic, the saturated form (perhydro form) or the partially unsaturated form (eg, the dihydro or tetrahydro form) for the second ring is also possible when the respective forms are known. and stable. The term aryl also includes in the present invention, for example, bicyclic radicals in which the two rings are aromatic and bicyclic radicals in which only one ring is aromatic. Examples of aryl groups are phenyl, naphthyl, indanyl, 1,2-dihydronaphtenyl, 1,4-dihydronaphtenyl, indenyl or 1,2,3,4-tetrahydronaphthyl. Unless otherwise indicated, the aryl radicals are preferably unsubstituted. The term "aryl" is particular and preferably phenyl or naphthyl. Heteroaryl radicals refer to radicals obtained from monocyclic or bicyclic aromatic compounds, which comprise heteroatoms in the ring, preferably N, O or S. On the other hand, statements made on aryl radicals are applied to heteroaryl radicals. A "tricycle" refers to structures that have 3 rings that are joined by more than one link. Examples of such systems are condensed systems with 3 rings and spirocycles with a fused ring system. A polycyclic group (structure of bi-, tri- or spirocyclic rings) refers, in the context of the present application, to a group obtained from spiroles, fused ring systems or linked ring systems. The espirans are distinguished by two rings that only have one carbon atom in common and because the planes of the rings of the two rings are perpendicular to each other. In the systems of condensed rings, two rings are united to each other in such a way that they have two atoms in common. This type of union implies an "ortho fusion". The linked ring systems are ring systems that have a bond of carbon atoms and / or heteroatoms between two non-adjacent atoms of a ring. A "chemically reasonable radical" refers, in the context of the present invention, to a radical that is stable at room temperature and at atmospheric pressure. In the context of the present invention, a "chemically reasonable radical" in the definition of the group A in compounds of the formula I preferably refers to groups that do not have heteroatom-heteroatom linkages between the individual members of the groups. Preferably, a "non-aromatic" ring refers, in the context of the present application, to a ring that is saturated or partially unsaturated. In this regard, a partially unsaturated ring according to the present application has one or, when appropriate, a plurality of double bonds, but the partially unsaturated ring is not aromatic. The term "non-aromatic" in the context of the present application also includes "non-heteroaromatic" rings. The compounds of formula I may have one or more centers of asymmetry. Therefore, the compounds of the formula I can exist in the form of their racemates, mixtures enriched in one enantiomer, pure enantiomers, diastereomers and mixtures of diastereomers. The present invention includes all these forms of the compounds of the formula I. These isomeric forms can be obtained by known methods, even if they are not expressly described in some cases.

The pharmaceutically acceptable salts, because their solubility in water is greater than that of the initial or basic compounds, are particularly suitable for medical applications. These salts must have a pharmaceutically acceptable anion or cation. The pharmaceutically acceptable acid addition salts of the compounds of the invention are salts of inorganic acids such as hydrochloric, hydrobromic, phosphoric, metaphosphoric, nitric and sulfuric acid, and of organic acids such as, for example, acetic, benzenesulfonic, benzoic acid , citric, ethanesulfonic, fumaric, gluconic, glycolic, isethionic, lactic, lactobionic, maleic, malic, methanesulfonic, succinic, p-toluenesulfonic and tartaric. Suitable pharmaceutically acceptable basic salts are ammonium salts, alkali metal salts (such as sodium and potassium salts), alkaline earth metal salts (such as magnesium and calcium salts) and trometamol salts (2-amino-2-hydroxymethyl). 1,3-propanediol), diethanolamine, lysine or ethylenediamine. Likewise, salts with a pharmaceutically unacceptable anion, such as, for example, trifluoroacetate, are also within the scope of the invention as useful intermediates for the preparation or purification of pharmaceutically acceptable salts and / or for their use in non-therapeutic applications, for example, in vitro. The term "physiologically functional derivative" as used herein refers to any physiologically tolerated derivative of a compound of the formula I of the invention, for example an ester, which after administration to a mammal such as, for example, a human being, it is capable of forming (directly or indirectly) a compound of the formula I or an active metabolite thereof. Physiologically functional derivatives also include prodrugs of the compounds of the invention, as described, for example, in H. Okada et al., Chem. Pharm. Bull. 1994, 42, 57-61. Such prodrugs can be metabolized in vivo to obtain a compound of the invention. These prodrugs can be active by themselves or not. The compounds of the invention can also exist in various forms of polymorphs, for example in amorphous and crystalline polymorph forms. All forms of polymorphs of the compounds of the invention are within the scope of the invention and as a further aspect of the invention. All references to "compound (s) of formula I" hereinafter refer to compound (s) of formula I as described above, and to their salts, solvates and physiologically functional derivatives as described herein. If the radicals or substituents can appear more than once in the compounds of the formula I, they can all have the meanings indicated independently of each other and can be the same or different. The symbols of compound I preferably have the following meanings independently of one another: Q is a structure of monocyclic, saturated, 6-membered rings, which has a nitrogen atom and a nitrogen atom additional, where group Q is linked to the group by a nitrogen atom of the ring of group Q; B is a non-aromatic ring, where the additional meanings for B have the meanings mentioned above for B; and in case Q is a saturated, 5- to 7-membered monocyclic ring structure, having a nitrogen atom and no additional heteroatom, where the ring structure is substituted with a substituent (C (R45) (R46) ) 0-R47, where R47 is N (R53) (R54), and group Q is linked to the group by a nitrogen atom of the ring of group Q; B is not an unsubstituted phenyl ring. R1, R1 ', R1", R1"' independently of each other H, F, Cl, Br, OH, CF3, N02, CN, OCF3, O-alkyl (Ci-C6), alkoxy (Ci-C4) -alkyl ( CrC4), S-alkyl (CrC6), alkyl (CrC6), alkenyl (C2-C6), cycloalkyl (C3-C8), O-cycloalkyl (C3-C8), alkynyl (C2-C6), O-alkylene (Co -CeJ-aryl or CO-alkyl (C1-C6); particular and preferably H, F, Cl, Br, CF3, CN, OCF3, O- (C1-C6) alkyl, alkoxy (CrC4) -alkyl (C4) or (C1-C6) alkyl; very particular and preferably H, F, Cl, O-(C1-C6) alkyl or (Ci-C6) alkyl, wherein preferably at least two, particularly and preferably at least three or all of the radicals R1, R1 ', R1"and R1"'are H. R2 H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (d-Ce), alkoxy (C4) -alkyl (Ci-C4), alkyl (Ci-Ce), (C2-C6) alkenyl or (C2-C6) alkynyl; particular and preferably H, F, Cl, Br, CF3, CN, OCF3, O-C6alkyl, (Ci-C4) alkoxy (Ci-C4) alkyl or (C1-C6) alkyl; very particular and preferably H, F, Cl, O- (C1-C6) alkyl or (CrC6) alkyl; in particular, very particular and preferably H. R27 is H. X S or O; particular and preferably S; To a link or a linker that has 1 to 6 members, where the members are selected from the group consisting of O, SO2, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ') and C = C, resulting in a radical chemically reasonable; Particularly and preferably a bond or linker having from 1 to 5 members, wherein the members are selected from the group consisting of O, S02, N (R31), CO, C (R32) (R33) and C = C, resulting in a chemically reasonable radical; very particular and preferably a bond or a linker having from 1 to 5 members, wherein the members are selected from the group consisting of O, S02, N (R31), CO, C (R32) (R33) and C = C , resulting in a chemically reasonable radical, wherein the linker does not comprise O-CO groups; in particular, preferably a bond or a linker having from 1 to 5 members, wherein the members are selected from the group consisting of O, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ') and C = C, resulting in a chemically reasonable radical; where the linker does not contain O-CO or CO-O groups; in particular, particularly and preferably a bond or an element selected from the group consisting of O, CH2, CO, O-CH2, CHOH, CH2-CH2, CH = CH, C (CH3) = CH, C = C, CH2 -0, N (CH3) CO, NH-CO, CH2-0-CH2, 0-CH = CH, C (OH) (CH3) -CH2-CH2 and C (OH) (CH3) -C = C; in particular, very particular and preferably an element selected from the group consisting of O, CH2, CO, 0-CH2, CHOH, CH2-CH2, CH = CH, C (CH3) = CH, C = C, CH2-0, N (CH3) CO, NH-CO, CH2-0-CH2, O-CH = CH, C (OH) (CH3) -CH2 -CH2 and C (OH) (CH3) -C = C; wherein R31, R34, R34 'are independently H or alkyl (C-i-Ce); R 32, R 33 are independently H, C 1 -C 6 alkyl, OH or O (C 1 -C 6) alkyl. In one embodiment of the present invention, A is: A linker having from 1 to 8 members, wherein the members are selected from the group consisting of O, S, SO2, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ') and cycloalkylene, preferably cyclopropylene and C = C, resulting in a chemically reasonable radical; preferably a linker having from 1 to 6 members, wherein the members are selected from the group consisting of O, SO2, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ' ) and C = C, resulting in a chemically reasonable radical; particularly preferably a linker having 1 to 5 members, wherein the members are selected from the group consisting of O, SO2, N (R31), CO, C (R32) (R33) and C = C, resulting in a chemically reasonable radical; very particular and preferably a linker having from 1 to 5 members, where the members are selected from the group that consists of O, N (R31), CO, C (R32) (R33) and C = C, resulting in a chemically reasonable radical, where the linker does not contain O-CO groups; in particular, preferably a bond or an element selected from the group consisting of O, CH2, CO, O-CH2, CHOH, CH2-CH2, CH = CH, C (CH3) = CH, C = C, CH2-O , N (CH3) CO, NH-CO, CH2-O-CH2, O-CH = CH, C (OH) (CH3) -CH2-CH2 and C (OH) (CH3) -C = C; wherein the radicals R31, R32, R33, R34 and R34 'have the meanings mentioned above. BH, hydroxy (C1-C4) alkyl, (Ci-C8) alkyl, (Ci-C4) alkoxy-alkyl (CrC4), (C2-C8) alkenyl, (C2-C8) alkynyl, a mono-, bi-ring - or spirocyclic of 3 to 10 members which can comprise from 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system can be additionally substituted with F, Cl, Br, CF3, NO2, CN, alkyl (CrC6), O-alkyl (d-C8), alkoxy (C4) -alkyl (CrC4), hydroxy-alkyl (C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (C C6), N (R42) (R43) or SO2CH3; or wherein the ring system can be linked to A by = C (R43 '); particularly preferably H, hydroxy (Ci-C4) alkyl, alkyl (CrC8), alkoxy (CrC4) -alkyl (CrC4), a mono-, bi- or spirocyclic ring of from 3 to 10 members which may comprise from 0 to 3 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the Ring system can be further substituted with F, Cl, Br, CF3 >; N02, CN, alkyl (Ci-C6), O-alkyl (Ci-C8), alkoxy (Ci-C4) -alkyl (C1-C4), hydroxy-alkyl (C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (CrC6), N (R42) (R43) or S02CH3; or wherein the ring system can be linked to A by = C (R43 '); very particular and preferably H, (Ci-C8) alkyl, (C1-C4) alkoxy-(C1-C4) alkyl, a 3- to 10-membered mono-, bi- or spirocyclic ring which may comprise from 0 to 3 selected heteroatoms between the oxygen, nitrogen and sulfur group, where the ring system can be further substituted with F, Cl, Br, CF3, N02, CN, alkyl (d-C6), O-alkyl (CrC8), alkoxy (CrC4) -alkyl (C1-C4), hydroxy-alkyl (CrC4), oxo, CO (R37), hydroxy, N (R41) COalkyl (Ci-C6), N (R42) (R43) or SO2CH3; where R37, R38, R39, R40, R41, R42, R43 are independently H or (Ci-C8) alkyl; or R38 and R39, R42 and R43 independently independently of each other together with the nitrogen atom to which they are attached are a 5-6 membered ring which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-alkyl (Ci-Ce), oxygen and sulfur. In a preferred embodiment, B is: B H, N (R35) (R36), hydroxy (C4) alkyl, (Ci-C8) alkyl, alkoxy (Ci-C4) -alkyl (CrC4), (C2-C8) alkenyl, (C2-C8) alkynyl, a non-aromatic, mono-, bi-, tri- or spirocyclic ring, from 3 to 10 members, which may comprise from 0 to 4 heteroatoms selected from the oxygen, nitrogen and sulfur group, wherein the ring system may be further substituted with one or more of the following substituents: F, Cl, Br, CF3, N02, CN, alkyl ( Ci-C6), O-alkyl (C8), alkoxy (C4) -alkyl (C4), hydroxy (C1-C4) alkyl, oxo, CO (R37), CON (R38) (R39), hydroxy , COO (R40), N (R41) COalkyl (Ci-C6), N (R42) (R43), S02CH3, SCF3 or S- (C1-C6) alkyl; or wherein the ring system can be linked to A by = C (R43 '); preferably H, hydroxy (C1-C4) alkyl, alkyl (CrC8), (C1-C4) alkoxy-(C1-C4) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, a non-aromatic ring, mono-, bi- or spirocyclic, from 3 to 10 members, which can comprise from 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system can be additionally substituted with F, Cl, Br, CF3 , N02, CN, alkyl (Ci-C6), O-alkyl (Ci-C8), alkoxy (CrC4) -alkyl (C1-C4), hydroxy-alkyl (C1-C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (C C6), N (R42) (R43) or S02CH3; or wherein the ring system can be linked to A by = C (R43 '); particularly preferably hydroxy (C1-C4) alkyl, (Ci-C8) alkyl, alkoxy (CrC4) -alkyl (C1-C4), a non-aromatic, mono-, bi- or spirocyclic ring, of 3 to 10 members, which can comprise 0 to 3 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system may be further substituted with F, Cl, Br, CF3, N02, CN, alkyl (Ci-C6), O-alkyl (Ci-CB), alkoxy (d-C4) -alkyl (C1-C4), hydroxy-alkyl (C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl ( C C6), N (R42) (R43) or S02CH3; very particular and preferably alkyl (CrC8), alkoxy (Ci-C4) -alkyl (C1-C4), a non-aromatic, mono-, bi- or spirocyclic ring, of 3 to 10 members, which may comprise from 0 to 3 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system can be further substituted with F, Cl, CF3, (C1-C6) alkyl, O-alkyl (CrC8), alkoxy (Ci-C4) -alkyl (C1-C4), hydroxy (Ci-C4) alkyl, oxo, CO (R37), hydroxy, N (R41) CO (C6) alkyl or S02CH3; in particular, preferably hydroxy (C1-C4) alkyl, alkyl (Ci-Ce), alkoxy (Ci-C4) -alkyl (C1-C4), alkenyl (C2-C8), alkynyl (C2-C8), a ring monocyclic, non-aromatic, 3-6 members, selected from the group: OR wherein the ring system may be further substituted with methyl, ethyl, OH or oxo; in particular, particularly and preferably hydroxy-C1-C4 alkyl, alkyl (Ci-Cs), alkoxy (CrC4) -alkyl (C1-C4), alkenyl (C2-C8), alkynyl (C2-Cs), a ring monocyclic, non-aromatic, 3-6 members, selected from the group: wherein the ring system may be further substituted with methyl, ethyl, OH or oxo; where R35, R36, R37, R38, R39, R40, R41, R42, R43 independently of each other H or alkyl (C-i-Ce); or R38 and R39, R42 and R43 independently independently of each other together with the nitrogen atom to which they are attached are a 5-6 membered ring which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-alkyl (Ci-C6), oxygen and sulfur; where R35, R36, R37, R38, R39, R40, R41, R42, R43 are preferably, independently of each other H or alkyl (C-i-Cs); Q structure of mono-, bi-, tri- or spirocyclic, saturated or partially unsaturated rings, having a nitrogen atom and 0-3 additional heteroatoms selected from the group of N, O and S, where the rings of the structure can be spiro-bound, condensed or linked, and wherein the ring system may be substituted with one or more of the following substituents: F, OH, CF3, CN, OCF3, oxo, O-alkyl (C Ce), alkoxy (Ci) -C4) -alkyl (C1-C4), alkyl (CrC6), alkenyl (C2-C6), alkynyl (C2-C6), CO (R44), (C (R45) (R46)) 0-R47 and CO ( C (R45) (R46)) p-R48, where Q comprises a total of at least two N atoms; Q is preferably linked to the group by a nitrogen atom of the group Q ring; R44 is H or (Ci-C8) alkyl; R45, R46 are independently H or alkyl (?? -?) Preferably H; or, p are independently of each other 0, 1, 2, 3 or 4; R47, R48 are independently from each other OH, F, O-alkyl (Ci-C8), CON (R49) (R50), N (R51) CO (R52), N (R53) (R54), C02 (R55), S02Me, CN , a ring system of 3-10 members having from 0 to 3 heteroatoms selected from the group of N, O and S, which may be substituted with one or more of the following substituents: F, Cl, Br, CF3, alkyl (CrC8), O-alkyl (Ci-C8), alkoxy (Ci-C4) -alkyl (C1-C4), CO (R56), oxo and OH; R49, R50, R51, R52, R55, R56 are independently of each other H or (d-C8) alkyl; or R49 and R50 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the group of NH, N-alkyl (C Ce ), oxygen and sulfur; R53 is H, (Ci-C8) alkyl, (C (R58) (R59)) q-R60, (C4-4) alkoxy-alkyl (d-C4), alkenyl (C3-C8), alkynyl (C3-C8), CO-alkyl (Ci-C8), CO- Oalkyl (C8) or CO (C (R61) (R62)) rN (R76) ) (R77); R54 is alkyl (Ci-CB), (C (R58) (R59)) q-R60, alkoxy (CrC4) -alkyl (C1-C4), (C3-C8) alkenyl or (C3-C8) alkynyl; or R53 and R54 preferably together with the nitrogen atom to which they are attached are a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, can comprise from 0 to 3 additional heteroatoms selected from the oxygen, nitrogen and sulfur group, where the heterocyclic ring system may be further substituted with F, Cl, Br, CF3, (C1-C6) alkyl, O-alkyl (Cs), alkoxy (CrC4) ) -alkyl (CrC4), hydroxy-alkyl (CrC4), oxo, CO (R64), CON (R65) (R66), hydroxy, COO (R71), N (R67) COalkyl (CrC6), N (R69) ( R70) or SO2alkyl (Ci-C6); R53, R54 are very particular and preferably: alkyl (Ci-C8), (C (R58) (R59)) q-R60 or alkoxy (Ci-C4) -alkyl (C-i-C4); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, can comprise from 0 to 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system can be further substituted with F, Cl, Br, CF3, alkyl (CrC6), O-alkyl (Ci-C8), alkoxy (d-C4) -alkyl (C C4), hydroxy-alkyl (CrC4), oxo, CO (R64), hydroxy, N (R67) CO (C6) alkyl or SO2alkyl (C6); R58, R59 are independently H, (C1-C6) alkyl or OH; R57, R61, R62, R64, R65, R66, R67, R69, R70, R71 are independently H or (Ci-C6) alkyl; or R69 and R70 optionally form together with the nitrogen atom to which they are linked a ring of 5-6 members which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the group of NH, N-alkyl (C Ce), oxygen and sulfur; q, r are independently of each other 0, 1, 2, 3, 4, 5 or 6; R60 is OH, F, O-alkyl (d-C6), CN, COO (R78), N (R74) CO alkyl (Ci-C6), N (R76) (R77), CON (R72) (R73), SO2alkyl (Ci-C6), a 3-12 membered mono-, bi- or spirocyclic ring which may comprise one or more heteroatoms of the group of N, O and S, and the ring of 3-12 additional substituent members such as F, Cl, Br, OH, CF 3, 2, CN, OCF 3, oxo, O-alkyl (CrC 6), alkoxy (Ci-C 4) -alkyl (Ci-C 4), S-alkyl (Ci-C 6), alkyl ( C1-C6), alkenyl (C2-C6), cycloalkyl (C3-C8), O-cycloalkyl (C3-Cs), cycloalkenyl (C3-C8), O-cycloalkenyl (C3-C8), alkynyl (C2-C6) , N (R76) (R77), COO (R78), SO2alkyl (C C6) and COOH; preferably OH, F, O-alkyl (C6), N (R74) CO (lower) alkyl (Ci-C6), SO2alkyl (C1-C6), a mono-, bi- or spirocyclic ring of 3-12 members which may comprise one or more heteroatoms of the N, O and S group, and the 3-12 membered ring may comprise additional substituents such as F, Cl, Br, OH, CF3, NO2, CN, OCF3, oxo, O-alkyl (Ci-C6) ), (Ci-C4) alkoxy-(C1-C4) alkyl, alkyl (CrCe), (C2-C6) alkenyl, (C2-C6) alkynyl, N (R76) (R77) and SO2alkyl (CrC6); R72, R73, R74, R76, R77, R78 are independently H or alkyl (C-i-Ce); R72 and R73, R76 and R77 independently independently optionally together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group, N-C 1 -C 6 alkyl, oxygen and sulfur. In a preferred embodiment, Q is: Q a group of the general formula: wherein ring D has the following meanings: saturated, 5-7 membered monocyclic azacry, comprising an element N (R53) or C (R45) ((CH2) 0-N (R53) (R54)); azabicyclo or saturated spirocycle, of 6-1 1 members, comprising an element N (R53) or C (R45) ((CH2) 0-N (R53) (R54)); Q is preferably: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (CrC6), O-alkyl (C6) or (Ci-C4) alkoxy-alkyl (C C4); preferably, the Q groups mentioned above have no additional substituents; Q is particular and preferably: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (CrC6), O-alkyl (CrC6) or alkoxy (CrC ^ -alkyl (CC); , the Q groups mentioned above do not have additional substituents; Q is particular and preferably: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (CrC6), O-alkyl (d-C6) or alkoxy (d-C4) -alkyl ( C C4); preferably, the Q groups mentioned above have no additional substituents; Q is very particular and preferably: wherein the groups, other than R53, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (d-Ce), O-alkyl (C Ce) or (C- | -C4) alkoxy-alkyl (C1-C4); preferably, the Q groups mentioned above have no additional substituents; In a very particularly preferred additional embodiment, Q has the meaning: wherein the group, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (Ci-C6), O-alkyl (Ci-C6) or alkoxy (CrC4) -alkyl ( CrC4); preferably, the Q groups mentioned above have no additional substituents; In a very particularly preferred additional embodiment, Q has the meaning: wherein the group, other than R53, may optionally be substituted with one or more substituents selected from F, OH, oxo, alkyl. { C ^ -Ce), O-alkyl (CrC6) or alkoxy (CrC4) -alkyl (C1-C4); preferably, the Q groups mentioned above have no additional substituents; where the radicals and groups R45, R53, R54 and o have the meanings mentioned above. The following conditions apply in the case where Q is a monocyclic, saturated, 6-membered ring structure, having a nitrogen atom and a nitrogen atom additional, where group Q is linked to the group by a nitrogen atom of the ring of group Q; B is a non-aromatic ring with the meanings mentioned above for B; and in case Q is a saturated, 5- to 7-membered monocyclic ring structure, having a nitrogen atom and no additional heteroatom, where the ring structure is substituted with a substituent (C (R45) (R46) ) 0-R47, where R47 is N (R53) (R54), and group Q is linked to the group by a nitrogen atom of the ring of group Q; B is not an unsubstituted phenyl ring. In a preferred embodiment, the present invention relates to compounds of the general formula I in which X has the meaning X or O. In a further preferred embodiment, the present invention relates to compounds of the general formula wherein ring D has the following meanings: saturated, 5-7 membered monocyclic azacry, comprising an element N (R53) or C (R45) ((CH2) 0-N (R53) (R54)); azabicyclo or 6-11 member saturated spirocycle comprising an element N (R53) or C (R45) ((CH2) 0-N (R53) (R54)); Q is preferably: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (C Ce), O-alkyl (?? -? ß) or alkoxy (Ci-C4) -alkyl (C1-C4); preferably, the Q groups mentioned above have no additional substituents; Q is particular and preferably: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, (C6) alkyl, O-C1-C6 alkyl or (Ci-C4) alkoxy-alkyl (C1-C4); preferably, the Q groups mentioned above have no additional substituents; Q is particular and preferably: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (Ci-C6), O-alkyl (CrC6) or alkoxy (CrC4) -alkyl (C1-) C4); preferably, the Q groups mentioned above have no additional substituents; Q is very particular and preferably: where the groups, other than R53, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (? -? -? e), O-alkyl (? -? -? ß) or alkoxy (CrC4 ) -alkyl (C1-C4); preferably, the Q groups mentioned above have no additional substituents; R45 H or alkyl (? -? -? ß); preferably H; ??, 1, 2, 3, 4, 5 or 6; preferably 0, 1 or 2; particular and preferably 0 or 1; very particular and preferably 0; R53, R54 independently of each other H, (Ci-C8) alkyl, alkoxy (CrC4) -alkyl (C1-C4), alkenyl (C3-C8), alkynyl (C3-C8), CO (R57), (C (R58 ) (R59)) q-R60, CO (C (R61) (R62)) r-R63 or CO-Oalkyl (C C8); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, comprises from 0 to 3 additional heteroatoms selected from the group of N, O and S, and may be further substituted with one or more of the following substituents: F, Cl, Br, CF3, O-alkyl (CrC8), alkyl (Ci-C6), CO (R64), oxo, OH , alkoxy (CC ^ - (C4) alkyl, hydroxy (C1-C4) alkyl, CON (R65) (R66), N (R67) CO (R68), N (R69) (R70), C02 (R71) and S02alkyl (C ^ C6); R53 is preferably: H, (Ci-C8) alkyl, (C (R58) (R59)) q-R60, alkoxy (Ci-C) -alkyl (C4), alkenyl (C3) -C8), alkynyl (C3-C8), CO-alkyl (C8), CO-Oalkyl (C8) or CO (C (R61) (R62)) rN (R76) (R77); R54 is preferably: alkyl (CrC8), (C (R58) (R59)) q-R60, (C4) alkoxy-(C4) alkyl, (C3-C8) alkenyl or (C3-C8) alkynyl, or R53 and R54 preferably together form with the nitrogen atom at that a mono-, bi- or spirocyclic ring of 4 to 10 members is attached which, apart from the nitrogen atom, can comprise from 0 to 3 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system Heterocyclics can be further substituted with F, Cl, Br, CF3, alkyl (CrC6), O-alkyl (CrC8), alkoxy (Ci-C4) -alkyl (C1-C4), hydroxy-alkyl (C- | -C4) , oxo, CO (R64), CON (R65) (R66), hydroxy, COO (R71), N (R67) COalkyl (C C6), N (R69) (R70) or S02alkyl (d-C6); R53, R54 are very particular and preferably: alkyl (CrC8), (C (R58) (R59)) q-R60 or (C4) alkoxy-alkyl (Ci-C4); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, can comprise from 0 to 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system can be further substituted with F, Cl, Br, CF3, alkyl (CrC6), O-alkyl (CrC8), alkoxy (Cr C4) -alkyl (Ci-C4) , hydroxy-alkyl (Ci-C), oxo, CO (R64), hydroxy, N (R67) CO (C6) alkyl or SO2alkyl (Ci-C6); R58, R59 independently of each other H, (Ci-C6) alkyl or OH; R57, R61, R62, R64, R65, R66, R67, R68, R69, R70, R71 independently of each other H or (Ci-C6) alkyl; R69 and R70 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the group of NH, N-alkyl (CrC6), oxygen and sulfur; q, r independently of each other 0, 1, 2, 3, 4, 5 or 6; R60, R63 independently of each other OH, F, O-alkyl (C ^ Ce), CN, COO (R78), N (R74) COalkyl (C C6), N (R76) (R77), CON (R72) (R73) ), S02alkyl (C Ce), a mono-, bi- or spirocyclic ring of 3-12 members which may comprise one or more heteroatoms of the group of N, O and S, and the ring of 3-12 members may comprise additional substituents such as F, Cl, Br, OH, CF3, N02, CN, OCF3, oxo, O-alkyl (C6C), alkoxy (C4C) -alkyl (Ci-C4), S-alkyl (Ci-C6) ), (C6) alkyl, (C2-?) alkenyl, (C3-C8) cycloalkyl, (C3-C8) O-cycloalkenyl (C3-Cs), (C3-C8) O-cycloalkenyl, alkynyl ( C2-C6), N (R76) (R77), COO (R78), S02alkyl (CrC6) and COOH; preferably OH, F, O-alkyl (Ci-C6), N (R74) COalkyl (Ci-C6), S02alkyl (CrC6), a mono-, bi- or spirocyclic ring of 3-12 members which may comprise one to three heteroatoms of the group of N, O and S, and the 3-12 membered ring may comprise additional substituents such as F, Cl, Br, OH, CF3lN02, CN, OCF3, oxo, O-alkyl (C6), (C4-4) alkoxy-alkyl (CrC4 ), alkyl (Ci-C6), alkenyl (C2-C6), (C2-C6) alkynyl, N (R76) (R77) and S02alkyl (CrC6); R72, R73, R74, R76, R77, R78 independently of each other H or alkyl (C-i-Ce); or R72 and R73, R76 and R77 independently optionally independently together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group , N-alkyl (Ci-C6), oxygen and sulfur. The radicals and groups R2 and B of the compounds of the general formula the particular one and preferably have the following meanings: R2 is H, F, Cl, Br, O-alkyl (CrC6), preferably H, F, Cl or alkyl (Ci -C6); particular and preferably H; and BH, N (R35) (R36), hydroxy (C1-C4) alkyl, alkyl (CrC8), alkoxy (CrC4) -alkyl (CrC4), alkenyl (C2-C8), alkynyl (C2-C8), a non-aromatic, mono-, bi-, tri- or spirocyclic ring, of 3 to 10 members, which may comprise from 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may be additionally substituted with one or more of the following substituents: F, Cl, Br, CF3, N02, CN, alkyl (CrC6), O-alkyl (CrC8), alkoxy (CC) -alkyl (C4), hydroxy-alkyl (C4) , oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (C C6), N (R42) (R43), S02CH3, SCF3 or S-alkyl (Ci -EC); or where the ring system can be attached a A by means = C (R43 '); preferably H, hydroxy (C1-C4) alkyl, (Ci-C8) alkyl, (C1-C4) alkoxy-(C1-C4) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, a ring not aromatic, mono-, bi- or spirocyclic, from 3 to 10 members, which may comprise from 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system may be further substituted with F, Cl, Br , CF3, N02, CN, (C1-C6) alkyl, O-alkyl (Ci-C8), alkoxy (Ci-C4) -alkyl (C1-C4), hydroxy-alkyl (Ci-C4), oxo, CO ( R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (Ci-C6), N (R42) (R43) or S02CH3; or wherein the ring system can be linked to A by = C (R43 '); particularly preferably hydroxy (C1-C4) alkyl, (Ci-C8) alkyl, alkoxy (CrC4) -alkyl (Ci-C4), a non-aromatic, mono-, bi- or spirocyclic ring, from 3 to 10 members , which may comprise from 0 to 3 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system may be further substituted with F, Cl, Br, CF3 > N02, CN, alkyl (C6), O-alkyl (Ci-C8), alkoxy (C1-C4) -alkyl (C1-C4), hydroxy-alkyl (C1-C4), oxo, oxo, CO (R37) , hydroxy, N (R41) COalkyl (Ci-C6) or S02CH3; very particular and preferably H, (C 8) alkyl, (C 1 -C 4) alkoxy-(C 1 -C 4) alkyl, a 3- to 10-membered mono-, bi- or spirocyclic ring which may comprise from 0 to 3 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system can additionally substituted with F, Cl, Br, CF3, N02, CN, alkyl (d-C6), O-alkyl (CrCs), alkoxy (CrC4) -alkyl (Ci-C4), hydroxy (C1-C4) alkyl , oxo, CO (R37), hydroxy, N (R41) COalkyl (C C6), N (R42) (R43) 0 SO2CH3; in particular, preferably hydroxy-alkyl (Ci-C), alkyl (Ci-C8), alkoxy (Ci-C4) -alkyl (C1-C4), alkenyl (C ^ Cs), alkynyl (C2-C8), a ring monocyclic, non-aromatic, 3-6 members, selected from the group: wherein the ring system may be further substituted with methyl, ethyl, OH or oxo; R35, R36, R37, R38, R39, R40, R41, R42, R43, R43 'independently of each other H or alkyl (CrCs); R38 and R39, R42 and R43 optionally independently together with the nitrogen atom to which they are attached are a 5-6 membered ring which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group, N-alkyl (? -? -? ß), oxygen and sulfur; where R35, R36, R37, R38, R39, R40, R41, R42, R43, R43 'are preferably independently of each other H or alkyl (Cr Ce), where the radicals and additional groups of the compound of the formula have the meanings mentioned above, The compounds of the invention of the general formula I can be prepared analogously to processes known to the person skilled in the art. Suitable processes for preparing the compounds of the invention of the general formula I are mentioned below by way of example (see, in particular, methods A, B, C, D, E, F, G, H, I, J) , K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z, AA, BA and schemes 1 to 10). A reaction sequence for preparing the compounds of the invention of the general formula I, wherein R27 is H, includes the following steps: resulting in the compounds of formula I: i) reaction of an aromatic ortho-amino carboxylic ester of the general formula (II) with dimethylformamide dimethyl acetal to give the corresponding aminal of the general formula (III): i) reaction of the resulting aminal (III) with a substituted primary aromatic amine to give a condensed pyrimidinone, and iii) where appropriate, additional reaction, to give the compounds of formula I: The symbols used in the compounds of the formulas II, Mi and IV have the meanings mentioned above with respect to the general formula I. Depending on the substitution pattern of the compounds of the general formula I, the desired compounds are obtained directly after the reaction of step ii), or an additional reaction is necessary (step iii)), when appropriate, to obtain the desired compounds of the general formula I. The reaction conditions suitable for carrying out the individual steps of the aforementioned process are known to the person skilled in the art. The preferred embodiments of said steps, as well as the preparation of the starting substances used in the steps, are known to the skilled worker and are mentioned below by way of example in said schemes, methods and examples. This invention also relates to the use of compounds of the formula I and their pharmaceutical compositions as ligands of the MCH receptor. The MCH receptor ligands of the invention are particularly suitable as modulators of the activity of MCH1 R. The role of MCH in the regulation of energy balance is now well documented (Qu, D. et al., Nature 1996, 380, 243-7; Shimada, M. et al., Nature 1998, 396, 670-4; Chen, Y et al., Endocrinology 2002, 143, 2469-77; Endocrinology 2003, 144, 4831-40; Review: G. Hervieu, Expert Opin, Ther .. Targets 2003, 7, 495-51 1; Shi, Y., Peptides 2004, 25, 1605-1 1). There are also indications that HCM antagonists may have a beneficial influence on centrally related disorders such as, for example, anxiety and depression states (Borowsky, B. et al., Nature Medicine 2002, 8, 825-30; Review: G. Hervieu, Expert Opin, Ther. Targets 2003, 7, 495-51 1; Chaki, S. et al., Drug Dev. Res. 2005, 65, 278-290; Dyck, B., Drug Dev. Res. 2005, 65, 291-300).

