Cycloalkylmethoxy-substituted acetic acid derivatives, processes for their preparation and their use as pharmaceuticals

1. A compound having the formula I:

in which:

Ring A is a (C 3 -C 8 )-cycloalkanediyl ring or a (C 3 -C 8 )-cycloalkenediyl ring,

R1 and R2 are:

(a) Independently of one another H, F, Cl, Br, CF 3 , OCF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, SCF 3 , SF 5 , OCF 2 —CHF 2 , (C 6 -C 10 )-aryl, (C 6 -C 10 )-aryloxy, OH, NO 2 ; or

(b) together with the phenyl, ring form fused, partially or unsaturated bicyclic (C 6 -C 10 )-aryl;

R3 is:

H, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 3 )-alkyl-(C 3 -C 8 )-cycloalkyl, phenyl, (C 1 -C 3 )-alkyl-phenyl, (C 5 -C 6 )-heteroaryl, (C 1 -C 3 )-alkyl-(C 5 -C 6 )-heteroaryl, or (C 1 -C 3 )-alkyl fully or partially substituted by F;

W is:

(a) CH and o=1, or

X is (C 1 -C 6 )-alkanediyl, wherein one or more carbon atoms of the (C 1 -C 6 ) alkanediyl may be replaced by oxygen atoms;

Y1 is (CR13R14) p , wherein p is 1 or 2;

Y2 is CH2, O, S, SO, SO 2 or NR9;

n is 0-2;

R4 is H, (C1-C6)-alkyl; F if Y2 is not O; NR9;

R5 is H, (C 1 -C 6 )-alkyl; F if Y2 is not O; NR9;

R6 is H, (C 1 -C 6 )-alkyl; or F if n is not 0;

R7 is:

H, F (if n is not 0), (C 1 -C 6 )-alkoxy, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, (C 3 -C 8 )-cycloalkyl, (C 1 -C 6 )-alkyl that may be unsubstituted or substituted by one or more radicals selected from the group consisting of:

hydroxyl, phenyl, (C 5 -C 11 )-heteroaryl, (C 1 -C 6 )-alkoxy and NR11R12, or phenyl that may be unsubstituted or substituted by one or more radicals from the group consisting of hydroxy, (C 1 -C 6 )-alkoxy, F and CF 3 ,

with the proviso that R7 is not NR11R12 or (C 1 -C 6 )-alkoxy if R6=F;

R6 and R7 are together with the carbon atom that carries them (C 3 -C 8 )-cycloalkyl;

R8 is H or (C 1 -C 6 )-alkyl;

R9 is:

H, (C 1 -C 6 )-alkyl, (C 2 -C 6 )-alkenyl, (C 2 -C 6 )-alkynyl, aryl-(C 1 -C 4 )-alkyl, CO—(C 1 -C 6 )-alkyl, CO—(C 6 -C 10 )-aryl, CO—(C 1 -C 6 )-alkyl-(C 6 -C 10 )-aryl, CO—(C 5 -C 11 )-heteroaryl, C(O)—O—(C 1 -C 6 )-alkyl, C(O)—O—(C 1 -C 6 )-alkyl-(C 6 -C 10 )-aryl, C(O)—O—(C 6 -C 10 )-aryl, C(O)—O—(C 5 -C 11 )-heteroaryl, SO 2 —(C 1 -C 6 )-alkyl, SO 2 —(C 1 -C 6 )-alkyl-(C 6 -C 10 )-aryl, SO 2 —(C 1 -C 6 )-alkyl-SO 2 —(C 1 -C 6 )-alkyl, SO 2 —(C 6 -C 10 )-aryl, SO 2 —(C 5 -C 11 )-heteroaryl, wherein aryl or heteroaryl, or both may be unsubstituted or substituted by (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, F, Cl, CO—(C 1 -C 6 )-alkyl;

R10 is H, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkyl-phenyl;

R11 is H, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkyl-phenyl;

R12 is H, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkyl-phenyl;

R13 is H or (C 1 -C 6 )-alkyl; and

R14 is H or (C 1 -C 6 )-alkyl; or

a physiologically acceptable salt of the compound;

a solvate of the compound; or

a physiologically active derivative of the compound.

