Imidazoles and triazoles, their preparation, and their use as pharmaceutical compositions
The present invention relates to imidazoles and triazoles of general formula wherein R 1 to R 4 and X are defined as in claims 1 to 8 , the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).
1. A method for inhibiting DPP-IV activity in a subject in need thereof comprising administering to the subject in need thereof a therapeutically effective amount of a compound of the following formula (I) having DPP-IV inhibiting activity:
wherein
R 1 denotes
an aryl-C 1-6 -alkyl or heteroaryl-C 1-6 -alkyl group wherein each methylene group of the alkyl group may be substituted by one or two fluorine atoms or a C 1-3 -alkyl group and a methylene group may be replaced by a carbonyl group,
or an aryl-C 2-6 -alkenyl or heteroaryl-C 2-6 -alkenyl group, wherein the alkenyl chain may be substituted by 1 to 10 fluorine atoms or a cyano, C 1-3 -alkyloxy-carbonyl, C 1-3 -alkyl or nitro group,
R 2 denotes
a hydrogen atom,
a C 1-6 -alkyl group,
a C 1-6 -alkyl group substituted by a group R a , where
R a denotes
a fluorine, chlorine or bromine atom, or
a trifluoromethyl, nitro, aryl, heteroaryl, cyano, carboxy, C 1-4 -alkoxy-carbonyl, aminocarbonyl, C 1-4 -alkylamino-carbonyl, di-(C 1-3 -alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C 1-4 -alkyl)-piperazin-1-ylcarbonyl, C 1-4 -alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, C 1-3 -alkylsulphinyl or C 1-3 -alkylsulphonyl group,
a C 2-6 -alkyl group substituted from position 2 by a group R b , where
R b denotes a hydroxy, C 1-3 -alkoxy, amino, C 1-3 -alkylamino, di-(C 1-3 -alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or 4-(C 1-3 -alkyl)-piperazin-1-yl group,
an NH group substituted by a group R c , where
R c denotes a C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 1-4 -alkoxy-carbonyl, aminocarbonyl, C 1-4 -alkylamino-carbonyl, di-(C 1-3 -alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C 1-4 -alkyl)-piperazin-1-ylcarbonyl, C 1-4 -alkyl-carbonyl, arylcarbonyl, heteroarylcarbonyl, C 1-3 -alkylsulphinyl or C 1-3 -alkylsulphonyl group,
a hydroxy group,
a C 1-4 -alkoxy group,
or a C 2-6 -alkenyl or C 2-6 -alkynyl group,
X denotes a nitrogen atom or a CH group,
R 3 denotes
a C 5-7 -cycloalkenylmethyl group optionally substituted by a C 1-3 -alkyl group,
an arylmethyl or heteroarylmethyl group,
a straight-chain or branched C 2-8 -alkenyl group that may be substituted by 1 to 15 fluorine atoms or a cyano, nitro or C 1-3 -alkoxy-carbonyl group,
or a straight-chain or branched C 3-6 -alkynyl group that may be substituted by 1 to 9 fluorine atoms or a cyano, nitro or C 2-8 -alkoxy-carbonyl group,
and
R 4 denotes
a pyrrolidin-1-yl or azetedin-1-yl group which is substituted in the 3 position by an amino or C 1-3 -alkylamino group and may additionally be substituted by one or two C 1-3 -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 group or C 1-3 -alkylamino group and may additionally be substituted by one or two C 1-3 -alkyl groups,
a piperazin-1-yl or homopiperazin-1-yl group which may be substituted by one or two C 1-3 -alkyl groups,
an amino group substituted by the groups R 15 and R 16 wherein
R 15 denotes a hydrogen atom, a C 1-6 -alkyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-3 -alkyl, aryl or aryl-C 1-3 -alkyl group, and
R 16 denotes a R 17 —C 2-3 -alkyl group, wherein the C 2-3 -alkyl moiety is straight-chained and may be substituted by 1 to 4 C 1-3 -alkyl groups, which may be identical or different, and the C 2-3 -alkyl group may be linked to R 17 from position 2, and
R 17 denotes an amino or C 1-3 -alkylamino group,
an amino group substituted by the groups R 15 and R 18 wherein
R 18 denotes a C 3-10 -cycloalkyl-C 1-2 -alkyl-group substituted by R 19 in the 1 position of the cycloalkyl group or a C 3-10 -cycloalkyl group substituted in the 1 or 2 position by a R 19 —C 1-2 -alkyl group, wherein R 19
R 17 denotes an amino or C 1-3 -alkylamino group,
