Heterobicyclic carboxamides as inhibitors for kinases

Abstract

The invention relates to novel compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula (I) and to the use of a compound of formula (I) for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.

1 - 19 . (canceled) 
     
     
         20 . A compound of the formula I, 
       
         
           
           
               
               
           
         
         wherein R 1  is hydroxyl, lower-alkoxy-lower alkyl, lower alkylsulfonylamino, amino-lower alkylamino, N-mono- or N,N-di-(lower alkyl)amino-lower alkylamino, N-mono- or N,N-di-(lower alkyl)amino-carbonyl-amino-, piperazinyl-lower alkylamino, N-lower alkylpiperazinyl-lower alkylamino, hydrazine, mono- di- or tri-(lower alkyl)-substituted hydrazine, 
         R 2  is phenyl substituted by a substituent selected from the group consisting of phenoxy, piperazinyl-lower alkyl, lower-alkylpiperazinyl- lower alkyl, C 3 -C 8 -cycloalkyl-piperazinyl-lower alkyl, piperidinyl-lower alkyl, lower-alkylpiperidinyl-lower alkyl, piperidinyliden-lower alkyl, lower-alkylpiperidinyliden-lower alkyl, piperidinyloxy, lower alkylpiperidinyloxy, pyrrolidinyl, amino-pyrrolidinyl, N-mono- or N,N-di-lower alkylaminopyrrolidinyl and 9-lower alkyl-3,9-diazabicyclo[3.3.1]non-3-yl-lower alkyl, or in all cases by one of the mentioned substituents and in addition by a moiety selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy and lower alkoxy; 
         or is 2H-pyrazolyl that is unsubstituted or substituted by lower alkyl and by one or two moieties independently selected from lower alkoxyphenyl and lower alkoxyphenylphenyl; or is phenyl substituted by one or two moieties independently selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy, or by lower alkoxy, or is 2H-pyrazolyl substituted by halophenyl and lower alkyl; 
         or is 2H-pyrazolyl subsisted by halophenyl and lower alkyl; 
         or wherein R 1  is halo, amino, lower alkylamino, lower alkanoylamino, lower alkoxycarbonylamino, C 3-8 cycloalkylcarbonyl amino or hydroxyl-lower alkyl and 
         R 2  is phenyl substituted by a substituent selected from the group consisting of phenoxy, piperazinyl-lower alkyl, lower-alkylpiperazinyl, lower-alkylpiperazinyl-lower alkyl, C 3 -C 8 -cycloalkyl-piperazinyl-lower alkyl, phenyl lower-alkyl piperazinyl, piperidinyl-lower alkyl, lower-alkylpiperidinyl-lower alkyl, amino piperidinyl, lower alkoxycarbonylamino piperidinyl, piperidinyliden-lower alkyl, lower-alkylpiperidinyliden-lower alkyl, piperidinyloxy, lower alkylpiperidinyloxy, pyrrolidinyl, amino-pyrrolidinyl, N-mono- or N,N-di-lower alkylaminopyrrolidinyl, N-mono- or N,N-di-lower alkylaminopyrrolidinyl lower alkyl, 1,1-dioxido-4-thiomorpholinyl, and 9-lower alkyl-3,9-diazabicyclo[3.3.1]non-3-yl-lower alkyl, or in all cases by one of the mentioned substituents and in addition by a moiety selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy and lower alkoxy; or is 2H-pyrazolyl that is unsubstituted or substituted by lower alkyl nad by one or two moieties independently selected from lower alkoxyphenyl and lower alkoxyphenylphenyl; 
         A, B and X are independently selected from C(R 3 ) or N, with the proviso that not more than one of A, B and X is N; 
         R 3  is lower alkyl, halo or hydrogen; 
         Y is O, S, S(O), S(O) 2 , CH 2  or CH 2 —CH 2 ; and 
         Q - - - Z is CH═CH—CH═C wherein the left CH is in the place of Q and the right C is in the place of Z in formula I, respectively; 
         W is absent or is lower alkylene; 
         with the proviso that 
         If one of A, B and X is N, and Y is O, then in addition or alternatively a compound of formula I wherein R 1  is hydroxyl-lower alkyl and at the same time 
         R 2  is phenyl that is substituted by one or two moieties independently selected from the group consisting of lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo lower alkyl, lower alkoxy, phenoxy, piperazinyl-lower alkyl, lower-alkylpiperazinyl-lower alkyl and halo-lower alkoxy, while the other symbols Q - - - Z and W are as defined above, is included; 
         and with the proviso that if one of A, B and X is N and Y is CH 2 , then in addition or alternatively a compound of the formula I wherein 
         R 1  is halo, amino, lower alkylamino, lower alkanoylamino or lower alkoxycarbonylamino and 
         R 2  is phenyl that is substituted by two moieties independently selected from halo, halo-lower alkyl, piperazinyl-lower alkyl and lower-alkyl-piperazinyl-lower alkyl, while the other symbols Q - - - Z and W are the same as defined above ins included; 
         and a tautomer and/or a salt thereof. 
       