Compounds of this type are particularly suitable for the treatment and / or prevention of 1. Obesity 2. Diabetes mellitus, especially type 2 diabetes, including the prevention of sequelae associated with this disease. Are particular aspects in this regard - hyperglycemia, - improvement of insulin resistance, - improvement of glucose tolerance, - protection of cells? pancreatic - prevention of macro- and microvascular disorders 3. Dyslipidemias and their sequelae such as, for example, atherosclerosis, coronary heart disease, cerebrovascular disorders, etc., especially (but without restriction) those characterized by one or more of the following factors: - high concentrations of triglycerides in plasma, high concentrations of triglycerides in postprandial plasma - low concentrations of HDL cholesterol. 4. Other various conditions that may be associated with the metabolic syndrome, such as: thrombosis, hypercoagulable and prothrombotic (arterial and venous) conditions, high blood pressure heart failure such as, for example (but without restriction), after myocardial infarction, hypertensive cardiac disease or cardiomyopathy Psychiatric indications such as depressions anxiety states circadian rhythm disturbances affective disorders schizophrenia addictive disorders FORMULATIONS The amount of a compound of formula I necessary to achieve the desired biological effect depends on several factors, for example, the specific compound chosen, the use for which it is intended, the mode of administration and the clinical condition of the patient. The daily dose is generally in the range of 0.001 mg to 100 mg (typically 0.01 mg to 50 mg) per day and per kilogram of body weight, eg, 0.1-10 mg / kg / day. An intravenous dose can be, for example, in the range of 0.001 mg to 1.0 mg / kg, which conveniently can be administered as an infusion of 10 ng to 100 ng per kilogram and per minute. Infusion solutions suitable for these purposes may contain, for example, 0.1 ng to 10 mg, typically 1 ng to 10 mg, per milliliter. The individual doses they may contain, for example, from 1 mg to 10 g of the active ingredient. In this manner, the ampoules for injections may contain, for example, from 1 mg to 100 mg, and the single-dose formulations that can be administered orally, such as, for example, tablets or capsules, may contain, for example , from 0.05 to 1000 mg, typically from 0.5 to 600 mg. For the therapy of the conditions mentioned above, the compounds of formula I can be used as the compound itself, but preferably they are administered in the form of a pharmaceutical composition with an acceptable carrier. The vehicle, of course, must be acceptable in the sense of being compatible with the other ingredients of the composition and not harmful to the patient's health. The vehicle can be a solid, a liquid or both and is preferably formulated with the compound as a single dose, for example, as a tablet, which can contain from 0.05% to 95% by weight of the active ingredient. Similarly, other pharmaceutically active substances may be present, including other compounds of formula I. The pharmaceutical compositions of the invention may be produced by one of the known pharmaceutical methods, which essentially consists of mixing the ingredients with pharmacologically acceptable carriers and / or excipients. The pharmaceutical compositions of the invention are those suitable for oral, rectal, topical, peroral (for example sublingual) and parenteral (for example subcutaneous, intramuscular, intradermal or intravenous) administration, although the most suitable mode of administration depends on each individual case of the nature and severity of the condition to be treated and of the nature of the compound of formula I used in each case. Coated formulations and slow release coated formulations are also included within the scope of the invention. Acid-resistant formulations and gastric juice are preferred. Suitable coatings resistant to gastric juice comprise cellulose acetate phthalate, polyvinyl acetate phthalate, hydroxypropylmethylcellulose phthalate and anionic polymers of methacrylic acid and methyl methacrylate. Pharmaceutical preparations suitable for oral administration may be in the form of separate units such as, for example, capsules, sachets, lozenges or tablets, each containing a defined amount of at least one compound of formula I; as powders or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil in water or water in oil emulsion. These compositions, as already mentioned, can be prepared by any suitable pharmaceutical method which includes a step in which the active ingredient and the carrier (which can consist of one or more additional ingredients) are contacted. The compositions are generally produced by a uniform and homogeneous mixture of the active ingredient with a liquid and / or finely divided solid carrier, after which the product is molded if necessary. Thus, for example, a tablet can be produced by compression or molding a powder or granules of the compound, when appropriate with one or more additional ingredients.

Compression tablets can be produced by compression to obtain tablets of the compound in a fluid form such as, for example, a powder or granulate, mixed in an appropriate manner with a binder, glidant, inert diluent and / or one (or more) surfactants / dispersants in a suitable machine. The molding tablets can be produced by molding the compound, which is in powder form and is moistened with an inert liquid diluent, in a suitable machine. Pharmaceutical compositions that are suitable for peroral (sublingual) administration comprise lozenges containing at least one compound of formula I with a flavorant, typically sucrose and gum arabic or tragacanth, and lozenges comprising the compound in an inert base such as gelatin and glycerol or sucrose and gum arabic. Pharmaceutical compositions suitable for parenteral administration comprise preferably sterile aqueous preparations of at least one compound of formula I, which are preferably isotonic with the blood of the recipient for which they are intended. These preparations are preferably administered intravenously, although administration can also be carried out by subcutaneous, intramuscular or intradermal injection. These preparations can preferably be produced by mixing the compound with water and making the resulting solution sterile and isotonic with the blood. The injectable compositions of the invention generally contain from 0.1 to 5% by weight of the active compound. Pharmaceutical compositions suitable for rectal administration preferably are in the form of single-dose suppositories. These can be produced by mixing at least one compound of the formula I with one or more conventional solid carriers, for example, cocoa butter, and shaping the resulting mixture. Pharmaceutical compositions suitable for topical use in the skin are preferably in the form of an ointment, cream, lotion, paste, spray, aerosol or oil. Vehicles that can be used are petrolatum, lanolin, polyethylene glycols, alcohols and combinations of two or more of these substances. The active ingredient is generally present in a concentration of 0.1 to 15% by weight of the composition, for example 0.5 to 2%. Transdermal administration is also possible. Pharmaceutical compositions suitable for transdermal uses may be in the form of individual patches that are suitable for direct long-term contact with the epidermis of the patient. These patches conveniently contain the active ingredient in an aqueous solution which is buffered when appropriate, dissolved and / or dispersed in an adhesive or dispersed in a polymer. A suitable concentration of active ingredient is from about 1% to 35%, preferably from about 3% to 15%. A particular possibility is that the ingredient active is released by electrotransport or iontophoresis as described, for example, in Pharmaceutical Research, 2 (6): 318 (1986). The compounds of formula I are distinguished by beneficial effects on lipid metabolism, and are particularly suitable for reducing weight and for maintaining a reduced weight after weight reduction has taken place in mammals and as anorexic agents. The compounds are distinguished as CH1 R selective antagonists because of their low toxicity, the small effect on metabolic enzymes and their few side effects. In particular, the preferred compounds of the invention are distinguished by the low blocking of the hERG channel. In addition, the preferred compounds of the formula I are significantly soluble in aqueous systems and, thus, are particularly suitable for pharmaceutical development. In addition, the pharmacological effect is achieved in in vivo test models after oral administration with well tolerated vehicles. The compounds can be used alone or in combination with other active weight reducing ingredients or anorexics. Other active anorexic ingredients of this type are mentioned, for example, in the Rote Liste, chapter 01, under weight-reducing agents / appetite suppressants, and can also include active ingredients that increase the renewal of energy of the organism and in this way lead to a reduction in weight or even those that they influence the overall metabolism of the body in such a way that an increase in caloric intake does not lead to an increase of fat deposits and a normal intake of calories leads to a reduction of body fat deposits. The compounds are suitable for prophylaxis and, in particular, for the treatment of excessive weight or obesity. The compounds are also suitable for the prophylaxis and, in particular, for the treatment of type II diabetes, arteriosclerosis, to normalize lipid metabolism and for the treatment of elevated blood pressure.

