N-(benzimimdazol-2-yl)-cyclopropane carboxamides as lysophosphatidic acid antagonists

A pharmaceutical composition comprising a compound of Formula (I)

• or its stereoisomers or tautomers, or pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, wherein
• R1′, R1″, R4′, R4″ are each independently H, Hal, OH, CN, NO2, NH2, A, NH(LA), N(LA)2, or COOH,
• R2, R3 are each independently H, LA or Hal,
• R5, R6 are each independently H or LA,
• X is C or N, wherein 0, 1 or 2 X are N, and the remaining X are C,
• A is a unbranched or branched alkyl based substituent having up to 15 carbon atoms, wherein one, two or three CH2 groups may be replaced by O, S, NH, N(LA), CONH, NHCO, SO2, COO or cyc, and 1-7H atoms may be replaced by Hal, and one CH3 group may be replaced by cyc,
• LA is unbranched or branched alkyl having 1, 2, 3 or 4 carbon atoms,
• cyc is a mononuclear, aliphatic or aromatic, 4, 5 or 6 membered homo or heterocycle having 1 to 3 N—, O— and/or S atoms, and
• Hal is F, Cl, Br or I, together with a pharmaceutically acceptable carrier.

A kit consisting of separate packs of

• a) an effective amount of a compound of Formula (I)
• or its stereoisomers or tautomers, or pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, wherein
• R1′, R1″, R4′, R4″ are each independently H, Hal, OH, CN, NO2, NH2, A, NH(LA), N(LA)2, or COOH,
• R2, R3 are each independently H, LA or Hal,
• R5, R6 are each independently H or LA,
• X is C or N, wherein 0, 1 or 2 X are N, and the remaining X are C,
• A is a unbranched or branched alkyl based substituent having up to 15 carbon atoms, wherein one, two or three CH2 groups may be replaced by O, S, NH, N(LA), CONH, NHCO, SO2, COO or cyc, and 1-7H atoms may be replaced by Hal, and one CH3 group may be replaced by cyc,
• LA is unbranched or branched alkyl having 1, 2, 3 or 4 carbon atoms,
• cyc is a mononuclear, aliphatic or aromatic, 4, 5 or 6 membered homo or heterocycle having 1 to 3 N—, O— and/or S atoms, and
• Hal is F, Cl, Br or I and
• b) an effective amount of a further medicament active ingredient.

A compound of Formula (I)

• or its stereoisomers or tautomers, or pharmaceutically acceptable salts of each of the foregoing, including mixtures thereof in all ratios, wherein
• R1′, R1″, R4′, R4″ are each independently H, Hal, OH, CN, NO2, NH2, A, NH(LA), N(LA)2, or COOH,
• R2, R3 are each independently H, LA or Hal,
• R5, R6 are each independently H or LA,
• X is C or N, wherein 0, 1 or 2 X are N, and the remaining X are C,
• A is a unbranched or branched alkyl based substituent having up to 15 carbon atoms, wherein one, two or three CH2 groups may be replaced by O, S, NH, N(LA), CONH, NHCO, SO2, COO or cyc, and 1-7H atoms may be replaced by Hal, and one CH3 group may be replaced by cyc,
• LA is unbranched or branched alkyl having 1, 2, 3 or 4 carbon atoms,
• cyc is a mononuclear, aliphatic or aromatic, 4, 5 or 6 membered homo or heterocycle having 1 to 3 N—, O— and/or S atoms, and
• Hal is F, Cl, Br or I,
• with the proviso that said compound is not
• 2-Phenyl-cyclopropanecarboxylic acid (6-methanesulfonyl-benzothiazol-2-yl)-amide,
• Phenyl-cyclopropanecarboxylic acid (1H-benzoimidazol-2-yl)-amide,
• N-[1-[2-(diethylamino)ethyl]-1H-benzimidazol-2-yl]-2-phenyl-cyclopropane carboxamide,
• N-(1-methyl-1H-benzimidazol-2-yl)-2-phenyl-cyclopropane carboxamide,
• 2-phenyl-N-(1-propyl-1H-benzimidazol-2-yl-cyclopropane carboxamide,
• N-(1-ethyl-1H-benzimidazol-2-yl)-2-phenyl-cyclopropane carboxamide,
• 2-(4-chlorophenyl)-N-(1-methyl-1H-benzimidazol-2-yl)-cyclopropane carboxamide, or
• N-1H-benzimidazol-2-yl-2-phenyl-cyclopropane carboxamide.