| US 7,482,337 B2 | ||
| Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions | ||
| Frank Himmelsbach, Mittelbiberach (Germany); Elke Langkopf, Warthausen (Germany); Matthias Eckhardt, Biberach (Germany); Roland Maier, Biberach (Germany); Michael Mark, Biberach (Germany); Mohammad Tadayyon, Ulm (Germany); and Ralf R. H. Lotz, Schemmerhofen (Germany) | ||
| Assigned to Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim (Germany) | ||
| Filed on Oct. 28, 2003, as Appl. No. 10/695,597. | ||
| Claims priority of provisional application 60/429173, filed on Nov. 26, 2002. | ||
| Claims priority of application No. 102 51 927 (DE), filed on Nov. 08, 2002. | ||
| Prior Publication US 2004/0138214 A1, Jul. 15, 2004 | ||
| Int. Cl. C07D 473/06 (2006.01); C07D 519/00 (2006.01); A61K 31/522 (2006.01); A61K 31/538 (2006.01); A61K 31/536 (2006.01); A61K 31/5415 (2006.01); A61K 31/5513 (2006.01); A61P 3/10 (2006.01); A61P 3/04 (2006.01) | ||
| U.S. Cl. 514—211.09 [514/211.11; 514/212.07; 514/224.2; 514/234.2; 514/263.2; 514/263.21; 514/263.22; 514/263.35; 514/263.34; 514/226.8; 514/228.5; 514/221; 540/552; 540/514; 540/545; 540/587; 540/569; 544/49; 544/50; 544/51; 544/63; 544/92; 544/105; 544/118; 544/268; 544/269; 544/272] | 9 Claims |
1. A Compound of formula (I):
![]() R1 denotes a C1-3-alkyl group substituted by a group Ra, wherein
Ra denotes a 1,4-dihydro-quinazolinyl or 3,4-dihydro-quinazolinyl group wherein in each case in the benzo moiety
one to three methyne groups may be replaced by nitrogen atoms,
a 3,4-dihydro-isoquinolinyl, 1H-benzo[d][1,2]oxazinyl,
4H-benzo[e][1,3]oxazinyl, 4H-benzo[d][1,3]oxazinyl or
2H-benzo[1,4]oxazinyl group, wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene
group may be replaced by a carbonyl group,
a 4H-benzo[e][1,3]thiazinyl, 4H-benzo[d][1,3]thiazinyl or 2H-benzo[1,4]thiazinyl group, wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene
group may be replaced by a carbonyl group and a sulphur atom may be replaced by a sulphinyl or sulphonyl group,
a 2-oxo-2H-benzo[e][1,3]oxazinyl or 2,2-dioxo-1H-benzo[c][1,2]thiazinyl group, wherein in each case in the benzo moiety
one to three methyne groups may be replaced by nitrogen atoms,
a 2,3-dihydro-1H-benzo[e][1,4]diazepinyl, 4,5-dihydro-3H-benzo[b]-[1,4]diazepinyl or 5-oxo-4,5-dihydro-3H-benzo[e][1,4]diazepinyl
group, wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene
group may be replaced by a carbonyl group,
a 2,3-dihydro-benzo[f][1,4]oxazepinyl or 2,3-dihydro-benzo[b][1,4]oxazepinyl group wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene
group may be replaced by a carbonyl group,
a 2,3-dihydro-benzo[f][1,4]thiazepinyl or 2,3-dihydro-benzo[b][1,4]thiazepinyl group, wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and in the heterocyclyl moiety a methylene
group may be replaced by a carbonyl group and a sulphur atom may be replaced by a sulphinyl or sulphonyl group,
a 5-oxo-4,5-dihydro-benzo[f][1,3,4]oxadiazepinyl group wherein in the benzo moiety
one to three methyne groups may be replaced by nitrogen atoms,
