CXCR2 inhibitors
View Patent ↗The invention relates to compounds of the formula I in which R1, R2, X, A, B, Z and Y1 to Y4 have the meanings indicated in the claims, and/or a pharmaceutically acceptable salt and/or a prodrug thereof. Because of their properties as inhibitors of chemokine receptors, especially as CXCR2 inhibitors, the compounds of the formula I and the pharmaceutically acceptable salts and prodrugs thereof are suitable for the prevention and treatment of chemokine mediated diseases.
1. A compound of the formula I
wherein
X is —CR3=CR4-;
R3 and R4 are, independently of one another, hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, OH, CN, NO 2 , NR27R28, C(O)R29, C(O)NR30R31, S(O) o R32, S(O) p NR33R34, aryl, heteroaryl, arylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms or heteroarylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms;
R27 is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
R28 is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, aryl, C(O)H, C(O)alkyl with alkyl having 1, 2, 3 or 4 carbon atoms or C(O)aryl;
R29 is hydrogen, OH, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
R30, R31, R33 and R34 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or aryl;
R32 is OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
o and p are, independently of one another, 1 or 2;
Y1, Y2, Y3 and Y4 are, independently of one another, —CR8-;
R8 is hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, OH, CN, NO 2 , NR36R37, C(O)R38, C(O)NR39R40, S(O) q R41, S(O) r NR42R43, aryl, heteroaryl, arylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms or heteroarylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms;
R36 is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
R37 is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, aryl, C(O)H, C(O)alkyl with alkyl having 1, 2, 3 or 4 carbon atoms or C(O)aryl;
R38 is hydrogen, OH, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
R39, R40, R42 and R43 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or aryl;
R41 is OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
q and r are, independently of one another, 1 or 2;
Z is —C(O)—, —S(O)— or —S(O) 2 —;
A is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl;
in which the said cycloalkyl or phenyl can be condensed to a cycloalkyl radical having 3, 4, 5, 6, 7 or 8 atoms or a phenyl radical,
and in which said cycloalkyl or phenyl and the optionally condensed cycloalkyl radical or phenyl radical are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms and —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms;
B is a linear linker consisting of 3, 4 or 5 carbon atoms, in which 1 or 2 carbon atoms can be replaced by a member of a heteroatom containing group consisting of O, NR19 or S(O) y and which linker may contain 0, 1 or 2 double or triple bonds between carbon atoms within the linker, with the provisos, that 2 of said heteroatom containing groups are separated by at least 2 carbon atoms, that heteroatom containing groups are not adjacent to a double or triple bond within the linker or to a non-aromatic double bond, which might be part of A, that double or triple bonds are not cumulated, and that, if A is
connected to the linker via a nitrogen atom being part of A, the atom of the linker which is connected to A is a carbon atom;
and in which linker saturated carbon atoms, which are not adjacent to heteroatom containing groups, which are not adjacent to double or triple bonds within the linker or which are not adjacent to a heteroatom, which might be part of A, can, independently of one another, be substituted by hydrogen, F, OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms; cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
and in which linker saturated carbon atoms, which are adjacent to heteroatom containing groups, which are adjacent to double or triple bonds in the linker, or which are adjacent to a heteroatom, which might be part of A, or carbon atoms being part of a double bond, can, independently of one another, be substituted by hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R19 is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, C(O)R44 or C(O)NR45R46;
R44, R45 and R46 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, in which 1, 2, 3, 4, 5, 6 or 7 hydrogen atoms may be substituted by fluorine atoms or cycloalkyl having 3 or 4 carbon atoms, in which 1, 2, 3, 4, 5 or 6 hydrogen atoms may be substituted by fluorine atoms;
y is 0, 1 or 2;
R1 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
which can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
and
R2 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or heterocyclyl having 3, 4, 5, 6, 7 or 8 atoms;
wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
m is 0 or 1;
n is 0, 1, 2 or 3;
R26 is hydrogen, phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or heterocyclyl having 3, 4 5, 6, 7 or 8 atoms, in which the phenyl, heteroaryl, cycloalkyl or heterocyclyl are unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br and I;
and wherein phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or heterocyclyl having 3, 4 5, 6, 7 or 8 atoms are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SCF 3 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms and cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
or
R1 and R2 form, together with the carbon atom to which they are attached, a 3-, 4-, 5- or 6 membered carbon ring, wherein the formed ring can be saturated or partially unsaturated, and in which the formed ring can optionally be condensed to a phenyl or cycloalkyl radical having 3, 4, 5, 6, 7 or 8 atoms;
wherein the formed ring and the optionally condensed phenyl or cycloalkyl radical can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, CN, NO 2 , SCF 3 , SF 5 and alkyl having 1, 2, 3 or 4 carbon atoms;
and/or a pharmaceutically acceptable salt thereof and/or an ester prodrug of a carboxylic acid group thereof.
