A method for the therapy or prevention of a disease in a warm-blooded animal selected from the group consisting of diabetes mellitus, hyperlipemia, obesity, impaired glucose tolerance, insulin-resistant non-IGT, fatty liver, diabetic complications, arteriosclerosis, gestational diabetes mellitus, polycystic ovary syndrome, atherosclerosis, arthrosteitis, rheumatic arthritis, allergic diseases, asthma, cancer, autoimmune diseases, pancreatitis and cataracts, which method comprises administering to said warm-blooded animal a pharmacologically effective amount of an active ingredient, wherein said active ingredient is an amidocarboxylic acid derivative of formula (I):
- 17
- wherein:
- R1 is selected from the group consisting of hydrogen atoms, straight or branched chain alkyl groups having from 1 to 6 carbon atoms and aralkyl groups having from 7 to 12 carbon atoms;
- R2 is selected from the group consisting of straight or branched chain alkylene groups having from 1 to 6 carbon atoms;
- R3 is selected from the group consisting of (i) hydrogen atoms, (ii) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (iii) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii) straight or branched chain dialkylamino groups in which each of said alkyl groups may be the same or different and each has from 1 to 4 carbon atoms, (viii) aryl groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents a defined below, (ix) aralkyl groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (x) hydroxyl groups and (xi) straight or branched chain aliphatic acyl groups having from 1 to 5 carbon atoms;
- R4 is selected from the group consisting of hydrogen atoms and straight or branched chain alkyl groups having from 1 to 6 carbon atoms;
- Z is selected from the group consisting of straight or branched chain alkylene group having from 1 to 6 carbon atoms;
- W is selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (vii) arylthio groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (x) aralkylthio groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an aryl group having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1 to 4 hetero atoms selected from the groups consisting of an oxygen atom, a nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero arylthio groups containing from 1 to 4 hetero atoms selected from the groups consisting of an oxygen atom, a nitrogen atom and a sulfur atom, (xv) mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups containing from 1 to 4 hetero atoms selected from the groups consisting of an oxygen atom, a nitrogen atom and a sulfur atom, (xvi) amino groups, (xvii) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms, (xviii) straight or branched chain dialkylamino groups in which each of said alkyl moieties may be the same or different and each has from 1 to 4 carbon atoms, (xix) N-alkyl-N-arylamino groups in which said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms and said aryl moiety is an aryl group having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below. (xx) arylamino groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (xxi) aralkylamino groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety and (xxii) aralkyloxycarbonylamino groups in which said aralkyl moiety has from 7 to 12 carbon atoms and which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety;
- X is selected from the group consisting of aryl groups having from 6 to 10 carbon atoms which may have from 1 to 3 substituents selected from substituents α defined below and mono- or dicyclic, 5- to 10-membered hetero aryl groups having from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and and a sulfur atom which may have from 1 to 3 substituents selected from substituents α defined below, when W represents a substituent selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (vii) arylthio groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (x) aralkylthio groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an aryl group having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, (xii) mono- or dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, (xiii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1 to 4 hetero atoms selected from the groups consisting of an oxygen atom, a nitrogen atom and a sulfur atom, (xiv) mono- or dicyclic, 5- to 10-membered hetero arylthio groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom and (xv) mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, or
- X is selected from the group consisting of aryl groups having from 6 to 10 carbon atoms which may have from 1 to 3 substituents selected from substituents α defined below when W is selected from the group consisting of (i) amino groups, (ii) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms, (iii) straight or branched chain dialkylamino groups in which each of said alkyl moieties may be the same or different and each has from 1 to 4 carbon atoms, (iv) N-alkyl-N-arylamino groups in which said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms and said aryl moiety has from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below, (v) arylamino groups having from 6 to 10 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety, (vi) aralkylamino groups having from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety and (vii) aralkyloxycarbonylamino groups in which said aralkyl moiety has from 7 to 12 carbon atoms which may have from 1 to 5 substituents selected from substituents α defined below on said aryl moiety;