an 11H-dibenzo[b,e]azepinyl or 5H-dibenzo[a,d]cycloheptenyl group, wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms and the methylene group in the heterocyclyl
moiety may be replaced by an oxygen or sulphur atom, a carbonyl, sulphinyl, sulphonyl or an imino group substituted by Rx, where
Rx denotes a hydrogen atom or a C1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-alkyl, aryl, aryl-C1-3-alkyl, hydroxy-C2-4-alkyl, C1-3-alkyloxy-C2-4-alkyl, C3-6-cycloalkyloxy-C2-4-alkyl, amino-C2-4-alkyl, C1-3-alkylamino-C2-4-alkyl, di-(C1-3-alkyl)-amino-C2-4-alkyl, C1-3-alkyl-carbonyl, C1-3-alkyloxy-carbonyl, C1-3-alkyloxy-carbonyl-C1-3-alkyl, aryl-carbonyl, C1-3-alkyl-sulphonyl or aryl-sulphonyl group,
a 1,2,3,4-tetrahydro-phenanthridinyl, benzo[f]quinoxalinyl, 5H-dibenzo[d,f][1,3]diazepinyl, 5H-benzo[e]pyrrolo[1,2-a][1,4]diazepinyl,
thieno[3,2-b][1,4]benzoxazepinyl or a 3-oxo-2,3-dihydro-isoindol-1-ylidene group, wherein in each case
in the benzo moiety one to three methyne groups may be replaced by nitrogen atoms,
a benzo[1,2,5]oxadiazolyl, dibenzofuranyl, Indolizinyl, 1H-perimidinyl, group,
a pyrazolo[1,5-c]quinazolinyl group or an imidazo[2,1-a]isoquinolinyl or imidazo[1,2-a]isoquinolinyl group
wherein the above-mentioned groups Ra may be substituted by the groups R10 to R13 and may additionally be substituted by a C1-3-alkyl group and
R10 denotes a hydrogen atom,
a fluorine, chlorine, bromine or iodine atom,
a C1-4-alkyl, hydroxy, or C1-4-alkyloxy group,
a nitro, amino, C1-3-alkylamino, di-(C1-3-alkyl)amino, cyano-C1-3-alkylamino, [N-(cyano-C1-3-alkyl)-N-C1-3-alkyl-amino], C1-3-alkyloxy-carbonyl-C1-3-alkylamino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, or 4-(C1-3-alkyl)-piperazin-1-yl group,
a C1-3-alkyl-carbonylamino, arylcarbonylamino, aryl-C1-3-alkyl-carbonylamino, C1-3-alkyloxy-carbonylamino, aminocarbonylamino, C1-3-alkyl-aminocarbonylamino, di-(C1-3-alkyl)aminocarbonylamino, pyrrolidin-1-yl-carbonylamino, piperidin-1-yl-carbonylamino, morpholin-4-yl-carbonylamino, piperazin-1-yl-carbonylamino
or 4-(C1-3-alkyl)-piperazin-1-yl-carbonylamino, C1-3-alkyl-sulphonylamino, bis-(C1-3-alkylsulphonyl)-amino, aminosulphonylamino, C1-3-alkylamino-sulphonylamino, di-(C1-3-alkyl)amino-sulphonylamino, pyrrolidin-1-yl-sulphonylamino, piperidin-1-yl-sulphonylamino, morpholin-4-yl-sulphonylamino,
piperazin-1-yl-sulphonylamino or 4-(C1-3-alkyl)-piperazin-1-yl-sulphonylamino, (C1-3-alkylamino)thiocarbonylamino, (C1-3-alkyloxy-carbonylamino)-carbonylamino, arylsulphonylamino or aryl-C1-3-alkyl-sulphonylamino group,
an N-(C1-3-alkyl)-C1-3-alkyl-carbonylamino, N-(C1-3-alkyl)-arylcarbonylamino, N-(C1-3-alkyl)-aryl-C1-3-alkyl-carbonylamino, N-(C1-3-alkyl)-C1-3-alkyloxy-carbonylamino, N-(aminocarbonyl)-C1-3-alkylamino, N-(C1-3-alkyl-aminocarbonyl)-C1-3-alkylamino, N-[di-(C1-3-alkyl)aminocarbonyl]-C1-3-alkylamino, N-(C1-3-alkyl)-C1-3-alkyl-sulphonylamino, N-(C1-3-alkyl)-arylsulphonylamino or N-(C1-3-alkyl)-aryl-C1-3-alkyl-sulphonylamino group,
a 2-oxo-imidazolidin-1-yl, 2,4-dioxo-imidazolidin-1-yl, 2,5-dioxo-imidazolidin-1-yl or 2-oxo-hexahydropyrimidin-1-yl group