2. A compound of the formula I as claimed in claim 1 , wherein
R3 and R4 are, independently of one another,
hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3 or 4 carbon atoms or alkoxy having 1, 2, 3 or 4 carbon atoms;
and
R8 is hydrogen, F, Cl, Br, I or alkyl having 1, 2, 3 or 4 carbon atoms.
3. A compound of the formula I as claimed in claim 1 , wherein
R3 and R4 are, independently of one another,
hydrogen, F, Cl or Br;
and
R8 is hydrogen, F or Cl.
4. A compound of the formula I as claimed in claim 1 , wherein
R3 and R4 are, independently of one another, hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, OH, CN or NO 2 ;
and
R8 is hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, OH, CN or NO 2 .
5. A compound of the formula I as claimed in claim 4 , wherein
R3 and R4 are, independently of one another, hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms;
and
R8 is hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms.
6. A compound of the formula I as claimed in claim 1 , wherein
A is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl;
in which the said phenyl can be condensed to a cycloalkyl radical having 3, 4, 5, 6, 7 or 8 atoms or a phenyl radical;
and in which said cycloalkyl, heterocyclyl, phenyl or heteroaryl and the optionally condensed cycloalkyl radical, heterocyclyl radical, phenyl radical or heteroaryl radical are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, and —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms.
7. A compound of the formula I as claimed in claim 1 , wherein
A is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl or;
in which the said phenyl can be condensed to form a naphthyl or an indanyl,
in which said cycloalkyl or phenyl or the optionally formed naphthyl or indanyl are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SF 5 , SCF 3 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, and alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms.
8. A compound of the formula I as claimed in claim 1 , wherein
A is cyclohexyl, phenyl, naphthyl, or indanyl; in which the phenyl radical is unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br, methoxy, and alkyl having 1, 2 or 3 carbon atoms in which 1, 2, 3, 4, 5, 6 or 7 hydrogen atoms may be substituted by fluorine atoms; and in which pyridinyl is unsubstituted or substituted by Cl.
9. A compound of the formula I as claimed in claim 1 , wherein
A is cyclohexyl, phenyl, naphthyl, or indanyl; in which the phenyl radical is unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br, methoxy, methyl, ethyl, propyl, iso-propyl and trifluoromethyl.
10. A compound of the formula I as claimed in claim 1 , wherein
B is —C(R11R12)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R15R16)-, —C(R13R14)-C≡C—, —C(R13R14)-C(R17)=C(R18)-, —C(R11R12)-C(R13R14)-NR19-, —C(R11R12)-C(R13R14)-S(O) y —, —O—C(R13R14)-C(R15R16), —C≡C—C(R13R14)-, —C(R17)=C(R18)-C(R13R14)-, —C(R13R14)-O—C(R13R14)-, —C(R11R12)-C(R15R16)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-NR19-, —C(R11R12)-C(R15R16)-C(R15R16)-C(R15R16)-, —O—C(R13R14)-C(R13R14)-O—, —O—C(R13R14)-C(R13R14)-NR19-, —O—C(R13R14)-C(R15R16)-C(R15R16)-, —C(R17)=C(R18)-C(R13R14)-O—, —C≡C—C(R13R14)-O—, —C(R11R12)-C(R13R14)-C(R17)=C(R18)-, —C(R11R12)-C(R13R14)-C≡C—, —O—C(R13R14)-C≡C—, —C(R13R14)-O—C(R13R14)-C(R15R16)-, —C(R11R12)-C(R13R14)-O—C(R13R14)-, —C(R11R12)-C(R15R16)-C(R13R14)-S(O) y —, —O—C(R13R14)-C(R13R14)-S(O) y —, —O—C(R13R14)-C(R17)=C(R18)-, —C≡C—C(R13R14)-C(R15R16)-, —C(R17)=C(R18)-C(R13R14)-C(R15R16)-, —C(R13R14)-C≡C—C(R13R14)-, —C(R13R14)-C(R17)=C(R18)-C(R13R14)-, —C(R11R12)-C(R15R16)-C(R15R16)-C(R15R16)-C(R15R16)-, —C(R11R12)-C(R15R16)-C(R15R16)-C(R13R14)-O—, —O—C(R13R14)-C(R15R16)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-C≡C—, —C(R13R14)-O—C(R13R14)-C(R13R14)-O—, —C(R13R14)-O—C(R13R14)-C(R15R16)-C(R15R16)-, —C(R11R12)-C(R15R16)-C(R13R14)-C(R17)=C(R18)-, —C(R13R14)-C(R17)=C(R18)-C(R13R14)-O—, —C(R13R14)-C≡C—C(R13R14)-O—, —C(R17)=C(R18)-C(R13R14)-C(R13R14)-O—, —C≡C—C(R13R14)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-O—C(R13R14)-, —C(R11R12)-C(R13R14)-O—C(R13R14)-C(R15R16)-, —O—C(R13R14)-C(R15R16)-C(R15R16)-C(R15R16)- or —O—C(R13R14)-C(R13R14)-O—C(R13R14)-,
with the proviso that, if A is connected to the linker B via a nitrogen atom being part of A, the atom of the linker which is connected to A is a carbon atom;
R11 and R12 are, independently of one another, hydrogen, F, OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
with the proviso that, if B is attached to a nitrogen atom being part of A, R11 or R12 are, independently of one another, hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R13, R14, R17 and R18 are, independently of one another, hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R15 and R16 are, independently of one another, hydrogen, F,
OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms or cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R19 is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, C(O)R44 or C(O)NR45R46;
R44, R45 and R46 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, in which 1, 2, 3, 4, 5, 6 or 7 hydrogen atoms may be substituted by fluorine atoms or cycloalkyl having 3 or 4 carbon atoms, in which 1, 2, 3, 4, 5 or 6 hydrogen atoms may be substituted by fluorine atoms;
y is 0, 1 or 2.
