Phenylacetamides suitable as protein kinase inhibitors

Abstract

The invention relates to compounds of the formula I, wherein the moieties R1, R2, R3, R9, R10 and Q and X, Y and Z are as defined in the specification, and salts thereof; as well as their use, methods of use for them and methods of their synthesis, and the like. The compounds are protein kinase inhibitors and can, inter alia, be used in the treatment of various proliferative diseases.

1 . A compound of the formula I, 
       
         
           
           
               
               
           
         
         wherein 
         each of R1 and R2, independently of the other, is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl; 
         R3 is absent if Z is nitrogen or, if Z is C (carbon), is hydrogen, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; 
         X is N (nitrogen) or CH (hydrogen-substituted carbon), 
         Y is CH or N, 
         Z is C or N, and 
         Q is a moiety of the formula (A) 
       
       
         
           
           
               
               
           
         
         
           wherein 
           R4 is hydrogen, halo, unsubstituted or substituted amino, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl bound via a ring atom other than nitrogen, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl or unsubstituted or substituted alkynyl; 
           R5 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted amino, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; and 
           R6 is hydrogen, unsubstituted or substituted cycloalkyl or unsubstituted or (preferably) substituted alkyl; 
         
         or a moiety of the formula (B) 
       
       
         
           
           
               
               
           
         
         
           wherein 
           R7 is unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl and 
           R8 is alkyl or cycloalkyl; 
         
         where the asterisk * in formulae (A) and (B) marks the bond through which the moiety is bound to the NH of the amide group in formula I; and 
         (a) each of R9 and R10, independently of the other, is selected from the group consisting of hydrogen, hydroxyl and C 1 -C 7 -alkyl; or 
         (b) R9 and R10 together represent oxo; or 
         R1 and R9 together form a group —C(O)—CH2- or —CH2-CH2-, R2 is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl, and R10 represents hydrogen; 
         or a salt thereof. 
       
     
     
         2 . A compound of the formula I according to  claim 1  wherein
 each of R1 and R2, independently of the other, is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl; 
 R3 is absent if Z is nitrogen or, if Z is C (carbon), is hydrogen, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; 
 R9 and R10 both represent hydrogen; and 
 X is N (nitrogen) or CH (hydrogen-substituted carbon), 
 Y is CH or N, 
 Z is C or N, 
 and 
 Q is a moiety of the formula (A) wherein
 R4 is hydrogen, halo, unsubstituted or substituted amino, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl bound via a ring atom other than nitrogen, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl or unsubstituted or substituted alkynyl; 
 R5 is hydrogen, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; and 
 R6 is unsubstituted or substituted cycloalkyl or unsubstituted or (preferably) substituted alkyl; 
 
 or a moiety of the formula (B) wherein
 R7 is unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl and 
 R8 is alkyl or cycloalkyl; 
 
 where the asterisk * in formulae (A) and (B) marks the bond through which the moiety is bound to the NH of the amide group in formula I; 
 or a salt thereof. 
 
     
     
         3 . A compound of the formula I according to  claim 2  wherein
 each of R1 and R2, independently of the other, is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl; 
 R3 is absent if Z is nitrogen or, if Z is C (carbon), is hydrogen or unsubstituted or substituted aryl; 
 R9 and R10 both represent hydrogen; 
 X is N or CH, 
 Y is CH; 
 Z is C or N 
 and 
 Q is a moiety of the formula (A)
 wherein R4 is hydrogen, halo, unsubstituted or substituted amino, unsubstituted or substituted aryl, unsubstituted or substituted alkyl or unsubstituted or substituted alkynyl; 
 R5 is hydrogen or unsubstituted or substituted aryl; and 
 R6 is unsubstituted or preferably substituted alkyl; 
 
 or a moiety of the formula (B)
 wherein 
 R7 is unsubstituted or substituted aryl and 
 R8 is alkyl; 
 
 or a salt thereof. 
 
     
     
