New chemical compounds

Abstract

The present invention encompasses compounds of general formula (1) wherein the groups R 2 to R 4 , L, Q and n are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.

1 . A compound of formula (1) 
       
         
           
           
               
               
           
         
       
       wherein
 Q has a partial structure selected from among the partial structures (i)-(v) 
 
       
         
           
           
               
               
           
         
         W, X and Y are each independently of one another selected from among ═CR 5a  and ═N—, 
         Z is in each case independently selected from among 
         —NR 6 —, —O— and —S—, 
         L is selected from among —C(O)NH—, —NHC(O)—, —C(S)NH—, —NHC(S)—, —C(O)—, —C(S)—, —NH—, —S(O)—, —S(O)O—, —S(O) 2 —, —S(O) 2 O—, —S(O)NH—, —S(O) 2 NH—, —OS(O)—, —OS(O) 2 —, —OS(O)NH—, —OS(O) 2 NH—, —C(O)O—, —C(O)S—, —C(NH)NH—, —OC(O)—, —OC(O)O—, —OC(O)NH—, —SC(O)—, —SC(O)O—, —SC(O)NH—, —NHC(NH)—, —NHS(O)—, —NHS(O)O—, —NHS(O) 2 —, —NHS(O) 2 O—, —NHS(O) 2 NH—, —NHC(O)O—, —NHC(O)NH— and —NHC(S)NH— or denotes a bond, 
         R 1  is selected from among R a  and R b , 
         R 2  denotes a 5-12 membered heteroaryl, optionally substituted by one or more, identical or different R 5b , 
         R 3  and each R 4  is in each case independently selected from among hydrogen, halogen, —CN, —NO 2 , —NR h R h , —OR h , —C(O)R h , —C(O)NR h R h , —SR h , —S(O)R h , —S(O) 2 R h , C 1-4 alkyl, C 1-4 haloalkyl, C 3-7 cycloalkyl and 3-7 membered heterocycloalkyl, 
         each R 5a  and R 5b  is selected independently of one another from among R a  and R b , 
         R 6  is defined in the same way as R a , 
         n has the value 0, 1, 2 or 3, 
         each R a  independently of one another denotes hydrogen or a group optionally substituted by one or more identical or different R b  and/or R c , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, 
         each R b  denotes a suitable group and is in each case independently selected from among ═O, —OR c , C 1-3 haloalkyloxy, —OCF 3 , ═S, —SR c , ═NR c , ═NOR c , ═NNR c R c , ═NN(NR g )C(O)NR c R c , —NR c R c , —ONR c R c , —N(OR c )R c , —N(R g )NR c R c , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R c , —S(O)OR c , —S(O) 2 R c , —S(O) 2 OR c , —S(O)NR c R c , —S(O) 2 NR c R c , —OS(O)R c , —OS(O) 2 R c , —OS(O) 2 OR c , —OS(O)NR c R c , —OS(O) 2 NR c R c , —C(O)R c , —C(O)OR c , —C(O)SR c , —C(O)NR c R c , —C(O)N(R g )NR c R c , —C(O)N(R g )OR c , —C(O)NR g )NR c R c , —C(NOH)R c , —C(NOH)NR c R c , —OC(O)R c , —OC(O)OR c , —OC(O)SR c , —OC(O)NR c R c , —OC(NR g )NR c R c , —SC(O)R c , —SC(O)OR c , —SC(O)NR c R c , —SC(NR g )NR c R c , —N(R g )C(O)R c , —N[C(O)R c ] 2 , —N(OR g )C(O)R c , —N(R g )C(NR g )R c , —N(R g )N(R g )C(O)R c , —N[C(O)R c ]NR c R c , —N(R g )C(S)R c , —N(R g )S(O)R c , —N(R g )S(O)OR c , —N(R g )S(O) 2 R c , —N[S(O) 2 R c ] 2 , —N(R g )S(O) 2 OR c , —N(R g )S(O) 2 NR c R c , —N(R g )[S(O) 2 ] 2 R c , —N(R g )C(O)OR c , —N(R g )C(O)SR c , —N(R g )C(O)NR c R c , —N(R g )C(O)NR g NR c R c , —N(R g )N(R g )C(O)NR c R c , —N(R g )C(S)NR c R c , —[N(R g )C(O)] 2 R c , —N(R g )[C(O)] 2 R c , —N{[C(O)] 2 R c } 2 , —N(R g )[C(O)] 2 OR c , —N(R g )[C(O)] 2 NR c R c , —N{[C(O)] 2 OR c } 2 , —N{[C(O)] 2 NR c R c } 2 , —[N(R g )C(O)] 2 OR c , —N(R g )C(NR g )OR c , —N(R g )C(NOH)R c , —N(R g )C(NR g )SR c  and —N(R g )C(NR g )NR c R c , 
         each R c  in each case independently of one another denotes hydrogen or a group optionally substituted by one or more identical or different R d  and/or R e , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, 
