Cyclopropylacetic acid derivatives and use thereof

1. A compound of the formula (I)

in which

A represents a bond, (C 1 -C 7 )-alkanediyl, (C 2 -C 7 )-alkenediyl or (C 2 -C 7 )-alkynediyl,

D represents hydrogen, trifluoromethyl or a group of the formula

 in which * represents the point of attachment to group A and E represents a bond, CH 2 , —CH 2 —CH 2 — or —CH═CH—,

n represents the number 1 or 2,

R 1 , R 2 , R 3 , R 4 and R 5 independently of one another represent a substituent selected from the group consisting of halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, (C 1 -C 6 )-alkoxy, trifluoromethoxy, cyano and nitro,

and

o, p, q, r and s independently of one another each represent the number 0, 1, 2, 3 or 4, where, if R 1 , R 2 , R 3 , R 4 or R 5 occurs more than once, their meanings may in each case be identical or different,

and salts thereof.

2. The compound of the formula (I) as claimed in claim 1 , in which

A represents a bond or (C 1 -C 7 )-alkanediyl,

D represents hydrogen, trifluoromethyl or a group of the formula

 in which * represents the point of attachment to group A,

n represents the number 1 or 2,

R 1 , R 3 , R 4 and R 5 independently of one another represent a substituent selected from the group consisting of fluorine, chlorine, bromine, (C 1 -C 4 )-alkyl, trifluoromethyl, (C 1 -C 4 )-alkoxy and trifluoromethoxy,

o, q, r and s independently of one another each represent the number 0, 1 or 2, where, if R 1 , R 3 , R 4 or R 5 occurs more than once, their meanings may in each case be identical or different,

R 2 represents fluorine

and

p represents the number 0 or 1,

and salts thereof.

3. A compound of the formula (I-A)

in which

A represents (C 1 -C 7 )-alkanediyl,

D represents hydrogen or a group of the formula

 in which * represents the point of attachment to group A and

R 3A represents hydrogen, fluorine, chlorine, methyl, tert-butyl, trifluoromethyl, methoxy or trifluoromethoxy,

and

n represents the number 1 or 2,

and salts thereof.

4. A process for preparing a compound of the formula (I) as defined in claim 1 , characterized in that compounds of the formula (II)

in which R 2 , n and p each have the meanings given in claim 1 and T 1 and T 2 are identical or different and represent cyano or (C 1 -C 4 ) -alkoxycarbonyl, are either

[A] reacted in an inert solvent in the presence of a base with a compound of the formula (III-A)

 in which A, D, R 1 and o each have the meanings given in claim 1 and

L represents phenyl or o-, m- or p-tolyl

and

X represents halide or tosylate,

to give compounds of the formula (IV-A)

in which A, D, R 1 , R 2 , n, o, p, T 1 and T 2 each have the meanings given above,

or

[B] reacted in an inert solvent in the presence of a base with a compound of the formula (III-B)

in which R 1 , o, L and X each have the meanings given above,

initially to give compounds of the formula (IV-B)

in which R 1 , R 2 , n, o, p, T 1 and T 2 each have the meanings given above,

and these compounds are then alkylated in an inert solvent in the presence of a base with a compound of the formula (V)

D- A 1 -Q  (V),

in which D has the meaning given above,

A 1 has the meaning of A given in claim 1 , but does not represent a bond,

and

Q represents halogen, tosylate or mesylate,

to give compounds of the formula (IV-C)

in which A 1 , D, R 1 , R 2 , n, o, p, T 1 and T 2 each have the meanings given above, and the resulting compounds of the formula (IV-A) or (IV-C) are then converted by hydrolysis of the ester or nitrile groups T 1 and T 2 into the dicarboxylic acids of the formula (I)

and the compounds of the formula (I) are, converted with the appropriate (i) solvents and/or (ii) bases or acids into their salts.

5. A pharmaceutical composition comprising a compound of claim 1 in combination with an inert, non-toxic, pharmaceutically suitable excipient.

6. The pharmaceutical composition of claim 5 further comprising an active compound selected from the group consisting of an organic nitrate, an NO donor, an cGMP-PDE inhibitor, a stimulator of guanylate cyclase, an agent having antithrombotic activity, an agent lowering blood pressure, and an agent altering lipid metabolism.