         4 . A compound of the formula I according to any one of  claims 1  to  3  wherein, as far as mentioned in any one of said claims or in the present claim, wherein
 the term “lower” or “C 1 -C 7 -” defines a moiety with up to and including maximally 7, especially up to and including maximally 4, carbon atoms, said moiety being branched (one or more times) or straight-chained and bound via a terminal or a non-terminal carbon; 
 halo or halogen is preferably fluoro, chloro, bromo or iodo; 
 in unsubstituted or substituted aryl, aryl is preferably an unsaturated carbocyclic system of not more than 20 carbon atoms, especially not more than 16 carbon atoms, is preferably mono-, bi- or tri-cyclic, and is unsubstituted or, as substituted aryl, substituted preferably by one or more, preferably up to three, e.g. one or two substituents independently selected from the group consisting of phenyl, naphthyl, phenyl- or naphthyl-lower alkyl, hydroxy-lower alkyl, lower-alkoxy-lower alkyl, (lower-alkoxy)-lower alkoxy-lower alkyl, lower alkanoyl-lower alkyl, halo-lower alkyl, phenoxy- or naphtyloxy-lower alkyl, phenyl- or naphthyl-lower alkoxy-lower alkyl, lower alkoxy-carbonyloxy-lower alkyl, phenyl- or naphthyl-lower alkoxycarbonyloxy-lower alkyl, cyano-lower alkyl, lower alkenyl, lower alkynyl, lower alkanoyl, hydroxy, lower alkoxy, lower-alkoxy-lower alkoxy, (lower-alkoxy)-lower alkoxy-lower alkoxy, phenoxy, naphthyloxy, phenyl- or naphthyl-lower alkoxy, amino-lower alkoxy, lower-alkanoyloxy, benzoyloxy, naphthoyloxy, nitro, amino, mono-di-substituted amino wherein the amino substituents are independently selected from lower alkyl, lower alkanoyl, phenyl, naphthyl, phenyl- and naphthyl-lower alkyl; cyano, carboxy, lower alkoxy carbonyl, phenyl- or naphthyl-lower alkoxycarbonyl, lower alkanoyl, benzoyl, naphthoyl, carbamoyl, N-mono- or N,N-disubstituted carbamoyl, wherein the substitutents are selected from lower alkyl and hydroxy-lower alkyl; amidino, guanidino, ureido, mercapto, lower alkylthio, phenyl- or naphthylthio, phenyl- or naphthyl-lower alkylthio, lower alkyl-phenylthio, lower alkyl-naphthylthio, halogen-lower alkylmercapto, lower alkylsulfinyl, phenyl- or naphthyl-sulfinyl, phenyl- or naphthyl-lower alkylsulfinyl, lower alkyl-phenylsulfinyl, lower alkyl-napthylsulfinyl, sulfo, lower alkanesulfonyl, phenyl- or naphthyl-sulfonyl, phenyl- or naphthyl-lower alkylsulfonyl, alkylphenylsulfonyl, halogen-lower alkyl-sulfonyl, sulfonamido and benzosulfonamido; where each phenyl or naphthyl (also in phenoxy or naphthoxy) mentioned above as substitutent or part of a substituent of substituted aryl is itself unsubstituted or substituted by one or more substituents independently selected from halo, halo-lower alkyl, hydroxy, lower alkoxy, amino, N-mono- or N,N-di-(lower alkyl, phenyl, naphthyl, phenyl-lower alkyl and/or naphthyl-lower alkyl)-amino, nitro, carboxy, lower-alkoxycarbonyl carbamoyl, cyano and/or sulfamoyl; 
 in unsubstituted or substituted heterocyclyl, heterocyclyl is preferably a heterocyclic radical that is unsaturated, saturated or partially saturated and is preferably a monocyclic or in a broader aspect of the invention bicyclic or tricyclic ring; and has 3 to 24, more preferably 4 to 16, most preferably 4 to 10 ring atoms; wherein one or more, preferably one to four, especially one or two carbon ring atoms are replaced by a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, the bonding ring preferably having 4 to 12, especially 5 to 7 ring atoms; where heterocyclyl is unsubstituted or substituted by one or more substituents independently selected from the group consisting of the substituents defined above under “substituted aryl”; where heterocyclyl is especially a heterocyclyl radical selected from the group consisting of oxiranyl, azirinyl, aziridinyl, 1,2-oxathiolanyl, thienyl, furyl, tetrahydrofuryl, pyranyl, thiopyranyl, thianthrenyl, isobenzofuranyl, benzo-furanyl, chromenyl, 2H-pyrrolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolidinyl, benzimidazolyl, pyrazolyl, pyrazinyl, pyrazolidinyl, thiazolyl, isothiazolyl, dithiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, piperidyl, piperazinyl, pyridazinyl, morpholinyl, thiomorpholinyl, (S-oxo or S,S-dioxo)-thiomorpholinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, benzimidazolyl, cumaryl, indazolyl, triazolyl, tetrazolyl, purinyl, 4H-quinolizinyl, isoquinolyl, quinolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, octahydroisoquinolyl, benzofuranyl, dibenzofuranyl, benzothiophenyl, dibenzothiophenyl, phthalazinyl, naphthyridinyl, quinoxalyl, quinazolinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, furazanyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromenyl, isochromanyl and chromanyl, each of which is unsubstituted or substituted by one to two radicals selected from the group consisting of lower alkyl, lower alkoxy and halo, where in the case of R4, unsubstituted or substituted heterocyclyl is not bound via a ring atom other than a ring nitrogen in order to avoid overlap with the definition of substituted amino; 
 in unsubstituted or substituted cycloalkyl, cycloalkyl is preferably a saturated mono- or bicyclic hydrocarbon group with 3 to 16, more preferably 3 to 9 ring carbon atoms, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl, and is substituted by one or more, preferably one to three, substitutents independently selected from those described for substituted aryl or is unsubstituted; 
