US2008306056A1PendingUtilityA1
PYRAZOLE-DERIVATIVES AS FACTOR Xa INHIBITORS
Est. expiryDec 23, 2022(expired)· nominal 20-yr term from priority
C07D 401/14C07D 409/14C07D 413/14C07D 401/12C07D 417/14
67
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Claims
Abstract
The present invention is directed to a compound of formula I, in which R 0 ; R 1 ; R 2 ; R 3 ; R 4 ; Q; V, G and M have the meanings indicated in the claims. the compound of formula I is valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore is directed to processes for the preparation of a compound of formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
Claims
exact text as granted — not AI-modified1 . A compound of formula I,
wherein
R 0 is
1) a monocyclic or bicyclic 6- to 14-membered aryl, wherein, the aryl is mono-, di- or trisubstituted independently of one another by R 8 ,
2) a monocyclic or bicyclic 4- to 15-membered heterocyclyl, selected from the group consisting of acridinyl, azaindole, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, 1,3-benzodioxolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, indazolyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2-oxathiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, oxetanyl, oxocanyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phenylpyridyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolyl, 4H-quinolizinyl, quinoxalinyl, 1,4,5,6-tetrahydropyridazinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, thiadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl,
thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xanthenyl, or
3) a monocyclic or bicyclic 4- to 15-membered heterocyclyl, containing one, two, three or four heteroatoms chosen from the group consisting of nitrogen, sulfur or oxygen, wherein, said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ;
R 8 is
1) halogen,
2) —NO 2 ,
3) —CN,
4) —C(O)—NH 2 ,
5) —OH,
6) —NH 2 ,
7) —O—CF 3
8) a monocyclic or bicyclic 6- to 14-membered aryl, wherein aryl is mono-, di- or trisubstituted independently of one another by halogen or —O—(C 1 -C 8 )-alkyl,
9) —(C 1 -C 8 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, NH 2 , —OH or a methoxy residue,
10) —O—(C 1 -C 8 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, NH 2 , —OH or a methoxy residue,
11) —SO 2 —CH 3 or
12) —SO 2 —CF 3 ,
provided that where R 0 is a monocyclic or bicyclic 6- to 14-membered aryl, then R 8 is at least one halogen, —C(O)—NH 2 or —O—(C 1 -C 8 )-alkyl residue;
Q is direct bond, —(C 0 -C 2 )-alkylene-C(O)—NR 10 —, —NR 10 —C(O)—NR 10 —, —NR 10 —C(O)—, —SO 2 —, —(C 1 -C 6 )-alkylene, —(CH 2 ) m —NR 10 —C(O)—NR 10 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —C(O)—(CH 2 ) n —, —(CH 2 ) m —S—(CH 2 ) n —, —(CH 2 ) m —C(O)—(CH 2 ) n —, —(CH 2 ) m —SO 2 —NR 10 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —SO 2 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —SO 2 —NR 10 —(CH 2 ) n —, —(CH 2 ) m —CH(OH)—(CH 2 ) n —, —(CH 2 ) m —O—C(O)—NR 10 —(CH 2 ) n —, —(C 2 -C 3 )-alkylene-O—(C 0 -C 3 )-alkylene-, —(C 2 -C 3 )-alkylene-S(O)—, —(C 2 -C 3 )-alkylene-S(O) 2 —, —(CH 2 ) m —NR 10 —C(O)—O—(CH 2 ) n —, —(C 2 -C 3 )-alkylene-S(O) 2 —NH—(R 10 )—, —(C 2 -C 3 )-alkylene-N(R 10 )— or —(C 0 -C 3 )-alkylene-C(O)—O—,
wherein R 10 is as defined below, and wherein n and m are independently of one another identical or different and are zero, 1, 2, 3, 4, 5 or 6, wherein the alkylene residues which are formed by —(CH 2 ) m — or —(CH 2 ) n — are unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, —NH 2 or —OH; or —(C 3 -C 6 )-cycloalkylene, wherein cycloalkylene is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, —NH 2 or —OH;
R 1 is hydrogen, —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or substituted one to three times by R 13 ; —(C 1 -C 3 )-alkylene-C(O)—NH—R 0 , —(C 1 -C 3 )-alkylene-C(O)—O—R 10 , a monocyclic or bicyclic 6- to 14-membered aryl, wherein aryl is mono-, di- or trisubstituted independently of one another by R 8 , a monocyclic or bicyclic 4- to 15-membered heterocyclyl, containing one, two, three or four heteroatoms chosen from nitrogen, sulfur or oxygen; —(C 1 -C 3 )-perfluoroalkyl, —(C 1 -C 3 )-alkylene-S(O)—(C 1 -C 4 )-alkyl, —(C 1 -C 3 )-alkylene-S(O) 2 —(C 1 -C 3 )-alkyl, —(C 1 -C 3 )-alkylene-S(O) 2 —N(R 4′ )—R 5′ , —(C 1 -C 3 )-alkylene-O—(C 1 -C 4 )-alkyl, —(C 0 -C 3 )-alkylene-(C 3 -C 8 )-cycloalkyl, or —(C 0 -C 3 )-alkylene-het, wherein het is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ;
R 4′ and R 5′ are independent of one another are identical or different and are hydrogen or —(C 1 -C 4 )-alkyl;
R 2 is direct bond or —(C 1 -C 4 )-alkylene, or
R 1 and R 3 together with the atoms to which they are bonded form a 6- to 8-membered cyclic group, containing 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, and wherein, said cyclic group is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ;
R 14 is halogen, —OH, ═O, —(C 1 -C 8 )-alkyl, —(C 1 -C 4 )-alkoxy, —NO 2 , —(C 0 -C 4 )-alkyl-C(O)—O—R 18 , —CN, —(C 0 -C 4 )-alkyl-N(R 18 )—R 21 , —(C 0 -C 4 )-alkyl-O—R 18 , —(C 0 -C 4 )-alkyl-het, —(C 0 -C 8 )-alkyl-SO 2 H, —SO 2 —(C 1 -C 4 )-alkyl, —SO 2 —N(R 18 )—R 21 , —C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—N—[(C 1 -C 8 )-alkyl] 2 , —NR 18 —C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—NH 2 , —S—R 18 , or —NR 18 —C(O)—NH—[(C 1 -C 8 )-alkyl] 2 ,
wherein R 18 and R 21 are independently from each other hydrogen atom, —(C 1 -C 3 )-perfluoroalkyl or —(C 1 -C 6 )-alkyl;
V is a 3- to 7-membered cyclic residue, containing 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ;
G is direct bond, —(CH 2 ) m —NR 10 —SO 2 —NR 10 —(CH 2 ) n —, —(CH 2 ) m —CH(OH)—(CH 2 ) n —, —(CH 2 ) m —, —(CH 2 ) m —O—(CH 2 ) n —, —(CH 2 ) m —C(O)—NR 10 —(CH 2 ) n —, —(CH 2 )—SO 2 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —C(O)—NR 10 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —C(O)—(CH 2 ) n —, —(CH 2 ) m —C(O)—(CH 2 ) n —, —(CH 2 )—S—(CH 2 ) n —, —(CH 2 ) m —SO 2 —NR 10 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —SO 2 —(CH 2 ) n —, —(CH 2 ) m —NR 10 —, —(CH 2 ) m —O—C(O)—NR 10 —(CH 2 ) n — or —(CH 2 ) m —NR 10 —C(O)—O—(CH 2 ) n —;
n and m are independently of one another identical or different and are zero, 1, 2, 3, 4, 5 or 6;
M is
1) hydrogen,
2) —(C 1 -C 8 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
3) —C(O)—N(R 11 )—R 12 ,
4) —(CH 2 ) m —NR 10 ,
5) a 6- to 14-membered aryl, wherein aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
6) a monocyclic or bicyclic 4- to 15-membered heterocyclyl, wherein heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
7) —(C 3 -C 8 )-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
8) a 3- to 7-membered cyclic residue, containing 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ;
R 3 and R 4 are independent of one another are identical or different and are
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 6 )-alkyl, —(C 0 -C 4 )-alkyl-OH, —(C 0 -C 4 )-alkyl-O—(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl;
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 6 )-alkyl, or together with the carbon atom to which they are bonded they can form a 3- to 6 membered carbocyclic ring which is unsubstituted or substituted one to three times by R 10 ; and
R 17 is —(C 1 -C 6 )-alkyl, —(C 1 -C 6 )-alkyl-OH, —(C 1 -C 6 )-alkyl-O—(C 1 -C 6 )-alkyl, —(C 3 -C 8 )-cycloalkyl, —(C 1 -C 6 )-alkyl-O—(C 1 -C 8 )-alkyl-(C 3 -C 8 )-cycloalkyl, —(C 1 -C 6 )-alkyl-(C 3 -C 8 )-cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by —OH, —O—(C 1 -C 4 )-alkyl or R 10 ; or
