NEW ACTIVATORS OF SOLUBLE GUANYLATE CYCLASE AND PHOSPHODIESTERASE INHIBITORS WITH DUAL ACTION MECHANISM AND THEIR APPLICATION

摘要

FIELD: chemistry; pharmaceutics.;SUBSTANCE: present group of inventions relates to the field of chemistry and pharmaceutics, namely to a compound of the formula I or its pharmaceutically acceptable salt, where at least one of R2, R4 or R5, each independently, includes at least one fragment of ONO2 or ONO; R1 is C1-C3-alkyl, optionally substituted with F; R2 is H, C1-C3-alkyl, optionally substituted with OH, ONO, ONO2; C(O)OH, C(O)OC1-C3-alkyl, CHO, CN, C(O)N(R6)OR7, CR8=N-OR9, CR8=NR12, CR8=N-ONO2, C1-C3-alkoxy; C1-C3-alkylene-Y, wherein Y is ONO, ONO2, C(O)OH, C(O)OC1-C3-alkyl, CHO, CN, OH, OC(O)H, OC(O)-C1-C3-alkyl, C(O)N(R6)OR7, OC1-C3-alkylene-C(O)OH, OC1-C3-alkylene-C(O)OC1-C3-alkyl, OC1-C3-alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3-alkyl, CR8=N-OR9, CR8=NR12 or CR8=N-ONO2; R3 is C1-C4-alkyl, optionally substituted with F, C1-C3-alkoxy, C3-cycloalkyl; R4 is C1-C6-alkyl, optionally substituted with C3-C6-cycloalkyl, C1-C6-alkoxy, F, ONO, ONO2; R5 is SO2NR13R14; R6 is H or C1-C3-alkyl; R7 is H, C1-C3-alkyl, C1-C3-alkoxy; R8 is H, CH3 or C2H5; R9 is H, C1-C3-alkyl, optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3-alkyl, C1-C3-alkoxy, OC(O)H, OC(O)-C1-C3-alkyl, C(O)N(R6)OR7, OC1-C3-alkylene-C(O)OH; R12 is C1-C3-alkyl, optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3-alkyl, C1-C3-alkoxy, OC(O)H, OC(O)-C1-C3-alkyl, C(O)N(R6)OR7, OC1-C3-alkylene-C(O)OH; R13 and R14 together with a nitrogen atom, to which they are attached, form heterocyclic ring, wherein the specified heterocyclic ring is selected from piperidine and piperazine, wherein the specified heterocyclic ring is optionally substituted with R15; R15 is C1-C6-alkyl, optionally substituted with halogen, OH, ONO, ONO2, C1-C3-alkoxy, C1-C3-halogenalkoxy, COOR16, NR17R18, C=NR19; R16 is H or C1-C4-alkyl, optionally substituted with F, OH, ONO, ONO2, NR17R18; R17 and R18, each independently, are H or C1-C4-alkyl, optionally substituted with ONO, ONO2; R19 is C1-C4-alkyl, optionally substituted with F, ONO, ONO2; C3-C6-cycloalkyl, in addition, a pharmaceutical composition for inhibiting PDE5 based on the specified compounds is described. ;EFFECT: new compounds are obtained and described that can be used to prevent a disease facilitated by PDE5 inhibition.; ;15 cl, 3 dwg, 2 tbl, 112 ex