Thiazolyl-Dihydro-Indazoles

Abstract

The present invention encompasses compounds of general formula (1) wherein R 1 to R 3 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 the formula (1), 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is selected from among —NHR c , —NHC(O)R c , —NHC(O)OR c , —NHC(O)NR c R c , —NHC(O)N(R g )OR e  and —NHC(O)SR c , and 
         R 2  denotes hydrogen or a group selected from among C 1-6 alkyl, C 3-8 cycloalkyl, 3-8 membered heterocycloalkyl, C 6-10 aryl, C 7-16 arylalkyl and 5-10 membered heteroaryl, optionally substituted by one or more identical or different R 4  and 
         R 3  denotes a 6 membered heteroaryl, substituted by one or more identical or different R a  and/or R b , or 
         R 3  denotes a 8-10 membered heteroaryl, optionally substituted by one or more identical or different R e  and/or R f , and 
         each R 4  denotes a group selected from among R a , R b  and R a  substituted by one or more identical or different R b  and/or R c ; and 
         each R a  independently of one another denotes 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 selected independently of one another from among ═O, —OR c , C 1-3 haloalkyloxy, —OCF 3 , ═S, —SR c , ═NR c , ═NOR c , ═NNR c R c , ═NN(R 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(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 , —N(R g )C(NR g )NR c R c , —N═R c R c  and —N═C(R g )NR c R c  and 
         each R c  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, and 
         each R d  denotes a suitable group and is selected independently of one another 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 , —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 , —N(R g )C(NR g )NR e R e , —N═R e R e  and —N═C(R g )NR e R e    
         each R e  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, and 
         each R f  denotes a suitable group and in each case is selected independently of one another 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   9   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(R h )C(NR h )OR g , —N(R h )C(NOH)R g , —N(R h )C(NR h )SR g , —N(R h )C(NR h )NR g R g , —N═R h R h  and —N═C(R h )NR h R h ; and 
         each R g  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 hetero aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl; and 
         each R h  is selected independently of one another 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, 
       
       or a tautomer or pharmacologically acceptable salt thereof. 
     
     
         2 . A compound according to  claim 1 , wherein R 3  is a radical selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl, optionally substituted by one or more R 4 . 
     
     
         3 . A compound according to  claim 2 , wherein R 3  is pyridyl. 
     
     
         4 . A compound according to  claim 3 ,
 wherein R 3  is substituted by a residue selected from the group consisting of halogen, —CN, —NR c R c  and C 1-6 alkyl optionally substituted by R b .   
     
     
         5 . A compound according to  claim 1 ,
 wherein R 1  is —NHC(O)R c .   
     
     
         6 . A compound according to  claim 5 , wherein R 1  is —NHC(O)CH 3 . 
     
     
         7 - 8 . (canceled) 
     
     
         9 . A pharmaceutical preparation comprising a compound of formula (1) according to one of  claims 1  to  6  or a pharmacologically effective salts thereof, in combination with conventional excipients and/or carriers. 
     
     
         10 . A method for treating cancer, infections, inflammatory and autoimmune diseases, which comprises administering to a host suffering one of said conditions a therapeutically effective amount of a compound of the formula (1) according to one of  claims 1  to  6  or a pharmacologically acceptable salt thereof. 
     
     
         11 . (canceled)