SYNTHESIS OF RESORCYLIC ACID LACTONES USED AS THERAPEUTIC AGENTS Russian patent published in 2014 - IPC C07D313/00 C07D405/12 C07D405/14 A61K31/335 A61P35/00 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new macrocyclic compounds of formula

or their tautomer, pharmaceutically acceptable salt, solvate or ester, wherein: X represents O or NR; Y represents -O-(CH₂)_mCOOR or -O-(CH₂)_mCON(R)₂, wherein groups related to a nitrogen atom, can be in a Z- or E-configuration; R¹ and R² independently represent hydrogen or halogen; R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and R¹⁰ independently represent hydrogen, alkyl, OR, -O(CH₂)_mC(O)(CH₂)_pN(R)₂, -O(CH₂)_mN(R)C(O)(CH₂)_pOR, -(CH₂)_mN₃ or -O(CH₂)_mN₃; and each R independently represents R¹¹, 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; R¹¹ represents a group

,

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 R⁹ and R¹⁰, then at least one of R⁵, R⁶, R⁷, R⁸, R⁹ or R¹⁰ 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 R⁹ and R¹⁰, represents the single bond, then at least one of R⁵, R⁶, R⁷ or R⁸ 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.

EFFECT: preparing the new macrocyclic compounds.

28 cl, 5 dwg, 3 tbl, 9 ex