a stereoisomer thereof, mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
2 . The compound according to claim 1 , wherein,
R 0 as
2) is benzothiophenyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pyridyl, pyrimidinyl, quinazolinyl or quinolyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ;
R 3 and R 4 as
25) is —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —O—(C 0 -C 3 )-alkyl; and
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 6 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl; or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
3 . The compound according to claim 1 , wherein,
R 0 as
1) is phenyl, naphthyl, biphenylyl, anthryl or fluorenyl, that is mono-, di- or trisubstituted independently of one another by R 8 ,
2) is benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 , or
3) is acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl,
each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 , and which is additionally substituted by acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ;
R 1 as —(C 6 -C 14 )-aryl is phenyl, naphthyl, biphenylyl, anthryl or fluorenyl, that is mono-, di- or trisubstituted independently of one another by R 8 , or
—(C 0 -C 3 )-alkylene-het, wherein the het is azepine, azetidine, aziridine, azirine, 1,4-diazapane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, 1,4-oxazepane, 1,2-oxa-thiepane, 1,2-oxathiolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazine thiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
R 1 and R 3 together with the atoms to which they are bonded form azocane, azocane-2-one, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4]diazocane, [1,2]diazocan-3-one, [1,3]diazocan-2-one, dioxazine, [1,4]dioxocane, dioxole, ketopiperazine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4]oxazocane, [1,3]oxazocan-2-one, oxocane, oxocan-2-one, piperazine, piperidine, pyran, pyrazine, pyridazine, pyrimidine or 5,6,7,8-tetrahydro-1H-azocin-2-one, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ; R 14 as —(C 0 -C 4 )-alkyl-het, then het is azetidine, azetidinone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, 1,4-oxazepane, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole or thiomorpholine; M is
1) hydrogen,
2) —(C 1 -C 8 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
3) —C(O)—N(R 11 )—R 12 ,
4) —(CH 2 ) m —NR 10 ,
5) —(C 6 -C 14 )-aryl, wherein aryl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
6) —(C 4 -C 15 )-heterocyclyl, wherein heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
7) —(C 3 -C 8 )-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
R 3 and R 4 as
5) —(C 0 -C 4 )-alkylene-O—R 19 , or
two —OR 19 residues and adjacent atoms through which they are attached form together a 5- or 6-membered ring, that is unsubstituted or substituted one, two, three or four times by R 13 ;
R 11 and R 12 together with the nitrogen atom to which they are bonded form azepine, azetidine, dioxazole, dioxazine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, [1,4]oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ; and R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 6 )-alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring is unsubstituted or substituted one to three times by R 10 , or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
4 . The compound according to claim 1 , wherein,
R 0 as
1) is phenyl, naphthyl, biphenyl, anthryl or fluorenyl, that is mono-, di- or trisubstituted independently of one another by R 8 ,
3) is benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 , or
3) is azabenzimidazolyl, benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzothiazolyl, benzothiophenyl, benzoxazolyl, chromanyl, cinnolinyl, 2-furyl, 3-furyl; imidazolyl, indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl, pyrrolyl; 2-pyrrolyl, 3-pyrrolyl, quinolinyl, quinazolinyl, quinoxalinyl, tetrazolyl, thiazolyl, 2-thienyl or 3-thienyl, which is additionally substituted by a heterocyclyl selected out of the group acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,4-oxazepinyl, 1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisochinolinyl, tetrahydrochinolinyl, 1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl, tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl, 1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl, thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thietanyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ;
R 8 as
1) is fluorine, chlorine or bromine,
provided that R 8 is at least one halogen, —C(O)—NH 2 or —O—(C 1 -C 8 )-alkyl residue; Q is a direct bond, —(C 0 -C 2 )-alkylene-C(O)—NR 10 —, —NR 10 —C(O)—NR 10 —, —NR 10 —C(O)—, —SO 2 — or —(C 1 -C 6 )-alkylene; R 1 is hydrogen, —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or substituted one to three times by R 13 ; —(C 1 -C 3 )-alkylene-C(O)—NH—R 0 , —(C 1 -C 3 )-alkylene-C(O)—O—R 10 , —(C 1 -C 3 )-perfluoroalkyl, —(C 1 -C 3 )-alkylene-S(O)—(C 1 -C 4 )-alkyl, —(C 1 -C 3 )-alkylene-S(O) 2 —(C 1 -C 3 )-alkyl, —(C 1 -C 3 )-alkylene-S(O) 2 —N(R 4′ )—R 5′ , —(C 1 -C 3 )-alkylene-O—(C 1 -C 4 )-alkyl, —(C 0 -C 3 )-alkylene-(C 3 -C 8 )-cycloalkyl, or —(C 0 -C 3 )-alkylene-het, wherein het is azepine, azetidine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, 1,2-oxa-thiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,4-oxazepine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazine thiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl, thietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ; R 14 is fluorine, chlorine, bromine, iodine, —OH, ═O, —(C 1 -C 8 )-alkyl, —(C 1 -C 4 )-alkoxy, —NO 2 ,
—C(O)—OH, —CN, —NH 2 , —C(O)—O—(C 1 -C 4 )-alkyl, —(C 1 -C 8 )-alkylsulfonyl, —SO 2 —N—(R 18 )—R 21 ,
—C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—N—[(C 1 -C 8 )-alkyl] 2 , —NR 18 —C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—NH 2 , —S—R 18 , or —NR 18 —C(O)—NH—[(C 1 -C 8 )-alkyl] 2 ,
wherein R 18 and R 21 are independently from each other hydrogen atom, —(C 1 -C 3 )-perfluoroalkyl or —(C 1 -C 6 )-alkyl;
M is
1) hydrogen,
2) —(C 1 -C 8 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
3) —C(O)—N(R 11 )—R 12 ,
4) —(CH 2 ) m —NR 10 ,
5) phenyl or naphthyl, wherein phenyl or naphthyl are unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
6) heterocyclyl, wherein heterocyclyl is a residue out of the group which can be derived from azepane, azepine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, isothiazole, isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine, morpholine, oxazole, [1,4]-oxazepane, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, tetrazine, tetrazole, thiadiazole, thiazole, thiophene, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
7) —(C 3 -C 8 )-cycloalkyl, wherein said cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ;
R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) halogen,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 4 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
14) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
17) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 ,
21) —(C 0 -C 4 )-alkylene-(C 6 -C 14 )-aryl, wherein aryl is mono-, di- or trisubstituted independently of one another by R 13 ,
23) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) residue selected from the group consisting of