11. A compound of the formula I as claimed in claim 1 , wherein
B is —C(R11R12)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-NR19-, —C(R11R12)-C(R15R16)-C(R15R16)-C(R15R16)-, —O—C(R13R14)-C(R13R14)-O—, —O—C(R13R14)-C(R13R14)-NR19-, —O—C(R13R14)-C(R15R16)-C(R15R16)-, —C(R17)=C(R18)-C(R13R14)-O—, —C≡C—C(R13R14)-O—, —C(R11R12)-C(R13R14)-C(R17)=C(R18)-, —C(R11R12)-C(R13R14)-C≡C—, —O—C(R13R14)-C≡C—, —C(R11R12)-C(R15R16)-C(R15R16)-C(R15R16)-C(R15R16)-, —C(R11R12)-C(R15R16)-C(R15R16)-C(R13R14)-O—, —O—C(R13R14)-C(R15R16)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-C≡C— or —C(R13R14)-O—C(R13R14)-C(R13R14)-O—,
with the proviso that, if A is connected to the linker via a nitrogen atom being part of A, the atom of the linker which is connected to A is a carbon atom;
R11 and R12 are, independently of one another, hydrogen, F, OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
with the proviso that, if B is attached to a nitrogen atom being part of A, R11 or R12 are, independently of one another, hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R13, R14, R17 and R18 are, independently of one another, hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R15 and R16 are, independently of one another, hydrogen, F,
OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms or cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R19 is H or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms.
12. A compound of the formula I as claimed in claim 1 , wherein
B is —C(R11R12)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-O—, —O—C(R13R14)-C(R13R14)-O—, —C(R17)=C(R18)-C(R13R14)-O—, —C≡C—C(R13R14)-O—, —C(R11R12)-C(R13R14)-C≡C—, —O—C(R13R14)-C≡C—, —C(R11R12)-C(R15R16)-C(R15R16)-C(R13R14)-O—, —O—C(R13R14)-C(R15R16)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-C≡C— or —C(R13R14)-O—C(R13R14)-C(R13R14)-O—,
with the proviso that, if A is connected to the linker via a nitrogen atom being part of A, the atom of the linker which is connected to A is a carbon atom;
R11 and R12 are, independently of one another, hydrogen, F, OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
with the proviso that, if B is attached to a nitrogen atom being part of A, R11 or R12 are, independently of one another, hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R13, R14, R17 and R18 are, independently of one another, hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R15 and R16 are, independently of one another, hydrogen, F,
OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms or cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms.
13. A compound of the formula I as claimed in claim 10 , wherein
R11-R18 are, independently of each other, hydrogen, F, or alkyl having 1, 2, 3, or 4 carbon atoms.
14. A compound of the formula I as claimed in claim 1 , wherein
R19 is hydrogen or methyl.
15. A compound of the formula I as claimed in claim 1 , wherein
y is 0.
16. A compound of the formula I as claimed in claim 1 , wherein
R1 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms
which can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
R2 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl,
wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
m is 0 or 1;
n is 0, 1, 2 or 3;
R26 is hydrogen, phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or heterocyclyl having 3, 4 5, 6, 7 or 8 atoms, in which the phenyl, heteroaryl, cycloalkyl or heterocyclyl are unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br and I;
and wherein phenyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SCF 3 , SF 5 , and alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms,
or
R1 and R2 form, together with the carbon atom to which they are attached, a 3-, 4-, 5- or 6-membered saturated or partly saturated carbon ring, which can optionally be condensed to a phenyl radical; wherein the formed ring and the optionally condensed phenyl can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, CN, NO 2 , SCF 3 , SF 5 and alkyl having 1, 2, 3 or 4 carbon atoms.