 unsubstituted or substituted amino is either amino (—NH 2 ) or amino in which one or both hydrogen atoms are replaced by a substituent independently selected from unsubstituted or substituted alkyl as described below, unsubstituted or substituted aryl as described above, unsubstituted or substituted heterocyclyl as described above, unsubstituted or substituted cycloalkyl as described above, and/or acyl as described below, or substituted amino in the form of an unsubstituted or substituted heterocyclyl as defined above with at least one nitrogen ring atom which is bound via ring nitrogen atom to the rest of the molecule, especially selected from the group consisting of aziridinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolidinyl, benzimidazolyl, pyrazolyl, pyrazinyl, pyrazolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, (S-oxo or S,S-dioxo)-thiomorpholinyl, isoindolyl, indolyl, benzimidazolyl, triazolyl, tetrazolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, decahydroquinolyl, octahydroisoquinolyl, preferably a monocyclic saturated heterocyclyl with at least one nitrogen atom from those just mentioned; where said heterocyclyl is unsubstituted or substituted by one or more radicals independently selected from those mentioned as substituents for substituted aryl, preferably from the group consisting of lower alkyl, lower alkoxy and halo; where as unsubstituted or substituted amino the following moieties are especially preferred: amino, N-mono- or N,N-di-[lower alkyl, N-mono- or N,N-di-(lower alkyl, phenyl and/or phenyl-lower alkyl)-amino-lower alkyl, (unsubstituted or lower alkyl-substituted)-piperidinyl, phenyl and/or phenyl-lower alkyl]-amino, N—[(N-mono- or N,N-di-(C 1 -C 7 -alkyl)-amino)-C 1 -C 7 -alkyl]-N-(unsubstituted or C 1 -C 7 -alkyl)-amino, N-piperidinylamino or N-lower alkyl-N-piperidin-ylamino wherein piperidinyl is unsubstituted or substituted by lower alkyl, pyrrolidino, piperidino, piperazino, 4-lower alkylpiperazino, morpholino or thiomorpholino; 
 unsubstituted or substituted alkyl is preferably C 1 - to C 20 -alkyl, more preferably lower alkyl, that can be linear or branched one or more times (provided the number of carbon atoms allows this) and that is unsubstituted or substituted by one or more, preferably up to three, substitutents independently selected from the group consisting of unsubstituted or substituted heterocyclyl as described above, unsubstituted or substituted cycloalkyl as described above, unsubstituted or substituted aryl as defined above, especially phenyl or naphthyl; lower alkenyl, lower alkynyl, lower alkanoyl, hydroxy, lower alkoxy, lower-alkoxy-lower alkoxy, (lower-alkoxy)-lower alkoxy-lower alkoxy, phenoxy, naphthyloxy, phenyl- or naphthyl-lower alkoxy, amino-lower alkoxy, lower-alkanoyloxy, benzoyloxy, naphthoyloxy, nitro, cyano, carboxy, lower alkoxy carbonyl, phenyl- or naphthyl-lower alkoxycarbonyl, lower alkanoyl, benzoyl, naphthoyl, carbamoyl, N-mono- or N,N-disubstituted carbamoyl wherein the substitutents are selected from lower alkyl and hydroxy-lower alkyl; amidino, guanidino, ureido, mercapto, lower alkylthio, phenyl- or naphthylthio, phenyl- or naphthyl-lower alkylthio, lower alkyl-phenylthio, lower alkyl-naphthylthio, halogen-lower alkylmercapto, lower alkylsulfinyl, phenyl- or naphthyl-sulfinyl, phenyl- or naphthyl-lower alkylsulfinyl, lower alkyl-phenylsulfinyl, lower alkyl-napthylsulfinyl, sulfo, lower alkanesulfonyl, phenyl- or naphthyl-sulfonyl, phenyl- or naphthyl-lower alkylsulfonyl, alkylphenyl-sulfonyl, halogen-lower alkylsulfonyl, sulfonamido, benzolsulfonamido, amino, N-mono- or N,N-di-[lower alkyl, piperidinyl, N-lower alkylpiperidin-yl wherein piperidinyl is unsubstituted or substituted by lower alkyl, N-mono- or N,N-di-(lower alkyl, phenyl and/or phenyl-lower alkyl)-amino]-lower alkyl, phenyl and/or phenyl-lower alkyl)-amino, pyrrolidino, piperidino, unsubstituted or N-lower alkyl substituted piperidinyl bound via a ring carbon atom, piperazino, 4-lower alkylpiperazino, morpholino or thiomorpholino; where each phenyl or naphthyl (also in phenoxy or naphthoxy) mentioned above as substituent or part of a substituent of substituted alkyl is itself unsubstituted or substituted by one or more substituents independently selected from halo, halo-lower alkyl, hydroxy, lower alkoxy, amino, N-mono- or N,N-di-(lower alkyl, phenyl, naphthyl, phenyl-lower alkyl and/or naphthyl-lower alkyl)amino, nitro, carboxy, lower-alkoxycarbonyl carbamoyl, cyano and/or sulfamoyl; especially preferred as unsubstituted or substituted alkyl are lower alkyl, halo-lower alkyl, amino-lower alkyl, N-mono- or N,N-di-(lower alkyl, piperidinyl, N-lower alkylpiperidinyl, phenyl and/or phenyl-lower alkyl)-amino-lower alkyl, pyrrolidino-lower alkyl, piperidino-lower alkyl, 1-lower alkylpiperidin-4-yl-lower alkyl, piperazino-lower alkyl, 4-lower alkylpiperazino-lower alkyl or (morpholino or thiomorpholino)-lower alkyl; 
 acyl is an organic moiety selected from unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl or unsubstituted or substituted cycloalkyl, each preferably as described above, bound via a carbonyl (—C(═O)—) or sulfonyl (—S(═O) 2 —) group to the rest of the molecule, that is, a moiety derived from an organic carboxylic or sulfonic acid; where alkanoyl, especially lower alkanoyl, e.g. acetyl, benzoyl, naphthoyl, phenyl-C 1 -C 7 -alkylcarbonyl, naphthyl-C 1 -C 7 -alkylcarbonyl, phenylsulfonyl or lower alkanesulfonyl are especially preferred; and where each lower alkanoyl as acyl or each phenyl or naphthyl mentioned as part of acyl are unsubstituted or substituted by one or more substituents independently selected from halo, halo-lower alkyl, hydroxy, lower alkoxy, amino, N-mono- or N,N-di-(lower alkyl, phenyl, naphthyl, phenyl-lower alkyl or naphthyl-lower alkyl)amino, nitro, carboxy, lower-alkoxycarbonyl, carbamoyl, cyano and/or sulfamoyl; and where lower alkanoyl, benzoyl, phenylsulfonyl or tolylsulfonyl is very preferred; 
 in unsubstituted or substituted alkenyl, alkenyl has one or more double bonds and preferably has 2 to 20, more preferably up to 12, carbon atoms; and is linear or can be branched one or more times; preferred is C 2 -C 7 -alkenyl, especially C 3  or C 4 -alkenyl, such as allyl or crotyl; and alkenyl can be unsubstituted or substituted by one or more of the substituents mentioned above as substitutents for substituted alkyl, with the proviso that N, S or O with an active hydrogen is preferably not bound at a carbon atom from which a double bond emerges; where unsubstituted alkenyl, in particular C 2 -C 7 -alkenyl, is particularly preferred; 
 unsubstituted or substituted alkynyl is a moiety with one or more triple bonds and preferably has 2 to 20, more preferably up to 12, carbon atoms; it is linear or can be branched one or more times; where C 2 -C 7 -alkynyl, especially C 3  or C 4 -alkynyl, such as ethynyl or propyn-2-yl is especially preferred; and where alkynyl can be unsubstituted or substituted by one or more of the substituents mentioned above for substituted alkyl; where substituents such as amino or hydroxy (with free dissociable hydrogen) preferably are not bound to carbon atoms that participate at a triple bond; where especially unsubstituted alkynyl, in particular C 2 -C 7 -alkynyl, or N,N-di-(lower alkyl, phenyl and/or phenyl lower alkyl)-C 3 -C 7 -alkynyl is preferred. 
 
