NOVEL OXABISPIDINIC COMPOUNDS AND USE THEREOF IN TREATING CARDIAC ARRHYTHMIA Russian patent published in 2010 - IPC C07D498/08 A61K31/5386 A61P9/06 

FIELD: chemistry.

SUBSTANCE: invention relate to oxabispidinic compounds of formula I, ,where R¹ is C_1-12alkyl (where the given alky group is substituted with a group selected from phenyl, Het¹, N(R^5a)R⁶, -OR^5c, -S(O)₂N(R^9b)R^9c and -N(R^9b)S(O)₂R^9d); R^5a is H; R^5c is C_1-6alkyl (which is substituted with phenol) or phenyl; R⁶ is H or -C(O)OR^10b; R^10b is C_1-6alkyl; R^9b in each case where it is used in the given description of the invention represents H or C_1-6alkyl; R^9c and R^9d in each case it is used in the given description of the invention independently presents C_1-6alkyl (possibly substituted with one or more substitutes, selected from halogen or phenyl), phenyl or Het⁷, or R^9c is H; R² is H or OR¹³; R³ is H; R¹³ is H; Het¹ and Het⁷ independently represent 5-12-member heterocyclic groups containing one or more heteroatoms, selected from oxygen and nitrogen, where these groups are possibly substituted with one or more substitutes selected from halogen and C_1-6alkyl; A is a direct bond, -J-, J-S(O)₂N(R^19b)- or -J-N(R^19c)S(O)₂- (where in the last two groups -J is bonded to the nitrogen of an oxabispidinic ring); B is Z-{[C(O)]_aC(H)(R^20a)}_b-, -Z-[C(O)]_cN(R^20b)-, -Z-N(R^20c)S(O)₂-, -Z-S(O)₂N(R^20d)-, -Z-S(O)_n-, -Z-O- (where in the last six groups Z is bonded to a carbon atom, carrying R² and R³), -N(R^20e)-Z-, -N(R^20f)S(O)₂-Z-, -S(O)₂N(R^20g)-Z- or -N(R^20h)C(O)O-Z- (where in the last four groups Z is bonded to a phenyl group which is possibly substituted with a R⁴ group); J is C_1-6alkylene, possibly broken by a -S(O)₂N(R^19d)- or -N(R^19e)S(O)₂- group and/or possibly substituted with a substitute selected form -OH; Z is a direct bond or C_1-4alkylene, possibly broken by a -N(R²⁰ⁱ)S(O)₂- or -S(O)₂N(R^20j)- group; a, b and c possibly represent 0 or 1; n is 0, 1 or 2; R^19b-R^19e in each case where used in the given description of the invention independently represents H or C_1-6alkyl; R^20a is H or together with the only substitute R4 on the position of the phenyl group, which is an ortho-position relative the position where group B is bonded, represents C_2-4alkylene, possibly broken or ending with O, N(H) or N(C_1-6alkyl) group; R^20b is H or C_1-6alkyl; R^20c-R^20j in each case when used in the given description of the invention independently represents H or C_1-6alkyl; or R^20g and R²⁰ⁱ independently represent C_1-6alkyl, substituted with 3,5-dimethylisoxazolyl; G is CH; R⁴ is one or more possible substitutes selected from cyano, halogen, C_1-4alkyl and C_1-6alkoxy, possibly substituted with one or more hanogen and a R⁴ substitute on the position of the phenyl group, which is an ortho-position relative the position where group B is bonded, together with R^20a can represent C_2-4alkylene; broken or ending with O or N(H) or a N(C_1-6alkyl) group; R⁴¹-R⁴⁶ independently represent H; where each phenyl group is possibly substituted with one or more substitutes selected from halogen, cyano, C_1-6alkyl and C_1-6alkoxy (where the last two groups are possibly substituted with one or more halogen atoms); or to their pharmaceutically acceptable salts. The invention also relates to methods of producing said compounds, as well as to a pharmaceutical composition based on said compounds, with HERG-channel blocking activity.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine for preventing and treating arrhythmia, particularly cardiac and ventricular arrhythmia.

32 cl, 1 tbl, 15 ex