     
     
         21 . A compound of the formula I according to  claim 20  wherein
 R 1  is hydroxyl, lower-alkoxy-lower alkyl, lower alkylsulfonylamino, amino-lower alkylamino, N-mono- or N,N-di-(lower alkylamino-lower alkylamino, N-mono- or N,N-di-(lower alkyl)amino-carbonyl-amino, piperazinyl-lower alkylamino, N-lower alkylpiperazinyl-lower alkylamino, hydrazine, mono-, di- or tri-(lower alkyl)-substituted hydrazine; 
 R 2  is phenyl substituted by a substituent selected from the group consisting of phenoxy, piperazinyl-lower alkyl, lower-alkylpiperazinyl- lower alkyl, C 3 -C 8 -cycloalkyl-piperazinyl-lower alkyl, piperidinyl-lower alkyl, lower-alkylpiperidinyl-lower alkyl, piperidinyliden-lower alkyl, lower-alkylpiperidinyliden-lower alkyl, piperidinyloxy, lower alkylpiperidinyloxy, pyrrolidinyl, amino-pyrrolidinyl, N-mono- or N,N-di-lower alkylaminopyrrolidinyl and 9-lower alkyl-3,9-diazabicyclo[3.3.1]non-3-yl-lower alkyl, or in all cases by one of the mentioned substituents and in addition by a moiety selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy and lower alkoxy; 
 or is 2H-pyrazolyl that is unsubstituted or substituted by lower alkyl and by one or two moieties independently selected from lower alkoxyphenyl and lower alkoxyphenylphenyl; and a tautomer and/or a salt thereof. 
 
     
     
         22 . A compound of the formula I according to  claim 20  wherein & is CH 2  and R 1 , R 2 , A, B, X, Y, Q - - - Z, W and R 2  are as defined in  claim 20 , respectively;
 a tautomer and/or a salt thereof. 
 
     
     
         23 . A compound of the formula I according to  claim 20  wherein
 R 1  is hydroxyl, lower alkoxy-lower alkyl, amino-lower alkylamino, or N-mono- or N,N-di-(lower alkyl)amino-lower alkylamino, and 
 R 2  is phenyl substituted by one or two moieties independently selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lowerlakoxy or by lower alkoxy, or is 2H-pyrazolyl substituted by halophenyl oand lower alkyl; and a tautomer and/or a salt thereof. 
 
     
     
         24 . A compound of the formula I according to  claim 20  wherein
 R 1  is halo, piperazinyl-lower alkylamino or N-lower alkylpiperazinyl-lower alkylamino, and R 2  is 2H-pyrazolyl substituted by halophenyl and lower alkyl; and a tautomer and/or a salt thereof. 
 