17. A compound of the formula I as claimed in claim 1 , wherein
R1 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms
and
R2 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl,
wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
m is 0 or 1;
n is 0, 1, 2 or 3;
R26 is hydrogen, phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or heterocyclyl having 3, 4 5, 6, 7 or 8 atoms, in which the phenyl, heteroaryl, cycloalkyl or heterocyclyl are unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br and I;
or
R1 and R2 form, together with the carbon atom to which they are attached, a 3-, 4-, 5- or 6-membered saturated or partly saturated carbon ring, which can optionally be condensed to a phenyl radical.
18. A compound of the formula I as claimed in claim 1 , wherein
R1 is alkyl having 1, 2, 3 or 4 carbon atoms and
R2 is alkyl having 1, 2, 3 or 4 carbon atoms, phenyl or benzyl;
or
R1 and R2 form, together with the carbon atom to which they are attached, a cyclopropane, cyclobutane, cyclopentane, cyclohexane, cyclopentene ring or indene.
19. A compound of the formula I as claimed in claim 1 , wherein
R1 is methyl or ethyl;
and
R2 is methyl or ethyl;
or
R1 and R2 form, together with the carbon atom to which they are attached, a cyclobutane or cyclopentane ring.
20. A compound of the formula I as claimed in claim 1 , wherein
Z is —S(O) 2 or —C(O)—.
21. A compound of the formula I as claimed in claim 1 , wherein
Z is —C(O)—.
22. A compound of formula I as claimed in claim 1 , wherein
R3 and R4 are, independently of one another, hydrogen,
F, Cl or Br;
Y1, Y2, Y3 and Y4 are, independently of one another, —CR8-, wherein R8 is hydrogen, F or Cl;
Z is —C(O)—;
A is cyclohexyl, phenyl, naphthyl, indanyl or thienyl;
in which the phenyl radical is unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br, methoxy, methyl, ethyl, propyl, iso-propyl and trifluoromethyl;
B is —C(R11R12)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-O—, —O—C(R13R14)-C(R13R14)-O—, —C(R17)=C(R18)-C(R13R14)-O—, —C≡C—C(R13R14)-O—, —C(R11R12)-C(R13R14)-C≡C—, —O—C(R13R14)-C≡C—, —C(R11R12)-C(R15R16)-C(R15R16)-C(R13R14)-O—, —O—C(R13R14)-C(R15R16)-C(R13R14)-O—, —C(R11R12)-C(R15R16)-C(R13R14)-C≡C— or —C(R13R14)-O—C(R13R14)-C(R13R14)-O—;
R11-R18 are, independently of each other, hydrogen or methyl;
R1 is methyl or ethyl; and
R2 is methyl or ethyl;
or
R1 and R2 form, together with the carbon atom to which they are attached, a cyclobutane or cyclopentane ring.
23. A compound of the formula I as claimed in claim 1 selected from the group consisting of:
2-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-propyl-pentanoic acid,
2-Ethyl-2-({1-[2-(4-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-hexanoic acid,
2-Ethyl-2-[(1-phenethyloxy-naphthalene-2-carbonyl)-amino]-hexanoic acid,
1-{[1-(3-Cyclohexyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
2-Methyl-2-({1-[2-(naphthalen-2-yloxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-propionic acid,
2-({1-[2-(2,3-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-({1-[2-(4-trifluoromethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-propionic acid,
2-Methyl-2-{[1-((E)-3-phenyl-allyloxy)-naphthalene-2-carbonyl]amino}-propionic acid,
2-Methyl-2-{[1-(3-phenoxy-propyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(4-Methoxy-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,4-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-phenoxy-ethylamino)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-[1-(2-phenoxy-ethoxy)-naphthalene-2-sulfonylamino]-propionic acid,
2-{[1-(3-Cyclohexyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-Methyl-2-{[1-(3-pyridin-2-yl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
1-{[1-(1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclohexanecarboxylic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-phenyl-butyric acid,
1-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclopent-3-enecarboxylic acid,
2,4-Dimethyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-pentanoic acid,
2-{[4-Fluoro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-butyric acid,
1-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-indan-1-carboxylic acid,
1-{[1-(2-Cyclohexyl-ethoxy)-4-fluoro-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-({4-Fluoro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclopentanecarboxylic acid,
1-{[4-Fluoro-1-(3-phenoxy-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-{[4-Fluoro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-[(4-Fluoro-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-cyclopentanecarboxylic acid,
1-{[4-Fluoro-1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-3-phenyl-propionic acid,
2-{[1-(2-Cyclohexyl-ethoxy)-naphthalene-2-carbonyl]-amino}-2-ethyl-hexanoic acid,
2-{[1-(3-Cyclohexyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-ethyl-hexanoic acid,
2-Ethyl-2-{[1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-hexanoic acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-ethyl-hexanoic acid,
2-Ethyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]amino}-hexanoic acid,
2-Ethyl-2-({1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-hexanoic acid,
1-({4-Chloro-1-[2-(4-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-{[4-Chloro-1-(2-cyclohexyl-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-[(4-Chloro-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-cyclobutanecarboxylic acid,
1-{[4-Chloro-1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-{[4-Chloro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-({4-Chloro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-({1-[2-(4-Fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-{[1-(2-Cyclohexyl-ethoxy)-naphthalene-2-carbonyl]amino}-cyclobutanecarboxylic acid,