     
     
         5 . A compound of the formula I according to  claim 2 , wherein
 R1 is hydrogen, halo, especially chloro, or C 1 -C 7 -alkyl,   R2 is hydrogen, halo, especially chloro, or C 1 -C 7 -alkyl,   R3 is absent if Z is nitrogen or, if Z is C, is hydrogen, phenyl that is unsubstituted or substituted by one or more moieties independently selected from C 1 -C 7 -alkyl, halo, hydroxy, C 1 -C 7 -alkoxy and cyano,   R9 and R10 both represent hydrogen,   X is N or CH,   Y is CH,   Z is C or N,   Q is a moiety of the formula (A) wherein   R4 is hydrogen, halogen, especially iodo, phenyl that is unsubstituted or substituted by one or more moieties independently selected from C 1 -C 7 -alkyl, halo, hydroxy, C 1 -C 7 -alkoxy and cyano; N,N-di-(C 1 -C 7 -alkyl)-amino-C 1 -C 7 -alkyl, N—[(N-mono- or N,N-di-(C 1 -C 7 -alkyl)-amino)-C 1 -C 7 -alkyl]N—C 1 -C 7 -alkylamino, pyrrolidino, piperidino, piperazino, 4-C 1 -C 7 -alkylpiperazino, morpholino, thiomorpholino, pyrrolidino-C 1 -C 7 -alkyl, piperidino-C 1 -C 7 -alkyl, piperazino-C 1 -C 7 -alkyl, 4-C 1 -C 7 -alkylpiperazino-C 1 -C 7 -alkyl, morpholino-C 1 -C 7 -alkyl, thiomorpholino-C 1 -C 7 -alkyl, N-piperidin-(2, 3 or 4)-yl-amino, N—C 1 -C 7 -alkyl-N-piperidin-ylamino wherein piperidinyl is bound via a ring carbon and is unsubstituted or substituted by lower alkyl, or N,N-di-(lower alkyl, phenyl and/or phenyl lower alkyl)-C 3 -C 7 -alkynyl;   R5 is hydrogen or phenyl that is unsubstituted or substituted by one or more moieties independently selected from C 1 -C 7 -alkyl, halo, hydroxy, C 1 -C 7 -alkoxy and cyano; and   R6 is C 1 -C 7 -alkyl, C 3 -C 8 -cycloalkyl or halo-C 1 -C 7 -alkyl, preferably trifluoromethyl, or a moiety of the formula (B) wherein   R7 is phenyl that is unsubstituted or substituted by one or more moieties independently selected from C 1 -C 7 -alkyl, halo, hydroxy, C 1 -C 7 -alkoxy and cyano; and   R8 is C 3 -C 8 cycloalkyl or especially C 1 -C 7 -alkyl, preferably isobutyl;   or a (preferably pharmaceutically acceptable) salt thereof.   
     