an amino group substituted by the groups R 15 and R 20 wherein
R 20 denotes a C 4-10 -cycloalkyl or C 4-10 -cycloalkyl-methyl group wherein a methylene group of the C 4-10 -cycloalkyl group is replaced by an —NH— group, or
an amino group substituted by the groups R 15 and R 21 wherein
R 21 denotes a C 3-10 -cycloalkyl group substituted in the 2 or 3 position by an amino or C 1-3 -alkylamino group,
while the above-mentioned groups R 18 , R 20 and R 21 may be mono- or disubstituted by R d , while the substituents may be identical or different, and R d denotes a fluorine atom, a C 1-3 -alkyl, trifluoromethyl, cyano, amino, C 1-3 -alkylamino, hydroxy or C 1-3 -alkyloxy group, and wherein one or two methylene groups of the cycloalkyl group may each be replaced independently of one another by an oxygen or sulphur atom or by an —NH— or —N(C 1-3 -alkyl)-group, or by a carbonyl, sulphinyl or sulphonyl group,
while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may be mono-, di- or trisubstituted independently of one another by R h , where the substituents may be identical or different and R h denotes a fluorine, chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, aminocarbonyl, C 1-3 -alkoxy-carbonyl, aminosulphonyl, methylsulphonyl, acetylamino, methylsulphonylamino, C 1-3 -alkyl, cyclopropyl, ethenyl, ethynyl, morpholinyl, hydroxy, C 1-3 -alkyloxy, difluoromethoxy or trifluoromethoxy group, and wherein additionally each hydrogen atom may be replaced by a fluorine atom,
by the heteroaryl groups mentioned in the definition of the above-mentioned groups are meant:
a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, phenanthridinyl, 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, phenanthridinyl, quinolinyl or isoquinolinyl group, wherein one to three methyne groups are replaced by nitrogen atoms, or
a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl, 1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, 1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 3,4-dihydro-4-oxo-quinazolinyl, 1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl, 1,2-dihydro-2-oxoquinoxalinyl, 1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl, 1,2-dihydro-1-oxo-phthalazinyl, 1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl, 2,3-dihydro-benzo[1,4]dioxinyl or 3,4-dihydro-3-oxo-2H-benzol-[1,4]oxazinyl group,
and the above-mentioned heteroaryl groups may be mono- or disubstituted by R h , while the substituents may be identical or different and R h is as hereinbefore defined,
by the cycloalkyl groups mentioned in the definition of the above-mentioned groups are meant both monocyclic and polycyclic ring systems, while the polycycles may be anellated, spiro-linked or bridged in structure, for example the term polycyclic groups denotes decalin, octahydroindene, norbornane, spiro[4.4]nonane, spiro[4.5]decane, bicyclo[2.1.1]hexane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, bicyclo[3.3.2]decane or adamantane,
while, unless otherwise stated, the above-mentioned alkyl, alkenyl and alkynyl groups may be straight-chain or branched,
a tautomer, enantiomer, or diastereomer thereof or a mixture thereof, or a physiologically acceptable salt thereof.
2. The method according to claim 1 , wherein for the compound of formula (I):
X denotes a nitrogen atom or a CH group,
R 3 denotes a 1-buten-1-yl, 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, cyclopent-1-enyl-methyl, furanylmethyl, thienylmethyl, chlorobenzyl, bromobenzyl, iodobenzyl, methoxybenzyl or cyanobenzyl group, and
R 4 denotes
an N-(2-aminoethyl)-N-methyl-amino group which may be substituted in the ethyl moiety by one or two C 1-3 -alkyl groups, or
a 3-aminopiperidin-1-yl, piperazin-1-yl or [1,4]diazepan-1-yl group, while the above-mentioned groups may each additionally be substituted by one or two C 1-3 -alkyl groups,
or an enantiomer or diastereomer thereof, or a mixture thereof or a physiologically acceptable salt thereof.
