Substituted dibenzoic acid derivatives and use thereof

1. A compound of the formula (I)

in which

A represents a group of the formula

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

E represents a bond, —CH 2 —, —CH 2 —CH 2 — or —CH═CH—,

D represents a bond or represents (C 1 -C 7 )-alkanediyl, (C 2 -C 6 )-alkanediyl-O— # , (C 2 -C 7 )-alkenediyl or (C 2 -C 7 )-alkynediyl, each of which may be mono- or polysubstituted by fluorine and in which # represents the point of attachment to group A,

R 1 , R 2 , R 3 , R 4 , R 5 and R 6 independently of one another represent a substituent selected from the group consisting of halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, cyano and nitro, where alkyl and alkoxy for their part may be mono- or polysubstituted by fluorine,

and

n, 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 , R 5 or R 6 is present 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 group of the formula

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

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

R 1 , R 4 , R 5 and R 6 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,

n, q, r and s independently of one another each represent the number 0, 1 or 2,

where, if R 1 , R 4 , R 5 or R 6 is present more than once, their meanings may in each case be identical or different,

R 2 and R 3 each represent fluorine,

and

and p independently of one another each represent the number 0 or 1,

and the salts thereof.

3. The compound as claimed in claim 1 of the formula (I-A)

in which

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

R 1 represents hydrogen or fluorine,

R 4 represents a substituent selected from the group consisting of fluorine, chlorine, methyl, tert-butyl, trifluoromethyl, methoxy and trifluoromethoxy,

and

q represents the number 0, 1 or 2,

where, if the substituent R 4 is present twice, its meanings may be identical or different,

and the salts thereof.

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

in which R 2 , R 3 , o and p each have the meanings given in claim 1 and

T 1 and T 2 are identical or different and represent (C 1 -C 4 )-alkoxycarbonyl, are either

[A] converted 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 n each have the meanings given in claim 1 and

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

and

X represents halide or tosylate,

into compounds of the formula (IV-A)

in which A, D, R 1 , R 2 , R 3 , n, o, p, T 1 and T 2 each have the meanings given above,

or

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

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

initially into compounds of the formula (IV-B)

in which R 1 , R 2 , R 3 , n, o, p, T 1 and T 2 each have the meanings given above,

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

A-D-Q  (V),

in which A and D have the meanings given in claim 1 and

Q represents a leaving group, such as, for example, halogen, tosylate or mesylate,

to give compounds of the formula (IV-C)

in which A, D, R 1 , R 2 , R 3 , 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 groups T 1 and T 2 into the dicarboxylic acids of the formula (I), and the compounds of the formula (I) are separated where appropriate by methods known to the skilled person into their enantiomers and/or diastereomers, and/or where appropriate reacted with the appropriate (i) solvents and/or (ii) bases or acids to give the salts thereof.

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

6. The pharmaceutical composition of claim 5 further comprising one or more further active ingredients selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.

7. The pharmaceutical composition as claimed in claim 5 for the treatment and/or prevention of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, thromboembolic disorders and arteriosclerosis.

8. A method for the treatment of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, thromboembolic disorders and arteriosclerosis in humans and animals by administration of an effective amount of at least one compound as defined in claim 1 .

9. A method for the treatment of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, thromboembolic disorders and arteriosclerosis in humans and animals by administration of an effective amount of a pharmaceutical composition of claim 5 .