COMBINATIONS WITH OTHER MEDICINES The compounds of the invention can be administered alone or in combination with one or more additional pharmacologically active substances which, for example, have beneficial effects on metabolic disorders or disorders frequently associated with these alterations. Examples of these medications are 1. medicines that reduce blood glucose, antidiabetics, 2. active ingredients for the treatment of dyslipidemias, 3. anti-atherosclerotic drugs, 4. antiobesity agents, 5. anti-inflammatory active ingredients 6. active ingredients for the treatment of malignant tumors 7. active ingredients antithrombotic 8. active ingredients for the treatment of the elevation of the blood pressure 9. active ingredients for the treatment of heart failure and 10. active ingredients for the treatment and / or prevention of complications caused by diabetes or associated with diabetes 11. active ingredients for the treatment of neurodegenerative disorders 12. active ingredients for the treatment of diseases of the central nervous system 13. active ingredients for the treatment of drug addiction, nicotine or alcohol 14. pain eliminators can be combined with the compounds of the invention of the formula I in particular to achieve a synergistic improvement of the effect. The administration of the active ingredient combination can be carried out by means of separate administration of the active ingredients to the patient or in the form of combination products in which a plurality of active ingredients are present in a pharmaceutical preparation. The following are examples of active ingredients suitable for combination products: All the antidiabetics mentioned in Rote Liste 2006, Chapter 12; all the weight-reducing agents / appetite suppressants mentioned in Rote Liste 2006, Chapter 1; all the agents lipid reducers that are mentioned in Rote Liste 2006, chapter 58. Most of the active ingredients mentioned later in this document are described in the USP Dictionary of USAN and International Drug Ñames, US Pharmacopeia, Rockville 2001. Antidiabetics include insulin and insulin derivatives such as, for example, Lantus® (see www.lantus.com) or Apidra® (HMR 1964) or those described in WO2005005477 (Novo Nordisk), fast-acting insulins (see US 6,221. 633), inhalable insulins such as, for example, Exubera® or oral insulins such as, for example, IN-105 (Nobex) or Oral-lyn ™ (Generex Biotechnology), GLP-1 derivatives such as, for example, exenatide , liraglutide or those described in WO98 / 08871 or WO2005027978 of Novo Nordisk A / S, in WO01 / 04156 of Zealand or in WO00 / 34331 of Beaufour-lpsen, Pramlintide Acétate (Symlin; Amylin Pharmaceuticals ), and ingr active hypoglycaemic active ingredients orally. The active ingredients preferably include sulfonylureas, biguanidines, meglitinides, oxadiazolidinediones, thiazolidinediones, glucosidase inhibitors, glycogen phosphorylase inhibitors, glucagon antagonists, glucokinase activators, fructose-1, 6-bisphosphatase inhibitors, glucose transporter modulators 4 (GLUT4), glutamine-fructose-6-phosphate amidotransferase (GFAT) inhibitors, GLP-1 agonists, opening of potassium channels such as, for example, those described in WO documents 97/26265 and WO 99/03861 of Novo Nordisk AS, dipeptidylpeptidase IV inhibitors (DPP-IV), insulin sensitizers, hepatic enzyme inhibitors involved in the stimulation of gluconeogenesis and / or glycogenolysis, modulators of glucose uptake , glucose transport and glucose reabsorption, inhibitors of? ? ß-HSDI, inhibitors of protein tyrosine phosphatase 1 B (PTP1 B), sodium-dependent glucose transporter modulators 1 or 2 (SGLT1, SGLT2), compounds that alter the metabolism of lipids such as active ingredients and antihyperlipidemics and ingredients antilipidemic active ingredients, compounds that reduce food intake, compounds that increase thermogenesis, modulators of PPAR and RXR and active ingredients that act on the ATP-dependent potassium channel of beta cells. In one embodiment of the invention, at least one compound of formula I is administered in combination with an HMGCoA reductase inhibitor such as simvastatin, fluvastatin, pravastatin, lovastatin, atorvastatin, cerivastatin, rosuvastatin or L-659699. In one embodiment of the invention, at least one compound of the formula I is administered in combination with a cholesterol absorption inhibitor such as, for example, ezetimibe, tiqueside, pamaqueside, FM-VP4 (sitostanol / campesterol ascorbyl phosphate; Medi-Tech, WO2005042692), MD-0727 (Microbia Inc., WO2005021497) or with compounds as described in WO2002066464 (Kotobuki Pharmaceutical Co. Ltd.), WO2005062824 (Merck &Co.) or WO2005061451 and WO2005061452 (AstraZeneca AB). In one embodiment of the invention, at least one compound of the formula I is administered in combination with a PPAR gamma agonist such as, for example, rosiglitazone, pioglitazone, JTT-501, Gl 262570, R-483 or CS-01 1 (rivoglitazone) In one embodiment of the invention, at least one compound of the formula I is administered in combination with a PPAR alpha agonist such as, for example, GW9578, GW-590735, K-1 11, LY-674, KRP-101 or DRF-10945, In one embodiment of the invention, at least one compound of the formula I is administered in combination with a mixed PPAR alpha / gamma agonist such as, for example, muraglitazar, tesaglitazar, naveglitazar, LY-510929, ONO-5129, E- 3030 or as described in WO00 / 64888, WO00 / 64876, WO03 / 020269, WO2004075891, WO2004076402, WO2004075815, WO2004076447, WO2004076428, WO2004076401, WO2004076426, WO2004076427, WO20060181 18, WO20060181 15 and WO20060181 6 or in JP. Berger et al., TRENDS in Pharmacological Sciences 28 (5), 244-251, 2005, In one embodiment of the invention, at least one compound of formula I is administered in combination with a delta PPAR agonist such as, for example, , GW-501516 or as described in WO2005097762, WO2005097786, WO2005097763 and WO2006029699, In one embodiment, at least one compound of formula I is administered in combination with metaglidasen or with MBX-2044 or another PPAR partial agonist / antagonist. gamma. In an embodiment of the invention, at least one compound of formula I is administered in combination with a fibrate such as, for example, fenofibrate, clofibrate or bezafibrate. In one embodiment of the invention, at least one compound of formula I is administered in combination with an MTP inhibitor such as, for example, implitapide, BMS-201038, R-103757 or those described in WO2005085226.

In an embodiment of the invention, at least one compound of the formula I is administered in combination with a CETP inhibitor such as, for example, torcetrapib or JTT-705. In one embodiment of the invention, at least one compound of formula I is administered in combination with an inhibitor of bile acid absorption (see, for example, US 6,245,744, US 6,221,897 or WO00 / 61568) , such as, for example, HMR 1741 or those described in DE 10 2005 033099.1 and DE 10 2005 033100.9. In an embodiment of the invention, at least one compound of formula I is administered in combination with a bile acid polymeric adsorbent such as, for example, cholestyramine or colesevelam. In one embodiment of the invention, at least one compound of the formula I is administered in combination with an inducer of the LDL receptor (see US 6,342,512), such as, for example, HMR1171, HMR1586 or those described in WO2005097738, In one embodiment, at least one compound of formula I is administered in combination with Omacor® (omega-3 fatty acids); ethyl esters of highly concentrated eicosapentaenoic acid and docosahexaenoic acid). In an embodiment of the invention, at least one compound of formula I is administered in combination with an ACAT inhibitor such as, for example, avasimibe.

In one embodiment of the invention, at least one compound of the formula I is administered in combination with an antioxidant such as, for example, OPC-14117, probucol, tocopherol, ascorbic acid, D-carotene or selenium. In an embodiment of the invention, at least one compound of the formula I is administered in combination with a vitamin such as, for example, vitamin B6 or vitamin B12. In one embodiment of the invention, at least one compound of formula I is administered in combination with a lipoprotein lipase modulator such as, for example, ibrolipim (NO-1886). In one embodiment of the invention, at least one compound of formula I is administered in combination with an ATP citrate lyase inhibitor such as, for example, SB-204990. In one embodiment of the invention, at least one compound of the formula I is administered in combination with an inhibitor of squalene synthetase such as, for example, BMS-188494 or as described in WO2005077907. In one embodiment of the invention, at least one compound of formula I is administered in combination with a lipoprotein (a) antagonist such as, for example, gemcabene (CI-1027). In one embodiment of the invention, at least one compound of formula I is administered in combination with an HM74A receptor agonist such as, for example, nicotinic acid.

In one embodiment of the invention, at least one compound of formula I is administered in combination with a lipase inhibitor such as, for example, orlistat or cetilistat (ATL-962). In one embodiment, at least one compound of formula I is administered in combination with insulin. In one embodiment, at least one compound of the formula I is administered in combination with a sulfonylurea such as, for example, tolbutamide, glibenclamide, glipizide or glimepiride. In one embodiment, at least one compound of formula I is administered in combination with a biguanide such as, for example, metformin. In another embodiment, at least one compound of the formula I is administered in combination with a meglitinide such as, for example, repaglinide or nateglinide. In one embodiment, at least one compound of the formula I is administered in combination with a thiazolidinedione such as, for example, troglitazone, ciglitazone, pioglitazone, rosigiitazone or the compounds described in WO 97/41097 of Dr. Reddy's Research Foundation, in particular 5 - [[4 - [(3,4-dihydro-3-methyl-4-oxo-2-quinazolinylmethoxy] phenyl] methyl] -2,4-thiazolidinedione In one embodiment, at least one compound of Formula I is administered in combination with an α-glucosidase inhibitor such as, for example, miglitol or acarbose.

In one embodiment, at least one compound of formula I is administered in combination with an active ingredient that acts on the ATP-dependent potassium channel of beta cells, such as, for example, tolbutamide, glibenclamide, glipizide, glimepiride or repaglinide . In one embodiment, at least one compound of formula I is administered in combination with more than one of the compounds mentioned above, for example, in combination with a sulfonylurea and metformin, a sulfonylurea and acarbose, repaglinide and metformin, insulin and a sulfonylurea , insulin and metformin, insulin and troglitazone, insulin and lovastatin, etc. In one embodiment, at least one compound of formula I is administered in combination with substances that influence hepatic glucose production, such as, for example, a glycogen phosphorylase inhibitor, such as, for example, PSN-357 or FR-258900 or those described in WO2003084922, WO2004007455, WO2005073229-31 or WO2005067932. In one embodiment, at least one compound of formula I is administered in combination with glucagon receptor antagonists such as, for example, A-770077, NNC-25-2504 or as described in WO2004100875 or WO2005065680. In one embodiment, at least one compound of formula I is administered in combination with giucokinase activators, such as, for example, RO-4389620, LY-2121260 (WO2004063179), PSN-105, PSN-110, GKA-50 or such as those described in WO2004072031, WO2004072066, WO 05103021, WO 06016178, WO 00058293, WO 00183465, WO 00183478, WO 00185706, WO 00185707, WO 01044216, GB 02385328, WO02008209, WO 02014312, WO 0246173, WO 0248106, DE 10259786, WO 03095438, US 04067939, WO 04052869, EP 1532980, WO 03055482, WO 04002481, WO 05049019, WO 05066145, WO 05123132, WO 03080585, WO03097824, WO 04081001, WO 05063738, WO 05090332, WO 04063194, WO 01020327, WO 03000262, WO 03000267, WO 03015774, WO 04045614, WO 04046139, WO 05044801, WO 05054200, WO 05054233, WO 05056530, WO 05080359, WO 05080360 or WO 05121110. In one embodiment, at least a compound of the formula I is administered in combination with an inhibitor of gluconeogenesis, such as, for example, FR-225654. In one embodiment, at least one compound of the formula I is administered in combination with inhibitors of fructose-1,6-bisphosphatase (FBPase), such as, for example, CS-917. In one embodiment, at least one compound of formula I is administered in combination with modulators of glucose transporter 4 (GLUT4), such as, for example, KST-48 (D.-O. Lee et al .: Arzneim.- Forsch, Drug Res. 54 (12), 835 (2004)). In one embodiment, at least one compound of formula I is administered in combination with inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), as described, for example, in the document In one embodiment, at least one compound of formula I is administered in combination with inhibitors of dipeptidylpeptidase IV (DPP-IV), such as, for example, vildagliptin (LAF-237), sitagliptin (MK-0431), saxagliptin ( BMS-4771 18), GSK-823093, PSN-9301, SYR-322, SYR-619, TA-6666, TS-021, GRC-8200, GW-825964X or as described in WO2003074500, WO2003106456, WO200450658, WO2005058901, WO2005012312, WO2005012308, PCT / EP2005 / 00782, PCT / EP2005 / 008005, PCT / EP2005 / 008002, PCT / EP2005 / 008004, PCT / EP2005 / 008283, DE 10 2005 012874.2 or DE 10 2005 012873.4. In one embodiment, at least one compound of formula I is administered in combination with inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 (11-HSD1), such as, for example, BVT-2733 or those described, for example, in WO200190090-94, WO200343999, WO20041 12782, WO200344000, WO200344009, WO2004112779, WO2004113310, WO2004103980, WO20041 12784, WO 2003065983, WO2003104207, WO2003104208, WO2004106294, WO200401 410, WO2004033427, WO2004041264, WO2004037251, WO2004056744, WO2004065351, WO2004089367, WO2004089380 documents , WO2004089470-71, WO2004089896, WO2005016877 or WO2005097759. In one embodiment, at least one compound of the formula I is administered in combination with inhibitors of the protein tyrosine phosphatase 1 B (PTP1 B), as described, for example, in WO2001 19830- 31, WO200117516, WO2004506446, WO2005012295, PCT / EP2005 / 00531 1, PCT / EP2005 / 005321, PCT / EP2005 / 007151, PCT / EP2005 / or DE 10 2004 060542.4. In one embodiment, at least one compound of formula I is administered in combination with sodium dependent glucose transporter modulators 1 or 2 (SGLT1, SGLT2), such as, for example, KGA-2727, T-1095, SGL- 0010, AVE 2268 and SAR 7226 or as described, for example, in WO2004007517, WO200452903, WO200452902, WO2005121161, PCT / EP2005 / 005959, WO2005085237, JP2004359630 or by AL Handlon in Expert Opin. Ther. Patents (2005) 15 (11), 1531-1540. In one embodiment, at least one compound of formula I is administered in combination with modulators of GPR40. In one embodiment, at least one compound of formula I is administered in combination with inhibitors of hormone-sensitive lipase (HSL) as described, for example, in WO01 / 17981, WO01 / 66531, WO2004035550, WO2005073199 or WO03. / 05 842. In one embodiment, at least one compound of the formula I is administered in combination with acetyl-CoA carboxylase (ACC) inhibitors, such as, for example, those described in W0199946262, WO200372197, WO2003072197 or WO2005044814 . In one embodiment, at least one compound of formula I is administered in combination with an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), such as, for example, those described in WO2004074288. In one embodiment, at least one compound of formula I is administered in combination with an inhibitor of glycogen synthase kinase 3 beta (GSK-3 beta), as described, for example, in US2005222220, WO2005085230, WO20051-11018, PCT / EP2005 / 005346, WO2003078403, WO2004022544, WO2003106410, WO2005058908, US2005038023, WO2005009997, US2005026984, WO2005000836, WO2004106343, EP1460075, WO2004014910, WO2003076442, WO2005087727 or WO2004046117. In one embodiment, at least one compound of formula I is administered in combination with an inhibitor of protein kinase C beta (PKC beta), such as, for example, ruboxistaurin. In one embodiment, at least one compound of formula I is administered in combination with an endothelin A receptor antagonist such as, for example, avosentan (SPP-301). In one embodiment, at least one compound of formula I is administered in combination with inhibitors of "kinase I-kappaB" (inhibitors of IKK), such as those described, for example, in WO2001000610, WO2001030774, WO2004022553 or WO2005097129. In one embodiment, at least one compound of formula I is administered in combination with glucocorticoid receptor modulators, such as those described, for example, in WO2005090336.

In another embodiment, at least one compound of formula I is administered in combination with CART modulators (see "Cocaine-amphetamine-regulated transcript influences energy metabolism, anxiety and gastric emptying in mice" Asakawa, A. et al .: Hormone and Metabolic Research (2001), 33 (9), 554-558); NPY antagonists such as, for example, hydrochloride. { 4 - [(4-amino-quinazolin-2-ylamino) methyl] cyclohexylmethyl} Naphthalene-1-sulfonic acid amide (CGP 71683A); peptide YY 3-36 (PYY3-36) or analogous compounds, such as, for example, CJC-1682 (PYY3-36 conjugated to human serum albumin via Cys34), CJC-1643 (derivative of PYY3-36 which is conjugated in vivo with serum albumin) or those described in WO2005080424; cannabinoid receptor antagonists 1 (such as, for example, rimonabant, SR147778 or those described, for example, in EP 0656354, WO 00/15609, WO02 / 076949, WO2005080345, WO2005080328, WO2005080343, WO2005075450, WO2005080357, WO200170700, WO2003026647-48, WO200302776, WO2003040107, WO2003007887, WO2003027069, US6.509.367, WO200132663, WO2003086288, WO2003087037, WO2004048317, WO2004058145, WO2003084930, WO2003084943, WO2004058744, WO2004013 20, WO2004029204, WO2004035566, WO2004058249, WO2004058255, WO2004058727, WO2004069838, US20040214837 , US20040214855, US20040214856, WO2004096209, WO2004096763, WO2004096794, WO2005000809, WO2004099157, US20040266845, WO2004110453, WO2004108728, WO2004000817, WO2005000820, US20050009870, WO200500974, WO2004111033-34, WO200411038-39, WO2005016286, WO2005007111, WO2005007628, US20050054679, WO2005027837, WO2005028456, WO2005063761-62, WO2005061509 or WO2005077897); MC4 agonists (eg, [2- (3a-benzyl-2-methyl-3-oxo-2,3,3a, 4,6,7-hexahydropyrazolo [4,3-c] pyridin-5-yl) - 1-amino-1, 2,3,4-tetrahydronaphthalene-2-carboxylic acid 1- (4-chlorophenyl) -2-oxoethyl] -amide; (WO 01/91752)) or LB53280, LB53279, LB53278 or THIQ, MB243, RY764, CHIR-785, PT-141 or those described in WO2005060985, WO2005009950, WO2004087159, WO2004078717, WO2004078716, WO2004024720, US20050124652, WO2005051391, WO20041 12793, WOUS20050222014, US20050176728, US20050164914, US20050 24636, US20050130988, US20040167201. , WO2004005324, WO2004037797, WO2005042516, WO2005040109, WO2005030797, US20040224901, WO200501921, WO200509184, WO2005000339, EP1460069, WO2005047253, WO2005047251, EP1538159, WO2004072076 or WO2004072077; orexin receptor antagonists (eg, 1- (2-methylbenzoxazol-6-yl) -3- [1,5] naphthyridin-4-ylurea hydrochloride (SB-334867-A) or those described, for example , in WO200196302, WO200185693, WO2004085403 or WO2005075458); histamine H3 receptor agonists (eg, ABT-834, ABT-239, 3-cyclohexyl-1 - (4,4-dimethyl-1, 4,6,7-tetrahydroimidazo [4,5-c] oxalate salt pyridin-5-yl) propan-1 -one (WO 00/63208) or those described in WO200064884, WO2005082893, FR2870846 WO2005037810, Celanire, S., et al. Drug Discovery Today 2005, 10, 1613-1627); CRF antagonists (e.g., [2-methyl-9- (2,4,6-trimethylphenyl) -9H-1, 3,9-triazafluoren-4-yl] dipropylamine (WO 00/66585)); CRF BP antagonists (e.g., urocortin); urocortin agonists; ß3 agonists (such as, for example, 1- (4-chloro-3-methanesulfonylmethyl) -2- [2- (2,3-dimethyl-1 H -indole-6-yloxy) ethylamino] hydrochloride] ethanol (WO 01/83451)); MSH agonists (melanocyte stimulating hormone); MCH receptor antagonists (melanin concentration hormone) (such as, for example, NGD-4715, AMG-076, NBI-845, A-761, A-665798, A-798, ATC-0175, T-226296 , T-71, GW-803430 or compounds such as those described in WO2003 / 15769, WO2005085200, W02005019240, WO200401 1438, WO2004012648, WO2003015769, WO2004072025, WO2005070898, WO2005070925, WO2004039780, WO2003033476, WO2002006245, WO2002002744, WO2003004027 or FR2868780).; CCK-A agonists (such as, for example,. {2- [4- (4-chloro-2,5-dimethoxyphenyl) -5- (2-cyclohexylethyl) thiazol-2-ylcarbamoyl] trifluoroacetate] - 5,7-dimethylindol-1-yl.} Acetic (WO 99/15525), SR-146131 (WO 0244150) or SSR-125180); inhibitors of serotonin reuptake (eg, dexfenfluramine); mixed serotonergic and noradrenergic compounds (for example, WO 00/71549); 5-HT receptor agonists, for example 1- (3-ethylbenzofuran-7-yl) piperazine oxalate salt (WO 01/091 1 1); 5-HT2C receptor agonists (such as, for example, APD-356, BVT-933 or those described in WO200077010, WO20077001-02, WO2005019180, WO2003064423, WO200242304 or WO2005082859); 5-HT6 receptor antagonists such as those described, for example, in WO2005058858; bombesin receptor agonists (BRS-3 agonists); Galanin receptor antagonists; growth hormone (e.g., human growth hormone or AOD-9604); growth hormone releasing compounds (6-benzyloxy-1- (2-diisopropyl-aminoethylcarbamoyl) -3,4-dihydro-1 H-isoquinoline-2-carboxylic tertiary butyl ester (WO 01/85695)); antagonists of the growth hormone secretagogue receptor (ghrelin antagonists) such as, for example, A-778193 or those described in WO2005030734; TRH agonists (see, for example, EP 0 462 884); modulators of decoupling protein 2 or 3; leptin agonists (see, for example, Lee, Daniel W, Leinung, Matthew C, Rozhavskaya-Arena, Marina, Grasso, Patricia, Leptin agonists as a potential approach to the treatment of obesity, Drugs of the Future (2001), 26 (9), 873-881); DA agonists (bromocriptine or Doprexin); lipase / amylase inhibitors (such as those described, for example, in WO 00/40569); diacylglycerol O-acyltransferase (DGAT) inhibitors as described, for example, in US2004 / 0224997, WO20040946 8, WO200058491 , WO2005044250, WO2005072740, JP2005206492 or WO20050 3907; fatty acid synthase (FAS) inhibitors such as, for example, C75 or those described in WO2004005277; oxintomodulin; oleoyl-estrone; or thyroid hormone receptor agonists such as, for example: KB-21 15 or those described in WO20058279, WO200172692, WO200194293, WO2003084915, WO2004018421 or WO2005092316. In one embodiment, the additional active ingredient is leptin; see, for example, "Perspectives in the therapeutic use of leptin", Salvador, Javier; Gomez-Ambrosi, Javier; Fruhbeck, Gema, Expert Opinion on Pharmacotherapy (2001), 2 (10), 16 5-1622. In one embodiment, the additional active ingredient is dexamfetamine or amphetamine. In one embodiment, the additional active ingredient is fenfluramine or dexfenfluramine. In another embodiment, the additional active ingredient is sibutramine. In one embodiment, the additional active ingredient is mazindol or phentermine. In one embodiment, at least one compound of the formula I is administered in combination with bulking agents, preferably insoluble agents that impart volume (see, for example, Carob / Caromax® (Zunft HJ; et al., Carob pulp preparation for treatment of hypercholesterolemia, ADVANCES IN THERAPY (2001 Sep-Oct), 18 (5), 230-6) Caromax is a product that contains Nutrinova carob, Nutrition Specialties & Food Ingredients GmbH, Industriepark Hóchst, 65926 Frankfurt / Main. The combination with Caromax® is possible in a preparation or by means of separate administration of compounds of formula I and Caromax®. Caromax® can also be administered in this respect in the form of food products such as, for example, in bakery products or muesli bars. In one embodiment, at least one compound of formula I is administered in combination with PDE (Phosphodiesterase) inhibitors such as, for example, those described in WO2003 / 077949 or WO2005012485. In one embodiment, at least one compound of the formula I is administered in combination with agonists of NAR-1 (nicotinic acid receptor) such as, for example, those described in WO2004094429. In one embodiment, at least one compound of the formula I is administered in combination with CB2 agonists (Cannabinoid Receptor 2) such as, for example, those described in US2005 / 143448. In one embodiment, at least one compound of formula I is administered in combination with H1 agonists (histamine receptor 1) such as, for example, those described in WO2005101979. In one embodiment, at least one compound of formula I is administered in combination with Bupropion, such as, for example, as described in WO2006017504.