1-({1-[2-(4-Chloro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-[(1-Phenethyloxy-naphthalene-2-carbonyl)-amino]-cyclobutanecarboxylic acid,
1-{[1-(3-Phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
2-{[4-Fluoro-1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({4-Fluoro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Fluoro-1-(3-phenoxy-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-butyric acid,
2-({4-Fluoro-1-[2-(4-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Fluoro-1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-{[4-Fluoro-1-(3-phenoxy-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-[(4-Fluoro-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid,
2-{[4-Fluoro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-{[1-(2-Cyclohexyl-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({1-[3-(4-Chloro-phenyl)-propoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
1-{[1-((R)-1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-{[1-((S)-1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
(R)-2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
(S)-2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
2-({4-Chloro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-butyric acid,
2-({4-Chloro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Chloro-4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Bromo-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({1-[2-(4-Fluoro-3-trifluoromethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(4-Bromo-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-butyric acid,
2-({4-Bromo-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-((S)-1-methyl-2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-((R)-1-methyl-2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(2-Isopropyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-m-tolyloxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(3-Methoxy-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3,5-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,6-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Chloro-5-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3,4-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(Indan-5-yloxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,4-Dimethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,3-Dimethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Isopropyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2-Chloro-4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3,4-Difluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2-Methoxy-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(3-phenyl-prop-2-ynyloxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[3-(4-Chloro-phenyl)-prop-2-ynyloxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2,3-Dimethyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
1-{[1-(1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclopentanecarboxylic acid,
2,3-Dimethyl-2-{[1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2,3-dimethyl-butyric acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2,3-dimethyl-butyric acid,
2-Methyl-2-{[1-(1-methyl-2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(5-phenyl-pentyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(5-phenyl-pent-1-ynyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(3-phenyl-butoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-butyric acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,4-Dichloro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(3-phenoxy-prop-1-ynyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(4-Chloro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-p-tolyl-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-{[1-(2-Benzyloxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]amino}-butyric acid,
2-({1-[2-(3,5-Difluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-((E)-4-phenyl-but-1-enyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(4-phenyl-butyl)-naphthalene-2-carbonyl]amino}-propionic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
2-Methyl-2-{[1-(4-phenyl-but-1-ynyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-[(4-Bromo-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid,
2-{[4-Bromo-1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-Methyl-2-({1-[2-(3-trifluoromethyl-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-propionic acid,
2-({1-[2-(4-Fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Bromo-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-((S)-1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-((R)-1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-[(1-phenethyloxy-naphthalene-2-carbonyl)-amino]-propionic acid, or
2-Methyl-2-{[1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({4-Fluoro-1-[2-(3-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Fluoro-1-(4-phenyl-butoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({4-Fluoro-1-[2-(2-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(4-Chloro-phenyl)-ethoxy]-4-fluoro-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Fluoro-1-[3-(2-fluoro-phenoxy)-propoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Fluoro-1-[3-(4-fluoro-phenoxy)-propoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Fluoro-1-[2-(naphthalen-2-yloxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid, and
2-({1-[2,2-Difluoro-2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid
or a pharmaceutically acceptable salt thereof or an ester prodrug of a carboxylic acid group thereof.