wherein Me is methyl, or
two —OR 19 residues and adjacent atoms through which they are attached form together a 5- or 6-membered ring, that is unsubstituted or substituted one, two, three or four times by R 13 ;
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 6 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
5) —(C 0 -C 6 )-alkyl-(C 6 -C 14 )-aryl, wherein alkyl and aryl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 ,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-(C 4 -C 15 )-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 , or
R 11 and R 12 together with the nitrogen atom to which they are bonded form azepine, azetidine, 1,4-diazepane, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, [1,4]oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ;
R 13 is fluorine, chlorine, bromine, iodine, —NO 2 , —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —N(R 10 )—S(O) 2 —R 10 , —S—R 10 , —SO 2 —R 10 , —S(O) 2 —N(R 10 )—R 20 , —C(O)—R 10 , —(C 1 -C 8 )-alkyl, —(C 1 -C 8 )-alkoxy, phenyl, phenyloxy-, —O—CF 3 , —(C 1 -C 3 )-perfluoroalkyl, —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 , —(C 1 -C 4 )-alkoxy-phenyl, —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 , —O—R 15 , —NH—C(O)—NH—R 10 , —NH—C(O)—O—R 10 , or a residue selected from the group consisting of
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 6 )-alkyl, or together form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, that is unsubstituted or substituted one to three times by R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
5 . The compound according to claim 1 , wherein,
R 0 as
1) is phenyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ,
2) is benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyrid azinyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 , or
3) a heterocyclyl out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ,
and in addition is substituted by a residue selected out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl or pyrazinyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ;
R 8 is
1) F, Cl, Br or I,
4) —C(O)—NH 2 ,
9) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, —OH or a methoxy residue, or
10) —O—(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen or a methoxy residue, provided that R 8 is at least one halogen, —C(O)—NH 2 or —O—(C 1 -C 8 )-alkyl residue;
Q is a direct bond, —C(O)—; —SO 2 —, —(C 1 -C 6 )-alkylene, or —(C 0 -C 2 )-alkylene-C(O)—NR 10 —; R 1 is hydrogen, —(C 1 -C 2 )-alkyl, —(C 1 -C 3 )-alkylene-C(O)—NH—R 0 , —(C 1 -C 3 )-perfluoroalkyl, —(C 1 -C 3 )-alkylene-C(O)—O—R 10 , —(C 1 -C 3 )-alkylene-S(O) 2 —(C 1 -C 3 )-alkyl or —(C 1 -C 3 )-alkylene-S(O) 2 —N(R 4′ )—R 5′ ,
wherein R 4′ and R 5′ are independent of one another are identical or different and are hydrogen or —(C 1 -C 4 )-alkyl;
R 14 is fluorine, chlorine, —OH, ═O, —(C 1 -C 8 )-alkyl, —C(O)—OH, —CN, —NH 2 , —C(O)—O—(C 1 -C 4 )-alkyl, —C(O)—NH—(C 1 -C 8 )-alkyl, —C(O)—N—[(C 1 -C 8 )-alkyl] 2 , —C(O)—NH 2 or —N(R 8 )—R 21 ,
wherein R 18 and R 21 are independently from each other hydrogen, —(C 1 -C 3 )-perfluoroalkyl or —(C 1 -C 4 )-alkyl;
V is azaindole, 1H-pyrrolopyridine, aziridine, azirine, azetidine, azetidinone, 1,4-diazepane, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, tetrazine, tetrazole, azepine, diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, pyridazine, piperidine, piperazine, pyrrolidinone, ketopiperazine, furan, pyran, dioxole, 1,4-oxazepane, 1,4-oxazepine, oxazole, isoxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane, oxaziridine, 1,3-dioxolene, 1,3-dioxolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine, thiophene, thiopyran, thietan, thiazole, isothiazole, isothiazoline, isothiazolidine, 1,2-oxathiolan, thiodiazole, thiopyran, 1,2-thiazine, 1,3-thiazole, 1,3-thiazine, 1,4-thiazine, thiadiazine or thiomorpholine, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ; G is a direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —; m is zero, 1, 2, 3 or 4; M is
1) hydrogen,
2) —(C 1 -C 6 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
3) —C(O)—N(R 11 )—R 12 ,
6) heterocyclyl, wherein the heterocyclyl is azepane, azepine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, isothiazole, isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine, morpholine, oxazole, [1,4]-oxazepane, 1,4-oxazepine, piperazine, piperazinone, piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine, pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, tetrazine, tetrazole, thiadiazole, thiazole, thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
7) —(C 3 -C 6 )-cycloalkyl;
R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) halogen,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 4 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
15) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
17) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 R 16 )—O—C(O)—O—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
23) —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) a residue selected from the group consisting of
wherein Me is methyl, or
two —OR 19 residues and adjacent atoms through which they are attached form together a 5- or 6-membered ring, that is unsubstituted or substituted one, two, three or four times by R 13 ;
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 6 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
5) —(C 0 -C 6 )-alkyl-(C 6 -C 14 )-aryl, wherein alkyl and aryl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 ,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-(C 4 -C 15 )-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 , or
R 11 and R 12 together with the nitrogen atom to which they are bonded form azepine, azetidine, 1,4-diazepane, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, [1,4]-oxazepane, 1,4-oxazepine, oxazole, piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline, thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ; and
R 13 is fluorine, chlorine, —NO 2 , —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —N(R 10 )—S(O) 2 —R 10 , —S—R 10 ,
—SO 2 —R 10 , —S(O) 2 —N(R 10 )—R 20 , —C(O)—R 10 , —(C 1 -C 8 )-alkyl, —(C 1 -C 8 )-alkoxy, phenyl, phenyloxy-, —O—CF 3 , —(C 1 -C 3 )-perfluoroalkyl, —NH—C(O)—NH—R 10 , —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 , —(C 1 -C 4 )-alkoxy-phenyl, —(C 0 -C 4 )-alkyl-C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 , —O—R 15 , —NH—C(O)—O—R 10 , or a residue selected from the group consisting of
wherein Me is methyl;
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
6 . The compound according to claim 1 , wherein,
R 0 is
3) a heterocyclyl selected from the group consisting of pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ,
and in addition is substituted by a residue selected out of the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl or pyrazinyl, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ;
R 8 is
1) F, Cl, Br, or I,
4) —C(O)—NH 2 ,
9) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, —OH or a methoxy residue, or
10) —O—(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen or a methoxy residue, provided that R 8 is at least one halogen, —C(O)—NH 2 or —O—(C 1 -C 8 )-alkyl residue;