- said substituents α are selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight or branched chain halogenated alkyl groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v) straight or branched chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight or branched chain halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii) straight or branched chain alkylenedioxy groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon atoms which may have from 1 to 3 substituents selected from substituents β defined below, (x) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino groups in which said alkoxy moiety has from 1 to 4 carbon atoms, (xiii) aralkyloxycarbonylamino groups in which said aralkyl moiety has from 7 to 12 carbon atoms, (xix) straight or branched chain dialkylamino groups in which said alkyl moieties may be the same or different and each has from 1 to 4 carbon atoms, (xx) aralkyl groups having from 7 to 12 carbon atoms which may have from 1 to 3 substituents selected from substituents β defined below on said aryl moiety, (xxi) aryl groups having from 6 to 10 carbon atoms and which may have from 1 to 3 substituents selected from substituents β, which may be the same or different, defined below, (xxii) aryloxy groups having from 6 to 10 carbon atoms which may have from 1 to 3 substituents selected from substituents β defined below on said aryl moiety, (xxiii) arylthio groups having from 6 to 10 carbon atoms which may have from 1 to 3 substituents selected from substituents β defined below on said aryl moiety, (xxiv) arylsulfonyl groups having from 6 to 10 carbon atoms which may have from 1 to 3 substituents selected from substituents β defined below on said aryl moiety, (xxv) arylsulfonylamino groups having from 6 to 10 carbon atoms which may have from 1 to 3 substituents selected from substituents β defined below on said aryl moiety, the nitrogen atom of said amino moiety may be substituted with a straight or branched chain alkyl group having from 1 to 6 carbon atoms, (xxvi) mono- or dicyclic, 5- to 10-membered hetero aryl groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom which may have from 1 to 3 substituents selected from substituents β defined below, (xxvii) mono- or dicyclic, 5- to 10-membered hetero aryloxy groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom which may have from 1 to 3 substituents selected from substituents β defined below, (xxviii) mono- or dicyclic, 5- to 10-membered hetero arylthio groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom which may have from 1 to 3 substituents selected from substituents β defined below, (xxix) mono- or dicyclic, 5- to 10-membered hetero arylsulfonyl groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom which may have from 1 to 3 substituents selected from substituents β defined below, (xxx) mono- or dicyclic, 5- to 10-membered hetero arylsulfonylamino groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom which may have from 1 to 3 substituents selected from substituents β defined below on said hetero aryl moiety, the nitrogen atom of said amino moiety may be substituted with a straight or branched chain alkyl group having from 1 to 6 carbon atoms and (xxxi) mono- or dicyclic, 5- to 10-membered saturated heterocyclic groups containing from 1 to 4 hetero atoms selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom;
- said substituents β are selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight or branched chain halogenated alkyl groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight or branched chain halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi) straight or branched chain alkylenedioxy groups having from 1 to 4 carbon atoms, (vii) straight or branched chain hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) straight or branched chain aliphatic acyl groups having from 1 to 5 carbon atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups, (xii) carboxyl groups. (xiii) amino groups, (xiv) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms. (xv) straight or branched chain dialkylamino groups in which said alkyl moieties may be the same or different and each has from 1 to 4 carbon atoms, (xvi) straight or branched chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii) monoalkylaminoalkyl groups in which said monoalkylamino moiety has one straight or branched chain alkyl group having from 1 to 4 carbon atoms and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, (xviii) dialkylaminoalkyl groups in which said dialkylamino moiety has two straight or branched chain alkyl groups which may be the same or different and each has from 1 to 4 carbon atoms and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, (xix) straight or branched chain alkoxycarbonylamino groups in which said alkoxy moiety has from 1 to 4 carbon atoms and (xx) aralkyloxycarbonylamino groups in which said aralkyl moiety has from 7 to 12 carbon atoms;
- and
- Y is selected from the group consisting of a single bond, an oxygen atom, a sulfur atom and a group of formula:
- >N—R5, wherein R5 is selected from the group consisting of hydrogen atoms, straight or branched chain alkyl groups having from 1 to 6 carbon atoms, straight or branched chain aliphatic acyl groups having from 1 to 8 carbon atoms and aromatic acyl groups having from 7 to 11 carbon atoms,
- a pharmacologically acceptable salt thereof or a pharmacologically acceptable ester thereof,
- with the proviso that the amidocarboxylic acid derivative does not include compounds wherein:
- R1 is selected from the group consisting of hydrogen atoms, straight or branched chain alkyl groups having from 1 to 6 carbon atoms and aralkyl groups having from 7 to 12 carbon atoms which include a straight or branched chain alkyl group having 1 to 4 carbon atoms substituted with an aryl moiety;
- R2 is selected from the group consisting of straight or branched chain alkylene groups having from 1 to 6 carbon atoms;
- R3 is selected from the group consisting of (i) hydrogen atoms, (ii) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (iii) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (v) halogen atoms, (vi) nitro groups, (vii) straight or branched chain dialkylamino groups in which each of said alkyl groups are the same or different and each has from 1 to 4 carbon atoms, (viii) aryl groups having from 6 to 10 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below, (ix) aralkyl groups having from 7 to 12 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below on said aryl moiety, (x) hydroxyl groups and (xi) straight or branched chain aliphatic acyl groups having from 1 to 5 carbon atoms;