24. A compound of the formula (I) as claimed in claim 1 selected from the group consisting of:
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-phenyl-butyric acid,
1-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclopent-3-enecarboxylic acid,
2,4-Dimethyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-pentanoic acid,
2-{[4-Fluoro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-butyric acid,
1-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-indan-1-carboxylic acid,
1-{[1-(2-Cyclohexyl-ethoxy)-4-fluoro-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-({4-Fluoro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclopentanecarboxylic acid,
1-{[4-Fluoro-1-(3-phenoxy-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-{[4-Fluoro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-[(4-Fluoro-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-cyclopentanecarboxylic acid,
1-{[4-Fluoro-1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-3-phenyl-propionic acid,
2-{[1-(2-Cyclohexyl-ethoxy)-naphthalene-2-carbonyl]-amino}-2-ethyl-hexanoic acid,
2-{[1-(3-Cyclohexyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-ethyl-hexanoic acid,
2-Ethyl-2-{[1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-hexanoic acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-ethyl-hexanoic acid,
2-Ethyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-hexanoic acid,
2-Ethyl-2-({1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-hexanoic acid,
1-({4-Chloro-1-[2-(4-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-{[4-Chloro-1-(2-cyclohexyl-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-[(4-Chloro-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-cyclobutanecarboxylic acid,
1-{[4-Chloro-1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-{[4-Chloro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-({4-Chloro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-({1-[2-(4-Fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-{[1-(2-Cyclohexyl-ethoxy)-naphthalene-2-carbonyl]amino}-cyclobutanecarboxylic acid,
1-({1-[2-(4-Chloro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-[(1-Phenethyloxy-naphthalene-2-carbonyl)-amino]-cyclobutanecarboxylic acid,
1-{[1-(3-Phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
1-{[1-(2-Phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-cyclobutanecarboxylic acid,
1-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclobutanecarboxylic acid,
2-{[4-Fluoro-1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({4-Fluoro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Fluoro-1-(3-phenoxy-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-butyric acid,
2-({4-Fluoro-1-[2-(4-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Fluoro-1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-{[4-Fluoro-1-(3-phenoxy-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-[(4-Fluoro-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid,
2-{[4-Fluoro-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-{[1-(2-Cyclohexyl-ethoxy)-naphthalene-2-carbonyl]amino}-2-methyl-propionic acid,
2-({1-[3-(4-Chloro-phenyl)-propoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
1-{[1-((R)-1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-{[1-((S)-1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
(R)-2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]amino}-butyric acid,
(S)-2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
2-({1-[2-(5-Chloro-pyridin-3-yloxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Chloro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-butyric acid,
2-({4-Chloro-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Chloro-4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Bromo-1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({1-[2-(4-Fluoro-3-trifluoromethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(4-Bromo-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-butyric acid,
2-({4-Bromo-1-[2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-((S)-1-methyl-2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-((R)-1-methyl-2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(2-Isopropyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-m-tolyloxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(3-Methoxy-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3,5-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,6-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Chloro-5-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3,4-Dichloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(Indan-5-yloxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,4-Dimethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,3-Dimethyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Isopropyl-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2-Chloro-4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3,4-Difluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2-Methoxy-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(3-phenyl-prop-2-ynyloxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[3-(4-Chloro-phenyl)-prop-2-ynyloxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2,3-Dimethyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
1-{[1-(1-Methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-cyclopentanecarboxylic acid,
1-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-cyclopentanecarboxylic acid,
2,3-Dimethyl-2-{[1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2,3-dimethyl-butyric acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2,3-dimethyl-butyric acid,
2-Methyl-2-{[1-(1-methyl-2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(5-phenyl-pentyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(5-phenyl-pent-1-ynyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(3-phenyl-butoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-butyric acid,
2-({1-[2-(4-Chloro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(2,4-Dichloro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(3-phenoxy-prop-1-ynyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(4-Chloro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-p-tolyl-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-{[1-(2-Benzyloxy-ethoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]amino}-butyric acid,
2-({1-[2-(3,5-Difluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-((E)-4-phenyl-but-1-enyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(4-phenyl-butyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({1-[2-(4-Fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-butyric acid,
2-Methyl-2-{[1-(4-phenyl-but-1-ynyl)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-[(4-Bromo-1-phenethyloxy-naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid,
2-{[4-Bromo-1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-Methyl-2-({1-[2-(3-trifluoromethyl-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-propionic acid,
2-({1-[2-(4-Fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(3-Bromo-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-Methyl-2-{[1-(2-phenoxy-ethoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-((S)-1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-(3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-{[1-((R)-1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-Methyl-2-[(1-phenethyloxy-naphthalene-2-carbonyl)-amino]-propionic acid, or
2-Methyl-2-{[1-(1-methyl-3-phenyl-propoxy)-naphthalene-2-carbonyl]-amino}-propionic acid,
2-({4-Fluoro-1-[2-(3-fluoro-phenyl)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-{[4-Fluoro-1-(4-phenyl-butoxy)-naphthalene-2-carbonyl]-amino}-2-methyl-propionic acid,
2-({4-Fluoro-1-[2-(2-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({1-[2-(4-Chloro-phenyl)-ethoxy]-4-fluoro-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Fluoro-1-[3-(2-fluoro-phenoxy)-propoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Fluoro-1-[3-(4-fluoro-phenoxy)-propoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid,
2-({4-Fluoro-1-[2-(naphthalen-2-yloxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid, and
2-({1-[2,2-Difluoro-2-(4-fluoro-phenoxy)-ethoxy]-naphthalene-2-carbonyl}-amino)-2-methyl-propionic acid
or a pharmaceutically acceptable salt thereof or an ester prodrug of a carboxylic acid group thereof.