Q is direct bond, —C(O)—; —SO 2 — or —(C 1 -C 6 )-alkylen, —(C 0 -C 2 )-alkylen-C(O)—NR 10 —; R 1 is hydrogen or —(C 1 -C 2 )-alkyl; R 2 is a direct bond or as —(C 1 -C 4 )-alkylene is —(C 1 -C 2 )-alkylene; R 14 is fluoro, chlorine, —(C 1 -C 4 )-alkyl or —NH 2 ; V is azaindolyl, azetidine, azepine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diazirine, 1,3-dioxolane, dioxazole, furan, imidazole, isoquinoline, isothiazole, isothiazolidine, isothiazoline, isoxazole, 2-isoxazoline, isoxazolidine, ketopiperazine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, 1,2-oxathiolan, piperidine, pyran, pyrazine, pyrazole, pyridazine, piperazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, quinazoline, quinoline, tetrazine, tetrazole, thiadiazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thietan, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or G is direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —; m is zero, 1, 2, 3 or 4; M is
1) hydrogen,
2) —(C 1 -C 6 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
6) heterocyclyl, wherein the heterocyclyl is 1,4-diazepane, ketomorpholine, thiophene, pyridazone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, thiadiazole or thiomorpholine, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
7) (C 3 -C 6 )-cycloalkyl;
R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) halogen,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 4 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
17) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
17) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 ,
23) —(C 0 -C 3 )-alkylene-(C 3 -C 6 )-cycloalkyl, or —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) a residue selected from the group consisting of
wherein Me is methyl;
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
3) —(C 0 -C 6 )-alkyl-(C 3 -C 6 )-cycloalkyl,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-(C 4 -C 15 )-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 and wherein heterocyclyl is selected out of the group azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, (1,4)-oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine, or
R 11 and R 12 together with the nitrogen atom to which they are bonded form azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, (1,4)-oxazepane, 1,4-oxazepine, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine;
R 13 is fluorine, —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 3 -C 6 )-cycloalkyl, —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —S—R 10 , —SO 2 —R 10 ,
—(C 1 -C 3 )-perfluoroalkyl, or a residue selected from the group consisting of
wherein Me is methyl;
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl; and
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl, or together form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, that is unsubstituted or substituted one to three times by R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
7 . The compound according to claim 1 , wherein
R 0 is phenyl, wherein phenyl is unsubstituted or mono- or disubstituted independently of one another by R 8 , R 8 is
1) F, Cl, Br, or I,
4) —C(O)—NH 2 ,
9) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, —OH or a methoxy residue, or
10) —O—(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen or a methoxy residue, provided that R 8 is at least one halogen, —C(O)—NH 2 or —O—(C 1 -C 8 )-alkyl residue;
Q is a direct bond, —C(O)—; —SO 2 — or —(C 1 -C 6 )-alkylen, —(C 0 -C 2 )-alkylen-C(O)—NR 10 —; R 1 is hydrogen or —(C 1 -C 2 )-alkyl; R 2 is a direct bond or as —(C 1 -C 4 )-alkylene is —(C 1 -C 2 )-alkylene; R 14 is fluoro, chlorine, —(C 1 -C 4 )-alkyl or —NH 2 ; V is azaindolyl, 1H-pyrrolopyridyl, azetidine, azepine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diazirine, 1,3-dioxolane, dioxazole, furan, imidazole, isoquinoline, isothiazole, isothiazolidine, isothiazoline, isoxazole, 2-isoxazoline, isoxazolidine, ketopiperazine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, 1,2-oxathiolan, piperidine, pyran, pyrazine, pyrazole, pyridazine, piperazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, quinazoline, quinoline, tetrazine, tetrazole, thiadiazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thietan, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ; G is direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 ; m is zero, 1, 2, 3 or 4; M is
1) hydrogen,
2) —(C 1 -C 6 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
6) heterocyclyl, wherein the heterocyclyl is 1,4-diazepane, ketomorpholine, thiophene, pyridazone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, thiadiazole or thiomorpholine, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
7) —(C 3 -C 6 )-cycloalkyl;
R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) halogen,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 4 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
18) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
17) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 R 16 )—O—C(O)—O—R 17 ,
23) —(C 0 -C 3 )-alkylene-(C 3 -C 6 )-cycloalkyl, or —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) a residue selected from the group consisting of
wherein Me is methyl;
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
3) —(C 0 -C 6 )-alkyl-(C 3 -C 6 )-cycloalkyl,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-(C 4 -C 15 )-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 and wherein heterocyclyl is selected out of the group azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, (1,4)-oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine, or
R 11 and R 12 together with the nitrogen atom to which they are bonded form azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, (1,4)-oxazepane, 1,4-oxazepine, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine;
R 13 is fluorine, —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 3 -C 6 )-cycloalkyl, —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —S—R 10 , —SO 2 —R 10 ,
—(C 1 -C 3 )-perfluoroalkyl, or a residue selected from the group consisting of
wherein Me is methyl;
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl; and
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl, or together form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, that is unsubstituted or substituted one to three times by R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
8 . The compound according to claim 1 , wherein
R 0 is
2) a heterocyclyl selected from the group consisting of indolyl, isoindolyl, benzofuranyl, benzothiophenyl, 1,3-benzodioxolyl, indazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, chromanyl, isochromanyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyridinyl, purinyl and pteridinyl,
wherein said heterocyclyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 8 ,
R 8 is
1) F, Cl, Br, or I,
4) —C(O)—NH 2 ,
9) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen, —OH or a methoxy residue, or
10) —O—(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by halogen or a methoxy residue, provided that R 8 is at least one halogen, —C(O)—NH 2 or —O—(C 1 -C 8 )-alkyl residue;
Q is direct bond, —C(O)—; —SO 2 — or —(C 1 -C 6 )-alkylen, —(C 0 -C 2 )-alkylen-C(O)—NR 10 —; —R 1 is hydrogen or —(C 1 -C 2 )-alkyl; R 2 is a direct bond or as —(C 1 -C 4 )-alkylene is —(C 1 -C 2 )-alkylene; R 14 is fluoro, chlorine, —(C 1 -C 4 )-alkyl or —NH 2 ; V is azaindolyl, azetidine, azepine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diazirine, 1,3-dioxolane, dioxazole, furan, imidazole, isoquinoline, isothiazole, isothiazolidine, isothiazoline, isoxazole, 2-isoxazoline, isoxazolidine, ketopiperazine, morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, 1,2-oxathiolan, piperidine, pyran, pyrazine, pyrazole, pyridazine, piperazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, quinazoline, quinoline, tetrazine, tetrazole, thiadiazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thietan, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ; G is direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —; m is zero, 1, 2, 3 or 4; M is
