AZASPIROALKANE DERIVATIVES METALLOPROTEASE INHIBITORS Russian patent published in 2010 - IPC C07D401/14 C07D401/02 C07D417/14 C07D413/14 A61K31/495 A61K31/438 A61P19/02 A61P9/00 A61P35/00 A61P37/08 

FIELD: medicine.

SUBSTANCE: invention refers to compounds of formula I or formula II, to their pharmaceutically acceptable salts, enantiomers and diastereoisomers as metalloprotease inhibitors, and also to a pharmaceutical composition based thereon and to versions of application thereof. Said compounds can find application in treatment of the diseases mediated by activity of metalloproteases, Her-2 SHEDDASE, ADAM-10 and ADAM-17, such as arthritis, cancer, cardiovascular disorders, skin diseases, inflammatory and allergic conditions, etc. In general formula I or II: A represents CWNHOH; B represents CH₂; G represents CH₂; D represents oxygen; X represents CH₂NR_b; Y represents CH₂; M represents C; U is absent or represents NR_b; V is absent or represents phenyl, or 4-10-members heterocyclyl containing 1-2 heteroatoms chosen from N and S, substituted with 0-5 groups R_e; U' is absent or represents C_1-10alkylene, O or combinations thereof; V' represents H, C_1-8alkyl, NR_bR_c, C_6-10carbocyclyl substituted with 0-3 groups R_e, or 5-14-members heterocyclyl containing 1-3 heteroatoms chosen from N, O and C substituted with 0-4 groups R_e; R_a and R_e, independently represents H, T, C_1-8alkylene-T, C(O)NR_a'(CR_b'R_c')_r-T, (CR_b'R_c')_r-O-(CR_b'R_c')_r-T, OH, Cl, F, CN, NO₂, NR^IR^II, COOR^IV, OR^IV, CONR^IR^II, C_1-8halogenalkyl, C_3-13carbocyclyl; R_b and R_c independently represents H, T, C_1-6alkylene-T, C(O)O(CR_b'R_c')_r-T, C(O)(CR_b'R_c')_r-T, S(O)_p(CR_b'R_c')_r-T; T represents H, C_1-10alkyl substituted with 0-1 groups R_b'; C_3-6carbocyclyl, 5-6-members heterocyclyl containing one oxygen atom; R_a' R_b' and R_c' independently represents H, OR^IV or phenyl; R₁ represents hydrogen; R₂ represents hydrogen; R₃ represents: (i) C_1-10alkyl; (ii) 4-14-members heterocyclyl containing 1-3 nitrogen atoms optionally substituted with one or two substitutes chosen from C_1-6alkyl, OR₁₃, 5-10-members heterocyclyl containing 1-3 heteroatoms chosen from N O and C, or phenyl; (iii) NR₁₆R₁₇; R₄ represents H; R_4' represents H; R_5' represents H; W represents oxygen; R₁₃ represents C₁-C₆alkyl; R₁₆ and R₁₇ independently represents C₁-C₁₀alkyl or phenyl where each is optionally substituted with one C_1-4alkyl; R^I and R^IIindependently represents H or C_1-6alkyl; R^IV represents C_1-6alkyl; i is equal to 0; p is equal to 1 or 2 and r is equal to 0, 1 or 2; provided that a) a spiro ring represents a stable chemical base unit and b) NR₈ and NR_b do not contain neither N-N, nor N-O bonds.

EFFECT: higher efficiency of the composition and method of treatment.

54 cl, 1 tbl, 9 dwg, 284 ex