NEW DIAMIDES PYRIMIDIN-4,6 OF DICARBOXYLIC ACID FOR SELECTIVE INHIBITION OF COLLAGENASES Russian patent published in 2009 - IPC C07D239/28 C07D409/12 C07D401/12 C07D413/14 C07D413/12 C07D405/14 C07D405/12 A61K31/505 A61K31/506 A61K31/541 A61P19/00 A61P19/02 A61P19/04 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns to new diamides of pyrimidine-4,6-dicarboxylic acid of I formula, selective inhibitors of collagenases possessing properties which concern to the metalloproteinase superfamily and the matrix metalloproteinases. The bonds render influence on hyperactivity of the matrix metalloproteinase-13 (MMP-13) and thus do not render influence on MMP-3 and MMP-8. In the formula I R1 means an atom of hydrogen, R2 means - (C₁-C₆)-alkyl where alkyl is unitary replaced by phenyl where phenyl is replaced 1) -(C₀-C₆)-alkyl-C(O)-N(R9)-(R10), where R9 and R10 identical or different and independently from each other mean i) atom of hydrogen or ii) - (C₁-C₆)-alkyl or R9 and R10 together with atom of nitrogen to which they are bound, form 5, 6-links the sated cycle, and instead of one or two other atoms of carbon there can be also a heteroatom from an oxygen row, sulphur and nitrogen, and in case of nitrogen atoms of nitrogen independently from each other can be unsubstituted or substituted with (C₁-C₆)-alkyl, 2) -(C₀-C₆)-alkyl-C(O)-NH-SN, 3) -O-(C₀-C₆)-alkyl-C(O)-N(R9)-(R10) where R9 and R10 have the specified above value, 4) -(C₀-C₆)-alkyl-C(O)-N (R8)-(C₀-C₆)-alkyl-N(R9)-(R10) where R8 means hydrogen, R9 and R10 have the specified above value, 5) -(C₀-C₆)-alkyl-C(O)-N(R8)-(C₀-C₆)-alkyl-Het, and R8 has the specified above value, and Het means the sated or nonsaturated monocyclic heterocyclic system with number of links from 3 to 6 which contains in a cycle of 1 or 2 identical or different heteroatoms from a number nitrogen, oxygen and sulphur and unsubstituted or one-, two- or triple independently from each other is replaced by halogen, b) hydroxy,) -(C₁-C₆)-alkyl, and alkyl is unsubstituted or one-, two- or triple is substituted by halogen, d)=0,e)-Het, R4 and R5 or R5 and R6 together with atom of Carboneum to which they are bound, independently from each other form 5 or 6-unit cycle which is sated and contains one or two heteroatoms from an oxygen row.

EFFECT: obtaining of bonds which can find application for treatment of degenerate diseases of joints, such as osteoarthritis, rheumatic disease.

7 cl, 3 tbl, 117 ex