2-heteroaryl carboxamides
View Patent ↗The invention relates to novel 2-heteroaryl carboxamides and to the use thereof for producing medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning and/or memory.
1. A compound of the formula
for the treatment of Alzheimer's disease or schizophrenia, wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl, which is optionally substituted via the nitrogen atom by a radical selected from the group of C 1 -C 4 -alkyl, benzyl and oxy,
R 2 is hydrogen or C 1 -C 6 -alkyl,
R 3 is hydrogen, halogen or C 1 -C 6 -alkyl,
R 4 is hydrogen, halogen, cyano, amino, trifluoromethyl, trifluoromethoxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylamino, formyl, hydroxycarbonyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylcarbonylamino, C 1 -C 6 -alkylaminocarbonyl, C 1 -C 4 -alkylsulphonylamino, C 3 -C 8 -cycloalkylcarbonylamino, C 3 -C 6 -cycloalkylaminocarbonyl, pyrrolyl, C 1 -C 6 -alkylaminocarbonylamino, heterocyclylcarbonyl, heterocyclylcarbonylamino, heteroarylcarbonylamino, hydroxyl, phenyl or heterocyclyl,
wherein C 1 -C 6 -alkyl is optionally substituted by hydroxyl, cyano, amino, C 1 -C 6 -alkylaminocarbonylamino, C 1 -C 6 -alkylaminocarboxyl, heterocyclyl or aryl, C 1 -C 6 -alkylaminocarbonyl is optionally substituted by C 1 -C 6 -alkoxy or C 1 -C 6 -alkylamino, C 1 -C 6 -alkylcarbonylamino is optionally substituted by C 1 -C 6 -alkoxy, and heterocyclyl is optionally substituted by oxo,
A is oxygen or sulphur,
the ring B is benzo, optionally substituted by radicals from the series halogen, cyano, formyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy,
and
E is C≡C, arylene and heteroarylene, wherein arylene and heteroarylene are optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkoxy and C 1 -C 6 -alkyl,
or a solvate, a salt or a solvate of a salt thereof.
2. The compound according to claim 1 , of the formula (I), wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
R 2 is hydrogen or C 1 -C 4 -alkyl,
R 3 is hydrogen, fluorine, chlorine, bromine or C 1 -C 4 -alkyl,
R 4 is hydrogen, fluorine, chlorine, bromine, cyano, amino, trifluoromethyl, trifluoromethoxy, C 1 -C 4 -alkyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkylamino, formyl, hydroxycarbonyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxycarbonyl, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylcarbonylamino, C 1 -C 4 -alkylaminocarbonyl, C 1 -C 4 -alkylsulphonylamino, C 3 -C 6 -cycloalkylcarbonylamino, C 3 -C 6 -cycloalkylaminocarbonyl, pyrrolyl, C 1 -C 4 -alkylaminocarbonylamino, heterocyclylcarbonyl, heterocyclylcarbonylamino, heteroarylcarbonylamino, hydroxyl, phenyl or heterocyclyl,
wherein C 1 -C 4 -alkyl is optionally substituted by hydroxyl, cyano, amino, C 1 -C 4 -alkylaminocarbonylamino, C 1 -C 4 -alkylaminocarboxyl, heterocyclyl or aryl, C 1 -C 4 -alkylaminocarbonyl is optionally substituted by C 1 -C 4 -alkoxy or C 1 -C 4 -alkylamino, C 1 -C 4 -alkylcarbonylamino is optionally substituted by C 1 -C 4 -alkoxy, and heterocyclyl is optionally substituted by oxo,
A is oxygen or sulphur,
the ring B is benzo, optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy and C 1 -C 4 -alkyl, and
E is C≡C, arylene and heteroarylene, where arylene and heteroarylene are optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 4 -alkoxy and C 1 -C 4 -alkyl,
or a solvate, a salt or solvate of a salt thereof.
3. The compound according to claim 1 , of the formula (I), wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
R 2 and R 3 are hydrogen,
R 4 is hydrogen, fluorine, chlorine, bromine, cyano, amino, trifluoromethyl, trifluoromethoxy, C 1 -C 4 -alkyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkylamino, formyl, hydroxycarbonyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxycarbonyl, C 1 -C 6 -alkylthio, C 1 -C 4 -alkylcarbonylamino, C 1 -C 4 -alkylaminocarbonyl, C 1 -C 4 -alkylsulphonylamino, C 3 -C 6 -cycloalkylcarbonylamino, C 3 -C 6 -cycloalkylaminocarbonyl, pyrrolyl, C 1 -C 4 -alkylaminocarbonylamino, heterocyclylcarbonyl, heterocyclylcarbonylamino, heteroarylcarbonylamino, hydroxyl, phenyl or heterocyclyl,
wherein C 1 -C 4 -alkyl is optionally substituted by hydroxyl, cyano, amino, C 1 -C 4 -alkylaminocarbonylamino, C 1 -C 4 -alkylaminocarboxyl, heterocyclyl or aryl, C 1 -C 4 -alkylaminocarbonyl is optionally substituted by C 1 -C 4 -alkoxy or C 1 -C 4 -alkylamino, C 1 -C 4 -alkylcarbonylamino is optionally substituted by C 1 -C 4 -alkoxy, and heterocyclyl is optionally substituted by oxo,
A is oxygen,
the ring B is benzo, optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy and C 1 -C 4 -alkyl, and
E is C≡C, arylene and heteroarylene, where arylene and heteroarylene are optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 4 -alkoxy and C 1 -C 4 -alkyl,
or a solvate, a salt, or a solvate of a salt thereof.