     
         6 . A compound of the formula I according to any one of  claims 2  to  5 , wherein
 R1 is hydrogen, 
 R2 is hydrogen or halo, especially chloro, 
 R3 is absent if Z is nitrogen or, if Z is C, is hydrogen, phenyl that is unsubstituted or substituted by C 1 -C 7 -alkoxy, e.g. methoxy, 
 R9 and R10 both represent hydrogen, 
 X is N or CH, 
 Y is CH, 
 Z is C or N, 
 Q is a moiety of the formula (A) wherein 
 R4 is hydrogen, halogen, especially iodo, phenyl that is unsubstituted or substituted by halo, e.g. chloro or bromo, or cyano; N—[(N-mono- or N,N-di-(C 1 -C 7 -alkyl)-amino)-C 1 -C 7 -alkyl]-N—C 1 -C 7 -alkylamino, such as N-3-[N—(N,N-dimethylamino)-propyl-N-methyl-amino, N-2-[N—(N,N-dimethylamino)-ethyl-N-methyl-amino or N—(N,N-dimethylamino)-methyl-N-methyl-amino, pyrrolidino-C 1 -C 7 -alkyl, such as pyrrolidinomethyl, piperidino-C 1 -C 7 -alkyl, such as piperidinomethyl, piperazino-C 1 -C 7 -alkyl, 4-C 1 -C 7 -alkylpiperazino-C 1 -C 7 -alkyl, such as 4-methyl-, 4-ethyl- or 4-isopropyl-piperazino-C 1 -C 7 -alkyl, N—C 1 -C 7 -alkyl-N-piperidin-ylamino wherein piperidinyl is bound via a ring carbon and is unsubstituted or substituted by lower alkyl, e.g. N-lower alkyl-N-(1-lower alkylpiperidin-(2, 3 or preferably 4)-yl)-amino, or N,N-di-(lower alkyl, phenyl and/or phenyl lower alkyl)-C 3 -C 7 -alkynyl, such as 3-(N,N-dimethylamino)-prop-1-ynyl; 
 R5 is hydrogen or phenyl that is unsubstituted or substituted by C 1 -C 7 -alkoxy, e.g. methoxy, and 
 R6 is halo-C 1 -C 7 -alkyl, preferably trifluoromethyl, 
 or a moiety of the formula (B) wherein 
 R7 is phenyl that is unsubstituted or substituted by C 1 -C 7 -alkyl, e.g. methyl; and 
 R8 is C 1 -C 7 -alkyl, preferably isobutyl; 
 or a (preferably pharmaceutically acceptable) salt thereof. 
 