wherein the nitrogen atom in the 3 position may be substituted in each case by a methyl or ethyl group,
a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-3-alkyl-aminocarbonyl, di-(C1-3-alkyl)-aminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl, morpholin-4-yl-carbonyl, piperazin-1-yl-carbonyl
or 4-(C1-3-alkyl)-piperazin-1-yl-carbonyl group,
a C1-3-alkyl-carbonyl or an arylcarbonyl group,
a carboxy-C1-3-alkyl, C1-3-alkyloxy-carbonyl-C1-3-alkyl, cyano-C1-3-alkyl, aminocarbonyl-C1-3-alkyl, C1-3-alkyl-aminocarbonyl-C1-3-alkyl, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyl, pyrrolidin-1-yl-carbonyl-C1-3-alkyl, piperidin-1-yl-carbonyl-C1-3-alkyl, morpholin-4-yl-carbonyl-C1-3-alkyl, piperazin-1-yl-carbonyl-C1-3-alkyl or 4-(C1-3-alkyl)-piperazin-1-yl-carbonyl-C1-3-alkyl group,
a carboxy-C1-3-alkyloxy, C1-3-alkyloxy-carbonyl-C1-3-alkyloxy, cyano-C1-3-alkyloxy, aminocarbonyl-C1-3-alkyloxy, C1-3-alkyl-aminocarbonyl-C1-3-alkyloxy, di-(C1-3-alkyl)-aminocarbonyl-C1-3-alkyloxy, pyrrolidin-1-yl-carbonyl-C1-3-alkyloxy, piperidin-1-yl-carbonyl-C1-3-alkyloxy, morpholin-4-yl-carbonyl-C1-3-alkyl-oxy, piperazin-1-yl-carbonyl-C1-3-alkyloxy or 4-(C1-3-alkyl)-piperazin-1-yl-carbonyl-C1-3-alkyloxy group,
a hydroxy-C1-3-alkyl, C1-3-alkyloxy-C1-3-alkyl, amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl, di-(C1-3-alkyl)-amino-C1-3-alkyl, pyrrolidin-1-yl-C1-3-alkyl, piperidin-1-yl-C1-3-alkyl, morpholin-4-yl-C1-3-alkyl, piperazin-1-yl-C1-3-alkyl, 4-(C1-3-alkyl)-piperazin-1-yl-C1-3-alkyl group,
a hydroxy-C1-3-alkyloxy, C1-3-alkyloxy-C1-3-alkyloxy, C1-3-alkylsulphanyl-C1-3-alkyloxy, C1-3-alkylsulphinyl-C1-3-alkyloxy, C1-3-alkylsulphonyl-C1-3-alkyloxy, amino-C1-3-alkyloxy, C1-3-alkylamino-C1-3-alkyloxy, di-(C1-3-alkyl)-amino-C1-3-alkyloxy, pyrrolidin-1-yl-C1-3-alkyloxy, piperidin-1-yl-C1-3-alkyloxy, morpholin-4-yl-C1-3-alkyloxy, piperazin-1-yl-C1-3-alkyloxy, 4-(C1-3-alkyl)-piperazin-1-yl-C1-3-alkyloxy group,
a mercapto, C1-3-alkylsulphanyl, C1-3-alkylsulphinyl, C1-3-alkylsulphonyl, C1-3-alkylsulphonyloxy, arylsulphonyloxy, trifluoromethylsulphanyl, trifluoromethylsulphinyl or trifluoromethylsulphonyl group,
a sulpho, aminosulphonyl, C1-3-alkyl-aminosulphonyl, di-(C1-3-alkyl)-aminosulphonyl, pyrrolidin-1-yl-sulphonyl, piperidin-1-yl-sulphonyl, morpholin-4-yl-sulphonyl, piperazin-1-yl-sulphonyl
or 4-(C1-3-alkyl)-piperazin-1-yl-sulphonyl group,
a methyl or methoxy group substituted by 1 to 3 fluorine atoms,
an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms,
a C2-4-alkenyl or C2-4-alkynyl group,
a C3-4-alkenyloxy or C3-4-alkynyloxy group,
a C3-6-cycloalkyl or C3-6-cycloalkyloxy group,
a C3-6-cycloalkyl-C1-3-alkyl or C3-6-cycloalkyl-C1-3-alkyloxy group or
an aryl, aryloxy, aryl-C1-3-alkyl or aryl-C1-3-alkyloxy group,
R11 and R12, which may be identical or different, in each case denote a hydrogen atom, a fluorine, chlorine, bromine or iodine atom,
a C1-3-alkyl, trifluoromethyl, hydroxy or C1-3-alkyloxy group or a cyano group, or
R11 together with R2, if they are bound to adjacent carbon atoms, also denote a methylenedioxy, difluoromethylenedioxy, ethylenedioxy or a straight-chain