In one embodiment, at least one compound of the formula I is administered in combination with opioid receptor antagonists such as, for example, those described in WO2005107806 or WO2004094429. In one embodiment, at least one compound of formula I is administered in combination with inhibitors of neutral endopeptidase such as, for example, those described in WO200202513, WO2002 / 06492, WO2002040008, WO2002040022 or WO2002047670. In one embodiment, at least one compound of formula I is administered in combination with NPY modulators (Neuropeptide Y), such as, for example, those described in WO2002047670. In one embodiment, at least one compound of the formula I is administered in combination with an inhibitor of the sodium / hydrogen replacement protein as described, for example, in WO2003092694. In one embodiment, at least one compound of formula I is administered in combination with glucocorticoid receptor modulators such as, for example, those described in WO2005090336. In one embodiment, at least one compound of formula I is administered in combination with nicotine receptor agonists such as, for example, those described in WO2004094429. In one embodiment, at least one compound of formula I is administered in combination with NRI (Reuptake inhibitors of norepinephrine) such as, for example, those described in WO2002053140. In one embodiment, at least one compound of formula I is administered in combination with MOA (E-beta-methoxyacrylate), such as, for example, segeline, or such as, for example, those described in WO2002053140. In one embodiment, at least one compound of formula I is administered in combination with an active antithrombotic ingredient such as, for example, Clopidrogel.

CS-011 rivoglitazone LY-674 KRP-101 twenty KB-2115 In one embodiment, the compounds of the formula I are administered in combination with drugs having effects on the coronary circulation and the vascular system, such as, for example, ACE inhibitors (e.g., ramipril), drugs that act on the angiotensin-renin system, calcium antagonists, beta-blockers, etc. In one embodiment, the compounds of formula I are administered in combination with drugs having an anti-inflammatory effect. In one embodiment, the compounds of formula I are administered in combination with drugs that are used for cancer therapy and cancer prevention. It will be appreciated that all suitable combinations of the compounds of the invention with one or more of the aforementioned compounds and optionally one or more other pharmacologically active substances are considered to be within the protection conferred by the present invention.

TEST MODELS The suitability of the compounds of the invention as active pharmaceutical ingredients can be tested by means of various test models. Descriptions of these test models are given below by way of example. Influence on the MCH receptor in vitro; Determination of the IC50 Functional Values of MCH1 R Antagonists The cloning of the cDNA to the human MCH receptor, the preparation of a recombinant HEK293 cell line expressing the human MCH receptor and the functional measurements with the recombinant cell line were performed analogous to the description of Audinot et al. (J. Biol. Chem. 276, 13554-13562, 2001). However, a difference of the reference was the use of the pEAK8 plasmid of EDGE Biosystems (United States) for the construction of the expression vector. The host used for the transfection was a transformed HEK cell line called "PEAK Stable Cells" (similarly from EDGE Biosystems). Functional measurements of the cellular calcium output after the addition of agonist (MCH) in the presence of the ligand of the invention took place with the aid of the FLIPR apparatus from Molecular Devices (United States), using protocols from the device manufacturer. The compounds of the invention show a significant inhibition (> 30%) of the signal induced by the agonist at a concentration of 100 DM, preferably at 10 DM, and particularly preferably at 1 DM, in a very particular way preferred at 100 nM and even more particularly preferred at 10 nM. Apart from the functional activity, it is also possible to determine the affinity for MCH1 R according to Audinot et al. (Br. J. Pharmacol., 2001, 133, 371-378). Preferred compounds of the invention show an IC50 value of less than 1 μ ?, particularly preferred lower 100 nM, more particularly preferred less than 10 nM and even more particularly preferred less than 1 nM. Milk Intake by NMRI Female Mice The anorectic effect is tested in female NMRI mice. After removing the feed for 24 hours, the test substance is administered intraperitoneally or preferably orally by means of a probe. The animals are enclosed individually with free access to drinking water and, 30 minutes after the administration of the product, they are offered condensed milk. The consumption of condensed milk is determined every half hour during a period of 7 hours, and the general state of the animals is observed. The measured consumption of milk is compared with that of control animals treated with vehicle. The vehicle itself has no influence on food intake. Preferred tolerated carriers are for administration, for example, hydroxyethylcellulose (0.5% in water) or Solutol HS15 (5% in hydroxyethylcellulose (0.5% in water)).

Food and Water Intake of Wistar Female Rats As an alternative to the anorexic effect assay in NMRI mice, it is also possible to use similarly female Wistar rats weighing approximately 220-250 g in an analogous manner. The animals become accustomed to the experimental environment before beginning the study. In one embodiment, the animals have free access to food and water until the beginning of the experiment. In another embodiment, the access of the animals to the feed is removed 24 hours before administration. For the investigation of the test substance, the animals are enclosed individually with free access to food and water. Food and water intake is measured continuously every 30 minutes for a period of 22 hours using a computer-assisted system (TSE Drinking &Feeding Monitor). The measured consumption of food and water is compared with that of control animals treated with vehicle. Increase in body weight of diet-induced and diet-fed obesity mice For these investigations, 5-week-old male C57BL6J mice (weaning age) are accustomed to a standard maintenance diet or a high-fat diet and therefore of high energy content. After 12 weeks, thin mice subjected to normal feeding have typically reached a body weight of about 25 g, and mice fed a high fat content have reached a weight of about 35 g. The animals are enclosed individually and the food intake and water intake. There is free access to food and water during the experiment. The test substances are administered orally in a vehicle and are always tested by comparison with the vehicle control that is included in parallel. The vehicle by itself has no influence on food intake, and is usually hydroxyethylcellulose (0.5% in water) or Solutol HS15 (5% in hydroxyethylcellulose (0.5% in water)). For each group of mice with obesity induced by the diet a corresponding group of thin mice is maintained. The consumption of food and water is determined every day in the first week and then once a week re-weighing the food and water offered respectively . Body weight is measured every day. Blood samples are collected before and at the end of treatment to determine serum parameters that provide information about changes in the intermediate metabolism. It is also possible to determine the body fat content in the live animal by means of an impedance measurement (TOBEC method). Micronucleus assay (in vitro) The objective of the micronucleus assay (in vitro) is to examine whether a test compound can induce the formation of micronuclei (small DNA fragments bound to the membrane) in various cell lines or primary cultures, with or without metabolic activation by hepatic homogenate S9. The test system allows differentiation between the clastogenic and aneugenic potential of a test compound by an immunochemical labeling of the kinetochores or by staining the DNA fragments by the FISH method (in situ hybridization with fluorescence). Brief description: the cells are treated in a 96-well microtiter plate with the test compound. The treatment time is typically 3 hours with metabolic activation or 24 hours without metabolic activation. Twenty-four hours after finishing the treatment, the cells are isolated, fixed and stained. The cytotoxicity of the test compound is evaluated according to the relative cell growth expressed as growth percentage or taking into account the doubling time as the doubling of the population compared to the negative control. The highest test concentration should not show less than 30% of surviving cells, or it should be the concentration at which a precipitate of the test compound is observed. Determinations should be made in duplicate with each test concentration. A detailed detailed description of the experiment can be found in Kirsch-Volders et al. (Mutation Res. 2003, 540, 153-163). Evaluation: structural or numerical chromosomal lesions are presented as the increase in the number of cells with micronuclei in a set of 1000 cells at three analysable test concentrations. The test is considered positive in the following cases: a) the increase in the number of cells with micronuclei is significant compared to the negative control (solvent or not) treated), or b) the number of micronuclei increases to a biologically relevant extent, in a concentration-dependent manner by comparison with the negative control. A positive control should show a clear statistically significant effect compared to the negative control. The preferred compounds of the invention are negative in the micronucleus test. AMES II Assay The objective of the AMES II assay is to examine whether a test compound has mutagenic potential. Brief description: a mixed bacterial strain (mixed strains, 6 different strains of Salmonella typhimurium with, in each case, a point mutation of missense in the histidine operon) and the strain of Salmonella typhimurium TA98 to detect phase change mutations, they are treated in a 374-well microtiter plate with various concentrations of the test substance with or without metabolic activation by means of the addition of hepatic homogenate S9 (precise descriptions of the experiment can be found in the literature: P. Gee, DM Marón, BN Ames, Proc. Nati, Acad. Sci. USA 1994, 91, 11606 and Flückiger-lsler et al., Mutation Res. 2004, 558, 181 and cit. Lit.). Mutagenic assay compounds produce back mutations and, in this way, restore the functionality of biosynthesis endogenous histidine. In this way, the mutated bacteria can divide and expand to produce bacterial colonies. Evaluation: if there is a higher bacterial growth due to mutations of the bacteria, then enzymes are digested in the growth medium. As a result, the pH of the medium is reduced and the color of the added indicator (bromocresol purple) changes from light violet to yellow. The test is considered positive if the number of wells in which a color change by concentration is observed increases significantly compared to the control. The preferred compounds of the invention are negative in the AMES II assay. Cytotoxicity assays a) LDH release The objective of the assay for the release of LDH (lactate dehydrogenase) is to examine whether a compound damages the integrity of the cell wall and, therefore, can cause cell death. Brief description: the LDH activity that enters the cell supernatant from the cytosol due to cell lesions is measured by colorimetry. The cells are treated with the test compound. 50 μ? of the culture supernatant and mixed with the reaction solution (LDH kit, Roche, Mannheim) according to the manufacturer's information. LDH catalyzes the conversion of lactate into pyruvate. During this process, NAD + is reduced to NADH / H +. The latter, in turn, is reduced under the influence of the added diaphorase, a yellow tetrazolium salt added similarly to the red formazan. Evaluation: formazan is quantified by measuring absorption at 492 nm (for example, with TECAN SPECTRAFluor Plus). The preferred compounds of the invention do not show a significant increase in LDH activity at concentrations below 10 μ. Particularly preferred compounds show no increase below a concentration of 50 μ ?. Even more preferred compounds show no increase below a concentration of 250 μ ?. b) intracellular ATP content The objective of the assay is to determine the total content of intracellular ATP, which is a measure of the energy level and therefore of the vitality of a cell. Brief description: 100 μ? of cell culture medium in a well of a microtiter plate with 100 μ? of the CelITiter-Glo reagent (Following the manufacturer's instructions: Promega Technical Bulletin No. 228, CelITiter-Glo Luminesent Cell Viability Assay). The cultures are stirred at room temperature for 2 minutes and then incubated for 10 minutes until the luminescence signal is stabilized. Evaluation: the luminescence is recorded, integrating for one second (for example, with TECAN SPECTRAFluor Plus).

Preferred compounds of the invention show no significant reduction in ATP levels at concentrations below 10 μ. Particularly preferred compounds show no reduction below a concentration of 50 μ ?. Even more preferred compounds show no reduction below a concentration of 250 μ ?. c) Neutral red uptake The objective of the test is to measure the uptake of neutral red (NR) in lysosomes / endosomes and vacuoles of living cells, which is a quantitative measure of the number and vitality of the cells. Brief description: the cells are washed with 150 μ? of a pre-warmed phosphate buffer solution (PBS) and incubated with 100 μ? of the NR medium at 37 ° C in a humidified atmosphere with 7.5% carbon dioxide for 3 hours. After incubation, the NR medium is removed and the cells are washed with 150 μ? of PBS. The elimination of PBS is continued by the addition of exactly 150 μ? of an ethanol / glacial acetic acid solution. After stirring for 10 minutes, the dye is extracted from the cells to give a homogeneous dye solution. An exact description of the assay can be found in the literature (E. Borenfreund, J.A. Puerner, Toxicol, Lett. 1985, 24 (2-3), 119-124). Evaluation: the absorption of the dye solution is determined at 540 nm using a microtitre plate reader as a difference of the absorption of the ethanol / glacial acetic acid solution.

Blocking of the HERG Channel The objective of the assay is to determine the range of concentrations at which the test compound blocks the cardiac hERG channel. The blocking of the hERG channel, which is responsible for the Ikr current in the human heart, is associated with arrhythmias that can be fatal. For the expression of the cDNA encoding the hERG channel, it was cloned into the vector pCDNA3 (Invitrogen). Chinese hamster oocytes (CHO, American Type Culture Collection, Rockville, MD) were transfected using lipofectamine (GIBCO / BRL, Grand Island, NY) with the hERG cDNA and selected using G418 (GIBCO / BRL, Grand Island, NY; 500 Dg / ml). CHO cells were cultured with stable expression of the hERG channel in an HAM F-12 medium that is supplemented with 10% native bovine serum, 1X penicillin / streptomycin and 500 Dg / ml G418 in a 95% air / 5 atmosphere. % carbon dioxide. The cells selected for the voltage clamping experiment are seeded on a plastic support 18-24 hours before the experiment. The hERG channel currents are recorded at room temperature by the whole cell variant of the voltage clamp technique using an Axopatch 200B amplifier (Axon Instruments, Foster City, CA). The electrodes (with a resistance of 3-6 megohms) are prepared from TW150F glass capillaries (World Precision Instruments, Sarasota, FL) and filled with the pipette solution (120 mM potassium aspartate, 20 mM KCI, Na2ATP 4 mM, 5 mM HEPES, 21 mM MgCl, adjusted to pH 7.2 with KOH). The hERG channel currents are induced by a positive voltage pulse (20 mV) followed by a negative pulse (-40 mV) and recorded for further analysis. Regarding the hERG channel current of the cell receiving the control solution (130 mM NaCl, 5 mM KCI, 2.8 mM NaOAc, 1 mM MgCl 2, 10 mM HEPES, 10 mM glucose, 1 mM CaCl 2, adjusted to pH 7.4 with NaOH) is stable, the cell is perfused with the test compound dissolved in the above control solution (by dilution of a 10 or 100 mM DMSO solution of the test compound so that the DMSO content is not greater than 0.1%). The current is monitored continuously until no further change occurs. The same procedure is repeated with increasing concentrations of the test compound. The maximum amplitude of the hERG current is measured in picoamperes (pA) for each concentration and for each cell. The maximum amplitude in pA for each concentration of the test compound is compared with that of the pure control solution in the same cell and calculated as a percentage of the control value. Evaluation: the test compound is tested at various concentrations in 3-5 CHO cells expressing the hERG channel. The IC50 value is obtained using a nonlinear least squares regression (GraphPAD software, San Diego, CA). General Selectivity To minimize the risk of unwanted side effects, it is desirable that the active pharmaceutical ingredient maintain a non-selective effect as small as possible on biologically functional units Important (eg, receptors, ion channels and enzymes, such as lists, see, for example, Whitebread, S. et al., Drug Discovery Today 2005, 10, 1421-33 and Rolland, C. et al., J. Med. Chem. 2005, 48, 6563-6574). Various specialized services (eg, Cerep, Panlabs) can perform general selectivity tests on a large number of in vitro test systems. The compounds of the invention of the formula I have, as selective antagonists of MCH1 R, selectivity factors of at least 30, preferably of 100, more preferably of 300 and even more preferably of 1000 in relation to the affinity for other proteins. Examples of these proteins are subtypes of serotonin receptors (e.g., the 5-HT2a receptor), subtypes of muscarinic receptors (e.g., the M1 receptor), adrenergic receptor subtypes (e.g., RA ally), and of sodium and calcium (for example, the type L calcium channel). Solubility in Aqueous Systems The adequate solubility of a substance in aqueous solvent systems is an important prerequisite for a pharmacological (reproducible) effect. The solubilities in aqueous systems can be determined by various methods. Suitable examples of solution precipitation methods ("kinetic solubility") and methods that investigate the dissolution of a solid sample are established until equilibrium is reached ("thermodynamic solubility"). a) Kinetic Solubility A solution in DMSO of the test compound (2.5 mM, 0.5 μm) is introduced with a pipette in 200 μ? of an aqueous test solution (eg, phosphate buffered saline, 10x, 1, Sigma, adjusted to 10 mM, pH 7.4) in a 96-well microtiter plate, and the turbidity is measured at the theoretical concentration resulting for the test compound of 6.25 μ? using a nephelometer (e.g., Nephelostar Galaxy, BMG Labtech): The concentration of the test compound in the aqueous test solution is then raised to a theoretical value of 12.5 μ? adding more solution in DMSO (2.5 mM, 0.5 μm), and the turbidity measurement is repeated. More additions of solutions in DMSO (1 μ ?, 2.5 mM; 0.5 μ ?, 10 mM; then 9 × 1 μ ?, 10 mM, obtaining theoretical concentrations of 25 μ ?, 50 μ ?, 100 μ ?, 150 μ ?, 200 μ ?, 250 μ ?, 300 μ ?, 350 μ ?, 400 μ ?, 450 μ? and 500 μ?) with turbidity measurements in between complete the measurement process. Evaluation: the cloudiness values of the nephelometer are plotted against the theoretical concentration of the test compound in the aqueous test solution. As soon as a significant turbidity is detected (for example, 5 times above the control value of the aqueous test solution) at a theoretical concentration, the concentration level below this is established as the limit of solubility of the test compound in the test solution. In this way, the maximum possible measurement interval is presented as values < 6.25 μ ?, 6.25 - 500 μ? and > 500 μ ?.