         each R d  denotes a suitable group and is in each case independently selected from among ═O, —OR e , C 1-3 haloalkyloxy, —OCF 3 , ═S, —SR e , ═NR e , ═NOR e , ═NNR e R e , ═NN(R g )C(O)NR e R e , —NR e R e , —ONR e R e , —N(R g )NR e R e , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R e , —S(O)OR e , —S(O) 2 R e , —S(O) 2 OR e , —S(O)NR e R e , —S(O) 2 NR e R e , —OS(O)R e , —OS(O) 2 R e , —OS(O) 2 OR e , —OS(O)NR e R e , —OS(O) 2 NR e R e , —C(O)R e , —C(O)OR e , —C(O)SR e , —C(O)NR e R e , —C(O)N(R g )NR e R e , —C(O)N(R g )OR e , —C(NR g )NR e R e , —C(NOH)R e R e , C(NOH)NR e R e , —OC(O)R e , —OC(O)OR e , —OC(O)SR e , —OC(O)NR e R e , —OC(NR g )NR e R e , —SC(O)R e , SC(O)OR e , SC(O)NR e R e , —SC(NR g )NR e R e , —N(R g )C(O)R e , —N[C(O)R e ] 2 , —N(OR g )C(O)R e , —N(R g )C(NR g )R e , —N(R g )N(R g )C(O)R e , —N[C(O)R e ]NR e R e , —N(R g )C(S)R e , —N(R g )S(O)R e , —N(R g )S(O)OR e , —N(R g )S(O) 2 R e , —N[S(O) 2 R e ] 2 , —N(R g )S(O) 2 OR e , —N(R g )S(O) 2 NR e R e , —N(R g )[S(O) 2 ] 2 R e , —N(R g )C(O)OR e , —N(R g )C(O)SR e , —N(R g )C(O)NR e R e , —N(R g )C(O)NR g NR e R e , —N(R g )N(R g )C(O)NR e R e , —N(R g )C(S)NR e R e , —[N(R g )C(O)] 2 R e , —N(R g )[C(O)] 2 R e , —N{[C(O)] 2 R e } 2 , —N(R g )[C(O)] 2 OR e , —N(R g )[C(O)] 2 NR e R e , —N{[C(O)] 2 OR e } 2 , —N{[C(O)] 2 NR e R e } 2 , —[N(R g )C(O)] 2 OR e , —N(R g )C(NR g )OR e , —N(R g )C(NOH)R e , —N(R g )C(NR g )SR e  and —N(R g )C(NR g )NR e R e , 
         each R e  in each case independently of one another denotes hydrogen or a group optionally substituted by one or more identical or different R f  and/or R g , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, 
         each R f  denotes a suitable group and is in each case independently selected from among ═O, —OR g , C 1-3 haloalkyloxy, —OCF 3 , ═S, —SR g , ═NR g , ═NOR g , ═NNR g R g , ═NN(R h )C(O)NR g R g , —NR g R g , —ONR g R g , —N(R h )NR g R g , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R g , —S(O)OR g , —S(O) 2 R g , —S(O) 2 OR g , —S(O)NR g R g , —S(O) 2 NR g R g , —OS(O)R g , —OS(O) 2 R g , —OS(O) 2 OR g , —OS(O)NR g R g , —OS(O) 2 NR g R g , —C(O)R g , —C(O)OR g , —C(O)SR g , —C(O)NR g R g , —C(O)N(R h )NR g R g , —C(O)N(R h )OR g , —C(NR h )NR g R g , —C(NOH)R g , —C(NOH)NR g R g , —OC(O)R g , —OC(O)OR g , —OC(O)SR g , —OC(O)NR g R g , —OC(NR h )NR g R g , —SC(O)R g , —SC(O)OR g , —SC(O)NR g R g , —SC(NR h )NR g R g , —N(R h )C(O)R g , —N[C(O)R g ] 2 , —N(OR h )C(O)R g , —N(R h )C(NR h )R g , —N(R h )N(R h )C(O)R g , —N[C(O)R g ]NR g R g , —N(R h )C(S)R g , —N(R h )S(O)R g , —N(R h )S(O)OR g , —N(R h )S(O) 2 R g , —N[S(O) 2 R g ] 2 , —N(R h )S(O) 2 OR g , —N(R h )S(O) 2 NR g R g , —N(R h )[S(O) 2 ] 2 R g , —N(R h )C(O)OR g , —N(R h )C(O)SR g , —N(R h )C(O)NR g R g , —N(R h )C(O)NR h NR g R g , —N(R h )N(R h )C(O)NR g R g , —N(R h )C(S)NR g R g , —[N(R h )C(O)] 2 R g , —N(R h )[C(O)] 2 R g , —N{[C(O)] 2 R g } 2 , —N(R h )[C(O)] 2 OR g , —N(R h )[C(O)] 2 NR g R g , —N{[C(O)] 2 OR g } 2 , —N{[C(O)] 2 NR g R g } 2 , —[N(R h )C(O)] 2 OR g , —N(O)C(NR h )OR g , —N(R h )C(NOH)R g , —N(R h )C(NR h )SR g  and —N(R h )C(NR h )NR g R g , 
         each R g  in each case independently of one another denotes hydrogen or a group optionally substituted by one or more identical or different R h , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, 
         each R h  is in each case independently selected from among hydrogen, C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, 
         optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable salts thereof 
       