25. A method for the treatment of a chemokine mediated disease, the method comprising inhibiting CXCR2 by administering to a patient in need thereof an effective amount of a pharmaceutically acceptable salt and/or an ester prodrug of a carboxylic acid group thereof as claimed in claim 1 alone or in combination with other medicaments or active ingredients.
26. The method of claim 25 , wherein said chemokine mediated disease is selected from acute and chronic inflammatory diseases.
27. The method of claim 25 , wherein said chemokine mediated disease is selected from atherosclerosis, ischemia/reperfusion injuries, chronic obstructive pulmonary disease, asthma, and rheumatoid arthritis, adult respiratory distress syndrome, inflammatory bowel disease, ulcerative colitis, Crohn's disease, atopic dermatitis, cystic fibrosis, psoriasis, dermatitis, multiple sclerosis, angiogenesis, restenosis, osteoarthritis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, stroke, glomerulonephritis, thrombosis, graft vs. host reaction, allograft rejections, alzheimers disease, malaria, viral infections, traumatic brain injury, pulmonary fibrosis, and cancer.
28. A medicine for human, veterinary and/or phytoprotective use comprising an effective amount of a compound of the formula I and/or a pharmaceutically acceptable salt and/or an ester prodrug of a carboxylic acid group hereof as claimed in claim 1 , together with pharmaceutically acceptable carriers and additives.
29. A medicine for human, veterinary and/or phytoprotective use comprising an effective amount of at least one compound of the formula I and/or a pharmaceutically acceptable salt and/or an ester prodrug of a carboxylic acid group thereof as claimed in claim 1 , together with pharmaceutically acceptable carriers and additives in combination with at least one other pharmacological active ingredient or medicament.
30. A method for the treatment of a chemokine mediated disease, the method comprising inhibiting CXCR2 by administering to a patient in need thereof an effective amount of a compound of the formula I and/or a pharmaceutically acceptable salt thereof and/or an ester prodrug of a carboxylic acid group thereof alone or in combination with other medicaments or active ingredients, wherein said compound of the formula I has the following structure:
wherein
X is —CR3=CR4-;
R3 and R4 are, independently of one another, hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, OH, CN, NO 2 , NR27R28, C(O)R29, C(O)NR30R31, S(O) o R32, S(O) p NR33R34, aryl, heteroaryl, arylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms or heteroarylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms;
R27 is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
R28 is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, aryl, C(O)H, C(O)alkyl with alkyl having 1, 2, 3 or 4 carbon atoms or C(O)aryl;
R29 is hydrogen, OH, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
R30, R31, R33 and R34 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or aryl;
R32 is OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
o and p are, independently of one another, 1 or 2;
Y1, Y2, Y3 and Y4 are, independently of one another, —CR8-;
R8 is hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, OH, CN, NO 2 , NR36R37, C(O)R38, C(O)NR39R40, S(O) q R41, S(O) r NR42R43, aryl, heteroaryl, arylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms or heteroarylalkyl with alkyl having 1, 2, 3 or 4 carbon atoms;
R36 is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
R37 is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, aryl, C(O)H, C(O)alkyl with alkyl having 1, 2, 3 or 4 carbon atoms or C(O)aryl;
R38 is hydrogen, OH, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
R39, R40, R42 and R43 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or aryl;
R41 is OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or aryl;
q and r are, independently of one another, 1 or 2;
Z is —C(O)—, S(O)— or —S(O) 2 —;
A is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, or phenyl; in which the said cycloalkyl, or phenyl can be condensed to a cycloalkyl radical having 3, 4, 5, 6, 7 or 8 atoms, or a phenyl radical, and in which said cycloalkyl, or phenyl and the optionally condensed cycloalkyl radical, or phenyl radical or heteroaryl radical are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, and —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms;
B is a linear linker consisting of 3, 4 or 5 carbon atoms, in which 1 or 2 carbon atoms can be replaced by a member of a heteroatom containing group consisting of O, NR19 or S(O) y and which linker may contain 0, 1 or 2 double or triple bonds between carbon atoms within the linker, with the provisos, that 2 of said heteroatom containing groups are separated by at least 2 carbon atoms, that heteroatom containing groups are not adjacent to a double or triple bond within the linker or to a non-aromatic double bond, which might be part of A, that double or triple bonds are not cumulated, and that, if A is connected to the linker via a nitrogen atom being part of A, the atom of the linker which is connected to A is a carbon atom;
and in which linker saturated carbon atoms, which are not adjacent to heteroatom containing groups, which are not adjacent to double or triple bonds within the linker or which are not adjacent to a heteroatom, which might be part of A, can, independently of one another, be substituted by hydrogen, F, OH, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms; cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
and in which linker saturated carbon atoms, which are adjacent to heteroatom containing groups, which are adjacent to double or triple bonds in the linker, or which are adjacent to a heteroatom, which might be part of A, or carbon atoms being part of a double bond, can, independently of one another, be substituted by hydrogen, F, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms or cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
R19 is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, C(O)R44 or C(O)NR45R46;
R44, R45 and R46 are, independently of one another, hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, in which 1, 2, 3, 4, 5, 6 or 7 hydrogen atoms may be substituted by fluorine atoms or cycloalkyl having 3 or 4 carbon atoms, in which 1, 2, 3, 4, 5 or 6 hydrogen atoms may be substituted by fluorine atoms;
y is 0, 1 or 2;
R1 is hydrogen;
and
R2 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or heterocyclyl having 3, 4, 5, 6, 7 or 8 atoms;
wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
m is 0 or 1;
n is 0, 1, 2 or 3;
R26 is hydrogen, phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms or heterocyclyl having 3, 4 5, 6, 7 or 8 atoms, in which the phenyl, heteroaryl, cycloalkyl or heterocyclyl are unsubstituted or substituted by 1, 2 or 3 radicals selected from the group consisting of F, Cl, Br and I;
and wherein phenyl, heteroaryl having 5 or 6 atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or heterocyclyl having 3, 4 5, 6, 7 or 8 atoms are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SCF 3 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, and cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms.