Preferred compounds of the invention show a kinetic solubility in phosphate buffer (pH 7.4) of at least 12.5 DM; more preferably at least 50 μ? and even more preferably at least 250 μ ?. b) Thermodynamic Solubility The integrated UV absorption in the HPLC UV measurement of serial dilutions of the test compound in DMSO (500 μ ?, 100 μ ?, 50 μ ?, 10 μ? and 1 μ?) shows a linear correlation with the concentration in a calibration line. The test compound (500 μg) is stirred together with the aqueous test solution (250 μ?) In a closed vessel (capacity: 1.5 mi) for 16 hours (Eppendorf thermoshaker, 1400 rpm, 25 ° C, with coverage). to protect from light). The sample is then centrifuged at a maximum rotational speed and finally the supernatant is filtered. A sample of the filtered supernatant is analyzed directly by UV HPLC measurement (see above). Another sample is analyzed after dilution (1 part by volume of supernatant, 39 parts by volume of test solution). Evaluation: the concentration of the test compound in the undiluted supernatant is calculated from the integrated UV absorptions resulting from the supernatant samples based on the constructed calibration lines and is presented as the solubility of the test compound in the aqueous test solution respective. Examples of aqueous test solutions are deionized water or aqueous phosphate buffer with various pH values (eg pH 1, 2, pH 4.0, pH 6.8, pH 7.4, pH 9.0) that can be prepared from the commercial solution (phosphate buffered saline, 10x , Sigma) by dilution and adjustment with phosphoric acid or sodium hydroxide solution by conventional methods. Preferred compounds of the invention show a solubility in phosphate buffer (pH 7.4) of at least 12.5 DM; more preferably at least 50 μ? and even more preferably at least 250 μ ?. Permeability The permeability test is performed on cultured CACO-2 / TC7 cells (DMEM / Glutamax l / Gibco with high glucose content, 25 mM HEPES, 1% NEAA, 10% FBS, 40 Dg / ml gentamicin, environment temperature 37 ° C, 95% humidity and 10% CO2 content) in Becton Dickinson filters (24 wells, uncoated) for 21 days. The permeability is tested at a concentration of 20 μ? for the test compound (1% DMSO in HBSS) with a pH gradient (apical: pH 6.5 and 0.5% BSA, basolateral: pH 7.4 and 5% BSA). The analysis is done through LCMS / MS. Additional descriptions of the assay system and references for the experimental procedure can be found in Balimane, P.V .; Drug Discovery Today 2005, 10 (5), 335-343. Inhibition of CYP Enzymes The inhibition of CYP enzymes is determined in recombinant enzymes (obtained in Becton Dickinson) and fluorescent substrates (BD / Gentest) as recommended by the manufacturer (see website http://www.bdbiosciences.com). In Zlokarnik, G .; Drug Discovery Today 2005, 10 (21), 1443-1450 can be found additional descriptions of the assay system and references for the experimental procedure. Metabolic Stability Metabolic stability is determined by incubating the test compound (5 μm) with microsomal hepatic fractions (1 mg / ml protein with 0.1% w / v BSA, 1mM NADPH, 0.5% DMSO) at 37 ° C. The incubation analysis of 0 and 20 minutes is carried out by means of LCMS / MS. In Plant, N .; Drug Discovery Today 2004, 9 (7), 328-336 and Lau, Y.Y. et al .; Pharmaceutical Res. 2002, 19 (11), 1606-1610, additional descriptions of the assay system and references for the experimental procedure can be found.

EXAMPLES The examples and methods of preparation detailed below serve to illustrate the invention, but without limiting it. The compounds of the invention of the formula I can be prepared by means of reactions known in principle. For example, the compounds were obtained according to the following general reaction schemes.

Method D for R2 = NBoc Scheme 1 Other compounds of the invention can be obtained by additional routes which are summarized by way of example in the following scheme.

Scheme 2 Again, other examples were obtained as indicated in the following scheme.

DMF Method B Scheme 3 Again, other examples were obtained as indicated in the following scheme.

Scheme 4 Again, other examples were obtained as indicated in the following scheme.

Scheme 5 Again, other examples were obtained as indicated in Scheme 6 Again, other examples were obtained as indicated below scheme.

Scheme 7 Again, other examples were obtained as indicated in the following scheme.

Scheme 8 Again, other examples were obtained as indicated below scheme.

Scheme 9 Again, other examples were obtained as indicated in the following diagram.

Scheme 10 The descriptions of the general methods used are described by way of example in the following places: Method A1, B, C and D in Example 1; Method A2, E, F and G in Example 2; Method H, I, J, K, L, M, N according to table 1; Method O in example 19; Method P in example 21; Method Q in Example 24; Method R in example 66; Method S, T and U in Example 69 Method V and W in Example 74; Method X in Example 75; Method Y in example 76; Method Z in Example 79; Method AA in Example 85; Method BA in example 93. General Explanations a) Mode of representing structural formulas For clarity, only atoms that are not hydrogen are represented in the structural formulas of the given examples. b) Salt forms Many of the compounds of the invention are bases and can form salts with appropriately strong acids. The compounds can be in particular in the form of hydrotrifluoroacetates after purification by HPLC chromatography using a mobile phase containing trifluoroacetic acid. They can be converted into the free bases shown by simple treatment of a solution of the salts for example with a sodium carbonate solution. c) Units of the characterization data The unit of the indicated molecular weights is "g / mol". The peaks observed in the mass spectrum are indicated as an integral ratio of the molar molecular ion mass and the molecular ion charge (m / z). Example 1 6- (4-Chlorophenyl) -3- [4- (3-dimethylaminopyrrolidin-1-yl) -2-methylphenyl] -3H-thieno [3,2-d] pyrimidin-4-one Method A1 A mixture of 5- (4-chlorophenyl) -3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester (100 mg), [1- (4-amino-3-methylphenyl) pyrrolidin-3- il] dimethylamine (68 mg) and phenol (29 mg) was heated at 80 ° C for 2 hours. The crude product was purified by preparative HPLC. (An alternative possibility is also to dilute the reaction mixture with a small amount of ethyl acetate and isolate the crystalline product by filtration). The product with the molecular weight of 465.02 (C25H25CIN40S) was obtained in this way; MS (ESI): 465 (M + H +).

Method B 5- (4-Chlorophenyl) -3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester A solution of 3-amino-5- (4-chlorophenyl) thiophene-2-carboxylic acid methyl ester (5, 0 g) in DMF (30 ml) was mixed with dimethoxymethyldimethylamine (5 ml) and stirred for 36 hours. The reaction solution was partitioned between water and ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated. The product with the molecular weight of 322.82 (C15H15CIN202S) was obtained in this way; MS (ESI): 323 (M + H +). Method C [1- (4-Amino-3-methylphenyl) pyrrolidin-3-yl] dimethylamine A suspension of dimethyl- [1- (3-methyl-4-nitrophenyl) pyrrolidin-3-yl] amine (200 mg) and Palladium (0% on carbon, 10 mg) in methanol (10 ml) was stirred vigorously in an atmosphere of hydrogen at atmospheric pressure for 5 hours. Then, the catalyst was removed by suction filtration and the filtrate was concentrated. The product with the molecular weight of 219.33 (C13H21 N3) was obtained in this way; MS (ESI): 220 (M + H +). Method D Dimethyl- [1- (3-methyl-4-nitrophenyl) pyrrolidin-3-yl] amine A mixture of 4-fluoro-2-methyl-1-nitrobenzene (13.6 g), dimethylpyrrolidin-3-ylamine ( 10.0 g), potassium carbonate (12 g) and DMF (100 ml) was stirred at room temperature for 4 hours. The reaction mixture is divided between water and ethyl acetate. The organic phase was dried and concentrated. The product with the molecular weight of 249.32 (C13H19N302) obtained in this way; MS (ESI): 250 (M + H +). Example 2 7-Butoxy-3- [4 - ((R) -3-dimethylaminopyrrolidin-1-yl) -2-methylphenyl] -3H-quinazolin-4-one Method A2 A mixture of 2-amino-4-butoxybenzoic acid (70 mg), [(R) -1 - (4-amino-3-methylphenyl) pyrrolidin-3-yl] dimethylamine (73.4 mg), triflate of Ytterbium (III) (2.1 mg) and ethyl orthoformate (49.6 mg) was heated at 100 ° C for 7 hours. The crude product was purified directly by preparative HPLC. The product with the molecular weight of 420.56 (C25H32N402) was obtained in this way; MS (ESI): 421 (M + H +). Methyl ester of 4-butoxy-2- (dimethylaminomethyleneamino) benzoic acid Methyl ester of 2-amino-4-butoxybenzoic acid was reacted with dimethoxymethyldimethylamine by method B. The product with the molecular weight of 278.35 (C15H22N203) was obtained in this way; MS (ESI): 279 (M + H +).

Method E 2-amino-4-butoxybenzoic acid methyl ester A mixture of 2-amino-4-butoxybenzoic acid (2.0 g), thionyl chloride (1.2 g) and methanol (33 ml) was brought to the point of boiling at reflux temperature for 24 hours. The reaction solution was diluted with MTBE and washed with a sodium hydroxide solution. The organic phase was dried and concentrated. The product with the molecular weight of 223.27 (C12H17N03) was obtained in this manner; MS (ESI): 224 (M + H +). 2-Amino-4-butoxybenzoic acid 4-Butoxy-2-nitrobenzoic acid was hydrogenated by the method C1. The product with the molecular weight of 209.25 (C1 1 H15N03) was obtained in this way; MS (ESI): 210 (M + H +). Method F 4-Butoxy-2-nitrobenzoic acid Potassium permanganate (9.8 g) was added in portions to a mixture of 4-butoxy-1-methyl-2-nitrobenzene (13.0 g), pyridine (100 ml) and water (100 ml) at 100 ° C. On each occasion, after 1.5 hours, the same amount of potassium permanganate was added four times more. The cooled reaction mixture was filtered with suction to remove the solids and the filtrate was partitioned between water and MTBE. The aqueous phase was acidified and extracted with ethyl acetate. The organic phase was dried and concentrated. The product with the molecular weight of 239.23 (C1 1 H13N05) was obtained in this way; MS (ESI): 240 (M + H +).

Method G 4-Butoxy-1-methyl-2-nitrobenzene A mixture of 4-methylene-3-nitrophenol (10.0 g), butyl bromide (9.4 g), sodium carbonate (6, 9 g) and DMF (50 ml) was heated at 80 ° C for 7 hours. The cooled reaction solution was diluted with MTBE and washed twice, each with water and a sodium hydroxide solution. The organic phase was dried and concentrated. The product with the molecular weight of 209.25 (C1 1 H15N03) was obtained in this way; MS (ESI): 210 (M + H +). The exemplary compounds of Table 1 were obtained by the method A1 or A2 from the appropriate esters and the appropriate anilines. Table 1.

Reaction of the appropriate aminocarboxylic acids with dimethoxymethyldimethylamine yielded the following compounds: 5- (4-Chlorophenyl) -3- (dimethylaminomethyleneamino) -furan-2-carboxylic acid methyl ester 2- (dimethylammonomethyleneamino) -methyl ester 5-methoxy-benzoic; 5-butoxy-2- (dimethylaminomethyleneamino) -benzoic acid methyl ester; 4'-chloro-4- (dimethylaminomethyleneamino) -b-phenyl-3-carboxylic acid methyl ester; and methyl 3- (dimethylmetilenoamino) -5- (5-fluoropyridin-2-yl) -thiophene-2-carboxylic acid methyl ester.

Method H 3-Amino-5- (4-chlorophenyl) -furan-2-carboxylic acid methyl ester D-tert-butyl azodicarboxylate (8.98 g) was added to a mixture of 3- (4-chlorophenyl) - 3-oxopropionitrile (5.0 g), hydroxyacetic acid ethyl ester (4.06 g), triphenylphosphine (10.2 g) and THF (100 ml). After 15 hours, sodium hydride (55% in oil, 3.4 g) was added. After 5 hours, the reaction mixture was carefully hydrolyzed with water and extracted with ethyl acetate. The organic phase was washed with hydrochloric acid, dried and concentrated. The residue was purified by preparative HPLC. The methyl ester was prepared by treatment with sodium methanolate in methanol. The product with the molecular weight of 251, 67 (C12H10CINO3) was obtained in this manner; MS (ESI): 252 (M + H +). Methyl ester of 2-amino-5-butoxybenzoic acid Methyl ester of 5-butoxy-2-nitrobenzoic acid was reduced by method C. The product with the molecular weight of 223.27 (C12H17N03) was obtained in this way; MS (ESI): 224 (M + H +). Method I Methyl ester of 5-butoxy-2-nitrobenzoic acid Sodium hydride (302.4 mg) was added to a solution of 1-butanol (0.634 mi) in DMF (15 ml). The reaction mixture was stirred until the evolution of CO 2 ended, then 5-fluoro-2-nitrobenzoic acid methyl ester (1.15 g) was added and the mixture was stirred at room temperature. during one night. Then, the reaction was mixed with ethyl acetate, washed with 10% sodium bicarbonate and a 10% solution of citric acid was added, dried over sodium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 253.26 (C12H15N05) was obtained in this way; MS (ESI): 254 (M + H +). 5-Fluoro-2-nitrobenzoic acid methyl ester 5-Fluoro-2-nitrobenzoic acid was esterified by the method E. The product with the molecular weight of 199.14 (C8H6FN04) was obtained in this manner; MS (ESI): 200 (M + H +). 3- [4- (3-Dimethylaminopyrrolidin-1-yl) phenyl] -6-methoxy-3H-quinazolin-4-one [1- (4-aminophenyl) pyrrolidin-3-yl] dimethylamine was reacted with methyl ester of the 5-Butoxy-2- [2-methylprop- (Z) -ylideneamino] benzoic acid, which had been previously rinsed with methanol, by method A1. The methanol residues produced a transesterification, which provided the product. Method J 4-Amino-4'-chlorobiphenyl-3-carboxylic acid methyl ester A solution of 2-amino-5-bromobenzoic acid methyl ester (460.1 mg) in degassed toluene was mixed with tetrakis (triphenylphosphine) palladium ( 0) (62.4 mg) and stirred at room temperature for 10 min. Then, 4-chlorophenylboronic acid (344 mg) in ethanol (0.76 ml) and a 2 M solution of sodium carbonate (1.34 ml) were added and the mixture of reaction was heated at 100 ° C overnight. Then, the reaction was mixed with ethyl acetate and water. The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 261, 71 (C14H12CIN02) was obtained in this way; MS (ESI): 262 (M + H +). Method K 3-Amino-5- (5-fluoropyridin-2-yl) thiophene-2-carboxylic acid methyl ester A solution of 3-tert-butoxycarbonylamino-5- (5-fluoropyridin-2-yl) methyl ester -thiophene-2-carboxylic acid (80 mg) in dichloromethane (1.35 ml) was mixed with trifluoroacetic acid (0.15 ml) and stirred at room temperature overnight. Then, the solvent was removed in vacuo and the residue was taken up again in dichloromethane and washed twice with a saturated solution of NaHCC >; 3 and once with water. The dichloromethane phase was dried over sodium sulfate and concentrated. The product with the molecular weight of 252.27 (C1 1 H9FN202S) was obtained in this way; MS (ESI): 253 (M + H +). Method L 3-tert-Butoxycarbonylamino-5- (5-fluoropyridin-2-yl) thiophene-2-carboxylic acid methyl ester Palladium (II) acetate (20 mg) was added to a solution of 5- methyl methacrylate. bromo-3-tert-butoxycarbonylaminothiophene-2-carboxylic acid (300 mg), 2-bromo-5-fluoropyridine (235.5 mg), bis (pinacolato) diboro (462.2 mg), tri-t-butylphosphonium tetrafluoroborate (77.64 mg) and cesium carbonate (871) , 9 mg) in dioxane / water (6 ml / 1.5 ml). The solution was heated at 90 ° C for 3 h. Then, the reaction solution was mixed with ethyl acetate and water. The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 352.39 (C16H17FN204S) was obtained in this way; MS (ESI): 353 (M + H +). Method M 5-Bromo-3-tert-butoxycarbonylaminothiophene-2-carboxylic acid methyl ester A 1.6 M solution of n-butyllithium in hexane (7.4 ml) was added to a solution of diisopropylamine (1.27 g) in THF (18 ml) at -78 ° C in a flask that had been heat-dried and washed abundantly with argon. The solution was warmed to 0 ° C and stirred at this temperature for 10 min. Then, the reaction solution was cooled again to -78 ° C and a solution of 3-tert-butoxycarbonylaminothiophene-2-carboxylic acid methyl ester (0.93 g) in THF (10 mL) was added. The mixture was stirred at -78 ° C for 30 min. Then, 1,2-dibromotetrafluoroethane (5.61 g) was added to the reaction solution, which was stirred at -78 ° C for an additional hour. After the addition of a saturated solution of ammonium chloride, the solution was allowed to warm to room temperature. The solution of The reaction was extracted twice with ethyl acetate and then the combined organic phases were washed with water and a saturated solution of sodium chloride, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel. The product with the molecular weight of 336.21 (C1 1 H14BrN04S) was obtained in this way; MS (ESI): 335, 337 (M + H +). Method N 3-tert-butoxycarbonylaminothiophene-2-carboxylic acid methyl ester Di-tert-butyl dicarbonate (41.6 g) and 4-dimethylaminopyridine (0.77 g) were added to a mixture of 3-aminothiophene-2 Methyl carboxylate (20 g) in dichloromethane (350 ml). The reaction was stirred at room temperature for 1 h and then the solvent was removed in vacuo. The residue was taken up in ethyl acetate and washed with a saturated solution of sodium bicarbonate, a citric acid solution with a power of 10% and a saturated solution of sodium chloride. Then, the ethyl acetate phase was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel. The product with the molecular weight of 257.31 (C11 H15N04S) was obtained in this manner; MS (ESI): 158 (M-Boc + H +). The following anilines were prepared by method D and C1 from the appropriate 4-fluoronitrobenzenes and the appropriate amines: [(R) -1- (4-amino-3-methylphenyl) pyrrolidin-3-yl] dimethylamine; [(R) -1- (4-amino-2-fluorophenyl) pyrrolidin-3-yl] dimethylamine; [(R) -1- (4-amino-3-phiuorophenyl) pyrrolidin-3-yl] dimethylamine (from 2-chloro-1,3-difluoro-4-nitrobenzene and dimethyl- (R) -pyrrolidin-3 -amine); [(R) -1- (4-aminophenyl) pyrrolidin-3-yl] dimethylamine; 4- (4-methylpiperazin-1-yl) phenylamine; 4- (4-methyl [1,4] diazepan-1-yl) phenylamine; [1- (4-aminophenyl) pyrrolidin-3-yl] dimethylamine; [1- (4-amino-3-fluorophenyl) pyrrolidin-3-yl] dimethylamine (from 2-chloro-1,3-difluoro-4-nitrobenzene and dimethylpyrrolidin-3-yl-amine); 4 - ((3aS, 6aS) -5-methylhexahydropyrrolo [3,4-b] pyrrol-1-yl) phenol amine; [1- (4-amino-2-fluorophenyl) pyrrolidin-3-yl] dimethylamine; 4- (3-dimethylaminomethylpyrrolidin-1-yl) -2-methylphenylamine; tert-butyl ester of (3aS, 6aS) -1- (4-amino-2-fluorophenyl) hexahydropyrrolo [3,4-b] pyrrole-5-carboxylic acid; 4- (7-methyl-2,7-diazaspiro [4,4] non-2-yl) phenylamine; (3R) -4- [1, 3 '] bipyrrolidinyl-1'-yl-3-methylphenylamine; and [(R) -1- (4-Aminophenyl) pyrrolidin-3-yl] - (2-methanesulfonylethyl) methylamine. [(R) -1- (2-Chloro-4-nitrophenyl) pyrrolidin-3-yl] - (2-methanesulfonylethyl) methylamine was decreated and the nitro group was reduced to give the amine under the conditions of method C1. The crude product was purified by preparative HPLC. The product with the molecular weight of 297.42 (C14H23N302S) was obtained in this manner; MS (ESI): 298 (M + H +). [(R) -1- (2-Chloro-4-nitrophenyl) pyrrolidin-3-yl] - (2-methanesulfonylethyl) methylamine A mixture of [(R) -1- (2-chloro-4-nitrophenyl) pyrrolidin-3-ylmethylamine (384 mg), methanesulfonylenete (318 mg) and methanol (5 ml) was stirred at room temperature for 12 hours. The volatiles were removed by evaporation and the residue was purified by preparative HPLC. The product with the molecular weight of 361, 85 (C14H20CIN3O4S) was obtained in this manner; MS (ESI): 362 (M + H +). [(R) -1- (2-Chloro-4-nitrophenyl) pyrrolidin-3-yl] methylamine [(R) -1- (2-Chloro-4-nitrophenyl) pyrrolidyl) tert -butyl ester was deblocked n-3-yl] methylcarbamic by the method K. The product with the molecular weight of 255.71 (C1 1 H14CIN302) was obtained in this manner; MS (ESI): 256 (M + H +). [(R) -1- (2-Chloro-4-nitrophenyl) pyrrolidin-3-yl] methylcarbamic acid tert-butyl ester was obtained from 2-chloro-1-fluoro-4-nitrobenzene and tert-butyl ester of methyl- (R) -pyrrolidin-3-yl-carbamic acid by the method D. (R) - [1, 3 '] Bipyrrolidinyl Methanesulfonyl chloride was added to a mixture of tert-butyl ester of (S) - 3-hydroxypyrrolidine-1-carboxylic acid (40 g) and pyridine (17.4 g) in dichloromethane (400 ml) at 0 ° C. The reaction mixture was stirred at this temperature for 15 min and then heated at 50 ° C for 8 h. The reaction mixture was subsequently mixed with ethyl acetate and water and the ethyl acetate phase was washed with a dil solution. of HCI. The ethyl acetate phase was dried over sodium sulfate and the solvent was removed in vacuo.

