The present invention relates, inter alia, to novel piperazines of the following formula: to the use of these compounds in the preparation of pharmaceutical compositions, to pharmaceutical compositions comprising the compounds, and to methods of treatment employing these compounds or compositions. The compounds show a high and selective binding affinity for the histamine H3 receptor, indicating histamine H3 receptor antagonistic, inverse agonistic or agonistic activity. As a result, the compounds are useful for the treatment of diseases or disorders related to the histamine H3 receptor.
1. A compound according to formula I
wherein R 1 is independently selected from fluoro, bromo, jodo, hydroxy, trifluoromethoxy, C 2-6 -alkoxy, C 1-6 -alkyl, amino, C 2-6 -alkylsulfanyl, C 2-6 -alkylsulfinyl, C 2-6 -alkylsutfonyl, C 1-6 -alkylamino, di-C 1-6 -alkylamino, cyano, nitro, aryl, heteroaryl and C 3-8 -cycloalkyl;
and pharmaceutically acceptable salts, solvates and prodrugs thereof.
2. A compound according to claim 1 , wherein R 1 represents bromo or cyano.
3. A pharmaceutical composition comprising, as an active ingredient, at least one compound according to claim 1 , together with one or more pharmaceutically acceptable carriers or excipients.
4. A pharmaceutical composition according to claim 3 , in unit dosage form, comprising from about 0.05 mg to about 1000 mg, from about 0.1 mg to about 500 mg, or from about 0.5 mg to about 200 mg of a compound according to claim 1 .
5. A method for the treatment of disorders or diseases related to the H3 histamine receptor selected from the following: obesity,
suppression of appetite or satiety induction, osteoarthritis, bulimia, binge eating, anorexia, impaired glucose tolerance (IGT), type 2 diabetes, allergic rhinitis, narcolepsy, asthma, and diarrhea, the method comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 .
6. A method according to claim 5 , wherein the effective amount of the compound is in the range of from about 0.05 mg to about 2000 mg, from about 0.1 mg to about 1000 mg, or from about 0.5 mg to about 500 mg per day.
7. A method according to claim 5 , for the treatment of obesity.
8. A method according to claim 5 , for the suppression of appetite or for satiety induction.
9. A method according to claim 5 , for the treatment of Impaired Glucose Tolerance (IGT).
10. A method according to claim 5 , for the treatment of type 2 diabetes.
11. A method according to claim 5 , for the treatment of allergic rhinitis or anorexia.
12. A method according to claim 5 , for the treatment of narcolepsy.