3,7-DIAZABICYCLO[3.3.0]OCTANES AND THEIR USING IN TREATMENT OF CARDIAC ARRHYTHMIA Russian patent published in 2007 - IPC C07D487/04 A61K31/40 A61P9/06 

FIELD: organic chemistry, medicine, cardiology, pharmacy.

SUBSTANCE: invention relates to novel 3,7-diazabicyclo[3.3.0]octanes of the formula (I): wherein wavy lines mean the possible relative cis- or trans-stereochemistry; R means (C₁-C₁₂)-alkyl (possibly substituted and/or terminating by one or more groups chosen from aryl, Het¹, -C(O)R^5a, -OR^5b, -N(R⁶)R^5c, -C(O)XR⁷, -C(O)N(R⁸)R^5d and -S(O)₂R⁹), Het², -C(O)R^5a, -C(O)XR⁷ or -S(O)₂R⁹ wherein R^5a - R^5d in each case mean independently hydrogen atom (H), (C₁-C₆)-alkyl (possibly substituted and/or terminating by one or more substitute chosen from -OH, (C₁-C₆)-alkoxy-group, cyano-group, aryl, Het³ and -NHC(O)R¹⁰), aryl or Het⁴; R¹⁰means H, (C₁-C₄)-alkyl; R⁶ means H, aryl; X means oxygen atom (O); R⁷ means in each case (C₁-C₁₂)-alkyl (wherein alkyl group can be substituted and/or terminating by one substitute chosen from -OH, cyano-group, (C₁-C₆)-alkoxy-group, -SO₂R^13a, -C(O)R^13b and Het⁵) wherein R^13a and R^13b mean independently (C₁-C₆)-alkyl; R⁸ means in each case H, (C₁-C₁₂)-alkyl, (C₁-C₆)-alkoxy-group (wherein two latter groups are substituted possibly and/or terminating by one substitute chosen from -OH, (C₁-C₄)-alkyl and (C₁-C₄)-alkoxy-group), -D-aryl, -D-Het⁶, -D-S(O)₂R^15a wherein R^15a means independently aryl; D means a direct bond or (C₁-C₆)-alkylene; R⁹ means in each case (C₁-C₆)-alkyl (possibly substituted and/or terminating by one substitute chosen from aryl) or aryl; R² means H, -E-OR¹⁶, -E-N(R¹⁷)R¹⁸ or in common with R³ represent =O; R³ means H or in common with R² represent =O; R¹⁶ means H, (C₁-C₆)-alkyl or -E-aryl; R¹⁷ means H; R¹⁸ means H; E means in each case a direct bond or (C₁-C₄)-alkylene; A means -G-; B means -Z-, -Z-N(R²²)-Z-, -Z-S(O)_n-. -Z-O- (wherein in two latter groups Z is bound to carbon atom carrying R² and R³); G means a direct bond or (C₁-C₆)-alkylene; Z means a direct bond or (C₁-C₄)-alkylene; R²² means independently H; R⁴ means aryl or het¹³ wherein both these groups are substituted possibly with one or more substitute chosen from -OH, cyano-group, halogen atom, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy-group, -C(O)R^24c or -S(O)_nR^23c; Het¹³ means 5-6-membered heterocyclic group comprising one or more heteroatoms chosen from oxygen, nitrogen and/or sulfur; Het¹ - Het⁶ in each case mean independently 5-6-membered heterocyclic groups comprising one or more heteroatoms chosen from oxygen, nitrogen and/or sulfur wherein these heterocyclic groups are substituted possibly with one or more substitutes comprising (C₁-C₆)-alkyl or -C(O)R^24c wherein R^23c means in each case independently (C₁-C₆)-alkyl; R^24c means in each case H or (C₁-C₆)-alkyl; n means 0, 1 or 2 in each case; R^a - R¹ mean independently H or (C₁-C₄)-alkyl wherein each aryl or aryloxy-group (if not indicated otherwise) is substituted possibly with one or more substitutes chosen from -OH, cyano-group, halogen atom, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy-group, -C(O)R^24c or -S(O)_nR^23c; or it pharmaceutically acceptable derivative under condition that: (a) when R² means -E-OR¹⁶ or -E-N(R¹⁷)R¹⁸ wherein E means a direct bond then: (1) A can't mean a direct bond; and (2) B doesn't mean -N(R²²)-, -S(O)_n-. -O- or -N(R²²)-Z- (wherein in the latter group -N(R²²) is bound to carbon atom carrying R² and R³; (b) this compound is not 3,7-bis-(1-phenylethyl)-3,7-diazabicyclo[3.3.0]octane, 3-methyl-7-benzyl-3,7-diazabicyclo[3.3.0], 3-cyclohexyl-7-benzyl-3,7-diazabicyclo[3.3.0]octane, 3-(thiazol-2-yl)-7-benzyl-3,7-diazabicyclo[3.3.0]octane, 3-(2-pyrimidyl)-7-benzyl-3,7-diazabicyclo[3.3.0]octane, 3-(5,5-dimethoxy)pentyl-7-benzyl-3,7-diazabicyclo[3.3.0]octane; (c) when R in common with R³ represent =O, and B means -Z-N(R²²)- or -N(R²²)-Z- then G is not a direct bond. Compounds of the formula (I) can be used as components of a pharmaceutical composition in treatment or prophylaxis of arrhythmia. Also, invention describes methods for its synthesis and intermediate compounds used in these methods.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

38 cl, 6 ex