The tert-butyl ester of (R) -3-methanesulfonyloxypyrrolidine-1-carboxylic acid obtained in this way was dissolved in pyrrolidine (18.2 ml) and the reaction mixture was heated to 100 ° C. Then, the reaction mixture was mixed with ethyl acetate and water. The ethyl acetate phase was washed several times with water. The organic phase was dried over sodium sulfate and the solvent was removed in vacuo. The (R) - [1, 3 '] bipyrrolidinyl-1'-carboxylic acid tert-butyl ester was deblocked by method K. The product with the molecular weight of 140.13 (C8H16N2) was thus obtained; MS (ESI): 141 (M + H +). Example 19 7-Butoxy-3- [2-fluoro-4 - ((R) -3-methylaminopyrrolidin-1-yl) phenyl] -3H-quinazolin-4-one The tert-butyl ester of the acid was treated. { (R) -1- [4- (7-Butoxy-4-oxo-4H-quinazolin-3-yl) -3-fluorophenyl] pyrrolidin-3-yl} methylcarbamate by the method K. The product with the molecular weight of 410.50 (C23H27FN402) was obtained in this manner; MS (ESI): 411 (M + H +). Tert-butyl acid ester. { (R) -1- [4- (7-Butoxy-4-oxo-4H-quinazolin-3-yl) -3-fluorophenyl] pyrrolidin-3-yl} Methylcarbamate 2-Amino-4-butoxybenzoic acid was reacted with [(R) -1- (4-amino-3-fluorophenyl) pyrrolidin-3-yl] methylcarbamic acid tert-butyl ester using the A2 method. The product with the molecular weight of 510.61 (C28H35FN404) was obtained in this manner; MS (ESI): 51 1 (M + H +). [(R) -1- (4-Amino-3-fluorophenyl) pyrrolidin-3-yl] methylcarbamic acid tert-butyl ester [[R] -1- (3-fluoro-4-tert -butyl] -ethyl ester] was hydrogenated -nitrophenyl) pyrrolidin-3-yl] methylcarbamic acid under the conditions of the method C1. The product with the molecular weight of 309.39 (C16H24FN302) was obtained in this way; MS (ESI): 310 (M + H +). Method O [(R) -1- (3-Fluoro-4-nitrophenyl) pyrrolidin-3-yl] methylcarbamic acid tert-butyl ester Sodium hydride (0.6 g) was added portionwise to a solution of ester ter- [(R) -1 - (3-Fluoro-4-nitrophenyl) pyrrolidin-3-yl] carbamic acid butyl ester (4.09 g) in DMF (10 ml). After the evolution of gas ceased, iodomethane (2.37 ml) was added dropwise. After 12 hours, the mixture was partitioned between water and ethyl acetate / hexane (1: 1), and the organic phase was dried and concentrated. The product with the molecular weight of 339.37 (C16H22FN304) was obtained in this way; MS (ESI): 340 (M + H +). [(R) -1- (3-Fluoro-4-nitrophenyl) pyrrolidin-3-yl] -carbamic acid tert-butyl ester was obtained by the method D from 1,3-difluoro-4-nitrobenzene and tert-butyl ester of (R) -pyrrolidin-3-ylcarbamic acid.

EXAMPLE 20 6- (4-Chlorophenyl) -3 - ((3aS, 6aS) -3-fluoro-4-hexahydro-pyrrolo [3,4-b] pyrrol-1-1-phenyl) -3H-Thieno [3,2-d] pyrimidin-4-one The tert-butyl ester of (3aS, 6aS) -1- acid was treated. { 4- [6- (4-Chlorophenyl) -4-oxo-4H-thieno [3,2-d] pyrimidin-3-yl] -2-fluoro-phenyl} hexahydropyrrolo [3,4-b] pyrrol-5-carboxylic acid by the method K. The product with the molecular weight of 466.97 (C24H20CIFN4OS) was obtained in this manner; MS (ESI): 467 (M + H +). EXAMPLE 21 6- (3-Hydroxy-but-1-ynyl) -3- [4- (4-meth1 [1,4] diazepan-1-yl) pheny] -3H-thieno [3.2 -d] pyrimidin-4-one Method P 6-Bromo-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one was introduced (33.6 mg), bis (tri-tert-butylphosphine) palladium (4.1 mg) and copper iodide (1.5 mg) in a flask that was heat-dried and ventilated with argon and a 3-methyl solution was added. -1-butine (28.0 mg) and morpholine (0.469 ml) in dioxane / water (0.47 ml / 0.01 ml). The reaction mixture was stirred at room temperature overnight. Then, the solvent was removed in vacuo and the residue was taken up again in ethyl acetate and water. The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 408.52 (C22H24N40S) was obtained in this way; MS (ESI): 409 (M + H +). The compounds of Table 2 were synthesized analogously, 6-Bromo-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidine. -4-one Methyl 5-bromo-3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester was reacted with 4- (4-methyl [1,4] diazepan-1-yl) phenylamine by the method A1 with additional addition of isopropanol. The product with the molecular weight of 419.34 (C18H19BrN40S) was obtained in this manner; MS (ESI): 419, 421 (M + H +). Table 2 Example 24 6- (1-Hydroxycyclopentiletinyl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one Method Q 6-Bromo-3- [3-methoxy-4- (2-pyrrolidin-1-yl-ethoxy) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one was introduced (50.3 mg), triphenylphosphine (6.3 mg), 1-ethynylcyclopentanol (66.1 mg) and bis (triphenylphosphine) palladium (II) chloride (4.2 mg) in NMP (1.5 ml) in a flask which was it was dried with heat and ventilated with argon and copper iodide (4.6 mg) was added. The reaction mixture was stirred at 85 ° C for 4 h. Then, the solvent was removed in vacuo and the residue was taken up again in ethyl acetate and water. The aqueous phase was lyophilized. The crude product was purified by preparative HPLC. The product with the molecular weight of 448.59 (C25H28N402S) was obtained in this way; MS (ESI): 449 (M + H +). The compounds of Table 3 were synthesized analogously.

Table 3 Example 29 6-Cyclopropylethynyl-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one -Cyclopropylethynyl-3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester was reacted with 4- (4-methyl [1,4] diazepan-1-yl) phenylamine by method A1. The product with the molecular weight of 404.53 (C23H24N40S) was obtained in this manner; MS (ESI): 405 (M + H +).

-Cyclopropylethynyl-3- (dimethylaminomethyIenoamino) thiophene-2-carboxylic acid methyl ester 3-Amino-5-cyclopropylethylthiophene-2-carboxylic acid methyl ester was reacted by method B. The product with the molecular weight of 276, 35 (C14H16N202S) was obtained in this manner; MS (ESI): 277 (M + H +). 3-Amino-5-cyclopropylethylthiophene-2-carboxylic acid methyl ester Tin chloride (11.8 g) was added to a solution of 5-cyclopropylethynyl-3-nitrothiophene-2-carboxylic acid methyl ester (6.26 g) ) in ethanol (250 ml) and the reaction mixture was heated to reflux for 4 h. Then, the solvent was removed in vacuo and the residue was taken up in ethyl acetate and washed with a sat. of salt of Rochelle. The organic phase was dried over sodium sulfate and the solvent was removed in vacuo. The product with the molecular weight of 221, 27 (C11 H 1 N02S) was obtained in this manner; MS (ESI): 222 (M + H +). 5-Cyclopropylethynyl-3-nitrothiophene-2-carboxylic acid methyl ester 5-Bromo-3-nitrothiophene-2-carboxylic acid methyl ester was reacted with ethynylcyclopropane by the Q method. The product with the molecular weight of 251, 26 (C11 H9N04S) was obtained in this manner; MS (ESI): 252 (M + H +).

Example 30 3- [4 - ((R) -3-Dimethylaminopyrrolidin-1-yl) phenyl] -6- (3-hydroxybut-1 3 H -thieno [3,2-d] pyrimidin-4-one 6-Bromo-3- [4 - ((R) -3-dimethylaminopyrrolidin-1-ylphenyl] -3H-thieno [3,2-d] pyrimidin-4-one was reacted with but-3-in-2- ol using the P method. The product with the molecular weight of 408.52 (C22H24N402S) was obtained in this way: MS (ESI): 409 (M + H +) The compounds of table 4 were prepared analogously. -Bromo-3- [4 - ((R) -3-d.methylaminopyrrolidin-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one Methyl ester was reacted of 5-bromo-3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid with [(R) -1 - (4-aminophenyl) pyrrolidin-3-yl] dimethylamine by method A. The product with the molecular weight of 418, 05 (C18H19BrN40S) was obtained in this manner, MS (ESI): 419 (M + H +).

Table 4 Example 44 6-Cyclopropylethynyl-3-. { 4- [4- (2-methanesulfonyl-ethyl) - [1,4] diazepan-1-yl] -phenyl} -3H-Thieno [3,2-d] pyrimidin-4-one -Cyclopropylethynyl-3- (dimethylamino-methyleneamino) -thiophene-2-carboxylic acid methyl ester was reacted with 4- [4- (2-methanesulfonyl-ethyl) - [1,4] diazepan-1-yl] - phenylamine by the method A1. The product with the molecular weight of 496.64 (C25H28N403S2) was obtained in this way; MS (ESI): 497 (M + H +). 4- [4- (2-Methanesulfonyl-ethyl) - [1,4] diazepan-1-yl] -phenylamine 1- (2-methanesulfonyl-ethyl) -4- (4-nitro-phenyl) - [1 , 4] diazepane using the C1 method. The product with the molecular weight of 297.42 (C14H23N302S) was obtained in this manner; MS (ESI): 298 (M + H +). 1 - (2-Methanesulfonyl-ethyl) -4- (4-nitro-phenyl) - [1,4] diazepane A mixture of 1- (4-nitro-phenyl) - [1,4] diazepane (4.90 g ), methanesulfonyl-ethene (2.35 g) and methanol (50 ml) was stirred for 2 h at room temperature. The volatiles were removed in vacuo. The product with the molecular weight of 327.40 (C14H21 N304S) was obtained in this manner; MS (ESI): 328 (M + H +). 1- (4-Nitro-phenyl) - [1,4] diazepane 4- (4-Nitro-phenyl) - [1,4] diazepane-1-carboxylic acid tert -butyl ester was reacted by method K. The product with the molecular weight of 221, 26 (C1 1 H15N302) was obtained in this manner; MS (ESI): 222 (M + H +). 4- (4-Nitro-phenyl) - [1,4] diazepane-1-carboxylic acid tert-butyl ester [1,4] diazepane-1-carboxylic acid tert-butyl ester was reacted with 1-fluoro- 4-Nitro-benzene at 60 ° C by method D. The product with the molecular weight of 321, 38 (C 16 H 23 N 304) was obtained in this manner; MS (ESI): 322 (M + H +).

Example 45 6-Cyclopropylethynyl-3- [4 - ((R) -3-dimethylamino-pyrrolidin-3H-thieno [3,2-d] pyrimidin-4-one -Cyclopropylethynyl-3- (dimethylamino-methyleneamino) -thiophene-2-carboxylic acid methyl ester was reacted with [(R) -1 - (4-amino-phenyl) -pyrrolidin-3-yl] -dimethyl -amine by the method A1. The product with the molecular weight of 404.53 (C23H24N40S) was obtained in this manner; MS (ESI): 405 (M + H +). The compounds of Table 5 were synthesized analogously.

Table 5 The precursors were obtained from the corresponding alkyne by reaction with 5-bromo-3-nitro-thiophene-2-carboxylic acid methyl ester by the Q method and subsequent reduction of the nitro group by the C2 method and further reaction by the B method (analogously to example 29). Example 50 6- (2-Cyclopropylethyl) -3- (4- { (R) -3 - [(2-methanesulfonylethyl) methylamino] pyrrolidin-1-yl}. Phenyl) -3H-thieno [3,2 -d] pyrimidin-4-one - (2-Cyclopropylethyl) -3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester was reacted with [(R) -1- (4-aminophenyl) pyrrolidin-3-yl] - (2- methanesulfonyl-ethyl) methylamine by the method A1. The product with the molecular weight of 500.57 (C25H32N403S2) was obtained in this way; MS (ESI): 501 (M + H +). 5- (2-Cyclopropylethyl) -3-dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester 3-Amino-5- (2-cyclopropylethyl) thiophene-2-carboxylic acid methyl ester was reacted by method B. product with the molecular weight of 280.39 (C14H20N2O2S) was obtained in this way; MS (ESI): 281 (M + H +). 3-Amino-5- (2-cyclopropylethyl) thiophene-2-carboxylic acid methyl ester Method C3 A suspension of 5-cyclopropylethynyl-3-nitrothiophene-2-carboxylic acid methyl ester (1.0 g) and palladium (al 5% on carbon) (170 mg) in methanol (50 ml) was stirred vigorously in a hydrogen atmosphere at atmospheric pressure for 5 h. Then, the catalyst was removed by filtration through kieselguhr and the solvent was removed in vacuo. The product with the molecular weight of 225.31 (C11 H15N02S) was obtained in this way; MS (ESI): 226 (M + H +). The compounds of Table 6 were prepared analogously.

Table 6 The precursors were obtained from the corresponding alkyne by reaction with 5-bromo-3-nitro-thiophene-2-carboxylic acid methyl ester by the Q method and subsequent reduction of the nitro group by the C3 method and further reaction by the B method (analogous to example 50). EXAMPLE 65 3- [4 - ((R) -3-D-methylamino-pyrrolidin-1-yl) phenyl] -6-piperidin-1-yl-3 H -thieno [3,2-d] pyrimidin-4-one A mixture of 6-bromo-3- [4 - ((R) -3-dimethylaminopyrrolidol-1-yl) phenyl] -3H-thieno [3,2-d] pyridinimide-4- ona (40 mg) and piperidine (492 mg) was heated at 100 ° C for 2 days. Then, water and ethyl acetate were added and the organic phase was washed twice with water. The ethyl acetate phase was dried over sodium sulfate and the solvent was removed in vacuo. The residue was purified by preparative HPLC. The product with the molecular weight of 423.58 (C23H29N50S) was obtained in this manner; MS (ESI): 424 (M + H +). Example 66 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (2-oxopyrrolidin-1-yl) -3 H -thieno [3,2-d] pyrimidin-4 -one Method R A mixture of 6-bromo-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one (100 mg ), cesium carbonate (116.6 mg) and tri (dibenzylideneacetone) dipalladium (O) -chloroform adduct (0.25 mg) was placed in a heat-dried container in a glove box. 2-Pyrrolidone (24.4 mg) and 9,9-dimethyl-4,5-bis (diphenylphosphino) xanthene (0.27 mg) in dioxane (2.5 ml) were added. The reaction was stirred at 100 ° C for 22 h. Then, the resulting precipitate was removed by filtration. The product with the molecular weight of 423.53 (C22H25N502S) was obtained in this way; MS (ESI): 424 (M + H +). The compounds of Table 7 were synthesized analogously. Table 7 1 - . 1-Ethyl-imidazolidin-2-one 1-Ethyl-1,3-dihydro-imidazol-2-one was hydrogenated by the method C1. The product with the molecular weight of 14.15 (C5H10N2O) was obtained in this way; MS (ESI): 115 (M + H +). 1-Ethyl-1,3-dihydro-imidazol-2-one was obtained according to the reference: O. Wong et al., Heterocycles 1987, 26 (12), 3 53-8. Example 69 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -6- (pyrrolidine-1 -carbonyl) -3H-thieno [3,2-d] pyrimidin-4 -one Etodo S HATU (39.9 mg), HOAt (13.6 mg) and triethylamine (0.028 ml) were added to a mixture of 3- [4- (4-methylperhydro-1,4-diazepin-1-yl)] phenyl] -4-oxo-3,4-dihydrothieno [3,2-d] pyrimidine-6-carboxylic acid (38.5 mg) and pyrrolidine (7.2 mg) in NMP (1 ml). The reaction mixture was stirred at room temperature overnight. Then, the mixture was mixed with ethyl acetate and water. The aqueous phase was extracted sevetimes with ethyl acetate. The combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The crude product was purified by preparative HPLC. The product with the molecular weight of 437.56 (C23H27N502S) was obtained in this way; MS (ESI): 438 (M + H +). 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -4-oxo-3,4-dihydrothieno [3,2-d] -pyrimidine-6-carboxylic acid Method T One solution 2 M LiOH (1.2 mL) was added to a solution of 3- [4- (4-methylperhydro-1,4-diazepin-1-yl) phenyl] -4-oxo-3,4-methyl ester. dihydrothieno [3,2-d] pyrimidine-6-carboxylic acid (477.8 mg) in THF (5 ml) and water (5 ml) and the mixture was stirred at room temperature for 5 h. Then, the solvent was removed in vacuo and the crude product was purified by preparative HPLC. The product with the molecular weight of 384.45 (C19H20N4O3S) was obtained in this way; MS (ESI): 385 (M + H +). 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -4-oxo-3,4-dihydrothieno [3,2-d] -pyrimidine-6-methyl ester carboxylic Method U Bis (triphenylphosphine) palladium (II) chloride (84.2 mg) and triethylamine (0.25 ml) were added to a mixture of 6-bromo-3- [4- (4-methylperhydro-1, 4- diazepin-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one (503.2 mg) in methanol (15 ml) and acetonitrile (15 ml). The reaction mixture was stirred at a pressure of 5 bar of CO at 60 ° C for 24 h. Then, the reaction mixture was removed by filtration through Celite and the solvent was removed in vacuo. The crude product was purified by preparative HPLC. The product with the molecular weight of 398.48 (C20H22N4O3S) was obtained in this way; MS (ESI): 399 (M + H +). The examples in Table 8 were prepared analogously. Table 8 Example 74 6 - ((Z) -2-Ethoxyvinyl) -3- [4- (4-methyl [1,4] d.azepan-1-yl) phen thieno [3,2-d] pyrimidin-4-one Method V A solution of ethoxyethine (85 mg) and tributyltin hydride (236 mg) in n-heptane (2 mL) was stirred at 80 ° C for 5 h. The solution was concentrated. 6-Bromo-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one (85 mg), tetrakis were added (triphenylphosphona) palladium (0) (12 mg) and DMF (1 mL) and the mixture was stirred at 80 ° C for 2 h. The solvent was removed. The crude product was purified by preparative HPLC. The product with the molecular weight of 410.54 (C22H26N402S C2HF302) was obtained in this manner; MS (ESI): 41 1 (M + H +). Example 75 6- (2-Ethoxyethyl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one. 6 - ((Z) -2-ethoxyvinyl) -3- [4- (4-methy1 [1,4] diazepan-1-yl) phenyl] -3H-t-ene [3,2 -d] pyrimidin-4-one by the method C1. The product with the molecular weight of 412.56 (C22H28N402S) was obtained in this way; MS (ESI): 413 (M + H +). Example 76 6-Cyclopentanecarbonyl-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one -Cyclopentanecarbonyl-3- (dimethylaminomethylenamino) thiophene-2-carboxylic acid methyl ester and 4- (4-methyl [1,4] diazepan-1-yl) phenylamine were reacted by the method A1 . The product with the molecular weight of 436.58 (C24H28N402S) was obtained in this manner; MS (ESI): 437 (M + H +). 5-Cyclopentanecarbonyl-3- (dimethylaminomethyleneamino) thiophene-2-carboxylic acid methyl ester 3-Amino-5-cyclopentanecarbonylthiophene-2-carboxylic acid methyl ester and dimethoxymethyldimethylamine were reacted by method B. The product with the molecular weight of 308.40 (C15H20N2O3S) was obtained in this manner; MS (ESI): 309 (M + H +). 3-Amino-5-cyclopentanecarbonylthiophene-2-carboxylic acid methyl ester Method X Potassium carbonate (2.275 g) was added to a solution of 5-cyclopentanecarbonyl-3- (2,2,2-tnfluoroacetylamino) thiophene methyl ester. 2-carboxylic acid (1, 150 g) in methanol (17 ml), and the mixture was stirred at room temperature for 2 h. Water and ethyl acetate were added. The organic phase was removed by separation and the aqueous phase was extracted twice again with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated. The product with the molecular weight of 253.32 (C12H15N03S) was obtained in this manner; MS (ESI): 254 (M + H +). 5-Cyclopentanecarbonyl-3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester. 3- (2,2,2-Trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester and methoxymethylamide of the cyclopentanecarboxylic acid by the method M. The product with the molecular weight of 349.33 (C14H14F3N04S) was obtained in this manner; MS (ESI): 350 (M + H +). Example 77 6- (Cyclopentylhydroxymethyl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one Method Y Sodium borohydride (100 mg) was added portionwise to a solution of 6-cyclopentanecarbonyl-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3.2 -d] pyrimidin-4-one (180 mg) in methanol (30 ml). After 1 h, methanol (150 ml) was added and the solvent was removed in vacuo. A solution of sodium bicarbonate and dichloromethane was added. The organic phase was removed by separation and the aqueous phase was extracted twice again with dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 438.60 (C24H30N4O2S) was obtained in this way; MS (ESI): 439 (M + H +). Example 78 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (tetrahydropyran-4-carbonyl) -3H-thieno [3,2-d] pyrimidin-4-one 3- (Dimethylaminomethyleneamino) -5- (tetrahydropyran-4-carbonyl) thiophene-2-carboxylic acid methyl ester and 4- (4-methyl [1,4] diazepan-1-yl) phenylamine were reacted by the method A1 . The product with the molecular weight of 452.58 (C24H28N403S) was obtained in this way; MS (ESI): 453 (M + H +). 3- (Dimethylaminomethyleneamino) -5- (tetrahydropyran-4-carbonyl) thiophene-2-carboxylic acid methyl ester 3-Amino-5- (tetrahydropyran-4-carbonyl) thiophene-2-carboxylic acid methyl ester was reacted and dimethoxymethyldimethylamine by method B. The product with the molecular weight of 324.40 (C15H20N2O4S) was obtained in this manner; MS (ESI): 325 (M + H +). 3-Amino-5- (tetrahydropyran-4-carbonyl) thiophene-2-carboxylic acid methyl ester. 5- (Tetrahydropyran-4-carbonyl) -3- (2,2,2-trifluoroacetylamino) methyl ester was reacted thiophene-2-carboxylic acid and potassium carbonate by the method X. The product with the molecular weight of 269.32 (C12H15N04S) was obtained in this manner; MS (ESI): 270 (M + H +).

