CARBOXAMIDE COMPOUNDS AND USE THEREOF AS CALPAIN INHIBITORS Russian patent published in 2013 - IPC C07D401/04 C07D401/14 C07D409/14 A61K31/4439 A61P25/00 

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new carboxamide compounds of formula I-A' or I-A" , as well as to tautomers thereof and pharmaceutically acceptable salts thereof, wherein R¹ means hydrogen, C₁-C₁₀-alkyl, C₃-C₇-cycloalkyl-C₁-C₄alkyl, aryl-C₁-C₆-alkyl or hetaryl-C₁-C₄-alkyl, wherein aryl and hetaryl in the two last mentioned radicals may be substituted or have 1 radical R^1c; wherein R^1a represents C₁-C₆-alkoxy, R^1c is independently specified in halogen, CN, CF₃, O-CF₃, O-CHF₂, C₁-C₆-alkyl, C₁-C₆-alkoxy, hetaryl, O-CH₂-aryl, - (CH₂)_p-NR^c6R^c7 with p = 0 or 1; wherein R^c6 represents C₁-C₆-alkyl or SO₂-C₁-C₆-alkyl, and R^c7 represents C₁-C₆-alkyl, or the two radicals R^c6 and R^c7 together with an N atom form 5- or 6-member, optionally substituted C₁-C₄-alkyl nitrogen-containing heterocyclyl which can optionally have 1 heteroatom from the group O and N as ring members, R² means C₁-C₁₀-alkyl, C₃-C₇-cycloalkyl, aryl, hetaryl, wherein aryl and hetaryl in the two last mentioned radicals may be unsubstituted or carry 1, 2 or 3 identical or different R^2c radicals; wherein R^2c have one of the values specified for R^1c; R^3a and R^3b together with a carbon atom whereto attached, are C=O; X means hydrogen or a radical of formulas C(=O)-O-R^x1 or C(=O)-NR^x2R^x3, wherein R^x1 means C₁-C₆-alkyl, R^x2 means H or C₁-C₆-alkyl, and R^x2 means H, one of the variables Y¹, Y², Y³ and Y⁴ forms a nitrogen atom, and the rest variables Y¹, Y², Y³ and Y⁴ mean CH, n is equal to 0 or 1, R^y is independently specified in halogen, CN, aryl, -NH-SO₂-R^y4, -(CH₂)_p-NR^y6R^y7 with p = 0; wherein R^y4 means C₁-C₆-alkyl, R^y6 has one of the values specified for R^c6, and R^y7 has one of the values specified for R^c7; m means 0 or 1 for formulas I-A', and R^w is specified in halogen, C₁-C₆-alkyl, C₁-C₆-alkoxy, wherein C₁-C₆-alkyl can have 1 substitute R^wa, aryl, -(CH₂)_p-NR^w6R^w7 with p = 0 or 1, R^wa has one of the values specified for R^1a, or represents NR^a2SO₂R^a4, R^a2 represents H, R^a4 represents C₁-C₆-alkyl, R^w6 has one of the values specified for R^c6, R^w7 has one of the values specified for R^c7, m is equal to 0, 1 or 2 for formula I-A", and R^w6* has one of the values specified for R^w, E has one of the values specified for: -CHR_E ²-CHR_E ³-, -CH₂-O-, -O-CH₂-, -S-CH₂-, -CH₂-S-, -CH₂-SO₂-, -SO₂-CH₂-, wherein R_e ², R_e ³ represent hydrogen; wherein aryls defined above, represent mono- or bicyclic aromatic hydrocarbon radicals such as phenyl or naphthyl, and hetaryls defined above, represent 5 - or 6-member aromatic heterocyclic radicals containing 1 or 2 heteroatoms specified in nitrogen, oxygen and sulphur and can additionally contain a condensed benzene ring. Also, the invention refers to specific compounds, pharmaceutical compositions containing them and use thereof.

EFFECT: there are prepared new derivatives of carboxamide compounds effective in the treating the disorders caused by higher activity of calpain.

15 cl, 1 tbl, 195 ex