3. The method according to claim 1 , wherein for the compound of formula (I):
R 1 denotes a phenylmethyl, phenylcarbonylmethyl, phenylprop-2-enyl, pyridinylmethyl, pyrimidinylmethyl, naphthylmethyl, quinolinylmethyl, isoquinolinylmethyl, quinazolinylmethyl, quinoxalinylmethyl, phenanthridinylmethyl, naphthyridinylmethyl or benzotriazolylmethyl group, while all the above-mentioned aryl and heteroaryl groups may be substituted by one or two fluorine, chlorine or bromine atoms or one or two cyano, nitro, amino, C 1-3 -alkyl, C 1-3 -alkyloxy or morpholinyl groups, while the substituents are identical or different,
R 2 denotes a hydrogen atom or a methyl group,
X denotes a nitrogen atom or a CH group,
R 3 denotes a 1-buten-1-yl, 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, cyclopent-1-enyl-methyl, furanylmethyl, thienylmethyl, benzyl, chlorobenzyl, bromobenzyl, iodobenzyl or cyanobenzyl group and
R 4 denotes an N-(2-aminoethyl)-N-methylamino, N-(2-aminopropyl)-N-methyl-amino, 3-aminopiperidin-1-yl, piperazin-1-yl or [1,4]diazepan-1-yl group,
or an enantiomer or diastereomer thereof, or a mixture thereof or a physiologically acceptable salt thereof.
4. The method according to claim 1 , wherein for the compound of formula (I):
R 1 denotes a phenylethyl, naphthylmethyl, methylisoquinolinylmethyl, quinolinylmethyl or phenanthridinylmethyl group,
R 2 denotes a hydrogen atom or a methyl group,
X denotes a nitrogen atom or a CH group,
R 3 denotes a 3-methyl-2-buten-1-yl, 2-butyn-1-yl, benzyl or 2-chlorobenzyl group and
R 4 denotes a 3-aminopiperidin-1-yl, [1,4]diazepan-1-yl or piperazin-1-yl group,
or an enantiomer or diastereomer thereof, or a mixture thereof or a physiologically acceptable salt thereof.
5. The method according to claim 1 , wherein for the compound of formula (I):
R 4 denotes a 3-aminopiperidin-1-yl group,
or a tautomer, enantiomer, or diastereomer thereof, or a mixture thereof, or a physiologically acceptable salt thereof.
6. The method according to claim 1 , wherein for the compound of formula (I):
X denotes a nitrogen atom,
or a tautomer, enantiomer, or diastereomer thereof, or a mixture thereof, or a physiologically acceptable salt thereof.
7. The method according to claim 1 , wherein for the compound of formula (I):
X denotes a CH group,
or a tautomer, enantiomer, or diastereomer thereof, or a mixture thereof, or a physiologically acceptable salt thereof.