- (Tetrahydropyran-4-carbonyl) -3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester. 3- (2,2,2-Trifluoroacetylamino) thiophene- methyl ester was reacted 2-carboxylic acid and methoxymethylamide of tetrahydropyran-4-carboxylic acid by the method M. The product with the weight molecular weight of 365.33 (C14H14F3N05S) was obtained in this manner; MS (ESI): 366 (M + H +). Example 79 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6-vinyl-3 H -thieno [3,2-d] pyrimidin-4-one Method Z A solution of 6-bromo-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one (300 mg ), vinyltributyltin (339 mg) and tetrakis (triphenylphosphona) palladium (0) (41 mg) in DMF (2 ml) was stirred at 80 ° C for 30 min. Then, the reaction solution was mixed with ethyl acetate and water. The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated. The crude product was purified by preparative HPLC. The product with the molecular weight of 366.49 (C20H22N4OS) was obtained in this manner; MS (ESI): 367 (M + H +).

Example 80 6- (4-Hydroxytetrahydropyran-4-yl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4 -one 3- (Dimethylaminomethyleneamino) -5- (4-hydroxytetrahydropyran-4-yl) thiophene-2-carboxylic acid methyl ester and 4- (4-methyl [1,4] diazepan-1-yl) phenylamine were reacted by method A1. The product with the molecular weight of 440.57 (C23H28N403S) was obtained in this manner; MS (ESI): 441 (M + H +). 3- (Dimethylaminomethyleneamino) -5- (4-hydroxytetrahydropyran-4-yl) thiophene-2-carboxylic acid methyl ester 3-Amino-5- (4-hydroxytetrahydropyran-4-yl) thiophene- methyl ester was reacted 2-carboxylic acid and dimethoxymethyldimethylamine by method B. The product with the molecular weight of 312.39 (C14H20N2O4S) was obtained in this manner; MS (ESI): 313 (M + H +). 3-Amino-5- (4-hydroxytetrahydropyran-4-yl) thiophene-2-carboxylic acid methyl ester Methyl 5- (tetrahydropyran-4-carbonyl) -3- (2,2,2-) methyl ester was reacted trifluoroacetylamino) thiophene-2-carboxylic acid and potassium carbonate by the method X. The product with the molecular weight of 257.31 (C1 1 H15N04S) was obtained in this manner; MS (ESI): 258 (M + H +). 5- (Tetrahydropyran-4-carbonyl) -3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester 3- (2,2,2-Trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester and tetrahydropyranone were reacted by the method M. The product with the molecular weight of 353.32 (C13H14F3N05S) was obtained in this manner; MS (ESI): 354 (M + H +). Example 81 6- (3-Hydroxy-2-methyltetrahydrofuran-3-yl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-t-ene [3.2 -d] pyrimidin-4-one 3- (Dimethylaminomethyleneamino) -5- (3-hydroxy-2-methyltetrahydrofuran-3-yl) thiophene-2-carboxylic acid methyl ester and 4- (4-methyl [1,4] diazepan-1-yl) were reacted. ) phenylamine by method A1. The product with the molecular weight of 440.57 (C23H28N403S) was obtained in this manner; MS (ESI): 441 (M + H +). 3- (Dimethylaminomethyleneamino) -5- (3-hydroxy-2-methyltetrahydrofuran-3-yl) thiophene-2-carboxylic acid methyl ester. 3-Amino-5- (3-hydroxy-2-) methyl ester was reacted methyltetrahydrofuran-3-yl) thiophene-2-carboxylic acid and dimethoxymethyldimethylamine by method B. The product with the molecular weight of 312.39 (C14H20N2O4S) was obtained in this manner; MS (ESI): 313 (M + H +). 3-Amino-5- (3-hydroxy-2-methyltetrahydrofuran-3-yl) thiophene-2-carboxylic acid methyl ester Methyl 5- (3-hydroxy-2-methyltetrahydrofuran-3-yl) methylester was reacted -3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid and potassium carbonate by the method X. The product with the molecular weight of 257.31 (C1 1 H15N04S) was obtained in this manner; MS (ESI): 258 (M + H +). 5- (3-Hydroxy-2-methyltetrahydrofuran-3-yl) -3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester Methyl ester of 3- (2,2, 2-trifluoroacetylamino) thiophene-2-carboxylic acid and 2-methyldihydrofuran-3-one by the method M. The product with the molecular weight of 353.32 (C13H14F3N05S) was obtained in this manner; MS (ESI): 354 (M + H +). Example 82 6- [Hydroxy (tetrahydropyran-4-yl) methyl] -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidine -4-one Reacted 3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -6- (tetrahydropyran-4-carbonyl) -3H-thieno [3,2-d] pyrimidine-4- ona and sodium borohydride by the method Y. The product with the molecular weight of 454.60 (C24H30N4O3S) was obtained in this manner; MS (ESI): 455 (M + H +).

Example 83 6-lsobutyryl-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pmmidin-4-one 3- (Dimethylaminomethyleneamino) -5-isobutyrylthiophene-2-carboxylic acid methyl ester and 4- (4-methyl [1,4] diazepan-1-yl) phenylamine were reacted by the method A1. The product with the molecular weight of 410.54 (C22H26N402S) was obtained in this way; MS (ESI): 41 1 (M + H +). 3- (Dimethylamomethyleneamino) -5-isobutyrylthiophene-2-carboxylic acid methyl ester 3-Amino-5-isobutyrylthiophene-2-carboxylic acid methyl ester and dimethoxymethyldimethylamine were reacted by method B. The product with the molecular weight of 382.36 (C13H18N203S) was obtained in this manner; MS (ESI): 383 (M + H +). 3-Amino-5-isobutyrylthiophene-2-carboxylic acid methyl ester 5-Isobutyryl-3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester and potassium carbonate were reacted by method X. The product with the molecular weight of 227.28 (C10H13NO3S) is got it this way; MS (ESI): 228 (M + H +). 5-Isobutyryl-3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester. 3- (2,2,2-Trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester and N were reacted. -methoxy-N-methylisobutyramide by the method M. The product with the molecular weight of 323.29 (C12H12F3N04S) was obtained in this manner; MS (ESI): 324 (M + H +). EXAMPLE 84 6- (1-Hydroxy-2-methylpropyl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4 -one 6-Isobutyryl-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one was reacted and sodium borohydride by the method Y. The product with the molecular weight of 412.56 (C22H28N402S) was obtained in this manner; MS (ESI): 41 1 (M + H +). Example 85 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (tetrahydro-pyran-4-ylidenemethyl) -3H-thieno [3,2-d] pyrimidin-4 -one Method AA p-Toluenesulfonic acid (200 mg) was added to a suspension of 6- [hydroxy (tetrahydropyran-4-yl) methyl] -3- [4- (4-methyl [1,4] diazepam) 1 -yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one (14 mg) in toluene (5 ml) and the mixture was refluxed for 30 h. After a cooling period, 1 N NaOH (50 ml) was added and the mixture was extracted with dichloromethane and dried over magnesium sulfate. The crude product was purified by preparative HPLC. The product with the molecular weight of 436.58 (C24H28N402S) was obtained in this manner; MS (ESI): 437 (M + H +). EXAMPLE 86 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (tetrah -dropiran-4-ylmethyl) -3H-t-ene [3,2-d] pyrimidine -4-one 3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -6- (tetrahydropyran-4-ylidenemethyl) -3H-thieno [3,2-d] pyrimidin-4 was reduced -one using the C1 method. The product with the molecular weight of 438.60 (C24H30N4O2S) was obtained in this way; MS (ESI): 439 (M + H +). Example 87 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (2-methyl-2,5-dihydrofuran-3-yl) -3H-thieno [3,2 -d] pyrimidin-4-one Reacted 6- (3-hydroxy-2-methyltetrahydrofuran-3-yl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-] d] pyrimidin-4-one and p-toluenesulfonic acid by the AA method. The product with the molecular weight of 422.55 (C23H26N402S) was obtained in this way; MS (ESI): 423 (M + H +). Example 88 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (2-methyl-4,5-dihydrofuran-3-yl) -3H-thieno [3,2 -d] pyrimidin-4-one Reacted 6- (3-hydroxy-2-methyltetrahydrofuran-3-yl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-] d] pyrimidin-4-one and p-toluenesulfonic acid by the AA method. The product with the molecular weight of 422.55 (C23H26N402S) was obtained in this way; MS (ESI): 423 (M + H +). Example 89 6- (3,6-Dihydro-2 H -pyran-4-ylmethyl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl) -3H-thieno [3 , 2-d] pyrimidin-4-one Reacted 6- [hydroxy (tetrahydropyran-4-yl) methyl] -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one and p-toluenesulfonic acid by the AA method. The product with the molecular weight of 436.58 (C24H28N402S) was obtained in this manner; MS (ESI): 437 (M + H +). Example 90 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (2-methylpropenyl) -3H-thieno [3,2-d] pyrimidin-4-one 6- (1-Hydroxy-2-methylpropyl) -3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidine was reacted 4-one and p-toluenesulfonic acid by the AA method. The crude product was purified by preparative HPLC. The product with the molecular weight of 394.54 (C22H26N40S) was obtained in this manner; MS (ESI): 395 (M + H +).

Example 91 6-lsobutyl-3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -3H-thieno [3,2-d] pyrimidin-4-one 3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -6- (2-methylpropenyl) -3H-thieno [3,2-d] pyrimidn-4 was reduced -one using the C1 method. The product with the molecular weight of 396.56 (C22H28N40S) was obtained in this manner; MS (ESI): 397 (M + H +). EXAMPLE 92 3- [4- (4-Methyl [1,4] diazepan-1-yl) phenyl] -6- (2-methyltetrahydrofuran-3-yl) -3H-thieno [3,2-d] p Rimidin-4-one It was reduced to 3- [4- (4-methyl [1,4] diazepan-1-yl) phenyl] -6- (2-methyl-4,5-dihydrofuran-3-yl) -3H-thieno [3,2 -d] pyrimidin-4-one by the method C1. The product with the molecular weight of 424.57 (C23H28N402S) was obtained in this way; MS (ESI): 425 (M + H +).

EXAMPLE 93 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -6-piperidin-1-ylmethyl-3 H -thieno [3,2-d] pyrimidin-4-one Method BA Sodium triacetoxyborohydride (143.8 mg) was added to a mixture of 3- [4- (4-methylperhydro-1,4-diazepin-1-yl) phenyl] -4-oxo-3,4-dihydrothien [3 , 2-d] pyrimidine-6-carbaldehyde (50 mg) and piperidine (1 1.6 mg) in methylene chloride (5 ml). The reaction mixture was stirred at room temperature for 2 h. Then, water was added. The aqueous phase was extracted several times with methylene chloride. The combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The crude product was purified by preparative HPLC. The product with the molecular weight of 437.22 (C24H3 N50S) was obtained in this way; MS (ESI): 438 (M + H +). 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -4-oxo-3,4-dihydrothieno [3,2-d] pyrimidine-6-carbaldehyde Methyl ester of 3- (dimethylaminomethyleneamino) -5-formylthiophene-2-carboxylic acid with 4- (4-methylperhydro-1,4-diazepin-1-yl) phenylamine by method A1. The product with the molecular weight of 368.46 (C19H20N4O2S) was obtained in this manner; MS (ESI): 369 (M + H +). 3- (Dimethylaminomethyleneamino) -5-formylthiophene-2-carboxylic acid methyl ester 3-Amino-5-formylthiophene-2-carboxylic acid methyl ester and dimethoxymethyldimethylamine were reacted by method B. The product with the molecular weight of 308 , 40 (C15H20N2O3S) was obtained in this manner; MS (ESI): 309 (M + H +). 3-Amino-5-formylthiophene-2-carboxylic acid methyl ester 5-formyl-3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester was deblocked by method X. The product with the Molecular weight of 185.01 (C7H7N03S) was obtained in this manner; MS (ESI): 186 (M + H +). 5-Formyl-3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester A 1.6 M solution of n-Buu in hexane (12 ml) was added dropwise to a solution of diisopropylamine (2.9 ml) in THF (30 ml) at -78 ° C. The reaction mixture was stirred at 0 ° C for 10 min, then cooled to -78 ° C and a solution of 3- (2,2,2-trifluoroacetylamino) thiophene-2-carboxylic acid methyl ester (1 , 5 g) in THF (15 ml). The reaction mixture was stirred at -78 ° C for 30 min, then 1-formylpiperidine (4 g) was added and the mixture was stirred again at this temperature for 1.5 h. Subsequently, a saturated solution of ammonium chloride was added and the reaction mixture was allowed to reach room temperature. The The aqueous phase was extracted several times with ethyl acetate. The combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The product with the molecular weight of 281.0 (C9H6F3N04S) was obtained in this manner; MS (ESI): 282 (M + H +). The reaction can also employ the compound protected with boc. Example 94 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -6-pyrrolidin-1-methylmethyl-3H-thieno [3,2-d] pyrimidin-4-one 3- [4- (4-Methylperhydro-1,4-diazepin-1-yl) phenyl] -4-oxo-3,4-dihydrothieno [3,2-d] pyrimidine-6-carbaldehyde was reacted with pyrrolidine by the BA method. The product with the molecular weight of 423.58 (C23H29N50S) was obtained in this manner; MS (ESI): 424 (M + H +). Example 95 3- [4- (3-Dimethylamino-pyrrolidin-1-yl) -phenyl] -6-propoxymethyl-3 H -thieno [3,2-d] pyrimidin-4-one A mixture of 3- [4- (3-dimethylamino-pyrrolidin-1-yl) -phenyl] -6-hydroxymethyl-3H-thieno [3,2-d] pihmindin-4 -one (50.0 mg), sodium hydride (5.24 mg) and DMF (1 ml) was stirred at 0 ° C for 15 min. Then, 1-bromopropane (22.0 mg) was added and the solution was warmed to room temperature and stirred for 2 h. Water and ethyl acetate were added and the aqueous phase was extracted with ethyl acetate several times. The combined organic phase was dried over sodium sulfate and the solvent was removed in vacuo. The crude product was purified by preparative HPLC. The product with the molecular weight of 412.55 (C22H28N402S) was obtained in this way; MS (ESI): 413 (M + H +). 3- [4- (3-Dimethylamino-pyrrolidin-1-yl) -phenyl] -6-hydroxymethyl-3H-thieno [3,2-d] pyrimidin-4-one A mixture of 6- (tert-butyl-diphenyl) -silyloxymethyl) -3- [4- (3-dimethylamino-pyrrolidin-1-yl) -phenyl] -3H-thieno [3,2-d] pyrimidin-4-one (1.4 g) and a 1 M solution of Tetra-N-butylammonium fluoride in THF (2.7 ml) in THF (20.0 ml) was stirred at room temperature for 3 h. The solvent was removed in vacuo and the crude product was purified by preparative HPLC. The product with the molecular weight of 370.47 (C19H22N402S) was obtained in this manner; MS (ESI): 371 (M + H +). 6- (tert-Butyl-diphenyl-silanyloxymethyl) -3- [4- (3-dimethylamino-pyrrolidin-1-yl) -phenyl] -3H-thieno [3,2-d] pyrimidin-4-one Reacted 5- (tert-Butyl-diphenyl-silanyloxymethyl) -3- (dimethylamine-methyleneamino) -thiophene-2-carboxylic acid methyl ester with [1- (4-amino-phenyl) -pyrrolidin-3) -yl] -dimethyl-amine by the method A1. The product with the molecular weight of 608.87 (C35H40N4O2SSI) was obtained in this manner; MS (ESI): 609 (M + H +). 5- (tert-Butyl-diphenyl-silanyloxymethyl) -3- (dimethylamino-methyleneamino) -thiophene-2-carboxylic acid methyl ester 3-Amino-5- (tert-butyl-diphenyl-silanyloxymethyl) methyl ester was reacted ) -thiophene-2-carboxylic acid by method B. The product with the molecular weight of 480.70 (C26H32N203SSI) was obtained in this manner; MS (ESI): 481 (M + H +). 3-Amino-5- (tert-butyl-diphenyl-silanyloxymethyl) -thiophene-2-carboxylic acid methyl ester 3-tert-butoxycarbonylamino-5- (tert-butyl-diphenyl-silanyloxymethyl) -thiophene methyl ester was deblocked -2-carboxylic acid by the method K. The product with the molecular weight of 425.62 (C23H27N03SSI) was obtained in this manner; MS (ESI): 426 (M + H +). 3-tert-Butoxycarbonylamino-5- (tert-butyl-diphenyl-silanyloxymethyl) -thiophene-2-carboxylic acid methyl ester A solution of tert-butyldiphenylchlorosilane (1.66 g) in methylene chloride (5 ml) was added to a mixture of methyl ester of 3-tert-acid butoxycarbonylamino-5-hydroxymethyl-thiophene-2-carboxylic acid (1.42 g), DIPEA (1.26 ml), DMAP (30.21 mg) and methylene chloride (25 ml) over the course of 10 hours. min. The mixture was stirred for 6 h at room temperature. Methylene chloride was added and washed with a saturated solution of ammonium chloride and water. The combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The product with the molecular weight of 525.74 (C28H35N05SSI) was obtained in this manner; MS (ESI): 426 (M-BOC + H +). 3-tert-Butoxycarbonylamino-5-hydroxymethyl-thiophene-2-carboxylic acid methyl ester To a suspension of 3-tert-butoxycarbonylamino-5-formyl-thiophene-2-carboxylic acid methyl ester (1.49 g) in ethanol water (95 ml / 95 ml) was added sodium borohydride (105.8 mg) at 0 ° C. The mixture was stirred for 1 h at this temperature. Then, ethyl acetate and water were added. The aqueous phase was extracted several times with ethyl acetate, the combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The product with the molecular weight of 287.33 (C12H17N05S) was obtained in this manner; MS (ESI): 288 (M + H +). Example 96 6-Cyclopropylmethoxymethyl-3- [4- (3-dimethylamino-pyrrolidin-1-yl) -phenyl] -3H-thieno [3,2-d] pyrimidin-4-one A mixture of 3- [4- (3-dimethylamino-pyrrolidin-1-yl) -phenyl] -6-hydroxymethyl-3H-thieno [3,2-d] pyrimidin-4-one (20.0 mg) and tert. Potassium butylate (7.65 mg) in DMF (0.3 ml) was stirred at 0 ° C for 5 min. Then, cyclopropylmethyl bromide (11.28 mg) was added. The solution was warmed to room temperature and stirred for 2 h. Then, ethyl acetate and water were added. The aqueous phase was extracted several times with ethyl acetate, the combined organic phases were dried over sodium sulfate and the solvent was removed in vacuo. The crude product was purified by preparative HPLC. The product with the molecular weight of 424.56 (C23H28N402S) was obtained in this way; MS (ESI): 425 (M + H +). Example 97 6-Cyclobutylmethoxymethyl-3- [4- (3-dimethylamino-pyrrolidin-1-yl) -phenyl] -3H-thieno [3,2-d] pyrimidin-4-one Example 97 was prepared analogously to example 96 using (bromomethyl) cyclobutane. The product with the molecular weight of 438.59 (C24H30N4O2S) was obtained in this manner; MS (ESI): 439 (M + H +). Table 9 summarizes the results that were obtained by the calcium immobilization assay described above Table 9