1) hydrogen,
2) —(C 1 -C 6 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 ,
6) heterocyclyl, wherein the heterocyclyl is 1,4-diazepane, ketomorpholine, thiophene, pyridazone, piperidine, piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole, tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, thiadiazole or thiomorpholine, that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , or
7) (C 3 -C 6 )-cycloalkyl;
R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) halogen,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 4 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
19) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
17) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 R 16 )—O—C(O)—O—R 17 ,
23) —(C 0 -C 3 )-alkylene-(C 3 -C 6 )-cycloalkyl, or —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) a residue selected from the group consisting of
wherein Me is methyl;
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
3) —(C 0 -C 6 )-alkyl-(C 3 -C 6 )-cycloalkyl,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-(C 4 -C 15 )-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 and wherein heterocyclyl is selected out of the group azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, (1,4)-oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine, or
R 11 and R 12 together with the nitrogen atom to which they are bonded form azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine, (1,4)-oxazepane, 1,4-oxazepine, oxazolidine, piperidine, piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine;
R 13 is fluorine, —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 3 -C 6 )-cycloalkyl, —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —S—R 10 , —SO 2 —R 10 ,
—(C 1 -C 3 )-perfluoroalkyl, or a residue selected from the group consisting of
wherein Me is methyl;
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl; and
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl, or together form cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, that is unsubstituted or substituted one to three times by R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
9 . The compound according to claim 1 , wherein
R 0 is
3) a heterocyclyl selected from the group consisting of thienyl, thiadiazolyl, isoxazolyl and thiazolyl, wherein said heterocyclyl is substituted by a residue selected from the group consisting of thienyl, 2-thienyl and 3-thienyl, wherein said residue is unsubstituted or mono- or disubstituted independently of one another by R 8 ,
R 8 is F, Cl, Br, —OCH 3 , —C(O)—NH 2 or —O—CF 3 , Q is a direct bond, —C(O)—; —SO 2 —, —CH 2 —C(O)—NH—, methylene or ethylene, R 1 is hydrogen, R 2 is a direct bond or methylene, R 14 is fluorine, chlorine, methyl, ethyl or —NH 2 , V is azaindolyl, azetidine, 1,4-diazepane, isoxazole, isoquinoline, piperazine, piperidine, pyrazine, pyridazine, pyrimidine, pyrrolidine, quinazoline, quinoline or tetrahydropyran, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , G is a direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —, m is zero, 1 or 2, M is hydrogen, (C 2 -C 4 )-alkyl, azepanyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, ketomorpholinyl, morpholinyl, 1,4-oxazepanyl, piperidinyl, piperidonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidyl, pyrrolidinyl, 1,4,5,6-tetrahydropyridazinyl, or tetrahydropyranyl, wherein the residues are unsubstituted or mono- or disubstituted independently of one another by R 14 , R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) fluorine or chlorine,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 2 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
14) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
16) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 ,
23) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl selected from the group consisting of —(C 0 -C 3 )-alkylene-(C 3 -C 6 )-cycloalkyl or —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
24) —(C 0 -C 4 )-alkylene-het selected from the group consisting of pyridinyl or thiazolyl that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 4 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —O—(C 0 -C 4 )-alkyl selected from the group consisting of —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) residue selected from the group consisting of the following
wherein Me is methyl,
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
3) —(C 0 -C 6 )-alkyl-(C 3 -C 6 )-cycloalkyl,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 and wherein heterocyclyl is selected out of the group azetidine, imidazolidine, morpholine, 1,4-oxazepane or pyrrolidine or
R 11 and R 12 together with the nitrogen atom to which they are bonded can form the 4- to 8-membered monocyclic heterocyclic ring selected from the group consisting of azetidine, imidazolidine, morpholine, 1,4-oxazepane, 1,4-oxazepine, piperazine, piperidine, pyrrolidine and thiomorpholine,
R 13 is fluorine, chlorine, —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 3 -C 6 )-cycloalkyl, —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —S—R 10 , —SO 2 —R 10 , —(C 1 -C 4 )-alkyl, —(C 1 -C 3 )-perfluoroalkyl, or residue selected from the group consisting of the following
wherein Me is methyl,
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl,
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl, or together form a 3- to 6 membered carbocyclic ring selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring is unsubstituted or substituted one to three times by R 10 , and
R 17 is —(C1-C6)-alkyl, —(C1-C6)-alkyl-OH, —(C1-C6)-alkyl-O—(C1-C6)-alkyl, —(C3-C8)-cycloalkyl, —(C1-C6)-alkyl-O—(C1-C8)-alkyl-(C3-C8)-cycloalkyl, —(C1-C6)-alkyl-(C3-C8)-cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by —OH, —O—(C1-C4)-alkyl or R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
10 . The compound according to claim 1 , wherein
R 0 is phenyl that is unsubstituted or mono- or disubstituted independently of one another by R 8 , R 8 is F, Cl, Br, —OCH 3 , —C(O)—NH 2 or —O—CF 3 , Q is a direct bond, —C(O)—; —SO 2 —, —CH 2 —C(O)—NH—, methylene or ethylene, R 1 is hydrogen, R 2 is a direct bond or methylene, R 14 is fluorine, chlorine, methyl, ethyl or —NH 2 , V is azaindolyl, azetidine, 1,4-diazepane, isoxazole, isoquinoline, piperazine, piperidine, pyrazine, pyridazine, pyrimidine, pyrrolidine, quinazoline, quinoline or tetrahydropyran, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , G is a direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —, m is zero, 1 or 2, M is hydrogen, or moiety selected from the group consisting of (C 2 -C 4 )-alkyl, azepanyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, ketomorpholinyl, morpholinyl, 1,4-oxazepanyl, piperidinyl, piperidonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidyl, pyrrolidinyl, 1,4,5,6-tetrahydropyridazinyl, or tetrahydropyranyl, wherein the moiety is unsubstituted or mono- or disubstituted independently of one another by R 14 R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) fluorine, chlorine,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 2 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
14) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
16) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 ,
23) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl selected from the group consisting of —(C 0 -C 3 )-alkylene-(C 3 -C 6 )-cycloalkyl or —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
24) —(C 0 -C 4 )-alkylene-het selected from the group consisting of pyridinyl or thiazolyl that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 4 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —O—(C 0 -C 4 )-alkyl selected from the group consisting of —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) residue selected from the group consisting of the following
wherein Me is methyl,
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
3) —(C 0 -C 6 )-alkyl-(C 3 -C 6 )-cycloalkyl,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 and wherein heterocyclyl is selected out of the group azetidine, imidazolidine, morpholine, 1,4-oxazepane or pyrrolidine or
R 11 and R 12 together with the nitrogen atom to which they are bonded can form the 4- to 8-membered monocyclic heterocyclic ring selected from the group consisting of azetidine, imidazolidine, morpholine, 1,4-oxazepane, 1,4-oxazepine, piperazine, piperidine, pyrrolidine and thiomorpholine,
R 13 is fluorine, chlorine, —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 3 -C 6 )-cycloalkyl, —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —S—R 10 , —SO 2 —R 10 , —(C 1 -C 4 )-alkyl, —(C 1 -C 3 )-perfluoroalkyl, or residue selected from the group consisting of the following
wherein Me is methyl,
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl,
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl, or together form a 3- to 6 membered carbocyclic ring selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring is unsubstituted or substituted one to three times by R 10 , and
R 17 is —(C1-C6)-alkyl, —(C1-C6)-alkyl-OH, —(C1-C6)-alkyl-O—(C1-C6)-alkyl, —(C3-C8)-cycloalkyl, —(C1-C6)-alkyl-O—(C1-C8)-alkyl-(C3-C8)-cycloalkyl, —(C1-C6)-alkyl-(C3-C8)-cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by —OH, —O—(C1-C4)-alkyl or R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
11 . The compound according to claim 1 , wherein
R 0 is pyridyl that is unsubstituted or mono- or disubstituted independently of one another by R 8 , R 8 is F, Cl, Br, —OCH 3 , —C(O)—NH 2 or —O—CF 3 , Q is a direct bond, —C(O)—; —SO 2 —, —CH 2 —C(O)—NH—, methylene or ethylene, R 1 is hydrogen, R 2 is a direct bond or methylene, R 14 is fluorine, chlorine, methyl, ethyl or —NH 2 , V is azaindolyl, azetidine, 1,4-diazepane, isoxazole, isoquinoline, piperazine, piperidine, pyrazine, pyridazine, pyrimidine, pyrrolidine, quinazoline, quinoline or tetrahydropyran, each of which is unsubstituted or mono-, di- or trisubstituted independently of one another by R 14 , G is a direct bond, —(CH 2 ) m —, or —(CH 2 ) m —NR 10 —, m is zero, 1 or 2, M is hydrogen, (C 2 -C 4 )-alkyl, azepanyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl, ketomorpholinyl, morpholinyl, 1,4-oxazepanyl, piperidinyl, piperidonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidyl, pyrrolidinyl, 1,4,5,6-tetrahydropyridazinyl, or tetrahydropyranyl, wherein the residues are unsubstituted or mono- or disubstituted independently of one another by R 14 , R 3 and R 4 are independent of one another are identical or different and are
1) hydrogen,
2) fluorine, chlorine,
3) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
4) —(C 1 -C 3 )-perfluoroalkyl,
5) phenyl that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
6) —(C 0 -C 2 )-alkylene-O—R 19 , wherein R 19 is
a) hydrogen,
b) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 , or
c) phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
d) —CF 3 , or
e) —CHF 2 ,
8) —CN,
9) —SO s —R 11 , wherein s is 1 or 2,
10) —SO t —N(R 11 )—R 12 , wherein t is 1 or 2,
11) —(C 0 -C 4 )-alkylene-C(O)—R 11 ,
12) —(C 0 -C 4 )-alkylene-C(O)—O—R 11 ,
13) —(C 0 -C 4 )-alkylene-C(O)—N(R 11 )—R 12 ,
14) —(C 0 -C 4 )-alkylene-N(R 11 )—R 12 ,
15) —NR 10 —SO 2 —R 10 ,
16) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—(C 1 -C 4 )-alkyl,
18) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—R 17 ,
19) —(C 0 -C 2 )alkylene-C(O)—O—(C 2 -C 4 )-alkylene-O—C(O)—O—(C 1 -C 6 )-alkyl,
20) —C(O)—O—C(R 15 ,R 16 )—O—C(O)—O—R 17 ,
23) —(C 0 -C 4 )-alkylene-(C 3 -C 8 )-cycloalkyl selected from the group consisting of —(C 0 -C 3 )-alkylene-(C 3 -C 6 )-cycloalkyl or —(C 0 -C 4 )-alkylene-(C 3 -C 6 )-cycloalkyl, wherein cycloalkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
24) —(C 0 -C 4 )-alkylene-het selected from the group consisting of pyridinyl or thiazolyl that is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
25) —(C 0 -C 4 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —O—(C 0 -C 4 )-alkyl selected from the group consisting of —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, —(C 0 -C 3 )-alkylene-O—CH 2 —CF 2 —CF 2 —CH 2 —O—(C 0 -C 3 )-alkyl, or —(C 0 -C 3 )-alkylene-O—CH 2 —(C 1 -C 3 )-perfluoroalkylene-CH 2 —OH, or
26) residue selected from the group consisting of the following
wherein Me is methyl,
R 11 and R 12 are independently of one another identical or different and are
1) hydrogen,
2) —(C 1 -C 4 )-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R 13 ,
3) —(C 0 -C 6 )-alkyl-(C 3 -C 6 )-cycloalkyl,
7) —O—R 17 , or
8) —(C 0 -C 6 )-alkyl-heterocyclyl, wherein alkyl and heterocyclyl independently from one another are unsubstituted or mono-, di- or trisubstituted by R 13 and wherein heterocyclyl is selected out of the group azetidine, imidazolidine, morpholine, 1,4-oxazepane or pyrrolidine or
R 11 and R 12 together with the nitrogen atom to which they are bonded can form the 4- to 8-membered monocyclic heterocyclic ring selected from the group consisting of azetidine, imidazolidine, morpholine, 1,4-oxazepane, 1,4-oxazepine, piperazine, piperidine, pyrrolidine and thiomorpholine,
R 13 is fluorine, chlorine, —CN, ═O, —OH, —CF 3 , —C(O)—O—R 10 , —C(O)—N(R 10 )—R 20 , —N(R 10 )—R 20 , —(C 3 -C 6 )-cycloalkyl, —(C 0 -C 3 )-alkylene-O—R 10 , —Si—(CH 3 ) 3 , —S—R 10 , —SO 2 —R 10 , —(C 1 -C 4 )-alkyl, —(C 1 -C 3 )-perfluoroalkyl, or residue selected from the group consisting of the following
wherein Me is methyl,
R 10 and R 20 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl or —(C 1 -C 3 )-perfluoroalkyl,
R 15 and R 16 are independently of one another hydrogen, —(C 1 -C 4 )-alkyl, or together form a 3- to 6 membered carbocyclic ring selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring is unsubstituted or substituted one to three times by R 10 , and
R 17 is —(C1-C6)-alkyl, —(C1-C6)-alkyl-OH, —(C1-C6)-alkyl-O—(C1-C6)-alkyl, —(C3-C8)-cycloalkyl, —(C1-C6)-alkyl-O—(C1-C8)-alkyl-(C3-C8)-cycloalkyl, —(C1-C6)-alkyl-(C3-C8)-cycloalkyl, wherein said cycloalkyl ring is unsubstituted or substituted one, two or three times by —OH, —O—(C1-C4)-alkyl or R 10 ,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
12 . The compound according to claim 1 , having the formula Ib,
13 . The compound according to claim 1 , having the formula Ic,
14 . The compound according to claim 1 , which is
