Heterocyclic compounds suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor
View Patent ↗The invention relates to compounds of the formula (I) wherein the variables have meanings given in the claims and the description. The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a medicament for the treatment of a medical disorder susceptible to the treatment with a 5HT 6 receptor ligand.
1. A compound of the formula (I)
wherein
D is a group of the formula C
R 1 is H, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl substituted by C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, fluorinated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 3 -C 6 -alkenyl, fluorinated C 3 -C 6 -alkenyl, formyl, acetyl, propionyl or benzyl;
R 2 , R 2′ , R 3 , R 4 and R 4′ are, independently of each other, H, methyl, fluoromethyl, difluoromethyl, or trifluoromethyl;
A is 2,4-pyridylene, 3,5-pyridylene or 2,6-pyridylene, which is optionally substituted by one, two or three substituents selected from halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy;
E is NR 7 , wherein R 7 is H or C 1 -C 3 -alkyl;
Ar is a cyclic radical selected from the group consisting of phenyl, where the cyclic radical Ar carries 1 substituent R a in the 3-position of the phenyl ring;
each R a is C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, or fluorinated C 1 -C 6 -alkylthio;
and physiologically tolerated acid addition salts thereof.
2. The compound as claimed in claim 1 , wherein
R 1 is H, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl substituted by C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, fluorinated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 3 -C 6 -alkenyl, fluorinated C 3 -C 6 -alkenyl, formyl, acetyl or propionyl.
3. The compound of claim 1 , wherein R 1 is hydrogen, methyl, ethyl, n-propyl, 2-fluoroethyl, 3-fluoropropyl, 3-hydroxypropyl, cyclo-propylmethyl or allyl.
4. The compound as claimed in claim 3 , wherein R 1 is n-propyl or allyl.
5. The compound of claim 1 , wherein R 2 , R 2′ , R 3 , R 4 and R 4′ are H.
6. The compound of claim 1 , wherein A is 2,4-pyridylene or 3,5-pyridylene, which is optionally substituted by one or more substituents selected from halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy.
7. The compound as claimed in claim 6 , wherein A is 3,5-pyridylene, which is optionally substituted by one or more substituents selected from halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy.
8. The compound of claim 1 , wherein R a is selected from fluorinated C 1 -C 4 -alkoxy.
9. A compound according to claim 1 that is 3-difluoromethoxy-N-[2-(4-methyl-piperazin-1-yl)-pyridin-4-yl]-benzene sulfonamide.
10. A method for treating depression, obesity, and cognitive dysfunctions associated with Alzheimer's disease and schizophrenia, said method comprising administering an effective amount of at least one compound of claim 1 to a subject in need thereof.
11. A pharmaceutical composition comprising at least one compound according to claim 1 and at least one physiologically acceptable carrier and/or auxiliary substance.