Claims

1. - A compound of the formula I wherein the meanings are R1, R1 \ R1", RT" independently of each other H, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-alkyl (Ci-C6), O-alkoxy (C C4) -alkyl (C C4), S- (C1-C6) alkyl, (C1-C6) alkyl, (C2-C6) alkenyl, (C3-C8) cycloalkyl, (C3-C8) O-cycloalkyl, (C3-C8) cycloalkenyl, (C2-C6) alkynyl, (C0-C8) alkylene-aryl, O-(C0-C8) alkylene-aryl, S-aryl, N (R3) (R4), SO2-CH3, COOH, COO-alkyl (CrC6), CON (R5) (R6), N (R7) CO (R8), N (R9) SO2 (R10), CO (R11) or (C (R12) (R13)) xO (R14); R3, R4, R5, R6, R7, R9 independently of each other H or (Ci-C8) alkyl; or R3 and R4, R5 and R6 independently form, optionally together with the nitrogen atom to which they are attached, a ring of 5-6 members which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH group, N-C 1 -C 6 alkyl, oxygen and sulfur; R8, R10, R1 1 independently of each other H or alkyl (CrC8); R12, R13 independently of each other H or alkyl (CrC8); R 14 H, alkyl (CrC 6) or aryl; x 0, 1, 2, 3, 4, 5 0 6; R2 H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (CrC6), O-alkoxy (C4) -alkyl (C1-C4), S-alkyl (Ci-C6) ), (Ci-C6) alkyl, (C2-C6) alkenyl, (C3-C8) cycloalkyl, (C3-C8) O-cycloalkyl (C3-C8), (C2-C6) alkynyl, alkylene (Co-C8) -aryl, O-alkylene (C0-C8) -aryl, S-aryl, N (R15) (R16), S02-CH3, COOH, COO-alkyl (Ci-C6), CON (R17) ) (R18), N (R19) CO (R20), N (R21) S02 (R22), CO (R23) or (C (R24) (R25)) X-0 (R26); R15, R16, R17, R18, R19, R21 independently of each other H or (Ci-C8) alkyl; or R15 and R16, R17 and R18 form independently of each other and optionally together with the nitrogen atom to which they are attached, a 5-6 membered ring which, apart from the nitrogen atom, may also comprise 0-1 additional heteroatoms of the group of NH, N-(C1-C6) alkyl, oxy- geno and sulfur; R20, R22, R23 independently of each other H or alkyl (CrCe); R24, R25 independently of each other H or alkyl (C-i-Ce); R26 H, alkyl (CrC6) or aryl; preferably H or alkyl (C-i-Ce); x '0, 1, 2, 3, 4, 5 0 6; R27, H or alkyl (CrC6); X S, O or C (R30) = C (R30 '); R30, R30 'independently of each other H, F, Cl, Br, I, OH, CF3, N02, CN, OCF3, O-alkyl (C6), O-alkoxy (Ci-C4) -alkyl (Ci-C4) , S-alkyl (Ci-Ce), alkyl (Ci-C6), alkenyl (C2-C6), cycloaicil (C3-C8), O-cycloalkyl (C3-C8), cycloalkenyl (C3-C8), alkynyl (C2) -C6) or aryl, optionally substituted ton F, Cl, Br, O-alkyl (Ci-C6) or alkyl (C6); A link or linker having from 1 to 8 members, where the members are selected from the group consisting of O, S, S02, N (R31), CO, C (R32) (R33), C (R34) = C (R34 '), cyclopropylene and C = C, resulting in a chemically reasonable radical; R31, R34, R34 'independently of each other H or alkyl (C-i-Cs); R32, R33 independently of each other H, (C1-C6) alkyl, OH or O-alkyl (CrCe); B?, N (R35) (R36), hydroxy-alkyl (CrC4), alkyl (CrC8), alkoxy (Ci-C4) -alkyl (C1-C4), alkenyl (C2-C8), alkynyl (C2-C8) , a non-aromatic, mono-, bi-, tri- or spirocyclic ring of from 3 to 10 members which may comprise from 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, wherein the ring system may be further substituted with one or more of the following substituents: F, Cl, Br, CF 3, NO 2, CN, alkyl (C Ce), O-alkyl (CrCe), alkoxy (Ci-C 4) -alkyl (C C 4), hydroxy-alkyl ( C1-C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (CrC6), N (R42) (R43), S02CH3, SCF3 or S- alkyl (C Ce); or where the ring system can be linked to A by = C (R43); R35, R36, R37, R38, R39, R40, R41, R42, R43, R43 'independently of each other H or (Ci-C8) alkyl; or R38 and R39, R42 and R43 form independently of each other, optionally together with the nitrogen atom to which they are attached, a 5-6 membered ring which, apart from the nitrogen atom, may also comprise 0-1 additional heteroatoms of the group NH, N-alkyl (C Ce), oxygen and sulfur; Q structure of mono-, bi-, tri- or spirocyclic, saturated or partially unsaturated rings, having a nitrogen atom and 0-3 additional heteroatoms selected from the group of N, O and S, where the rings of the structure can be spiro-bound, condensed or linked, and wherein the ring system may be substituted with one or more of the following substituents: F, OH, CF3, CN, OCF3, oxo, O-alkyl (CrC8), alkoxy (CC) -alkyl (d-C4), alkyl (C6), alkenyl (C2-C6), alkynyl (C2-C6), CO (R44), (C (R45) (R46)) 0-R47 and CO (C ( R45) (R46)) p-R48, where Q comprises in total at least two N atoms; R44 H or alkyl (CrC8); R45, R46 independently of each other H, alkyl (CrC8), OH, (C3-C8) cycloalkyl or (Ci-C4) alkoxy (Ci-C4) alkyl, or independently of each other 0, 1, 2, 3, 4, 5 or 6; R47, R48 independently of each other OH, F, O-alkyl (CrC8), CON (R49) (R50), N (R51) CO (R52), N (R53) (R54), C02 (R55), S02Me, CN , a ring system of 3-10 members having from 0 to 3 heteroatoms selected from the group of N, O and S, which may be substituted with one or more of the following substitutes: F, Cl, Br, CF3 , alkyl (C8), O-alkyl (Ci-C8), alkoxy (C4) -alkyl (CC), CO (R56), oxo and OH; R49, R50, R51, R52, R55, R56 independently of each other H or (C-i-C8) alkyl; or R49 and R50 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, can also comprise 0-1 additional heteroatoms of the NH, N-alkyl group Ce), oxygen and sulfur; R53, R54 independently of each other H, alkyl (Ci-Cs), alkoxy (Cr C4) -alkyl (CrC4), alkenyl (C3-C8), alkynyl (C3-C8), CO (R57), (C (R58) (R59)) q-R60, CO (C (R61) (R62)) r-R63 or CO-Oalkyl (Ci-C8); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, comprises from 0 to 3 additional heteroatoms selected from the group of N, O and S and may be further substituted with one or more of the following substituents: F, Cl, Br, CF3, CN, O-alkyl (C8), alkyl (C6), CO (R64), oxo, OH, (d-C4) alkoxy-(C1-C4) alkyl, hydroxy-alkyl (d-C4), CON (R65) (R66), N (R67) CO (R68), N (R69) (R70) ), CO2 (R71) and S02alkyl (Ci-C6); R58, R59 independently of each other H, alkyl (CrC6) or OH; R57, R61, R62, R64, R65, R66, R67, R68, R69, R70, R71 independently of each other H or (C1-C6) alkyl; or R69 and R70 optionally form together with the nitrogen atom to which a 5-6 membered ring is attached which, apart from the nitrogen atom, may also comprise 0-1 additional heteroatoms of the group of NH, N-alkyl (C1-) C6), oxygen and sulfur; q, r independently of each other 0, 1, 2, 3, 4, 5 or 6; R60, R63 independently of one another OH, F, O-alkyl (Ci-C6), CN, COO (R78), N (R74) CO (lower) alkyl (Ci-C6), N (R76) (R77), CON (R72) ( R73), SO2alkyl (Ci-C6), a 3-12 membered mono-, bi- or spirocyclic ring which may comprise one or more heteroatoms from the group of N, O and S, and the 3-12 membered ring may comprise additional substituents such as F, Cl, Br, OH, CF3, NO2, CN, OCF3, oxo, O-alkyl (d-Ce), alkoxy (CrC4) -alkyl (C1-C4), S-alkyl (Ci -C6), alkyl (C6), alkenyl (C2-C6), cycloalkyl (C3-C8), O-cycloalkyl (C3-C8), cycloalkenyl (C3-C8), O-cycloalkenyl (C3-C8) , (C2-C6) alkynyl, N (R76) (R77), COO (R78), SO2alkyl (Ci-C6) and COOH; R72, R73, R74, R76, R77, R78 independently of each other H or (Ci-C8) alkyl; R72 and R73, R76 and R77 independently form, optionally together with the nitrogen atom to which they are attached, a 5-6 membered ring which, apart from the nitrogen atom, may also comprise 0-1 additional heteroatoms from the group of NH, N-C 1 -C 6 alkyl, oxygen and sulfur; and the pharmaceutically acceptable salts thereof.

2. - A compound according to claim 1, in ne the following meanings: B N (R35) (R36), hydroxyalkyl (Ci-C4), alkyl (CrC8), alkoxy (CrC4) -alkyl (C1-C4), alkenyl (C2-Cs), alkynyl (C2-C8), a non-aromatic ring, mono-, bi -, tri- or spirocyclic, from 3 to 10 members, which may comprise from 0 to 4 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system may be additionally substituted with one or more of the following substituents: F, Cl, Br, CF3, N02, CN, alkyl (Ci-C6), O-alkyl (CrC8), alkoxy (d-C4) -alkyl (C4), hydroxy-alkyl (Ci-C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (C C6), N (R42) (R43), S02CH3, SCF3 or S-alkyl (Ci-C6); or where the ring system can be linked to A by = C (R43 ').

3. - A compound according to claim 1, wherein B has the following meanings: B hydroxyalkyl (C1-C4) alkyl, (C Ce), alkoxy (CrC4) -alkyl (C1-C4), alkenyl (C2) -C8), (C2-C8) alkynyl, a non-aromatic, mono-, bi- or spirocyclic ring, of 3 to 10 members, which may comprise from 0 to 4 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system can be further substituted with F, Cl, Br, CF3, NO2, CN, alkyl (Ci-C6), O-alkyl (CrC8), alkoxy (d-C4) -alkyl (C1-C4), hydroxy - alkyl (Ci-C4), oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (CrC6), N (R42) (R43) or S02CH3; or where the ring system can be linked to A by = C (R43).

4. - A compound according to claim 1, wherein B has the following meanings: B hydroxy-alkyl (Ci-C4), alkyl (CrC8), alkoxy (Ci-C4) -alkyl (CrC), a non-aromatic ring , mono-, bi- or spirocyclic, from 3 to 10 members, which can comprise from 0 to 3 heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the ring system can be additionally substituted with F, Cl, Br, CF3, N02, CN, alkyl (CrC6), O-alkyl (d-C8), alkoxy (d-C4) -alkyl (Ci-C4), hydroxy-C1-C4 alkyl, oxo, CO (R37), CON (R38) (R39), hydroxy, COO (R40), N (R41) COalkyl (CrC6), N (R42) (R43) or S02CH3.

5. - A compound according to claim 1, wherein B has the following meanings: B alkyl (Ci-C8), alkoxy (Ci-C4) -alkyl (C1-C4), a non-aromatic ring, mono-, bi - or spirocyclic, from 3 to 10 members, which may comprise from 0 to 3 heteroatoms selected from the oxygen, nitrogen and sulfur group, where the ring system may be further substituted with F, Cl, CF3, alkyl (d- Ce) ), O-alkyl (C Ce), alkoxy (d-C4) -alkyl (CrC), hydroxy (C4) alkyl, oxo, CO (R37), hydroxy, N (R41) COalkyl (d-C6)

6. - A compound according to any of claims 1 to 5, wherein Q is: Q a group of the general formula: wherein ring D has the following meanings: saturated, 5-7 membered monocyclic azacry, comprising an element N (R53) or C (R45) ((CH2) 0-N (R53) (R54)); azabicyclo or saturated spirocycle, of 6-1 1 members, comprising an element N (R53) or C (R45) ((CH2) 0-N (R53) (R54)); H or alkyl (C-i-Ce); preferably H; 0, 1,2,3, 4, 506.

7. - A compound according to any of claims 1 to 6, wherein Q has the meanings: - 179 - wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (CI C6), O-alkyl (CrC6) or alkoxy (d-C4) -alkyl (C C4).

8. - A compound according to any of claims 1 to 7, wherein Q has the meanings: wherein the groups, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (Ci-C6), O-alkyl (Ci-C6) or alkoxy (Ci-C4) - alkyl (CrC).

9. - A compound according to any of claims 1 to 8, wherein Q has the meanings: wherein the groups, other than R53, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (CrC6), O-alkyl (CrC6) or alkoxy (Ci-C4) -alkyl (C1-C4) .

10. - A compound according to any of claims 1 to 8, wherein Q has the meaning: wherein the group, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (CrC6), O-alkyl (Ci-C6) or (C4) alkoxy-alkyl (C C4).

11. - A compound according to any of claims 1 to 8, wherein Q has the meaning: wherein the group, other than R53 and R54, may be optionally substituted with one or more substituents selected from F, OH, oxo, alkyl (Ci-C6), O-alkyl (C6) or akoxy (C4) -alkyl; lo (C C4).

12. - A compound according to any of claims 1 to 11, wherein the meanings are: R53 H, alkyl (Ci-C8), (C (R58) (R59)) q-R60, akoxy (C C4) - I rent (C1-C4), (C3-C8) alkenyl, (C3-C8) alkynyl, CO-C8 alkyl, CO- O-alkyl (Ci-C8) or CO (C (R61) (R62)) rN (R76) ) (R77); R54 alkyl (C8), (C (R58) (R59)) q-R60, akoxy (C C) -alkyl (CrC4), (C3-C8) alkenyl or (C3-C8) alkynyl; or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, may comprise from 0 to 3 additional heteroatoms selected from among the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system can be further substituted with F, Cl, Br, CF3, alkyl (C6), O-alkyl (C8), akoxy (Ci-C4) -alkyl (C1-C4), hydroxy (C1-C4) alkyl, oxo, CO (R64), CON (R65) (R66), hydroxy, C00 (R71), N (R67) Coalkyl (C C6), N (R69) (R70) or S02alkyl (CrC6).

13. - A compound according to any of claims 1 to 12, wherein the meanings are: R53, R54 independently of each other alkyl (Ci-C8), (C (R58) (R59)) q- R60 or alkoxy (CrC4) ) -alkyl (C1-C4); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, may comprise from 0 to 2 additional heteroatoms selected from the group of oxygen, nitrogen and sulfur, where the heterocyclic ring system can be further substituted with F, Cl, Br, CF3, alkyl (C Ce), O-alkyl (Ci-C8), alkoxy (Ci) -C4) -alkyl (C1-C4), hydroxy (C1-C4) alkyl, oxo, CO (R64), hydroxy, N (R67) CO (lower) alkyl (C6) or S02alkyl (CrCe).

14. - A compound according to any of claims 1 to 13, wherein the meanings are: R60, R63 independently of each other OH, F, O-alkyl (Ci-C6), N (R74) COalkyl (CrC6), SO2alkyl (CrC6), a 3-12 membered mono-, bi- or pyrocyclic ring which may comprise one or more heteroatoms of the group of N, O and S, and the 3-12 membered ring may comprise additional substituents such as F, Cl, Br, OH, CF3, NC-2, CN, OCF3 > oxo, 0-alkyl (Ci-C6), alkoxy (C4) -alkyl (C4), alkyloyl (Ci-C6), alkenyl (C2-C6), alkynyl (C2-C6), N (R76) (R77) ) and S02alkyl (Ci-C6);

15. - A compound according to any of claims 1 to 14, wherein the meanings are: To a bond or a linker having 1 to 6 members, wherein the members are selected from the group consisting of O, S02, N (R31), CO, C (R32) (R33), C (R34) = C (R34 ') and C = C, resulting in a chemically reasonable radical; R31, R34, R34 'independently of each other H or alkyl (Ci-Cs); R32, R33 independently of each other H, (Ci-C6) alkyl, OH or O-alkyl (????).

16. - A compound according to any of claims 1 to 15, wherein R2 has the meanings: R2 H, F, Cl, O-alkyl (CrC6) or alkyl (Ci-Ce).

17. - A compound according to any of claims 1 to 16, wherein X has the meanings: X S or O.

18. - A compound according to any of claims 1 to 16, wherein X is S.

19. - A compound according to any of claims 1 to 18, wherein the meanings are: R1, R1 ', R1", R1"' independently of each other H, F, Cl, OH, CN, O-alkyl (Ci - C6) or alkyl (C6); R2 H; R27 H or alkyl (C C6); X S, O or C (R30) = C (R30 '); R30, R30 'independently of each other H, F, Cl, OH, CF3, NO2, CN, OCF3, O-alkyl (Ci-C6) or alkyl (C6); A link or linker having from 1 to 5 members, where the members are selected from the group consisting of O, N (R31), CO, C (R32) (R33), C (R34) = C (R34) ') and C = C, resulting in a chemically reasonable radical; where the linker does not contain O-CO or CO-O groups; R31, R34, R34 'independently of each other H or alkyl (Ci-Cs); R32, R33 independently of each other H, alkyl (Ci-C6), OH or O-alkyl (C1-C6); BH, hydroxy (C1-C4) alkyl, (C Ce) alkyl, (C1-C4) alkoxy-(C1-C4) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, a non-aromatic ring, monocyclic, from 3 to 7 members, which can comprise from 0 to 2 heteroatoms selected from the group of oxygen and nitrogen, where the ring system can be further substituted with F, Cl, Br, CF3, alkyl (C C6), or -alkyl (C-pC-e), (C4) alkoxy-(C1-C4) alkyl, hydroxy (C1-C4) alkyl, oxo, CO (R37) or hydroxy; R37 H or alkyl (Ci-C8); a group selected among R53, R54 independently of each other H, alkyl (CrC8), alkoxy (Ci- C4) -alkyl (C1-C4), alkenyl (C3-C8), alkynyl (C3-C8), CO (R57), (C (R58 ) (R59)) q-R60, CO (C (R61) (R62)) r-R63 or CO-Oalkyl (Ci-C8); or R53 and R54 form, together with the nitrogen atom to which they are attached, a mono-, bi- or spirocyclic ring, of 4 to 10 members which, apart from the nitrogen atom, comprises from 0 to 2 additional heteroatoms selected between the group of N, O and S, and may be further substituted with one or more of the following substituents: F, Cl, Br, CF3, alkyl (CrC8), O-alkyl (CrC6), alkoxy (CC) -alkyl (C1-C4), hydroxy (C4) alkyl, oxo, CO (R64), hydroxy, N (R67) CO (lower) alkyl (Ci-C6) or S02alkyl (C6); R58, R59 independently of each other H, alkyl (CrCe) or OH; R57, R61, R62, R64, R67 independently of each other H or alkyl (d-Ce); q, r independently of each other 0, 1 or 2; R60, R63 independently of one another OH, F, O-alkyl (CC ^), N (R74) COalkyl (C C6), N (R76) (R77), CON (R72) (R73), SO2alkyl (Ci-C6) , a 3-12 membered mono-, bi- or spirocyclic ring which may comprise from one to three heteroatoms of the group of N, O and S, and the ring of 3-12 members may comprise additional substituents such as F, Cl, Br, OH, CF3, NO2, CN, OCF3, oxo, O-(C1-C6) alkyl, alkoxy (CrC4) -alkyl (C1-C4), alkyl (Ci-C6), alkenyl (C2-C6), alkynyl (C2-C6), N (R76) (R77) and SO2alkyl (CrC6); R72, R73, R74, R76, R77 independently of each other H or alkyl (Ci-Ce).

20. - A compound according to any of claims 1 to 19, wherein the meanings are: R1, R1 \ R1", RT" independently of each other H, F, Cl, O-methyl or methyl; R2 H; R27 H; X S, O or C (R30) = C (R30 '); R30, R30 'H; To a bond or element selected from the group consisting of O, CH2, CO, O-CH2, CHOH, CH2-CH2, CH = CH, C (CH3) = CH, C = C, CH2-O, N ( CH3) CO, NH-CO, CH2-O-CH2, O-CH = CH, C (OH) (CH3) -CH2-CH2 and C (OH) (CH3) -C = C; B hydroxyalkyl (C1-C4) alkyl, (CrC8) alkyl, (Ci-C4) alkoxy-(C1-C4) alkyl, (C2-C8) alkenyl, alkynyl (C2-Ce), a monocyclic, non-aromatic ring, 3-6 members, selected from the group: wherein the ring system may be further substituted with methyl, ethyl, OH or oxo.

21. - A compound according to claims 19 and 20, wherein X is S.

22. - A process for preparing compounds of formula I according to any of claims 1 to 21, wherein R27 is H, including the steps: i) reaction of an aromatic ortho-amino carboxylic ester of the general formula (II) with dimethylformamide dimethyl acetal to give the corresponding aminal of the general formula (III): I) reaction of the resulting aminal (III) with a substituted primary aromatic amine to give a condensed pyrimidinone, and iii) where appropriate, further reaction, to produce compounds of formula I:

23. - A medicament comprising one or more of the compounds of formula I according to one or more of claims 1 to 21 or prepared according to claim 22.

24. - A medicament comprising one or more of the compounds of the formula I according to one or more of the claims 1 to 21 or preparations according to claim 22 and one or more active ingredients, which have beneficial effects on metabolic alterations or disorders associated therewith.

25. - A medicament comprising one or more of the compounds of formula I according to one or more of claims 1 to 21 or preparations according to claim 22 and one or more antidiabetics.

26. - A medicament comprising one or more of the compounds of formula I according to one or more of claims 1 to 21 or prepared according to claim 22 and one or more lipid modulators.

27. - A medicament comprising one or more of the compounds of formula I according to one or more of claims 1 to 21 or preparations according to claim 22 and one or more anti-obesity agents.

28. The use of the compounds of the formula I according to one or more of claims 1 to 21 or prepared according to claim 22, for the treatment and / or prevention of disorders of fatty acid metabolism and disorders of use of the glucose

29. The use of the compounds of formula I according to one or more of claims 1 to 21 or preparations according to claim 22, for the treatment and / or prevention of disorders in which insulin resistance is involved .

30. The use of the compounds of formula I according to one or more of claims 1 to 21 or prepared according to claim 22, for the treatment and / or prevention of diabetes mellitus and the sequelae associated therewith.

31. The use of the compounds of formula I according to one or more of claims 1 to 21 or prepared according to claim 22, for the treatment and / or prevention of dyslipidemias and the sequelae thereof.

32. The use of the compounds of the formula I according to one or more of claims 1 to 21 or prepared according to claim 22, for the treatment and / or prevention of conditions associated with the metabolic syndrome.

33. - The use of the compounds of the formula I according to one or more of claims 1 to 21 or prepared according to claim 22 for the treatment and / or prevention of obesity and of the sequels associated with it.

34. The use of the compounds according to one or more of claims 1 to 21 or preparations according to claim 22 together with at least one additional activated ingredient for the treatment and / or prevention of disorders of fatty acid metabolism and disorders of glucose utilization.

35. The use of the compounds according to one or more of claims 1 to 21 or preparations according to claim 22 together with at least one additional active ingredient for the treatment and / or prevention of disorders in which the resistance is involved to insulin.

36. The use of the compounds according to one or more of claims 1 to 21 or preparations according to claim 22 together with at least one additional active ingredient for the treatment and / or prevention of obesity.

37. - A process for producing a medicament comprising one or more of the compounds according to one or more of claims 1 to 21 or prepared according to claim 22, which comprises mixing the active ingredient with a suitable pharmaceutically vehicle, and converting this mixture in a form suitable for administration.