4. The compound according to claim 1 , of the formula (I), wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
R 2 is hydrogen or C 1 -C 6 -alkyl,
R 3 is hydrogen, halogen or C 1 -C 6 -alkyl,
R 4 is hydrogen, halogen, cyano, amino, trifluoromethyl, trifluoromethoxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylamino, formyl, hydroxycarbonyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxycarbonyl, C 1 -C 6 -alkylthio, C 1 -C 6 -alkylcarbonylamino, C 1 -C 4 -alkylsulphonylamino, C 3 -C 8 -cycloalkylcarbonylamino, pyrrolyl, C 1 -C 6 -alkylaminocarbonylamino, heterocyclylcarbonyl, phenyl or heterocyclyl,
wherein C 1 -C 6 -alkyl is optionally substituted by hydroxyl, amino, C 1 -C 6 -alkylaminocarbonylamino, C 1 -C 6 -alkylaminocarboxyl, heterocyclyl or aryl, C 1 -C 6 -alkylcarbonylamino is optionally substituted by C 1 -C 6 -alkoxy, and heterocyclyl is optionally substituted by oxo,
A is oxygen or sulphur,
the ring B is benzo, optionally substituted by radicals from the series halogen, cyano, formyl, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy, and
E is C≡C, arylene and heteroarylene, where arylene and heteroarylene are optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkoxy and C 1 -C 6 -alkyl,
or a solvate, a salt, or a solvate of a salt thereof.
5. The compound of the formula (I) according claim 1 , wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
R 2 is hydrogen or C 1 -C 6 -alkyl,
R 3 is hydrogen, halogen or C 1 -C 6 -alkyl,
R 4 is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or heterocyclyl, where alkyl is optionally substituted by a hydroxyl radical,
A is oxygen or sulphur,
the ring B is benzo, optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy, and
E is C≡C, arylene or heteroarylene, where arylene and heteroarylene are optionally substituted by radicals from the series halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy,
or a solvate, a salt, or a solvate of a salt thereof.
6. The compound according to claim 1 , of the formula
wherein
R 1 is (3R)-1-azabicyclo[2.2.2]oct-3-yl,
R 2 and R 3 are, independently of one another, hydrogen or methyl,
R 4 is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or heterocyclyl, where alkyl is optionally substituted by a hydroxyl radical, and
R B is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy,
or a solvate, a salt, or a solvate of a salt thereof.
7. The compound according to claim 1 , of the formula
wherein
R 1 is (3R)-1-azabicyclo[2.2.2]oct-3-yl,
R 2 and R 3 are, independently of one another, hydrogen or methyl,
R 4 is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or heterocyclyl, where alkyl is optionally substituted by a hydroxyl radical,
R B is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, amino, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy,
or a solvate, a salt, or a solvate of a salt thereof.
8. The compound according to claim 6 , wherein
R 1 is (3R)-1-azabicyclo[2.2.2]oct-3-yl,
R 2 and R 3 are hydrogen,
R 4 is hydrogen, fluorine, chlorine, bromine, trifluoromethoxy, hydroxymethyl, methoxy or 6-membered heterocyclyl, and
R B is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy or C 1 -C 4 -alkyl,
or a solvate, a salt, or a solvate of a salt thereof.
9. The compound according to claim 1 , of the formula
wherein
E is phenylene,
R 4 is C 1 -C 6 -alkoxy, aminomethyl, hydroxycarbonyl, C 3 -C 8 -cycloalkylcarbonylamino, a group of the formula
wherein
R 5 is C 1 -C 6 -alkyl,
n is zero, 1, 2, 3 or 4, or
5- to 6-membered heterocyclyl which is optionally substituted by oxo, and
A is sulphur or oxygen,
or a solvate, a salt, or a solvate of a salt thereof.
10. The compound according to claim 9 , of the formula (Ic)
wherein
E is phenylene,
R 4 is C 1 -C 4 -alkoxy, aminomethyl, hydroxycarbonyl, C 3 -C 6 -cycloalkylcarbonylamino, a group of the formula
wherein
R 5 is C 1 -C 4 -alkyl,
n is zero, 1 or 2, or
5- to 6-membered heterocyclyl which is optionally substituted by oxo, and
A is sulphur or oxygen,
or a solvate, a salt, or a solvate of a salt thereof.
11. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
or a solvate, a salt, or a solvate of a salt thereof.
12. Medicament comprising at least one compound according to claim 1 and at least one pharmaceutically acceptable, essentially nontoxic carrier or excipient.
13. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
or a solvate, a salt, or a solvate of a salt thereof.