abstract |
FIELD: medicine, pharmaceutics. n SUBSTANCE: invention refers to new macrocyclic compounds of formula n or their tautomer, pharmaceutically acceptable salt, solvate or ester, wherein: X represents O or NR; Y represents -O-(CH 2 ) m COOR or -O-(CH 2 ) m CON(R) 2 , wherein groups related to a nitrogen atom, can be in a Z- or E-configuration; R 1 and R 2 independently represent hydrogen or halogen; R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 independently represent hydrogen, alkyl, OR, -O(CH 2 ) m C(O)(CH 2 ) p N(R) 2 , -O(CH 2 ) m N(R)C(O)(CH 2 ) p OR, -(CH 2 ) m N 3 or -O(CH 2 ) m N 3 ; and each R independently represents R 11 , hydrogen, alkyl, alkylamino, dialkylamino, alkoxycarbonyl, phenyl or a protective group; or two R on the same nitrogen are taken together with nitrogen for producing a 5-6-merous heterocyclic or heteroaryl ring; wherein the group contains more than one substitute R; wherein R is optionally substituted, and each R can be identical or different, and wherein the protective group is specified in ethoxymethyl, methoxymethyl, tert-butyldimethylsilyl (TBS), phenylmethylsilyl, trimethylsilyl (TMS), 2-trimethylsilyl ethoxymethyl (SEM), 2-trimethylsilylethyl, benzyl and substituted benzyl; R 11 represents a group n , n wherein Z represents an inorganic or organic counter-ion specified in a halogen, -O-alkyl, toluene sulphonate, methylsulphonate, sulphonate, phosphate, formiate or carboxylate; n represents 0, 1 or 2; m and p independently represent 0, 1 or 2; and dashed lines mean either a single, or a double bond, wherein the necessary conditions of the valence are observed by additional hydrogen atoms; and wherein in formula I′, when n represents 1, and X represents O, and the double bond is present between the carbon atoms having R 9 and R 10 , then at least one of R 5 , R 6 , R 7 , R 8 , R 9 or R 10 are other than hydrogen; and wherein in formula I′, when n represents 1, and X represents O, and the bond between the carbon atoms having R 9 and R 10 , represents the single bond, then at least one of R 5 , R 6 , R 7 or R 8 is other than hydrogen. The invention also refers to pharmaceutical compositions containing these compounds, using them and methods of treating diseases mediated by kinases and a heat-shock protein 90 HSP90. n EFFECT: preparing the new macrocyclic compounds. n 28 cl, 5 dwg, 3 tbl, 9 ex |