FIELD: medicine.
SUBSTANCE: invention relates to compounds with a structure selected from formulas I-a, I-b, I-f, I-g and I-h, or their pharmaceutically acceptable salts, which have modulating activity against calpains CAPN1, CAPN2 and CAPN9. In the specified formulas, A2 is selected from a group consisting of C6-10 aryl, 5-10-element heteroaryl containing from 1 to 2 heteroatoms selected from N, O and/or S, and a single bond; A4 is selected from a group consisting of C6-10 aryl, 5-10-element heteroaryl containing from 1 to 2 heteroatoms selected from N, O and/or S, -(CR2)n-S-(CR2)n-, -(CR2)n-S(=O)-(CR2)n-, -(CR2)n-SO2-(CR2)n-, -(CR2)n-O-(CR2)n-, -(CR2)n-C(=S)-(CR2)n-, -(CR2)n-C(=O)-(CR2)n-, -(CR2)n-CH=CH-(CR2)n-, etc., where each R is -H; A3 is selected from a group consisting of optionally substituted C6-10 aryl, optionally substituted 5-10-element heteroaryl containing from 1 to 2 heteroatoms selected from N, O and/or S, optionally substituted 3-10-element heterocyclyl containing from 1 to 2 heteroatoms selected from N, O and/or S, and optionally substituted C3-10 carbocyclyl, etc.; A5 is C1-4 alkyl; A6 is selected from a group consisting of C6-10 aryl, 5-10-element heteroaryl containing from 1 to 2 heteroatoms selected from N, O and/or S, C1-4 alkyl and C2-4 alkenyl; A7 is a single bond; R1 is selected from a group consisting of H and -CONR2R3; each R2 and R3 are independently selected from -H, optionally substituted C1-4 alkyl, 2-5-element polyethylene glycol, C3-7 carbocyclyl and optionally substituted C6-10 aryl(C1-C6)alkyl; R6 is -H; each n is independently selected from integers from 0 to 3; each of A and Z is independently selected from a group consisting of C(R4) and N. When the compound has the structure of the formula I-a, B and D are C(R4); when the compound has the structure of the formula I-b, B is selected from a group consisting of C(R4) and N, and D is C(R4); each R4 is independently selected from a group consisting of -H, C1-4 alkyl, C1-4 halogenalkyl, C3-7 carbocyclyl, halogen, hydroxy and C1-C3 alkoxy; when the compound has the structure of the formula I-f, Y is selected from a group consisting of NR5, O, S and SO2, and X is selected from a group consisting of C(R4) and N; when the compound has the structure of the formula I-g or formula the I-h, Y is selected from a group consisting of NR5 and S, and X is C(R4), or Y is selected from O and SO2, and X is selected from a group consisting of C(R4) and N; R5 is selected from a group consisting of -H, C1-4 alkyl, C1-4 halogenalkyl and C3-7 carbocyclyl. The invention also relates to specific compounds, a pharmaceutical composition containing the specified compounds, a method for the treatment of fibrotic disease using them, as well as their use for the treatment of fibrotic disease.
EFFECT: obtaining compounds for the treatment of fibrotic disease.
60 cl, 7 tbl, 239 ex
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