     
     
         7 . A compound of the formula I according to claim I wherein
 each of R1 and R2, independently of the other, is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl;   R3 is absent if Z is nitrogen or, if Z is C (carbon), is hydrogen or unsubstituted or substituted aryl;   X is N (nitrogen) or CH (hydrogen-substituted carbon),   Y is CH,   Z is C or N, and   Q is a moiety of the formula (A) wherein
 R4 is hydrogen, halo, unsubstituted or substituted amino, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl bound via a ring atom other than nitrogen, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl or unsubstituted or substituted alkynyl; 
 R5 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted amino, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; and 
 R6 is hydrogen, unsubstituted or substituted cycloalkyl or unsubstituted or (preferably) substituted alkyl; 
   or a moiety of the formula (B) wherein
 R7 is unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl and 
 R8 is alkyl or cycloalkyl; 
   where the asterisk * in formulae (A) and (B) marks the bond through which the moiety is bound to the NH of the amide group in formula I; and   (a) each of R9 and R10, independently of the other, is selected from the group consisting of hydrogen, hydroxyl and C 1 -C 7 -alkyl; or   (b) R9 and R10 together represent oxo; or   R1 and R9 together form a group —C(O)—CH2- or —CH2-CH2-, R2 is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl, and R10 represents hydrogen;   or a salt thereof.   
     
     
         8 . A compound of the formula I according to claim I wherein
 each of R1 and R2, independently of the other, is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl;   R3 is absent if Z is nitrogen or, if Z is C (carbon), is hydrogen or unsubstituted or substituted aryl;   X is N (nitrogen) or CH (hydrogen-substituted carbon),   Y is CH,   Z is C or N, and   Q is a moiety of the formula (A) wherein
 R4 is hydrogen, halo, unsubstituted or substituted amino, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl bound via a ring atom other than nitrogen, unsubstituted or substituted alkyl or unsubstituted or substituted alkynyl; 
 R5 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted amino, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; and 
 R6 is hydrogen or substituted alkyl; 
   or a moiety of the formula (B) wherein
 R7 is unsubstituted or substituted aryl and 
 R8 is alkyl or cycloalkyl; 
   where the asterisk * in formulae (A) and (B) marks the bond through which the moiety is bound to the NH of the amide group in formula I; and   (a) each of R9 and R10, independently of the other, is selected from the group consisting of hydrogen, hydroxyl and C 1 -C 7 -alkyl; or   (b) R9 and R10 together represent oxo; or   R1 and R9 together form a group —C(O)—CH2- or —CH2-CH2-, R2 is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl, and R10 represents hydrogen;   or a salt thereof.   
     
     
         9 . A compound of the formula I according to claim I wherein
 each of R1 and R2, independently of the other, is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl;   R3 is absent if Z is nitrogen or, if Z is C (carbon), is hydrogen or unsubstituted or substituted aryl;   X is N (nitrogen) or CH (hydrogen-substituted carbon),   Y is CH,   Z is C or N, and   Q is a moiety of the formula (A) wherein
 R4 is hydrogen, halo, unsubstituted or substituted amino, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl bound via a ring atom other than nitrogen, unsubstituted or substituted alkyl or unsubstituted or substituted alkynyl; 
 R5 is hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted amino, unsubstituted or substituted aryl or unsubstituted or substituted heterocyclyl; and 
 R6 is hydrogen or substituted alkyl; 
   or a moiety of the formula (B) wherein
 R7 is unsubstituted or substituted aryl and 
 R8 is alkyl or cycloalkyl; 
   where the asterisk * in formulae (A) and (B) marks the bond through which the moiety is bound to the NH of the amide group in formula I; and   (a) each of R9 and R10, independently of the other, is selected from the group consisting of hydrogen, hydroxyl and C 1 -C 7 -alkyl; or   (b) R9 and R10 together represent oxo; or   R1 and R9 together form a group —C(O)—CH2- or —CH2-CH2-, R2 is selected from the group consisting of hydrogen, halo and C 1 -C 7 -alkyl, and R10 represents hydrogen;   or a salt thereof.   
     