- R4 is selected from the group consisting of hydrogen atoms and straight or branched chain alkyl groups having from 1 to 6 carbon atoms;
- Z is selected from the group consisting of straight or branched chain alkylene group having from 1 to 6 carbon atoms;
- W is selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) hydroxyl groups, (iii) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (iv) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (v) aryl groups having from 6 to 10 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below, (vi) aryloxy groups having from 6 to 10 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below on said aryl moiety, (vii) arylthio groups having from 6 to 10 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below on said aryl moiety, (viii) aralkyl groups having from 7 to 12 carbon atoms which include a straight or branched chain alkyl group having 1 to 4 carbon atoms substituted with an aryl moiety which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below on said aryl moiety, (ix) aralkyloxy groups having from 7 to 12 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below on said aryl moiety, (x) aralkylthio groups having from 7 to 12 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below on said aryl moiety, (xi) aryloxyalkyl groups in which said aryl moiety is an aryl group having from 6 to 10 carbon atoms which are unsubstituted or have from 1 to 5 substituents selected from substituents α′ defined below and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, (xii) pyridyl, (xiii) quinolyl, (xiv) amino groups, (xv) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms, and (xvi) straight or branched chain dialkylamino groups in which each of said alkyl moieties may be the same or different and each has from 1 to 4 carbon atoms,
- X is a phenyl group which is unsubstituted or has 1 to 3 substituents α′ defined below or a hetero aryl group selected from the group consisting of pyridyl, quinolyl and isoquinolyl, said hetero aryl group being unsubstituted or having from 1 to 3 substituents selected from substituents α′ defined below;
- said substituents α′ are selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight or branched chain halogenated alkyl groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched chain aliphatic acyloxy groups having from 1 to 5 carbon atoms, (v) straight or branched chain aliphatic acyl groups having from 1 to 5 carbon atoms, (vi) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (vii) straight or branched chain halogenated alkoxy groups having from 1 to 4 carbon atoms, (viii) straight or branched chain alkylenedioxy groups having from 1 to 4 carbon atoms, (ix) aralkyloxy groups having from 7 to 12 carbon atoms which are unsubstituted or have from 1 to 3 substituents selected from substituents β′ defined below, (x) straight or branched chain alkylthio groups having from 1 to 4 carbon atoms, (xi) straight or branched chain alkylsulfonyl groups having from 1 to 4 carbon atoms, (xii) halogen atoms, (xiii) nitro groups, (xiv) cyano groups, (xv) amino groups, (xvi) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms, (xvii) straight or branched chain alkoxycarbonylamino groups in which said alkoxy moiety has from 1 to 4 carbon atoms, (xviii) straight or branched chain dialkylamino groups in which said alkyl moieties are the same or different and each has from 1 to 4 carbon atoms, (xix) a phenyl group which is unsubstituted or has 1 to 3 substituents β′ defined below and (xx) a hetero aryl group selected from the group consisting of pyridyl, quinolyl and isoquinolyl, said hetero aryl group being unsubstituted or having from 1 to 3 substituents β′ defined below;
- said substituents β′ are selected from the group consisting of (i) straight or branched chain alkyl groups having from 1 to 6 carbon atoms, (ii) straight or branched chain halogenated alkyl groups having from 1 to 4 carbon atoms, (iii) hydroxyl groups, (iv) straight or branched chain alkoxy groups having from 1 to 4 carbon atoms, (v) straight or branched chain halogenated alkoxy groups having from 1 to 4 carbon atoms, (vi) straight or branched chain alkylenedioxy groups having from 1 to 4 carbon atoms, (vii) straight or branched chain hydroxyalkyl groups having from 1 to 4 carbon atoms, (viii) straight or branched chain aliphatic acyl groups having from 1 to 5 carbon atoms, (ix) halogen atoms, (x) nitro groups, (xi) cyano groups, (xii) carboxyl groups, (xiii) amino groups, (xiv) straight or branched chain monoalkylamino groups in which said alkyl moiety has from 1 to 4 carbon atoms, (xv) straight or branched chain dialkylamino groups in which said alkyl moieties are the same or different and each has from 1 to 4 carbon atoms, (xvi) straight or branched chain aminoalkyl groups having from 1 to 4 carbon atoms, (xvii) monoalkylaminoalkyl groups in which said monoalkylamino moiety has one straight or branched chain alkyl group having from 1 to 4 carbon atoms and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, (xviii) dialkylaminoalkyl groups in which said dialkylamino moiety has two straight or branched chain alkyl groups which are the same or different and each has from 1 to 4 carbon atoms and said alkyl moiety is a straight or branched chain alkyl group having from 1 to 4 carbon atoms, and (xix) straight or branched chain alkoxycarbonylamino groups in which said alkoxy moiety has from 1 to 4 carbon atoms;
- and
- Y is selected from the group consisting of a single bond, an oxygen atom, a sulfur atom and a group of formula:
- >N—R5 wherein R5 is selected from the group consisting of hydrogen atoms, straight or branched chain alkyl groups having from 1 to 6 carbon atoms, and straight or branched chain aliphatic acyl groups having from 1 to 8 carbon atoms.