     
     
         25 . A compound of the formula I according to  claim 20  wherein R 1  is halo, amino, lower alkylamino, lower alkanoylamino, lower alkoxycarbonylamino or hydroxyl-lower alkyl and
 R 2  is phenyl substituted by a substituent selected from the group consisting of phenoxy, piperzinyl-lower alkyl, lower-alkylpiperazinyl-lower alkyl, C 3 -C 8 -cycloalkyl-piperazinyl-lower alkyl, piperidinyl-lower alkyl, lower-alkylpiperidinyl-lower alkyl, piperidinyliden-lower alkyl, lower-alkylpiperidinyliden-lower alkyl, piperidinyloxy, lower alkylpiperidinyloxy, pyrrolidinyl, amino-pyrrolidinyl, N-mono- or N,N-di-lower alkylaminopyrrolidinyl and 9-lower alkyl-3,9-diazabicyclo[3.3.1]non-3-yl-lower alkyl, 
 or in all cases by one of the mentioned substituents and in addition by a moiety selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy and lower alkoxy; 
 or is 2H-pyrazolyl that is unsubstituted or substituted by lower alkyl and by one or two moieties independently selected from lower alkoxyphenyl and lower alkoxyphenylphenyl; 
 while the other symbols A, B, X, Y, Q - - - Z and W are as defined for formula I in  claim 20 ; 
 a tautomer and/or a salt thereof. 
 
     
     
         26 . A compound of the formula I according to  claim 20  wherein R 1  is hydroxyl-lower alkyl or lower alkoxy-lower alkyl;
 R 2  is phenyl that is substituted by one or two moieties independently selected from the group consisting of lower alkyl, C 3 -C 8 cycloalkyl, halo, halo lower alkyl, lower alkoxy, phenoxy, piperazinyl-lower alkyl, lower-alkylpiperazinyl-lower alkyl and halo-lower alkoxy, one of A, B and X is N, the other s are CH 2 ; and a tautomer and/or a salt thereof. 
 
     
     
         27 . A compound of the formula I according to  claim 20  wherein
 R 1  is halo, amino, lower alkylamino, lower alkanoylamino or lower alkoxycarbonylamino and 
 R 2  is phenyl that is substituted by two moieties independently selected from halo, halo-lower alkyl, piperzinyl-lower alkyl and lower-alkyl-piperazinyl-lower alkyl, 
 one of A, B and X is N and the others are CH 2 , and 
 Y is CH 2 ; and a tautomer and/or a salt thereof. 
 
     
     
         28 . A compound of the formula I according to  claim 20  wherein
 R1 is lower alkoxy-lower alkyl, 
 R 2  is phenyl substituted by a substituent selected from the group consisting of phenoxy, piperazinyl-lower alkyl, lower-alkylpiperazinyl-lower alkyl, C 3 -C 8 -cycloalkyl-piperazinyl-lower alkyl, piperidinyl-lower alkyl, lower-alkylpiperidinyl-lower alkyl, piperidinyliden-lower alkyl, lower-alkylpiperidinyliden-lower alkyl, piperidinyloxy, lower alkylpiperidinyloxy, pyrrolidinyl, amino-pyrrolidinyl, N-mono- or N,N-di-lower alkylaminopyrrolidinyl and 9-lower alkyl-3,9-diazabicyclo[3.3.1]non-3-yl-lower alkyl, 
 or in all cases by one of the mentioned substituents and in addition by a moiety selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy and lower alkoxy; 
 or is 2H-pyrazolyl that is unsubstituted or substituted by lower alkyl and by one or two moieties independently selected from lower alkoxyphenyl and lower alkoxyphenylphenyl; 
 or is phenyl substituted by one or two moieties independently selected from lower alkyl, C 3 -C 8 -cycloalkyl, halo, halo-lower alkyl, halo-lower alkoxy or by lower alkoxy, or is 2H-pyrazolyl substituted by halophenyl and lower alkyl; 
 Or is 2H-pyrazolyl substituted by halophenyl and lower alkyl; and a tautomer and/or salt thereof. 
 
