Substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines
AssigneeNovo Nordisk A/S
InventorsBernd Peschke, Rolf Hohlweg
Life of this patent
Estimating the term…
Abstract
Novel substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1 ,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines, use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds, and a method of treatment employing these compounds and compositions. The compounds show a high and selective binding affinity to 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 and disorders related to the histamine H3 receptor.
Claims16
A compound of the general formula (I):
- 30
- wherein
- n is 1, 2 or 3,
- R1a and R1b independently are hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl, C3-8-cycloalkenyl or fluoro,
- R2 is hydrogen, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl or C3-8-cycloalkenyl,
- X is
- 31
- R3a, R3b, R3c and R3d independently are hydrogen, halogen, C1-6-alkyl or C3-8-cycloalkyl, or R3a and R3b, R3a and R3c, or R3b and R3d can be taken together to form a C1-6-alkylene bridge,
- R4, R5, R6 and R7 independently are hydrogen, halogen, C1-6-alkyl or C3-8-cycloalkyl,
- Z is
- 32
- R8, R9, R10, R11 and R12 independently are
- hydrogen, cyano, nitro, halogen, carboxy, guanidino, or amidino,
- C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, C2-6-alkynyl, C1-6-alkylsulfonyl, C1-6-alkylsulfinyl, C1-6-alkylthio, C1-6-alkylcarbonyl, C3-8-cycloalkyl, C3-8-cycloalkylcarbonyl, C3-8-cycloalkenyl, aryl, arylsulfonyl, arylsulfinyl or arylthio,
- each of which may optionally be substituted with one or more groups selected from cyano, nitro, halogen, carboxy, guanidino, amidino, trifluoromethyl, trifluoromethoxy, —NR13R14—NHC(═O)R15 or —C(═O)NR13R14,
- —NR13R14, —NHC(═O)R15, —OC(═O)NR13R14, —NHC(═O)OR16 or —C(═O)NR13R14, or
- R8 and R9, R9 and R10, R10 and R11, or R11 and R12 can be taken together to form a bridge selected from C1-6-alkylene, —O—(CH2)o—O— and —O—(CH2)o—,
- o is 1, 2, 3, 4 or 5,
- R13, R14 and R15 independently are hydrogen or
- aryl, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl or C3-8-cycloalkenyl,
- each of which may optionally be substituted with one or more groups selected from cyano, nitro and halogen,
- R16 is
- aryl, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C3-8-cycloalkyl or C3-8-cycloalkenyl,
- each of which may optionally be substituted with one or more groups selected from cyano, nitro and halogen,
- as well as any diastereomer or enantiomer or tautomeric form thereof or mixtures of these or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.