CCR2 receptor antagonists and uses thereof
The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD.
1. A compound of general formula (I),
A-L-D-L′-E-G (I)
wherein
A is a group selected from
C 1-4 alkyl or
piperidinyl, optionally substituted by one or more —C 1 -C 4 -alkyl, or -cyclopropyl or
morpholinyl, optionally substituted by one or more —C 1-4 -alkyl, -cyclohexyl,or -benzyl; or
pyrrolidinyl, optionally substituted by one or more —C 1 -C 4 -alkyl,-cyclopentyl,or -benzyl; or
piperazinyl, optionally substituted by one or more —C 1-4 -alkyl; or
azepanyl, optionally substituted by one or more —C 1-4 -alkyl,
L is a linker selected from
a single bond, or
M, with M being —C 1-8 -alkylene-, optionally being substituted by one or more ═O groups,
D is
L′ is
a single bond,
E is
G is a
group selected from 4-bromo-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 3,4-dichloro-phenyl, 3,5-dichloro-phenyl, 2,3-dichloro-phenyl, 2,4-dichloro-phenyl, 2,5-dichloro-phenyl, 3,5-di-trifluoromethyl-phenyl, 3-trifluoromethyl-phenyl, 3-fluoro-5-trifluoromethyl-phenyl, 3-chloro-5-trifluoromethyl-phenyl, 3-chloro-4-trifluoromethyl-phenyl, 3-isopropyl-phenyl, 4-isopropyl-phenyl, 3,5-dimethoxy-phenyl, 3-chloro-4-methoxy-phenyl and 2-methyl-4-chloro-phenyl,
optionally in form of their individual optical isomers, mixtures of their individual optical isomers, or racemates, as well as in form of their acid addition salts with pharmacologically acceptable acids.
2. The compound according to claim 1 , wherein
L is a linker selected from
a single bond, or C 1-3 -alkylene-, optionally being substituted by one ═O group,
optionally in form of their individual optical isomers, mixtures of their individual optical isomers, or racemates, as well as in form of their acid addition salts with pharmacologically acceptable acids.
3. The compound according to claim 1 , wherein
A is a group selected from
methyl, piperidin-1-yl, piperidin-3-yl, 1-methyl-piperidin-2-yl, 1-methyl-piperidin-3-yl, 1-ethyl-piperidin-3-yl, 1-propyl-piperidin-3-yl, 1-i-propyl-piperidin-3-yl, 1-cyclopropyl-piperidin-3-yl, 1-methyl-piperidin-4-yl, morpholin-4-yl, 4-i-propyl-morpholin-2-yl, 4-cyclohexyl-morpholin-2-yl, 4-benzyl-morpholin-2-yl, 4-methyl-morpholin-2-yl, 4-methyl-morpholin-3-yl, pyrrolidin-1-yl, pyrrolidin-3-yl, 1-methyl-pyrrolidin-2-yl, 1-methyl-pyrrolidin-3-yl, 1-cyclopentyl-pyrrolidin-3-yl, 1-benzyl-pyrrolidin-3-yl, 1-methyl-piperazin-4-yl, 1-i-propyl-piperazin-3-yl, 1-i-propyl-4-methyl-piperazin-3-yl, azepan-1-yl, azepan-3-yl, 1-methyl-azepan-3-yl,
L is a linker selected from
a single bond and —CH 2 —,
optionally in form of their individual optical isomers, mixtures of their individual optical isomers, or racemates, as well as in form of their acid addition salts with pharmacologically acceptable acids.
4. A compound selected from the group consisting of
and their acid addition salts with pharmacologically acceptable acids.