     
     
         29 . A compound of the formula I according to  claim 20  wherein
 R 1  is lower alkoxycarbonyl or lower alkanoyl; 
 R 2  is phenyl substituted in 4-position by halo and in 3-position by halo-lower alkyl; 
 X is CH; 
 B is N; 
 Y is O; and tautomers and salts thereof. 
 
     
     
         30 . A compound of the formula I according to  claim 20  wherein W is absent. 
     
     
         31 . A compound of the formula I according to  claim 20  having the formula IB, 
       
         
           
           
               
               
           
         
         And a tautomer thereof or a pharmaceutically acceptable salt thereof. 
       
     
     
         32 . A compound of the formula I according to  claim 20 , selected from the group of compounds consisting of
 6-(6-hydroxy-pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(6-hydroxy-pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide;   6-(6-chloro-pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(6-methylamino-pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(6-amino-pyrimidin-4-ylmethyl)-naphthalene-l-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   {6-[5-(4-fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-ylmethyl]-pyrimidin-4-yl}-carbamic acid methyl ester;   6-(6-acetylamino-pyrimidin-4-ylmethyl)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   {4-[5-(4-fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidin-2-yl}-carbamic acid methyl ester;   {4-[5-(4-fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidin-2-yl}-carbamic acid isobutyl ester;   {4-(5-(4-fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidin-2-yl}-carbamic acid isobutyl ester;   6-(2-acetylamino-pyrimidin-4-yloxy)-naphthalene-l-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(2-methanesulfonylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylicacid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-[2-(3-methyl-ureido)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(2-methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-cyclopropyl-phenyl)-amide;   6-[6-(2-dimethylamino-ethylamino)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid [5-tert-butyl-2-(4-methoxy-phenyl)-2H-pyrazol-3-yl]amide;   6-[6-(2-dimethylamino-ethylamino)-pyrimidin-4-yloxy]l-naphthalene-1-carboxylic acid [5-tert-butyl-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]amide;   6-[6-(2-dimethylamino-propylamino)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid [5-tert-butyl-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]amide;   6-{6-[3-(4-methyl-piperazin-1yl)-propylamino)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid [5-tert-butyl-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]amide;   6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)phenyl-amide;   6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(1-methyl-piperidin-4-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(1-methyl-piperidin-4-ylidenemethyl)-3-trifluoromethyl-phenyl]-amide;   6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(1-methyl-piperidin-4-yloxy)-3-trifluoromethyl-phenyl]-amide;   (rac)-6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(3-dimethylamino-pyrrolidin-1-yl)-3-trifluoromethyl-phenyl]-amide;   6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(9-methyl-3,9-diaza-bicyclo[3.3.1]non-3-ylmethyl)-3-trifluoromethyl-phenyl]-amide; and   6-(6-acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-(4-cyclopropyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-(1,1-dioxido-4-thiomorpholinyl)-3-trifluoromethyl-phenyl]-amide;   6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-[[(+/−)-3-(dimethylamino)-1-pyrrolidinyl]methyl1-3-(trifluoromethyl)phenyl]-amide;   6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [3-(4-methyl-1-piperazinyl)-5-(trifluoromethyl)phenyl]-amide;   6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [3-(4-phenylmethyl-1-piperazinyl)-5-(trifluoromethyl)phenyl]-amide;   [(3S)-1-[4-[[[6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalen-1yl]carbonyl-]-amino]-2-(trifluoromethyl)phenyl]-3-piperidinyl)-carbamic acid, 1,1-dimethylethyl ester;   [(3R)-1-[4-[[[6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalen-1yl]carbonyl-]-amino]-2-(trifluoromethyl)phenyl]-3-piperidinyl]-carbamic acid, 1,1-dimethylethyl ester;   6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-[(3S)-3-amino-1-piperidinyl]-3-trifluoromethyl-phenyl)-amide;   6-(6-Acetylamino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-[(3R)-3-amino-1-piperidinyl]-3-trifluoromethyl-phenyl]-amide;   6-[6-(Cyclopropylcarbonyl)amino-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid [4-(1,1-dioxido-4-thiomorpholinyl)-3-trifluoromethyl-phenyl]-amide;   6-[6-(Cyclopropylcarbonyl)amino-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid [4-[(3R)-3-amino-1-piperidinyl]-3-trifluoromethylphenyl]-amide;   6-[[6-[(Cyclopropylcarbonyl)amino]-4-pyrimidinyl]oxy]-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-1-naphthalenecarboxamide;   4-[5-(4-Fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-2-carboxylic acid ethyl ester;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-[5-(4-tert-Butyl-phenylcarbamoyl-naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester;   6-(6-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-tert-butyl-phenyl)-amide;   6-(6-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-methyl-3-trifluoromethyl-phenyl)-amide;   a tautomer thereof and/or a pharmaceutically acceptable salt thereof.   
     
