Anticholinergics which may be used as medicaments as well as processes for preparing them
View Patent ↗The present invention relates to new anticholinergics of general formula 1 wherein A, X − , and the groups R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 may have the meanings given in the claims and in the specification, processes for preparing them and their use as pharmaceutical compositions.
1. A method of treating asthma or COPD in a host in need thereof comprising administering by inhalation to the host an effective amount of a compound of formula 1
wherein:
A is a group selected from
X − is an anion with a single negative charge;
R 1 and R 2 , which are identical or different, are each C 1 -C 4 -alkyl, which are optionally substituted by hydroxy or halogen;
R 3 , R 4 , R 5 , and R 6 , which are identical or different, are each hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkyloxy, hydroxy, CF 3 , CN, NO 2 , or halogen;
R 7 is C 1 -C 4 -alkyl, C 1 -C 4 -alkyloxy, C 1 -C 4 -alkylene-halogen, halogen-C 1 -C 4 -alkyloxy, C 1 -C 4 -alkylene-OH, CF 3 , —C 1 -C 4 -alkylene-C 1 -C 4 -alkyloxy, —O—COC 1 -C 4 -alkyl, —O—COC 1 -C 4 -alkyl-halogen, —O—COCF 3 , or halogen.
2. The method according to claim 1 , wherein in the compound of formula 1:
X − is an anion with a single negative charge selected from chloride, bromide, methylsulphate, 4-toluenesulphonate, and methanesulphonate;
R 1 and R 2 , which are identical or different, are each a group selected from methyl, ethyl, n-propyl, and isopropyl, which are optionally substituted by hydroxy or fluorine;
R 3 , R 4 , R 5 , and R 6 , which are identical or different, are each hydrogen, methyl, ethyl, methyloxy, ethyloxy, hydroxy, fluorine, chlorine, bromine, CN, CF 3 , or NO 2 ; and
R 7 is methyl, ethyl, methyloxy, ethyloxy, —CH 2 —F, —CH 2 —CH 2 —F, —O—CH 2 —F, —O—CH 2 —CH 2 —F, —CH 2 —OH, —CH 2 —CH 2 —OH, CF 3 , —CH 2 —OMe, —CH 2 —CH 2 —OMe, —CH 2 —OEt, —CH 2 —CH 2 —OEt, —O—COMe, —O—COEt, —O—COCF 3 , —O—COCF 3 , fluorine, chlorine, or bromine.
3. The method according to claim 2 , wherein in the compound of formula 1:
X − is an anion with a single negative charge selected from chloride, bromide, and methanesulphonate;
R 1 and R 2 , which are identical or different, are each methyl or ethyl, which are optionally substituted by hydroxy or fluorine;
R 3 , R 4 , R 5 , and R 6 , which are identical or different, are each hydrogen, methyl, ethyl, methyloxy, ethyloxy, hydroxy, fluorine, chlorine, or bromine; and
R 7 is methyl, ethyl, methyloxy, ethyloxy, CF 3 , or fluorine.
4. The method according to claim 3 , wherein in the compound of formula 1:
X − is bromide;
R 1 and R 2 , which are identical or different, are each methyl or ethyl;
R 3 , R 4 , R 5 , and R 6 , which are identical or different, are each hydrogen, methyl, methyloxy, chlorine, or fluorine; and
R 7 is methyl or fluorine.
5. The method according to claim 4 , wherein in the compound of formula 1:
X − is bromide;
R 1 and R 2 , which are identical or different, are each methyl or ethyl;
R 3 , R 4 , R 5 , and R 6 , which are identical or different, denote hydrogen or fluorine; and
R 7 is methyl or fluorine.
6. The method according to one of claim 1 to 5 , wherein the method further comprises administering by inhalation to the host at least one additional active substance selected from the group consisting of: betamimetics, antiallergic agents, PAF-antagonists, leukotriene-antagonists, and steroids.
7. The method according to claim 1 or 5 , wherein the compound of formula 1 is scopine 2,2-diphenylpropionate methobromide.
8. The method according to claim 1 or 5 , wherein the compound of formula 1 is scopine 2-fluoro-2,2-diphenylacetate methobromide.
9. The method according to claim 1 or 5 , wherein the compound of formula 1 is tropenol 2,2-diphenylpropionate methobromide.
10. The method according to claim 1 or 5 , wherein the compound of formula 1 is tropenol 2-fluoro-2,2-bis(3 ,4-difluorophenyl)acetate methobromide.
11. The method according to claim 1 or 5 , wherein the compound of formula 1 is scopine 2,2-diphenylpropionate ethylbromide.
12. The method according to claim 1 or 5 , wherein the compound of formula 1 is scopine 2-fluoro-2,2-bis(3,4-difluorophenyl)acetate methobromide.
13. The method according to claim 1 or 5 , wherein the compound of formula 1 is tropenol 2-fluoro-2,2-bis(4-fluorophenyl)acetate methobromide.
14. The method according to claim 1 or 5 , wherein the compound of formula 1 is scopine 2-fluoro-2,2-bis(4-fluorophenyl)acetate methobromide.
15. The method according to claim 1 or 5 , wherein the compound of formula 1 is tropenol 2-fluoro-2,2-diphenylacetate methobromide.
16. The method according to claim 1 or 5 , wherein the compound of formula 1 is tropenol 2-fluoro-2,2-(3-chlorophenyl)acetate methobromide.