     
         10 . A compound of the formula I, selected from the group of compounds consisting of
 2-(4-imidazo[4,5-c]pyridin-1-yl-phenyl)-N-(3-trifluoromethyl-phenyl]-acetamide;   2-(4-imidazo[4,5-c]pyridin-1-yl-phenyl)-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   N-(3′-chloro-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-c]pyridin-1-yl-phenyl)-acetamide;   N-(3′-bromo-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-c]pyridin-1-yl-phenyl)-acetamide;   N-{4-[(3-dimethylamino-propyl)-methyl-amino]-3-trifluoromethyl-phenyl}-2-(4-imidazo[4,5-c]pyridin-1-yl-phenyl)-acetamide;   N-{4-[(2-dimethylamino-ethyl)-methyl-amino]-3-trifluoromethyl-phenyl}-2-(4-imidazo[4,5-c]pyridin-1-yl-phenyl)-acetamide;   N-(3′-bromo-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide;   2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   N-[4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide;   2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-[4-(4-isopropyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   N-{4-[(3-dimethylamino-propyl)-methyl-amino]-3-trifluoromethyl-phenyl}-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide;   2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4-iodo-3-trifluoromethyl-phenyl)-acetamide;   N-(4′-cyano-2-trifluoromethyl-biphen-4-yl)-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide;   2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-(4′-methoxy-5-trifluoromethyl-biphen-3-yl)-acetamide;   2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-{4-[methyl-(1-methyl-piperidin-4-yl)-amino]-3-trifluoromethyl-phenyl}-acetamide;   2-(2-chloro-4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-[4-(4-isopropyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   2-(2-chloro-4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   2-(2-chloro-4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-[4-(4-ethyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   2-(2-chloro-4-imidazo[4,5-b]pyridin-3-yl-phenyl)-N-{4-[(3-dimethylamino-propyl)-methyl-amino]-3-trifluoromethyl-phenyl}-acetamide;   2-(4-benzoimidazol-1-yl-phenyl)-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   2-(4-benzoimidazol-1-yl-phenyl)-N-{4-[methyl-(1-methyl-piperidin-4-yl)-amino]-3-trifluoromethyl-phenyl}-acetamide;   2-(4-benzoimidazol-1-yl-phenyl)-N-{4-[(3-dimethylamino-propyl)-methyl-amino]-3-trifluoromethyl-phenyl}-acetamide;   2-(4-benzoimidazol-1-yl-phenyl)-N-{4-[(2-dimethylamino-ethyl)-methyl-amino]-3-trifluoromethyl-phenyl}-acetamide;   2-(4-benzoimidazol-1-yl-phenyl)-N-(4′-cyano-2-trifluoromethyl-biphen-4-yl)-acetamide;   2-{4-[5-(4-methoxy-phenyl)-benzoimidazol-1-yl]-phenyl}-N-[4-(4-methyl-piperazin-1-ylmethyl)-3-trifluoromethyl-phenyl]-acetamide;   N-[4-(3-dimethylamino-prop-1-ynyl)-3-trifluoromethyl-phenyl]-2-(4-imidazo[4,5-b]pyridin-3-yl-phenyl)-acetamide and   N-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-2-(4-imidazo[4,5-b]pyridine-3-yl-phenyl)-acetamide, or a salt thereof.   
     
     
         11 . A pharmaceutically acceptable salt of a compound of the formula I according to any one of  claims 1  to  10 . 
     
     
         12 . A pharmaceutical preparation comprising at least a compound of the formula I, or a pharmaceutically acceptable salt thereof, according to any one of  claims 1  to  11  and a pharmaceutically acceptable carrier material. 
     
     
         13 . The pharmaceutical preparation according to  claim 12  for the treatment of a disease that responds to modulation of one or more protein kinases, especially at least one selected from the group consisting of tie-2 and/or more especially PDGFR, VEGFR-2, c-Abl, Flt3, Ret and kit, as well as aberrant forms thereof, such as mutant forms, or allelic variants. 
     
     
         14 . A compound of the formula I, or a pharmaceutically acceptable salt thereof, according to any one of  claims 1  to  11  for use in the diagnostic or therapeutic treatment of an animal, preferably a warm-blooded animal, especially a human. 
     
     
         15 . A compound of the formula I, or a pharmaceutically acceptable salt thereof, according to any one of  claims 1  to  11  for use in the treatment of an animal, preferably a warm-blooded animal, especially a human, that suffers from a disease that respond to modulation, especially inhibition, of one or more tyrosine kinases, especially at least one selected from the group consisting of tie-2 and/or more especially PDGFR, VEGFR-2, c-Abl, Flt3, Ret and kit, as well as aberrant forms thereof, such as mutant forms, or allelic variants. 
     
