N-biarylamides
The invention relates to N-biarylamides, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improvement in cognition, concentration power, learning power and/or memory.
1. A method for treating impairments of perception, concentration, learning and/or memory in a patient suffering from Alzheimer's disease or schizophrenia, comprising administering to the patient a compound represented by Formula (I):
in an amount effective to stimulate an alpha7 nicotinic acetylcholine receptor (α7 nAChR), in which
R 1 is a group of the formula —NR 2 —CO—NR 3 R 4 , —NR 2 —CO—CO—OR 5 , —NH—SO 2 R 6 , —SO 2 NHR 7 or —NH—CO—R 8 , where
R 2 is hydrogen or C 1 -C 6 -alkyl,
R 3 and R 4 are independently of one another hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl or phenyl, which is optionally substituted by up to 3 radicals independently of one another selected from the group of halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, trifluoromethyl and trifluoromethoxy, or
R 3 and R 4 together with the nitrogen atom to which they are bonded form a 5- to 6-membered heterocyclyl,
R 5 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl or aryl, where C 1 -C 6 -alkyl is optionally substituted by aryl,
R 6 is C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, 5- to 6-membered heterocyclyl, aryl or 5- to 6-membered heteroaryl, where C 1 -C 6 -alkyl is optionally substituted by aryl,
R 7 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, 5- to 6-membered heterocyclyl, aryl or 5- to 6-membered heteroaryl, where C 1 -C 6 -alkyl is optionally substituted by aryl,
R 8 is C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkyl or phenyl, where C 1 -C 6 -alkyl is substituted by C 1 -C 6 -alkoxy and phenyl by 1 to 3 radicals independently of one another selected from the group of halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, trifluoromethyl and trifluoromethoxy,
or a salt thereof.
2. The method of claim 1 , further comprising co-administering a second active ingredient for the treatment of Alzheimer's disease or schizophrenia.
3. The method of claim 1 , wherein the administering is by an oral, transdermal, parenteral or inhalation route.
4. The method of claim 1 , wherein the compound is selected from the group consisting of:
[(4′-{[(3R)-1-Azabicyclo[2.2.2]oct-3-ylcarbonyl]amino}biphenyl-4-yl)amino]-(oxo)acetic acid hydrochloride;
(3R)-N-{4′-[(Methylsulfonyl)amino]biphenyl-4-yl}quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{3′-[(Methylsulfonyl)amino]biphenyl-4-yl}quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{4′-[(Ethylsulfonyl)amino]biphenyl-4-yl}quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{4′-[(Phenylsulfonyl)amino]biphenyl-4-yl}quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{4′-[(Benzylsulfonyl)amino]biphenyl-4-yl }quinuclidine-3-carboxamide;
(3R)-N-[4′-(Aminosulfonyl)biphenyl-4-yl]quinuclidine-3-carboxamide hydrochloride;
(3R)-N-(4′-[(Isopropylamino)sulfonyl]biphenyl-4-yl)quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{4′-[(Benzylamino)sulfonyl]biphenyl-4-yl}quinuclidine-3-carboxamide hydrochloride;
(3R)-N-(4′-{[(Methylamino)carbonyl]amino}biphenyl-4-yl)quinuclidine-3-carboxamide;
(3R)-N-(4′-{([(Cyclopentylamino)carbonyl]amino}biphenyl-4-yl)quinuclidine-3-carboxamide hydrochloride;
(3R)-N-(4′-{([(Ethylamino)carbonyl]amino}biphenyl-4 -yl)quinuclidine-3-carboxamide;
(3R)-N-[4′-({[(3 -Methoxyphenyl)amino]carbonyl }amino)biphenyl4-yl]quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{4′-[(3 -Chlorobenzoyl)amino]biphenyl-4-yl }quinuclidine-3-carboxamide hydrochloride;
(3R)-N-{4′-[(3-Fluorobenzoyl)amino]biphenyl-4-yl }quinuclidine-3-carboxamide hydrochloride;
(3R)-N- {4′-[(2-Methoxyacetyl)amino]biphenyl-4-yl }quinuclidine-3-carboxamide hydrochloride; and
(3R)-N- {4′-[(Cyclopentylcarbonyl)amino]biphenyl-4-yl }quinuclidine-3-carboxamide hydrochloride;
or a salt thereof.
5. A method for treating impairments of perception, concentration, learning and/or memory in a patient suffering from Alzheimer' s disease or schizophrenia, comprising administering to the patient a pharmaceutical composition comprising:
i) a compound represented by Formula (I):
in an amount effective to stimulate an alpha7 nicotinic acetylcholine receptor (α7 nAChR),
in which
R 1 is a group of the formula —NR 2 —CO—NR 3 R 4 , —NR 2 —CO—CO—OR 5 , —NH—SO 2 R 6 , —SO 2 NHR 7 or —NH—CO—R 8 , where
R 2 is hydrogen or C 1 -C 6 -alkyl,
R 3 and R 4 are independently of one another hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl or phenyl, which is optionally substituted by up to 3 radicals independently of one another selected from the group of halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, trifluoromethyl and trifluoromethoxy, or
R 3 and R 4 together with the nitrogen atom to which they are bonded form a 5- to 6-membered heterocyclyl,
R 5 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl or aryl, where C 1 -C 6 -alkyl is optionally substituted by aryl,
R 6 is C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, 5- to 6-membered heterocyclyl, aryl or 5-to 6-membered heteroaryl, where C 1 -C 6 -alkyl is optionally substituted by aryl,
R 7 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, 5- to 6-membered heterocyclyl, aryl or 5- to 6-membered heteroaryl, where C 1 -C 6 -alkyl is optionally substituted by aryl,
R 8 is C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkyl or phenyl, where C 1 -C 6 -alkyl is substituted by C 1 -C 6 -alkoxy and phenyl by 1 to 3 radicals independently of one another selected from the group of halogen, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, trifluoromethyl and trifluoromethoxy,
or a salt thereof; and
ii) a pharmaceutically acceptable carrier.
6. The method of claim 5 , further comprising co-administering a second active ingredient for the treatment of Alzheimer's disease or schizophrenia.
7. The method of claim 5 , wherein the administering is by an oral, transdermal, parenteral or inhalation route.