The invention relates to N-biarylamides useful for the prophylaxis and/or treatment of impairments of perception, concentration, learning and/or memory, and to processes for preparing them, and pharmaceutical compositions containing them.
1. A compound of the formula
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 compound as claimed in claim 1 , where
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 4 -alkyl,
R 3 and R 4 are independently of one another hydrogen, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl or phenyl, which is optionally substituted by up to 2 radicals independently of one another selected from the group of fluorine, chlorine, bromine, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -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 4 -alkyl, C 3 -C 6 -cycloalkyl, or aryl, where C 1 -C 4 -alkyl is optionally substituted by aryl,
R 6 is C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, 5- to 6-membered heterocyclyl, aryl or 5- to 6-membered heteroaryl, where C 1 -C 4 -alkyl is optionally substituted by aryl,
R 7 is hydrogen, C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkyl, 5- to 6-membered heterocyclyl, aryl or 5- to 6-membered heteroaryl, where C 1 -C 4 -alkyl is optionally substituted by aryl,
R 8 is C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkyl or phenyl, where C 1 -C 4 -alkyl is substituted by C 1 -C 4 -alkoxy and phenyl by 1 to 2 radicals independently of one another selected from the group of fluorine, chlorine, bromine, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, trifluoromethyl and trifluoromethoxy,
or a salt thereof.
3. The compound as claimed in claim 1 , where
R 1 is a group of the formula —NH—CO—NHR 3 , —NH—CO—CO—OH, —NH—SO 2 R 6 , —SO 2 NHR 7 or —NH—CO—R 8 , where
R 3 is hydrogen, C 1 -C 4 -alkyl, C 5 -C 6 -cycloalkyl or phenyl, which is optionally substituted by C 1 -C 4 -alkoxy,
R 6 is C 1 -C 4 -alkyl or phenyl, where C 1 -C 4 -alkyl is optionally substituted by phenyl,
R 7 is hydrogen or C 1 -C 4 -alkyl which is optionally substituted by phenyl,
R 8 is C 5 -C 6 -cycloalkyl, methoxymethyl or phenyl which is substituted by fluorine or chlorine,
or a salt thereof.
4. A compound of the formula
in which R 1 has the meanings indicated in claim 1 , or a salt thereof.
5. A process for preparing compound as claimed in any one of claims 1 to 4 , characterized in that
(A) compound of the formula
in which
X is hydroxy or a suitable leaving group,
is reacted with a compound of the formula
in which
R 1 has the meanings indicated in claim 1 ,
in an inert solvent, where appropriate in the presence of a condensing agent and where appropriate in the presence of a base,
or
(B) compound of the formula (II) initially is reacted with a compound of the formula
in which
Y is a suitable leaving group,
where appropriate in an inert solvent, where appropriate in the presence of a condensing agent and where appropriate in the presence of a base to give compounds of the formula
in which
Y has the abovementioned meanings,
and the latter is then reacted in a coupling reaction with compound of the formula
in which
R 1 has the meanings indicated in claim 1 , and
R 9 is hydrogen or methyl, or the two radicals together form a CH 2 CH 2 or C(CH 3 ) 2 —C(CH 3 ) 2 bridge,
in an inert solvent in the presence of a suitable catalyst and in the presence of a base, and the resulting compound of the formula I is reacted where appropriate with an appropriate acid or base to give a salt thereof.
6. A pharmaceutical composition comprising at least one of the compounds as claimed in any of claims 1 to 4 mixed with at least one pharmaceutically acceptable carrier or excipient.
7. The process of claim 5 , where X is a suitable leaving group selected from chlorine and pentafluorophenoxy.
8. The process of claim 5 , where Y is a suitable leaving group selected from triflate and halogen.
9. The process of claim 8 , where the halogen is bromine or iodine.