2. The compound of claim 1 in which

Ring A is (C 3 -C 8 )-cycloalkanediyl or (C 3 -C 8 )-cycloalkenediyl, wherein one carbon atom of the (C 3 -C 8 )-cycloalkanediyl ring or the (C 3 -C 8 ) cycloalkenediyl ring may be replaced by an oxygen atom; and

X is (C 1 -C 6 )-alkanediyl, wherein the C 1 or C 2 carbon atom (to Ring A) may be replaced by an oxygen atom.

3. The compound of claim 1 , in which

Ring A is cis-cyclohexane-1,3-diyl;

R1 and R2 are:

independently of one another H, F, CF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, or phenyl; or

together with a phenyl ring of the compound form a naphthyl;

R3 is (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, or phenyl;

W is:

CH if o=1, or

O or S if o=0;

X is CH 2 —O or CH 2 —O—CH 2 ;

Y1 is CH 2 ;

Y2 is CH 2 , O, S, SO, SO 2 or NR9;

n is 0;

R4 is H;

R5 is H;

R6 is H, (C 1 -C 6 )-alkyl, or benzyl;

R7 is H, (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, phenyl, or benzyl,

R6 and R7 together with the carbon atom that carries them are (C 3 -C 6 )-cycloalkyl;

R8 is H; and

R9 is:

H, or

(C 1 -C 6 )-alkyl, which may be unsubstituted or substituted by:

(C 3 -C 6 )-cycloalkyl, phenyl; CO—(C 1 -C 6 )-alkyl, CO—(C 1 -C 6 )-alkyl-phenyl, CO-phenyl, C(O)—O—(C 1 -C 6 )-alkyl, CO—NH-phenyl, SO 2 —(C 1 -C 4 )-alkyl, SO 2 —(C 1 -C 4 )-alkyl-SO 2 —(C 1 -C 4 )-alkyl, SO 2 -tolyl, or a combination thereof, wherein the phenyl of the substituent for its part may be substituted by O—(C 1 -C 3 )-alkyl;

a physiologically acceptable salt of the compound;

a solvate of the compound; or

a physiologically acceptable derivative of the compound.

4. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4 , further comprising an antidiabetic.

6. The pharmaceutical composition of claim 4 , further comprising a lipid modulator.

7. The compound of claim 2 , in which

Ring A is cis-cyclohexane-1,3-diyl;

R1 and R2 are:

independently of one another H, F, CF 3 , (C 1 -C 6 )-alkyl, O—(C 1 -C 6 )-alkyl, or phenyl; or together with a phenyl ring of the compound form a naphthyl;

R3 is (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl, or phenyl;

W is:

CH if o=1, or

O or S if o=0;

X is CH 2 —O or CH 2 —O—CH 2 ;

Y1 is CH 2 ;

Y2 is CH 2 , O, S, SO, SO 2 or NR9;

n is 0;

R4 is H;

R5 is H;

R6 is H, (C 1 -C 6 )-alkyl, or benzyl;

R7 is H, (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, phenyl, or benzyl,

R6 and R7 together with the carbon atom that carries them are (C 3 -C 6 )-cycloalkyl;

R8 is H; and

R9 is:

H, or

(C 1 -C 6 )-alkyl, which may be unsubstituted or substituted by:

(C 3 -C 6 )-cycloalkyl, phenyl; CO—(C 1 -C 6 )-alkyl, CO—(C 1 -C 6 )-alkyl-phenyl, CO-phenyl, C(O)—O—(C 1 -C 6 )-alkyl, CO—NH-phenyl, SO 2 —(C 1 -C 4 )-alkyl, SO 2 —(C 1 -C 4 )-alkyl-SO 2 —(C 1 -C 4 )-alkyl, SO 2 -tolyl, or a combination thereof, wherein the phenyl of the substituent for its part may be substituted by O—(C 1 -C 3 )-alkyl;

a physiologically acceptable salt of the compound;

a solvate of the compound; or

a physiologically acceptable derivative of the compound.

8. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier.

9. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising the compound of claim 7 and a pharmaceutically acceptable carrier.