8. The method according to claim 1 , wherein the compound of formula (I) is selected from the group consisting of:
(1) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(naphth-1-ylmethylaminocarbonyl)-1H-imidazole;
(2) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-[N-(naphth-1-ylmethyl)-N-methyl-aminocarbonyl]-1H-imidazole;
(3) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(phenanthridin-6-ylmethylamino-carbonyl)-1H-imidazole;
(4) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(3-methyl-isoquinolin-1-ylmethylaminocarbonyl)-1H-imidazole;
(5) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(quinolin-3-ylmethylaminocarbonyl)-1H-imidazole;
(6) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(2-phenyl-ethylaminocarbonyl)-1H-imidazole
(7) 3-(piperazin-1-yl)-4-(3-methyl-but-2-enyl)-5-(naphth-1-ylmethylaminocarbonyl)-4H-[1,2,4]triazole;
(8) 3-(piperazin-1-yl)-4-benzyl-5-(naphth-1-ylmethylaminocarbonyl)-4H-[1,2,4]triazole;
(9) 3-([1,4]diazepan-1-yl)-4-(3-methyl-but-2-enyl)-5-(naphth-1-ylmethylamino-carbonyl)-4H-[2,4]triazole;
(10) 3-(3-amino-piperidin-1-yl)-4-(3-methyl-but-2-enyl)-5-(naphth-1-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
(11) 3-(3-amino-piperidin-1-yl)-4-benzyl-5-(naphth-1-ylmethylaminocarbonyl)-4H-[1,2,4]triazole;
(12) 3-(3-amino-piperidin-1-yl)-4-(2-chloro-benzyl)-5-(naphth-1-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
(13) 3-(3-amino-piperidin-1-yl)-4-(but-2-ynyl)-5-(3-methyl-isoquinolin-1-ylmethyl-aminocarbonyl)-4H-[1,2,4]triazole;
(14) 3-(3-amino-piperidin-1-yl)-4-(but-2-ynyl)-5-(quinolin-6-ylmethylaminocarbonyl)-4H-[1,2,4]triazole; and
(15) 3-(3-amino-piperidin-1-yl)-4-(but-2-ynyl)-5-(phenanthridin-6-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
or a physiologically acceptable salt thereof.
9. A method for treating type 2 diabetes mellitus comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of the following formula (I):
wherein
R 1 denotes
an aryl-C 1-6 -alkyl or heteroaryl-C 1-6 -alkyl group wherein each methylene group of the alkyl group may be substituted by one or two fluorine atoms or a C 1-3 -alkyl group and a methylene group may be replaced by a carbonyl group,
or an aryl-C 2-6 -alkenyl or heteroaryl-C 2-6 -alkenyl group, wherein the alkenyl chain may be substituted by 1 to 10 fluorine atoms or a cyano, C 1-3 -alkyloxy-carbonyl, C 1-3 -alkyl or nitro group,
R 2 denotes
a hydrogen atom,
a C 1-6 -alkyl group,
a C 1-6 -alkyl group substituted by a group R a , where
R a denotes
a fluorine, chlorine or bromine atom, or
a trifluoromethyl, nitro, aryl, heteroaryl, cyano, carboxy, C 1-4 -alkoxy-carbonyl, aminocarbonyl, C 1-4 -alkylamino-carbonyl, di-(C 1-3 -alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C 1-4 -alkyl)-piperazin-1-ylcarbonyl, C 1-4 -alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, C 1-3 -alkylsulphinyl or C 1-3 -alkylsulphonyl group,
a C 2-6 -alkyl group substituted from position 2 by a group R b , where
R b denotes a hydroxy, C 1-3 -alkoxy, amino, C 1-3 -alkylamino, di-(C 1-3 -alkyl)-amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl or 4-(C 1- 3-alkyl)-piperazin-1-yl group,
an NH group substituted by a group R c , where
R c denotes a C 1-6 -alkyl, C 2-6 -alkenyl, aryl, heteroaryl, C 1-4 -alkoxy-carbonyl, aminocarbonyl, C 1-4 -alkylamino-carbonyl, di-(C 1-3 -alkyl)-amino-carbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, piperazin-1-ylcarbonyl, 4-(C 1-4 -alkyl)-piperazin-1-ylcarbonyl, C 1-4 -alkyl-carbonyl, arylcarbonyl, heteroarylcarbonyl, C 1-3 -alkylsulphinyl or C 1-3 -alkylsulphonyl group,
a hydroxy group,
a C 1-4 -alkoxy group,
or a C 2-6 -alkenyl or C 2-6 -alkynyl group,
X denotes a nitrogen atom or a CH group,