     
         33 . A compound of the formula I according to  claim 20 , selected from the group of compounds consisting of
 6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethoxy-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-isopropyl-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3,4-dimethyl-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3,5-dimethoxy-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-methyl-3-trifluoromethyl-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-tert-butyl-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-phenoxy-phenyl)-amide;   6-(2-Methoxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-tert-butyl-phenyl)-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethoxy-phenyl)-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3,5-dimethoxy-phenyl)-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-tert-butyl-phenyl)-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (3-cyclopropyl-phenyl)-amide;   6-(2-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(1-methyl-piperidin-4-yloxy)-3-trifluoromethyl-phenyl]-amide;   6-[5-(4-Fluoro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-[5-(3-trifluoromethoxy-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethoxy-phenyl)-amide;   6-[5-(4-Methyl-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]l-pyrimidine-4-carboxylic acid ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (4-methyl-3-trifluoromethyl-phenyl)-amide;   6-[5-(3,5-dimethoxy-phenylcarbamoyl)-naphthalen-2-yloxyπ-pyrimidine-4-carboxylic acid ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3,5-dimethoxy-phenyl)-amide;   6-[5-(3-tert-Butyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-4-carboxylic add ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-tert-butyl-phenyl-phenyl)-amide;   6-[5-(3-Cyclopropyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-cyclopropyl-phenyl -phenyl)-amide;   6-{5-[4-(4-Methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenylcarbamoyl]-naphthalen-2-yloxy}-pyrimidine-4-carboxylic acid ethyl ester;   6-(6-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   6-{5-[4-(1-Methyl-piperidin-4-yloxy)-3-trifluoromethyl-phenylcarbamoyl]-naphthalen-2-yloxy}-pyrimidine-4-carboxylic acid ethyl ester,   6-(6-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [4-(1-methyl-piperidin-4-yloxy)-3-trifluoromethyl-phenyl]-amide;   6-{5-[3-(1,1-Difluoro-ethyl)-phenylcarbamoyl]-naphthalen-2-yloxy}-pyrimidine-4-carboxylic acid ethyl ester;   6-(6-Hydroxymethyl-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid [3-(1,1-difluoro-ethyl)-phenyl]-amide;   6-[5-(4-Chloro-3-trifluoromethyl-phenylcarbamoyl)-naphthalen-2-yloxy]-pyrimidine-4-carboxylic acid ethyl ester;   6-(4-Hydroxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (4-chloro-3-trifluoromethyl-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethoxy-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3,5-dimethoxy-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-tert-butyl-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (3-cyclopropyl-phenyl)-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid [4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid [4-(1-methyl-piperidin-4-yloxy)-3-trifluoromethyl-phenyl]-amide;   6-(4-Methoxymethyl-pyrimidin-6-yloxy)-naphthalene-1-carboxylic acid (4-tert-butyl-phenyl)-amide;   or a tautomer thereof and/or a pharmaceutically acceptable salt thereof.   
     
     
         34 . A pharmaceutical preparation comprising a compound of the formula I, a tautomer and/or a salt thereof according to  claim 20  and at least one pharmaceutically acceptable carrier material.