31. The method of claim 30 , wherein said chemokine mediated disease is selected from acute and chronic inflammatory diseases.
32. The method of claim 30 , wherein said chemokine mediated disease is selected from atherosclerosis, ischemia/reperfusion injuries, chronic obstructive pulmonary disease, asthma, and rheumatoid arthritis, adult respiratory distress syndrome, inflammatory bowel disease, ulcerative colitis, Crohn's disease, atopic dermatitis, cystic fibrosis, psoriasis, dermatitis, multiple sclerosis, angiogenesis, restenosis, osteoarthritis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, stroke, glomerulonephritis, thrombosis, graft vs. host reaction, allograft rejections, alzheimers disease, malaria, viral infections, traumatic brain injury, pulmonary fibrosis, and cancer.
33. A compound of the formula I as claimed in claim 1 , wherein:
R1 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, which can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26; and
R2 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, or phenyl, wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
R26 is hydrogen, phenyl, or cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which phenyl or cycloalkyl are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SCF 3 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, and cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
m is 0 or 1;
n is 0, 1, 2 or 3;
or
R1 and R2 form, together with the carbon atom to which they are attached, a 3-, 4-, 5- or 6-membered carbon ring, wherein the formed ring can be saturated or partially unsaturated, and in which the formed ring can optionally be condensed to a phenyl or cycloalkyl radical having 3, 4, 5, 6, 7 or 8 carbon atoms;
wherein the formed ring and the optionally condensed phenyl or cycloalkyl radical can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, CN, NO 2 , SCF 3 , SF 5 and alkyl having 1, 2, 3 or 4 carbon atoms.
34. A compound of the formula I as claimed in claim 1 , wherein:
A is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, or phenyl, in which said phenyl can be condensed to a cycloalkyl radical having 3, 4, 5, 6, 7 or 8 atoms, or a phenyl radical;
and in which said cycloalkyl or phenyl, and the optionally condensed cycloalkyl or phenyl radical are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, and —S-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms;
R1 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, which can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26; and
R2 is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, or phenyl, wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, and —O m —(CH 2 ) n —R26;
R26 is hydrogen, phenyl, or cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which phenyl or cycloalkyl are unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, OH, CN, NO 2 , SCF 3 , SF 5 , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, cycloalkylalkyl having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms, alkoxy having 1, 2, 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 hydrogen atoms may be substituted by fluorine atoms, cycloalkoxy having 3, 4, 5 or 6 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 hydrogen atoms may be substituted by fluorine atoms, and cycloalkylalkoxy having 4, 5, 6, 7 or 8 carbon atoms, in which 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 hydrogen atoms may be substituted by fluorine atoms;
m is 0 or 1;
n is 0, 1, 2 or 3;
or
R1 and R2 form, together with the carbon atom to which they are attached, a 3-, 4-, 5- or 6-membered carbon ring, wherein the formed ring can be saturated or partially unsaturated, and in which the formed ring can optionally be condensed to a phenyl or cycloalkyl radical having 3, 4, 5, 6, 7 or 8 carbon atoms;
wherein the formed ring and the optionally condensed phenyl or cycloalkyl radical can be unsubstituted or substituted by 1, 2, 3, 4 or 5 radicals selected from the group consisting of F, Cl, Br, I, CN, NO 2 , SCF 3 , SF 5 and alkyl having 1, 2, 3 or 4 carbon atoms.