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-methyl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-methyl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-(6-Chloro-benzothiazol-2-yl)-5-methyl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(5-Chloro-thiophen-2-yl)-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(5-Chloro-thiophen-2-yl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(2,4-dichloro-phenyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(2,4-dichloro-phenyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-propyl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-propyl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-tert-Butyl-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-tert-Butyl-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-propyl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-propyl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[2-(5-Chloro-thiophen-2-yl)-thiazol-4-ylmethyl]-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[2-(5-Chloro-thiophen-2-yl)-thiazol-4-ylmethyl]-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-(6-Chloro-benzo[b]thiophen-2-ylmethyl)-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-(6-Chloro-benzo[b]thiophen-2-ylmethyl)-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-ylmethyl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-ylmethyl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-ylmethyl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-ylmethyl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (3,4,5,6-tetrahydro-2H-[1,4′]bipyridinyl-4-yl)-amide,
2-(4-Chloro-benzyl)-4-cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-(4-Chloro-benzyl)-4-cyano-5-thiophen-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid methyl ester,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carboxylic acid methyl ester,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carboxylic acid,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid ethyl ester,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carboxylic acid ethyl ester,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(morpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(morpholine-4-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-dimethylamide 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-dimethylamide 3-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(2-hydroxy-ethyl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(2-hydroxy-ethyl)-amide] 3-[(1-isopropyl-piperidin-4-yl)-amide],
{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid,
{[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-amino}-acetic acid,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
Sulfuric acid mono-(2-{[1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-ethyl) ester,
Sulfuric acid mono-(2-{[2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-amino}-ethyl) ester,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[4-(2-hydroxy-ethyl)-piperazine-1-carbonyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[4-(2-hydroxy-ethyl)-piperazine-1-carbonyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-oxo-oxazolidine-3-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-oxo-oxazolidine-3-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-[(2-morpholin-4-yl-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(1-isopropyl-piperidin-4-yl)-amide] 5-[(2-morpholin-4-yl-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[bis-(2-methoxy-ethyl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[bis-(2-methoxy-ethyl)-amide] 3-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(4,5-dihydro-oxazol-2-yl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(4,5-dihydro-oxazol-2-yl)-amide] 3-[(1-isopropyl-piperidin-4-yl)-amide],
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[3-(2-hydroxy-ethyl)-2-oxo-imidazolidine-1-carbonyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[3-(2-hydroxy-ethyl)-2-oxo-imidazolidine-1-carbonyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-methoxymethyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-methoxymethyl-pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-methyl-amino}-acetic acid,
{[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-methyl-amino}-acetic acid,
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-piperidine-4-carboxylic acid ethyl ester,
1-[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-piperidine-4-carboxylic acid ethyl ester,
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-azetidine-2-carboxylic acid,
1-[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-azetidine-2-carboxylic acid,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(thiomorpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(thiomorpholine-4-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-pyrrolidine-2-carboxylic acid,
1-[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-pyrrolidine-2-carboxylic acid,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4-hydroxy-piperidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4-hydroxy-piperidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-hydroxymethyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-hydroxymethyl-pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(2,5-Bis-methoxymethyl-pyrrolidine-1-carbonyl)-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(2,5-Bis-methoxymethyl-pyrrolidine-1-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4-hydroxymethyl-piperidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4-hydroxymethyl-piperidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(8-Aza-spiro[4.5]decane-8-carbonyl)-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(8-Aza-spiro[4.5]decane-8-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-methanesulfonyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-methanesulfonyl-pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(1,1-dioxo-tetrahydro-1-thiophen-3-yl)-methyl-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1,1-dioxo-tetrahydro-1-thiophen-3-yl)-methyl-amide] 3-[(1-isopropyl-piperidin-4-yl)-amide],
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-azetidine-3-carboxylic acid,
1-[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-azetidine-3-carboxylic acid,
5-(Azetidine-1-carbonyl)-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(Azetidine-1-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-oxo-piperazine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-oxo-piperazine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4,4-difluoro-piperidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4,4-difluoro-piperidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-([1,4]oxazepane-4-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-([1,4]oxazepane-4-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-azetidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-azetidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-trifluoromethyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-trifluoromethyl-pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2,2-dimethyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2,2-dimethyl-pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-[(2-sulfamoyl-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(1-isopropyl-piperidin-4-yl)-amide] 5-[(2-sulfamoyl-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-cyclopropylamide 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-cyclopropylamide 3-[(1-isopropyl-piperidin-4-yl)-amide],
{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-methanesulfonic acid,