R 3 denotes
a C 5-7 -cycloalkenylmethyl group optionally substituted by a C 1-3 -alkyl group,
an arylmethyl or heteroarylmethyl group,
a straight-chain or branched C 2-8 -alkenyl group that may be substituted by 1 to 15 fluorine atoms or a cyano, nitro or C 1-3 -alkoxy-carbonyl group,
or a straight-chain or branched C 3-6 -alkynyl group that may be substituted by 1 to 9 fluorine atoms or a cyano, nitro or C 2-8 -alkoxy-carbonyl group,
and
R 4 denotes
a pyrrolidin-1-yl or azetedin-1-yl group which is substituted in the 3 position by an amino or C 1-3 -alkylamino group and may additionally be substituted by one or two C 1-3 -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 group or C 1-3 -alkylamino group and may additionally be substituted by one or two C 1-3 -alkyl groups,
a piperazin-1-yl or homopiperazin-1-yl group which may be substituted by one or two C 1-3 -alkyl groups,
an amino group substituted by the groups R 15 and R 16 wherein
R 15 denotes a hydrogen atom, a C 1-6 -alkyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-3 -alkyl, aryl or aryl-C 1-3 -alkyl group, and
R 16 denotes a R 17 —C 2-3 -alkyl group, wherein the C 2-3 -alkyl moiety is straight-chained and may be substituted by 1 to 4 C 1-3 -alkyl groups, which may be identical or different, and the C 2-3 -alkyl group may be linked to R 17 from position 2, and
R 17 denotes an amino or C 1-3 -alkylamino group,
an amino group substituted by the groups R 15 and R 18 wherein
R 18 denotes a C 3-10 -cycloalkyl-C 1-2 -alkyl-group substituted by R 19 in the 1 position of the cycloalkyl group or a C 3-10 -cycloalkyl group substituted in the 1 or 2 position by a R 19 —C 1-2 -alkyl group, wherein R 19 denotes an amino or C 1-3 -alkylamino group,
an amino group substituted by the groups R 15 and R 20 wherein
R 20 denotes a C 4-10 -cycloalkyl or C 4-10 -cycloalkyl-methyl group wherein a methylene group of the C 4-10 -cycloalkyl group is replaced by an —NH— group, or
an amino group substituted by the groups R 15 and R 21 wherein
R 21 denotes a C 3-10 -cycloalkyl group substituted in the 2 or 3 position by an amino or C 1-3 -alkylamino group,
while the above-mentioned groups R 18 , R 20 and R 21 may be mono- or disubstituted by R d , while the substituents may be identical or different, and R d denotes a fluorine atom, a C 1-3 -alkyl, trifluoromethyl, cyano, amino, C 1-3 -alkylamino, hydroxy or C 1-3 -alkyloxy group, and wherein one or two methylene groups of the cycloalkyl group may each be replaced independently of one another by an oxygen or sulphur atom or by an —NH— or —N(C 1-3 -alkyl)-group, or by a carbonyl, sulphinyl or sulphonyl group,
while by the aryl groups mentioned in the definition of the above groups are meant phenyl or naphthyl groups, which may be mono-, di- or trisubstituted independently of one another by R where the substituents may be identical or different and R denotes a fluorine chlorine, bromine or iodine atom, a trifluoromethyl, cyano, nitro, amino, aminocarbonyl, C 1-3 -alkoxy-carbonyl, aminosulphonyl, methylsulphonyl, acetylamino, methylsulphonylamino, C 1-3 -alkyl, cyclopropyl, ethenyl, ethynyl, morpholinyl, hydroxy, C 1-3 -alkyloxy, difluoromethoxy or trifluoromethoxy group, and wherein additionally each hydrogen atom may be replaced by a fluorine atom,
by the heteroaryl groups mentioned in the definition of the above-mentioned groups are meant:
a pyrrolyl, furanyl, thienyl, pyridyl, indolyl, benzofuranyl, benzothiophenyl, phenanthridinyl, 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, phenanthridinyl, quinolinyl or isoquinolinyl group, wherein one to three methyne groups are replaced by nitrogen atoms, or