     
         16 . The use of a compound of the formula I, or a pharmaceutically acceptable salt thereof, according to any one of  claims 1  to  11 , in the treatment or in the manufacture of a medicament for the treatment of a disease that responds to modulation of one or more protein kinases, especially at least one selected from the group consisting of tie-2 and/or more especially PDGFR, VEGFR-2, c-Abl, Flt3, Ret and kit, as well as aberrant forms thereof, such as mutant forms, or allelic variants. 
     
     
         17 . The use, especially according to  claim 16 , of a compound of the formula I, or a pharmaceutically acceptable salt thereof, according to any one of  claims 1  to  11 , in the treatment or in the manufacture of a medicament for the treatment of one or more diseases selected from the group consisting of leukemias, especially chronic myelogenous leukaemia, acute myeloid leukemia, acute myeloid leukemia, with trilineage myelodysplasia, acute lymphoblastic leukemia, myelodysplastic syndrome, mixed-lineage leukemia; different (especially primary, but also derived) solid tumors (including benign or especially malign types), preferably sarcoma, gastrointestinal stromal tumors, seminoma, carcinoids, mast cell tumors, lung carcinomas, bronchial carcinomas, seminomas, dysgerminomas, testicular intraepithelial neoplasias, melanomas, mamma carcinomas, neuroblastomas, papillary/follicular thyroid carcinoma, malign lymphomas, Non Hodgkin's lymphoma, multiple endocrine neoplasia type 2, pheochromocytoma, thyroid carcinoma, parathyroid hyperplasia/adenoma, mamma carcinoma, colon cancer, colorectal adenoma, ovarian cancer, prostate carcinoma, glioblastoma, brain tumors, prostate carcinoma (including adenocarcinomas and bone metastasis), malign gliomes, (anaplastic astrocytomas/glioblastomas, pancreatic cancer, malignant pleural mesothelioma, haemangioblastoma, haemangioma, carcinoma of the kidney, liver, adrenal gland, bladder, stomach (especially gastric tumors), rectum, vagina, cervix, endometrium, multiple myeloma, tumors of the neck and head, including neoplasias, especially of epithelial character, malignant nephrosclerosis; other hyperplasias or proliferative diseases, especially mastocytosis, associated myeloproliferative syndrome, Urticaria Pigmentosa, an epidermal hyperproliferation, especially psoriasis; prostate hyperplasia; inflammatory diseases, especially rheumatoid or rheumatic inflammatory diseases, preferably arthritis, more preferably rheumatoid arthritis, other chronic inflammatory disorders, especially chronic asthma, arterial or post-transplantational atherosclerosis, other diseases associated with deregulated angiogenesis, especially fibrosis (preferably pulmonary, but also other types of fibrosis, especially renal fibrosis), angiogenesis, smooth muscle proliferation in the blood vessels, especially stenosis orrestenosis following angioplasty; retinopathies, macula degeneration, other eye diseases, especially diabetic retinopathy or neovascular glaucoma; renal diseases, especially glomerulonephritis; diabetic nephropathy; inflammatory bowel disease, especially Crohn's disease, thrombotic microangiopathic syndromes; transplant rejections or glomerulopathy; fibrotic diseases, especially cirrhosis of the liver; mesangial cell-proliferative diseases and injuries of the nerve tissue; and/or from diseases that respond to the effect of said compound or pharmaceutically acceptable salts as immunosuppressants, as an aid in scar-free wound healing, and for treating age spots and contact dermatitis. 
     
     
         18 . A method of treatment of a disease or disorder that depends on (especially inappropriate) or protein kinase activity or responds to modulation, especially inhibition, of such a protein kinase, especially the disorders or diseases mentioned in  claim 17 , comprising administering a prophylactically or especially therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, according to any one of  claims 1  to  8  to an animal, especially a warm-blooded animal, more especially a human, that, on account of one or more of the mentioned diseases, is in need of such treatment. 
     
     
         19 . A process for the manufacture of a compound of the formula I, or a salt thereof, according to  claim 1  or  2 , comprising reacting a carboxylic acid compound of the formula II, 
       
         
           
           
               
               
           
         
         or a reactive derivative thereof, wherein R1, R2, R3, R9 (if present), R10 (if present), X, Y and Z are as defined for a compound of the formula I, 
         with an amino compound of the formula III,
   Q-NH 2   (III)
 
 
         wherein Q is as defined for a compound of the formula I, 
         and, if desired, transforming an obtainable compound of formula I into a different compound of formula I, transforming a salt of an obtainable compound of formula I into the free compound or a different salt, transforming an obtainable free compound of formula I into a salt thereof, and/or separating an obtainable mixture of isomers of a compound of formula I into individual isomers; 
         where in any one or both starting materials of the formula II and/or III functional groups that shall not take part in the reaction may be present in protected form and protecting groups are removed to obtain a compound of the formula I.