       with the provisos that
 (a) if R 2  corresponds to pyridyl, this pyridyl is linked to L through a carbon atom adjacent to the pyridylnitrogen; and 
 (b) the compounds 
 
       1-[5-(6-tert-butyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-8-ylcarbamoyl)-2-methyl-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid-(2,2-dimethyl-propyl)-amide, 
       1-[5-(5-tert-butyl-2-methyl-benzoxazol-7-ylcarbamoyl)-2-methyl-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid-(2,2-dimethyl-propyl)-amide, 
       1-[5-(6-tert-butyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-ylcarbamoyl)-2-methyl-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid-(2,2-dimethyl-propyl)-amide, 
       1-[5-(5-tert-butyl-2-oxo-2,3-dihydro-benzoxazol-7-ylcarbamoyl)-2-methyl-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid-(2,2-dimethyl-propyl)-amide, 
       1-[5-(5-tert-butyl-2,2-dimethyl-3-oxo-2,3-dihydro-benzofuran-7-ylcarbamoyl)-2-methyl-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid-(2,2-dimethyl-propyl)-amide, 
       1-[5-(1-acetyl-6-methoxy-3,3-dimethyl-2,3-dihydro-1H-indol-5-ylcarbamoyl)-2-methyl-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid-(2,2-dimethyl-propyl)-amide, 
       5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid-{3-[4-(5-methoxy-pyridin-3-yl)-[1,2,3]triazol-1-yl]-4-methyl-phenyl}-amide, 
       5-tert-butyl-2-p-tolyl-2H-pyrazole-3-carboxylic acid-{3-[4-(5-methoxy-pyridin-3-yl)-[1,2,3]triazol-1-yl]-4-methyl-phenyl}-amide, 
       5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid-[4-methyl-3-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-phenyl]-amide, 
       5-tert-butyl-2-p-tolyl-2H-pyrazole-3-carboxylic acid-[4-methyl-3-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-phenyl]-amide, 
       5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid-(3-{4-[6-(cyclopropylmethyl-amino)-pyridin-3-yl]-[1,2,3]triazol-1-yl}-4-methyl-phenyl)-amide, 
       5-tert-butyl-2-p-tolyl-2H-pyrazole-3-carboxylic acid-(3-{4-[6-(cyclopropylmethyl-amino)-pyridin-3-yl]-[1,2,3]triazol-1-yl}-4-methyl-phenyl)-amide, 
       5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid-{4-methyl-3-[4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-[1,2,3]triazol-1-yl]-phenyl}-amide, 
       5-tert-butyl-2-p-tolyl-2H-pyrazole-3-carboxylic acid-{4-methyl-3-[4-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-[1,2,3]triazol-1-yl]-phenyl}-amide, 
       5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid-{3-[4-(2-cyclopropyl-3-methyl-3H-imidazol-4-yl)-[1,2,3]triazol-1-yl]-4-methyl-phenyl}-amide and 
       5-tert-butyl-2-p-tolyl-2H-pyrazole-3-carboxylic acid-{3-[4-(2-cyclopropyl-3-methyl-3H-imidazol-4-yl)-[1,2,3]triazol-1-yl]-4-methyl-phenyl}-amide 
       are excluded. 
     
     
         2 . The compound according to  claim 1  with the provisos that
 (a) if R 1  denotes —C(O)NR c R c  and L denotes (R 2 )—NHC(O)—, then R 2  may be an at most 6-membered heteroaryl; and   (b) if R 2  denotes pyrazolyl and L denotes (R 2 )—C(O)NH—, then the hydrogen at the nitrogen atom of the pyrazole ring may not be substituted by methyl or 4-methylphenyl.   
     
     
         3 . The compound according to  claim 1  wherein
 L is selected from among —C(O)NH—, —NHC(O)—, —S(O)NH—, —S(O) 2 NH—, —C(NH)NH—, —NHC(NH)—, —NHS(O)— and —NHS(O) 2 — or denotes a bond.   
     
     
         4 . The compound according to  claim 1  wherein
 n has the value 0.   
     