C3-5-alkylene group and
R13 denotes a hydrogen atom, a fluorine, chlorine or bromine atom, a trifluoromethyl, C1-3-alkyl or C1-3-alkyloxy group,
R2 denotes a hydrogen atom,
a C1-6alkyl group,
a C2-4-alkenyl group,
a C3-4-alkynyl group,
a C3-6-cycloalkyl group,
a C3-6-cycloalkyl-C1-3-alkyl group,
a tetrahydrofuran-3-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranylmethyl or tetrahydropyranylmethyl group,
an aryl group,
an aryl-C1-4-alkyl group,
an aryl-C2-3-alkenyl group,
an arylcarbonyl-C1-2-alkyl group,
a heteroaryl-C1-3-alkyl group,
a furanylcarbonylmethyl, thienylcarbonylmethyl, thiazolylcarbonylmethyl or pyridylcarbonylmethyl group,
a C1-4-alkyl-carbonyl-C1-2-alkyl group,
a C3-6-cycloalkyl-carbonyl-C1-2-alkyl group,
an aryl-A-C1-3-alkyl group, wherein A denotes an oxygen or sulphur atom, —NH—, N(C1-3-alkyl), sulphinyl or sulphonyl group,
a C1-4-alkyl group substituted by a group Rb, wherein
Rb denotes a cyano, carboxy, C1-3-alkyloxy-carbonyl, aminocarbonyl, C1-3-alkylamino-carbonyl, di-(C1-3-alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl
or 4-ethylpiperazin-1-ylcarbonyl group,
or a C2-4-alkyl group substituted by a group Rc, wherein
Rc denotes a hydroxy, C1-3-alkyloxy, amino, C1-3-alkylamino, di-(C1-3-alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl or 4-ethyl-piperazin-1-yl
group and is isolated from the cyclic nitrogen atom in the 3 position of the xanthine structure by at least two carbon atoms,
R3 denotes a C3-8-alkyl group,
a C1-3-alkyl group substituted by a group Rd, wherein
Rd denotes a C3-7-cycloalkyl group optionally substituted by one or two C1-3-alkyl groups,
a C5-7-cycloalkenyl group optionally substituted by one or two C1-3-alkyl groups,
an aryl group or
a furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl-, pyridyl, pyridazinyl, pyrimidyl or pyrazinyl group, wherein
the above-mentioned heterocyclic groups may be substituted in each case by one or two C1-3-alkyl groups or by a fluorine, chlorine, bromine or iodine atom or by a trifluoromethyl, cyano or C1-3-alkyloxy group,
a C3-8-alkenyl group,
a C3-6-alkenyl group substituted by a fluorine, chlorine or bromine atom or a trifluoromethyl group,
a C3-8-alkynyl group,
an aryl group or
an aryl-C2-4-alkenyl group, and
R4 denotes an azetidin-1-yl or pyrrolidin-1-yl group which is substituted in the 3 position by an amino, C1-3-alkylamino or a di-(C1-3-alkyl)amino group and may additionally be substituted by one or two C1-3-alkyl groups,
a piperidin-1-yl or hexahydroazepin-1-yl group which is substituted in the 3 position or in the 4 position by an amino, C1-3-alkylamino or a di-(C1-3-alkyl)amino group and may additionally be substituted by one or two C1-3-alkyl groups,
a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl-moiety is additionally substituted by an aminocarbonyl, C1-2-alkyl-aminocarbonyl, di-(C1-2-alkyl)aminocarbonyl, pyrrolidin-1-yl-carbonyl, (2-cyano-pyrrolidin-1-yl)-carbonyl, thiazolidin-3-yl-carbonyl, (4-cyano-thiazolidin-3-yl)carbonyl,
piperidin-1-ylcarbonyl or morpholin-4-ylcarbonyl group,
