Patent RU-2293085-C2 (RU)
Title: 3,7-diazabicyclo[3.3.0]octanes and their using in treatment of cardiac arrhythmia
Inventor: B ERSNE MAGNUS
IPC: A61P9/06
Filed: 2002-01-29
Granted: 2007-02-10
Abstract: 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 (C 1 -C 12 )-alkyl (possibly substituted and/or terminating by one or more groups chosen from aryl, Het 1 , -C(O)R 5a , -OR 5b , -N(R 6 )R 5c , -C(O)XR 7 , -C(O)N(R 8 )R 5d  and -S(O) 2 R 9 ), Het 2 , -C(O)R 5a , -C(O)XR 7  or -S(O) 2 R 9  wherein R 5a  - R 5d  in each case mean independently hydrogen atom (H), (C 1 -C 6 )-alkyl (possibly substituted and/or terminating by one or more substitute chosen from -OH, (C 1 -C 6 )-alkoxy-group, cyano-group, aryl, Het 3  and -NHC(O)R 10 ), aryl or Het 4 ; R 10 means H, (C 1 -C 4 )-alkyl; R 6  means H, aryl; X means oxygen atom (O); R 7  means in each case (C 1 -C 12 )-alkyl (wherein alkyl group can be substituted and/or terminating by one substitute chosen from -OH, cyano-group, (C 1 -C 6 )-alkoxy-group, -SO 2 R 13a , -C(O)R 13b  and Het 5 ) wherein R 13a  and R 13b  mean independently (C 1 -C 6 )-alkyl; R 8  means in each case H, (C 1 -C 12 )-alkyl, (C 1 -C 6 )-alkoxy-group (wherein two latter groups are substituted possibly and/or terminating by one substitute chosen from -OH, (C 1 -C 4 )-alkyl and (C 1 -C 4 )-alkoxy-group), -D-aryl, -D-Het 6 , -D-S(O) 2 R 15a  wherein R 15a  means independently aryl; D means a direct bond or (C 1 -C 6 )-alkylene; R 9  means in each case (C 1 -C 6 )-alkyl (possibly substituted and/or terminating by one substitute chosen from aryl) or aryl; R 2  means H, -E-OR 16 , -E-N(R 17 )R 18  or in common with R 3  represent =O; R 3  means H or in common with R 2  represent =O; R 16  means H, (C 1 -C 6 )-alkyl or -E-aryl; R 17  means H; R 18  means H; E means in each case a direct bond or (C 1 -C 4 )-alkylene; A means -G-; B means -Z-, -Z-N(R 22 )-Z-, -Z-S(O) n -. -Z-O- (wherein in two latter groups Z is bound to carbon atom carrying R 2  and R 3 ); G means a direct bond or (C 1 -C 6 )-alkylene; Z means a direct bond or (C 1 -C 4 )-alkylene; R 22  means independently H; R 4  means aryl or het 13  wherein both these groups are substituted possibly with one or more substitute chosen from -OH, cyano-group, halogen atom, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy-group, -C(O)R 24c  or -S(O) n R 23c ; Het 13  means 5-6-membered heterocyclic group comprising one or more heteroatoms chosen from oxygen, nitrogen and/or sulfur; Het 1  - Het 6  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 (C 1 -C 6 )-alkyl or -C(O)R 24c  wherein R 23c  means in each case independently (C 1 -C 6 )-alkyl; R 24c  means in each case H or (C 1 -C 6 )-alkyl; n means 0, 1 or 2 in each case; R a  - R 1  mean independently H or (C 1 -C 4 )-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, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy-group, -C(O)R 24c  or -S(O) n R 23c ; or it pharmaceutically acceptable derivative under condition that: (a) when R 2  means -E-OR 16  or -E-N(R 17 )R 18  wherein E means a direct bond then: (1) A can't mean a direct bond; and (2) B doesn't mean -N(R 22 )-, -S(O) n -. -O- or -N(R 22 )-Z- (wherein in the latter group -N(R 22 ) is bound to carbon atom carrying R 2  and R 3 ; (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 R 3  represent =O, and B means -Z-N(R 22 )- or -N(R 22 )-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