     
         5 . The compound according to  claim 1  wherein
 Q has a partial structure selected from among the partial structures (vi)-(xiii)   
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound according to  claim 5 , wherein
 Q has a partial structure selected from among the partial structures (vi) and (vii)   
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound according to  claim 1  wherein
 R 1  denotes a group optionally substituted by one or more identical or different R b1  and/or R c1 , selected from among C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, or   R 1  is selected from among —C(O)OR c1 , —C(O)NR c1 R c1  and —C(O)R c1 ,   each R b1  denotes a suitable group and is in each case independently selected from among ═O, —OR c1 , —SR c1 , —NR c1 R c1 , halogen, —CN, —NO 2 , —C(O)R c1 , —C(O)OR c1 , —C(O)NR c1 R c1 , —NHC(O)R c1 , —NHC(O)OR c1 , —NHC(O)NR c1 R c1 , —S(O)R c1  and —S(O) 2 R c1 ,   each R c1  in each case independently of one another denotes hydrogen or a group optionally substituted by one or more identical or different R d1  and/or R e1 , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl,   each R d1  a suitable group and is in each case independently selected from among ═O, —OR e1 , —NR e1 R e1 , halogen, —CN, —NO 2 , —C(O)R e1 , C(O)OR e1 , C(O)NR e1 R e1 , —C(O)R e1 , —OC(O)OR e1 , OC(O)NR e1 R e1 , —NHC(O)R e1 , —NHC(O)OR e1  and —NHC(O)NR e1 R e1  and each R e1  is in each case independently selected from among hydrogen, C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl.   
     
     
         8 . The compound according to  claim 7 , wherein
 R 1  is a group optionally substituted by one or more identical or different R b1  and/or R c1 , selected from among C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl and 6-18 membered heteroarylalkyl.   
     
     
         9 . The compound according to  claim 8 , wherein
 R 1  is a group optionally substituted by one or more identical or different R b1  and/or R c1 , selected from among pyridyl, pyrimidyl, thiazolyl, imidazolyl, triazolyl, pyrazolyl, pyrrolyl, furanyl, phenyl, benzyl, imidazo[2.1-b]thiazolyl, imidazo[1,2-a]pyridyl, thiazolyl-methyl and oxazolylmethyl.   
     
     
         10 . The compound according to  claim 1  wherein
 R 2  is selected from among pyridyl, pyrazolyl, isoxazolyl, thiazolyl, imidazolyl and oxazolyl, all the above-mentioned groups optionally being substituted by one or more, identical or different R 5b .   
     
     
         11 . The compound according to  claim 1  wherein
 each R 5b  independently of one another is selected from among R a2  and R b2 ,   each R a2  is a group optionally substituted by one or more identical or different R b2  and/or R c2 , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl,   each R b2  denotes a suitable group and is in each case independently selected from among ═O, —OR c2 , —SR c2 , —NR c2 R c2 , halogen, —CF 3 , —CN, —NO 2 , —S(O)R c2 , —S(O) 2 R c2 , —S(O)NR c2 R c2 , —S(O) 2 NR c2 R c2 , —C(O)R c2 , —C(O)OR c2 , —C(O)NR c2 R c2 , —OC(O)R c2 , —OC(O)OR c2 , —OC(O)NR c2 R c2 , —NHC(O)R c2 , —NHS(O) 2 R c2 , —NHC(O)OR c2 , —NHC(O)NR c2 R c2 ,   each R c2  independently of one another denotes hydrogen or a group optionally substituted by one or more identical or different R d2  and/or R e2 , selected from among C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl,   each R d2  denotes a suitable group and is in each case independently selected from among ═O, —OR e2 , —NR e2 R e2 , halogen, —CN, —NO 2 , —C(O)R e2 , —C(O)OR e2 , —C(O)NR e2 R e2 , —OC(O)R e2 , —OC(O)OR e2 , —OC(O)NR e2 R e2 , —NHC(O)R e2 , —NHC(O)OR e2  and —NHC(O)NR e2 R e2  and   each R e2  is in each case independently selected from among hydrogen, C 1-6 alkyl, 2-6 membered heteroalkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, C 4-16 cycloalkylalkyl, C 6-10 aryl, C 7-16 arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl.   
     
     
         12 . A pharmaceutical composition comprising a compound or the pharmacologically acceptable salts thereof of formula (1) according to  claim 1  together with a pharmacologically acceptable carrier or excipient. 
     
     
         13 . A method for the treatment and/or prevention of cancer, infections, inflammations and autoimmune diseases in a warm-blooded animal which comprises administering to the animal a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         14 . A pharmaceutical composition comprising a compound or the pharmacologically acceptable salt thereof of formula (1) according to  claim 1  together with at least or other cytostatic or cytotoxic active substance, different from the compound of formula (1), optionally in the form of the tautomers, the racemates, the enantiomers, the diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable salts thereof.