Fluorenecarboxylic acid esters, process for the manufacture thereof, and use thereof as medicaments

1. Propellent-free inhalable solution or suspension containing the

i) active substance according to formula 1 wherein

A denotes a double-bonded group selected from among

X- denotes an anion with a single negative charge,

R denotes hydrogen, hydroxy, methyl, ethyl, —CF 3 , CHF 2 or fluorine;

R 1 and R 2 which may be identical or different denotes C 1 -C 5 -alkyl which may optionally be substituted by C 3 -C 6 -cycloalkyl, hydroxyl or halogen,or

R 1 and R 2 together denote a C 3 -C 5 -alkylene-bridge; and

R 3 , R 4 , R 3′ and R 4′ which may be identical or different denote hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkyloxy, hydroxy, —CF 3 , —CHF 2 , CN, NO 2 or halogen,

ii) an aqueous or alcoholic solvent, or a mixture of water and ethanol and

iii) an inorganic or organic acid.

2. Propellent-free inhalable solution or suspension according to claim 1 , which has a pH of 2 to 7.

3. Propellent-free inhalable solution or suspension according to claim 1 , which has a pH of 2 to 5.

4. Propellent-free inhalable solution or suspension according to claim 1 , wherein the solvent is ethanol.

5. Propellent-free inhalable solution or suspension according to claim 1 , wherein the solvent is water.

6. Propellent-free inhalable solution or suspension according to claim 1 , wherein the solvent is a mixture of water and ethanol.

7. Propellent-free inhalable solution or suspension according to claim 1 , wherein the inorganic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid and phosphoric acid or wherein the organic acid is selected from the group consisting of ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and propionic acid.

8. Propellent-free inhalable solution or suspension according to claim 1 , which additionally contains editic acid (EDTA) or one of the known salts thereof, as a stabiliser or complexing agent.

9. Propellent-free inhalable solution or suspension according to claim 1 , which additionally contains a cosolvent, excipient or additive.

10. Propellent-free inhalable solution or suspension according to claim 1 , wherein in the active substance according to formula 1

X- denotes an anion with a single negative charge selected from among chloride, bromide, 4-toluenesulphonate and methanesulphonate;

R denotes hydroxy, methyl or fluorine;

R 1 and R 2 which may be identical or different denote methyl, ethyl or fluoroethyl; and

R 3 , R 4 , R 3′ and R 4′ which may be identical or different represent hydrogen, methyl, methyloxy, hydroxy, —CF 3 , —CHF 2 or fluorine.

11. Propellent-free inhalable solution or suspension according to claim 1 , wherein in the active substance according to formula 1

A denotes a double-bonded group selected from among

X- denotes an anion with a single negative charge selected from among chloride, bromide and methanesulphonate;

R denotes hydroxy, methyl or fluorine;

R 1 and R 2 which may be identical or different denote methyl or ethyl; and

R 3 , R 4 , R 3′ and R 4′ which may be identical or different represent hydrogen, —CF 3 , —CHF 2 or fluorine.

12. Propellent-free inhalable solution or suspension according to claim 1 , wherein in the active substance according to formula 1

A denotes a double-bonded group selected from among

X- denotes bromide;

R denotes hydroxy or methyl;

R 1 and R 2 which may be identical or different denote methyl or ethyl; and

R 3, R 4, R 3′ and R 4′ which may be identical or different represent hydrogen or fluorine.

13. Propellent-free inhalable solution or suspension according to claim 1 , wherein in the active substance according to formula 1

A denotes

X- denotes bromide;

R denotes methyl;

R 1 and R 2 denotes methyl; and

R 3, R 4, R 3′ and R 4′ denote hydrogen.

14. Propellent-free inhalable solution or suspension according to claim 1 , which additionally contains sodium edetate as a stabiliser or complexing agent.

15. Propellent-free inhalable solution or suspension according to claim 9 , wherein the cosolvent, excipient or additive is selected from the group consisting of surfactants, sorbitan esters, other stabilizers, complexing agents, antioxidants, preservatives, flavourings and vitamins.

16. Propellent-free inhalable solution or suspension according to claim 10 , wherein in the active substance according to formula 1

X- denotes a bromide ion.

17. Propellent-free inhalable solution or suspension according to claim 11 , wherein in the active substance according to formula 1

X- denotes a bromide anion;

R denotes methyl or hydroxy;

R 1 and R 2 denote methyl; and

R 3 , R 4 , R 3′ and R 4′ which may be identical or different represent hydrogen, or fluorine.

18. Propellent-free inhalable solution or suspension according to claim 12 , wherein in the active substance according to formula 1

R denotes methyl; and

R 1 and R 2 denote methyl.

19. Propellent-free inhalable solution or suspension according to claim 1 , wherein in the active substance according to formula 1

A denotes a double-bonded group selected from among

20. Propellent-free inhalable solution or suspension according to claim 1 , wherein in the active substance according to formula 1

R denotes hydrogen, hydroxy, methyl, ethyl, —CF 3, CHF 2 fluorine.