a 1,2-dihydro-2-oxo-pyridinyl, 1,4-dihydro-4-oxo-pyridinyl, 2,3-dihydro-3-oxo-pyridazinyl, 1,2,3,6-tetrahydro-3,6-dioxo-pyridazinyl, 1,2-dihydro-2-oxo-pyrimidinyl, 3,4-dihydro-4-oxo-pyrimidinyl, 1,2,3,4-tetrahydro-2,4-dioxo-pyrimidinyl, 1,2-dihydro-2-oxo-pyrazinyl, 1,2,3,4-tetrahydro-2,3-dioxo-pyrazinyl, 2,3-dihydro-2-oxo-indolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydro-2-oxo-1H-benzimidazolyl, 2,3-dihydro-2-oxo-benzoxazolyl, 1,2-dihydro-2-oxo-quinolinyl, 1,4-dihydro-4-oxo-quinolinyl, 1,2-dihydro-1-oxo-isoquinolinyl, 1,4-dihydro-4-oxo-cinnolinyl, 1,2-dihydro-2-oxo-quinazolinyl, 3,4-dihydro-4-oxo-quinazolinyl, 1,2,3,4-tetrahydro-2,4-dioxo-quinazolinyl, 1,2-dihydro-2-oxoquinoxalinyl, 1,2,3,4-tetrahydro-2,3-dioxo-quinoxalinyl, 1,2-dihydro-1-oxo-phthalazinyl, 1,2,3,4-tetrahydro-1,4-dioxo-phthalazinyl, chromanyl, cumarinyl, 2,3-dihydro-benzol-[1,4]dioxinyl or 3,4-dihydro-3-oxo-2H-benzol-[1,4]oxazinyl group,
and the above-mentioned heteroaryl groups may be mono- or disubstituted by R h , while the substituents may be identical or different and R h is as hereinbefore defined,
by the cycloalkyl groups mentioned in the definition of the above-mentioned groups are meant both monocyclic and polycyclic ring systems, while the polycycles may be anellated, spiro-linked or bridged in structure, for example the term polycyclic groups denotes decalin, octahydroindene, norbornane, spiro[4.4]nonane, spiro[4.5]decane, bicyclo[2.1.1]hexane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2]nonane, bicyclo[3.3.1]nonane, bicyclo[3.3.2]decane or adamantane,
while, unless otherwise stated, the above-mentioned alkyl, alkenyl and alkynyl groups may be straight-chain or branched,
a tautomer, enantiomer, or diastereomer thereof or a mixture thereof, or a physiologically acceptable salt thereof.
10. The method according to claim 9 , wherein for the compound of formula (I):
X denotes a nitrogen atom or a CH group,
R 3 denotes a 1-buten-1-yl, 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, cyclopent-1-enyl-methyl, furanylmethyl, thienylmethyl, chlorobenzyl, bromobenzyl, iodobenzyl, methoxybenzyl or cyanobenzyl group, and
R 4 denotes
an N-(2-aminoethyl)-N-methyl-amino group which may be substituted in the ethyl moiety by one or two C 1-3 -alkyl groups, or
a 3-aminopiperidin-1-yl, piperazin-1-yl or [1,4]diazepan-1-yl group, while the above-mentioned groups may each additionally be substituted by one or two C 1-3 -alkyl groups,
or an enantiomer or diastereomer thereof, or a mixture thereof or a physiologically acceptable salt thereof.
11. The method according to claim 9 , wherein for the compound of formula (I):
R 1 denotes a phenylmethyl, phenylcarbonylmethyl, phenylprop-2-enyl, pyridinylmethyl, pyrimidinylmethyl, naphthylmethyl, quinolinylmethyl, isoquinolinylmethyl, quinazolinylmethyl, quinoxalinylmethyl, phenanthridinylmethyl, naphthyridinylmethyl or benzotriazolylmethyl group, while all the above-mentioned aryl and heteroaryl groups may be substituted by one or two fluorine, chlorine or bromine atoms or one or two cyano, nitro, amino, C 1-3 -alkyl, C 1-3 -alkyloxy or morpholinyl groups, while the substituents are identical or different,
R 2 denotes a hydrogen atom or a methyl group,
X denotes a nitrogen atom or a CH group,
R 3 denotes a 1-buten-1-yl, 2-buten-1-yl, 3-methyl-2-buten-1-yl, 2-butyn-1-yl, cyclopent-1-enyl-methyl, furanylmethyl, thienylmethyl, benzyl, chlorobenzyl, bromobenzyl, iodobenzyl or cyanobenzyl group and
R 4 denotes an N-(2-aminoethyl)-N-methylamino, N-(2-aminopropyl)-N-methyl-amino, 3-aminopiperidin-1-yl, piperazin-1-yl or [1,4]diazepan-1-yl group,
or an enantiomer or diastereomer thereof, or a mixture thereof or a physiologically acceptable salt thereof.