{[2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-amino}-methanesulfonic acid,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-cyclobutylamide 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-cyclobutylamide 3-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-[(2-methoxy-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(1-isopropyl-piperidin-4-yl)-amide] 5-[(2-methoxy-ethyl)-amide],
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(pyrrolidine-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(cyanamide-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(cyanamide-1-carbonyl)-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
Phosphoric acid mono-(2-{[1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-ethyl) ester,
Phosphoric acid mono-(2-{[2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carbonyl]-amino}-ethyl) ester,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid methyl ester,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-pyrazole-3,5-dicarboxylic acid 3-cyclobutylamide 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid bis-[(1-isopropyl-piperidin-4-yl)-amide],
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[(4-Chloro-phenylcarbamoyl)-methyl]-4-cyano-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
3-{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-(methoxy-amide),
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-carbamoylmethyl-amide 5-[(1-isopropyl-piperidin-4-yl)-amide],
{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid ethyl ester,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(3-hydroxy-propyl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-(2S)-azetidine-2-carboxylic acid,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2S,2-hydroxymethyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-2S-pyrrolidine-2-carboxylic acid,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2S,2-methoxymethyl-pyrrolidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(2R,5R,2,5-Bis-methoxymethyl-pyrrolidine-1-carbonyl)-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(4,5-dihydro-oxazol-2-yl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-piperidine-4-carboxylic acid ethyl ester,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-[(2-morpholin-4-yl-ethyl)-amide],
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(4,4-difluoro-piperidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-oxo-oxazolidine-3-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-{[2-(2-oxo-imidazolidin-1-yl)-ethyl]-amide},
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-[(2,2,2-trifluoro-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(1,1-dioxo-tetrahydro-1-thiophen-3-yl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-{[3-(2-oxo-pyrrolidin-1-yl)-propyl]-amide},
5-(Azetidine-1-carbonyl)-2-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(thiazolidine-3-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-3,3,3-trifluoro-propionic acid,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 5-[(1-isopropyl-piperidin-4-yl)-amide] 3-trimethylsilanylmethyl-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carbonyl]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-methanesulfonylaminocarbonyl-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-azetidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-furan-2-yl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-2H-pyrazole-3-carboxylic acid,
5-(Azetidine-1-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(1-isopropyl-piperidin-4-yl)-amide] 5-[(2-sulfamoyl-ethyl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[bis-(2-hydroxy-ethyl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrazole-3,5-dicarboxylic acid 3-[(2-hydroxy-1,1-bis-hydroxymethyl-ethyl)-amide] 5-[(1-isopropyl-piperidin-4-yl)-amide],
{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid isopropyl ester,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid ethyl ester,
{[1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid isopropyl ester,
{[1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid ethyl ester,
{[1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid,
2-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(3-hydroxy-azetidine-1-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid cyclopropylmethyl ester,
2-{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-3-methyl-butyric acid ethyl ester,
2-{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carbonyl]-amino}-3-methyl-butyric acid,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(2-methoxy-ethoxymethyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-[2-(2-methoxy-ethoxy)-ethoxymethyl]-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-[2-(2-methoxy-ethoxy)-ethoxy]-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
2-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(2,2,2-trifluoro-ethoxy)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid 2-methoxy-ethyl ester,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid 2-hydroxy-ethyl ester,
2-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-([1,4]oxazepane-4-carbonyl)-2H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
5-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1-(3-methoxy-benzyl)-1H-pyrazole-3-carboxylic acid,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid 2-hydroxy-ethyl ester,
1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-pyrazole-3-carboxylic acid carboxymethyl ester,
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-(1-isopropyl-piperidin-4-ylcarbamoyl)-4-(2,2,2-trifluoro-ethoxy)-1H-pyrazole-3-carboxylic acid ethyl ester, or
1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-hydroxymethyl-1H-pyrazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide,
or a stereoisomer thereof, a mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof.
15 . A process for preparing the compound according to claim 1 , comprising condensing a carboxylic acid of formula 2
with a compound of formula HR 8′ or with an amine of formula HN(R 1 ′)R 2 ′—V-G-M to give a compound of formula 3
and optionally converting the compound of formula 3 into a compound of the formula I, wherein the groups R 8′ and R 87 are respectively the groups —N(R 1 )—R 2 —V-G-M and R 0 -Q-, which are as defined in claim 1 , and R 1 a and R 1 b have respectively the meaning of R 3 and R 4 in claim 1 .
16 . A pharmaceutical preparation comprising a pharmaceutically effective amount of at least one compound according to claim 1 , or a stereoisomer thereof, mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof, and a pharmaceutically acceptable carrier.
17 . A method of inhibiting the activity of factor Xa or factor VIIa comprising contacting an inhibitory amount of the compound according to claim 1 , or a stereoisomer thereof, mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof, with a composition containing factor Xa or factor VIIa to influence blood coagulation, wherein the blood coagulation is connected with abnormal thrombus formation.
18 . A method of inhibiting the activity of factor Xa or factor VIIa comprising contacting an inhibitory amount of the compound according to claim 1 , or a stereoisomer thereof, mixture of stereoisomers thereof in any ratio, or a physiological tolerable salt thereof, with a composition containing factor Xa or factor VIIa to influence fibrinolysis.Join the waitlist — get patent alerts
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