a 3-amino-piperidin-1-yl group wherein the piperidin-1-yl-moiety is additionally substituted in the 4 position or in the 5
position by a hydroxy or methoxy group,
a 3-amino-piperidin-1-yl group wherein the methylene group in 2 position or in 6 position is replaced by a carbonyl group,
a piperidin-1-yl or hexahydroazepin-1-yl group substituted in the 3 position by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, wherein in each case two hydrogen atoms on the carbon skeleton of the piperidin-1-yl or hexahydroazepin-1-yl
group are replaced by a straight-chain alkylene bridge, wherein this bridge contains 2 to 5 carbon atoms, if the two hydrogen
atoms are located on the same carbon atom, or contains 1 to 4 carbon atoms if the hydrogen atoms are located on adjacent carbon
atoms, or contains 1 to 4 carbon atoms, if the hydrogen atoms are located on carbon atoms which by are separated by one atom,
or contains 1 to 3 carbon atoms if the two hydrogen atoms are located on carbon atoms which are separated by two atoms,
an azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl or hexahydroazepin-1-yl group which is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
a piperazin-1-yl or [1,4]diazepan-1-yl group optionally substituted on the carbon skeleton by one or two C1-3-alkyl groups,
a 3-imino-piperazin-1-yl, 3-imino-[1,4]diazepan-1-yl or 5-imino-[1,4]diazepan-1-yl group optionally substituted on the carbon
skeleton by one or two C1-3-alkyl groups,
a [1,4]diazepan-1-yl group optionally substituted by one or two C1-3-alkyl groups, which is substituted by an amino group in the 6 position,
a C3-7-cycloalkyl group which is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group,
a C3-7-cycloalkyl group which is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
a C3-7-cycloalkyl-C1-2-alkyl group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group,
a C3-7-cycloalkyl-C1-2-alkyl group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
a C3-7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, wherein the two nitrogen atoms on the cycloalkyl moiety are separated from one another by at least two
carbon atoms,
an N-(C3-7-cycloalkyl)-N-(C1-3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group, wherein the two nitrogen atoms on the cycloalkyl moiety are separated from one another by at least two
carbon atoms,
a C3-7-cycloalkylamino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
an N-(C3-7-cycloalkyl)-N-(C1-3-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
a C3-7-cycloalkyl-C1-2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group,
an N-(C3-7-cycloalkyl-C1-2-alkyl)-N-(C1-2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group,
a C3-7-cycloalkyl-C1-2-alkyl-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
an N-(C3-7-cycloalkyl-C1-2-alkyl)-N-(C1-2-alkyl)-amino group wherein the cycloalkyl moiety is substituted by an amino-C1-3-alkyl, C1-3-alkylamino-C1-3-alkyl or a di-(C1-3-alkyl)amino-C1-3-alkyl group,
an R19—C2-4-alkylamino group wherein R19 is separated from the nitrogen atom of the C2-4-alkylamino moiety by at least two carbon atoms and