12. The method according to claim 9 , wherein for the compound of formula (I):
R 1 denotes a phenylethyl, naphthylmethyl, methylisoquinolinylmethyl, quinolinylmethyl or phenanthridinylmethyl group,
R 2 denotes a hydrogen atom or a methyl group,
X denotes a nitrogen atom or a CH group,
R 3 denotes a 3-methyl-2-buten-1-yl, 2-butyn-1-yl, benzyl or 2-chlorobenzyl group and
R 4 denotes a 3-aminopiperidin-1-yl, [1,4]diazepan-1-yl or piperazin-1-yl group,
or an enantiomer or diastereomer thereof, or a mixture thereof or a physiologically acceptable salt thereof.
13. The method according to claim 9 , wherein for the compound of formula (I):
R 4 denotes a 3-aminopiperidin-1-yl group,
or a tautomer, enantiomer, or diastereomer thereof, or a mixture thereof, or a physiologically acceptable salt thereof.
14. The method according to claim 9 , wherein for the compound of formula (I):
X denotes a nitrogen atom,
or a tautomer, enantiomer, or diastereomer thereof, or a mixture thereof, or a physiologically acceptable salt thereof.
15. The method according to claim 9 , wherein for the compound of formula (I):
X denotes a CH group,
or a tautomer, enantiomer, or diastereomer thereof, or a mixture thereof, or a physiologically acceptable salt thereof.
16. The method according to claim 9 , wherein the compound of formula (I) is selected from the group consisting of:
(1) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(naphth-1-ylmethylaminocarbonyl)-1H-imidazole;
(2) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-[N-(naphth-1-ylmethyl)-N-methyl-aminocarbonyl]-1H-imidazole;
(3) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(phenanthridin-6-ylmethylamino-carbonyl)-1H-imidazole;
(4) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(3-methyl-isoquinolin-1-ylmethylaminocarbonyl)-1H-imidazole;
(5) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(quinolin-3-ylmethylaminocarbonyl)-1H-imidazole;
(6) 1-(but-2-ynyl)-2-(3-amino-piperidin-1-yl)-5-(2-phenyl-ethylaminocarbonyl)-1H-imidazole
(7) 3-(piperazin-1-yl)-4-(3-methyl-but-2-enyl)-5-(naphth-1-ylmethylaminocarbonyl)-4H-[1,2,4]triazole;
(8) 3-(piperazin-1-yl)-4-benzyl-5-(naphth-1-ylmethylaminocarbonyl)-4H-[1,2,4]triazole;
(9) 3-([1,4]diazepan-1-yl)-4-(3-methyl-but-2-enyl)-5-(naphth-1-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
(10) 3-(3-amino-piperidin-1-yl)-4-(3-methyl-but-2-enyl)-5-(naphth-1-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
(11) 3-(3-amino-piperidin-1-yl)-4-benzyl-5-(naphth-1-ylmethylaminocarbonyl)-4H-[1,2,4]triazole;
(12) 3-(3-amino-piperidin-1-yl)-4-(2-chloro-benzyl)-5-(naphth-1-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
(13) 3-(3-amino-piperidin-1-yl)-4-(but-2-ynyl)-5-(3-methyl-isoquinolin-1-ylmethyl-aminocarbonyl)-4H-[1,2,4]triazole;
(14) 3-(3-amino-piperidin-1-yl)-4-(but-2-ynyl)-5-(quinolin-6-ylmethylaminocarbonyl)-4H-[1,2,4]triazole; and
(15) 3-(3-amino-piperidin-1-yl)-4-(but-2-ynyl)-5-(phenanthridin-6-ylmethylamino-carbonyl)-4H-[1,2,4]triazole;
or a physiologically acceptable salt thereof.