R19 denotes an amino, C1-3-alkylamino or di-(C1-3-alkyl)-amino group,
an R19—C2-4-alkylamino group wherein the nitrogen atom of the C2-4-alkylamino moiety is substituted by a C1-3-alkyl group and R19 is separated from the nitrogen atom of the C2-4-alkylamino moiety by at least two carbon atoms, wherein R19 is as hereinbefore defined,
an amino group substituted by the group R20 wherein
R20 denotes an azetidin-3-yl, azetidin-2-ylmethyl, azetidin-3-ylmethyl, pyrrolidin-3-yl, pyrrolidin-2-ylmethyl, pyrrolidin-3-ylmethyl,
piperidin-3-yl, piperidin-4-yl, piperidin-2-ylmethyl, piperidin-3-ylmethyl or piperidin-4-ylmethyl group, wherein the groups
mentioned for R20 may each be substituted by one or two C1-3-alkyl groups,
an amino group substituted by the group R20 and a C1-3-alkyl group wherein R20 is as hereinbefore defined, wherein the groups mentioned for R20 may each be substituted by one or two C1-3-alkyl groups,
a R19—C3-4-alkyl group wherein the C3-4-alkyl moiety is straight-chain and may additionally be substituted by one or two C1-3-alkyl groups, wherein R19 is as hereinbefore defined,
a 3-amino-2-oxo-piperidin-5-yl or 3-amino-2-oxo-1-methyl-piperidin-5-yl group,
a pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, hexahydroazepin-3-yl or hexahydroazepin-4-yl group which is substituted
in the 1 position by an amino, C1-3-alkylamino or di-(C1-3-alkyl)amino group,
or an azetidin-2-yl-C1-2-alkyl, azetidin-3-yl-C1-2-alkyl, pyrrolidin-2-yl-C1-2-alkyl, pyrrolidin-3-yl, pyrrolidin-3-yl-C1-2-alkyl, piperidin-2-yl-C1-2-alkyl, piperidin-3-yl, piperidin-3-yl-C1-2-alkyl, piperidin-4-yl or piperidin-4-yl-C1-2-alkyl group, wherein the above-mentioned groups may each be substituted by one or two C1-3-alkyl groups,
wherein by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may
be mono- or disubstituted by Rh independently of one another, where the substituents are identical or different and Rh denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, aminocarbonyl, aminosulphonyl,
methylsulphonyl, acetylamino, methylsulphonylamino, C1-3-alkyl, cyclopropyl, ethenyl, ethynyl, hydroxy, C1-3-alkyloxy, difluoromethoxy or trifluoromethoxy group,
by the heteroaryl groups mentioned in the definitions of the above mentioned groups are meant a pyrrolyl, furanyl, thienyl,
pyridyl, indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group,
or a pyrrolyl, furanyl, thienyl or pyridyl group wherein one or two methyne groups are replaced by nitrogen atoms,
or an indolyl, benzofuranyl, benzothiophenyl, quinolinyl or isoquinolinyl group wherein one to three methyne groups are replaced
by nitrogen atoms,
and the above-mentioned heteroaryl groups may be mono- or disubstituted by Rh, wherein the substituents may be identical or different and Rh is as hereinbefore defined,
and, unless otherwise specified, the above-mentioned alkyl, alkenyl and alkynyl groups may be straight-chain or branched,
or the tautomers, enantiomers, diastereomers, the mixtures thereof, the prodrugs thereof and the salts thereof.
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