Patent RU-2379311-C9 (RU)
Inventor: BJOERE ANNIKA
IPC: A61K31/5386
Filed: 2005-06-13
Granted: 2010-05-27
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relate to oxabispidinic compounds of formula I,   ,where R 1  is C 1-12 alkyl (where the given alky group is substituted with a group selected from phenyl, Het 1 , N(R 5a )R 6 , -OR 5c , -S(O) 2 N(R 9b )R 9c  and -N(R 9b )S(O) 2 R 9d ); R 5a  is H; R 5c  is C 1-6 alkyl (which is substituted with phenol) or phenyl; R 6  is H or -C(O)OR 10b ; R 10b  is C 1-6 alkyl; R 9b  in each case where it is used in the given description of the invention represents H or C 1-6 alkyl; R 9c  and R 9d  in each case it is used in the given description of the invention independently presents C 1-6 alkyl (possibly substituted with one or more substitutes, selected from halogen or phenyl), phenyl or Het 7 , or R 9c  is H; R 2  is H or OR 13 ; R 3  is H; R 13  is H; Het 1  and Het 7  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 1-6 alkyl; A is a direct bond, -J-, J-S(O) 2 N(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)] a C(H)(R 20a )} b -, -Z-[C(O)] c N(R 20b )-, -Z-N(R 20c )S(O) 2 -, -Z-S(O) 2 N(R 20d )-, -Z-S(O) n -, -Z-O- (where in the last six groups Z is bonded to a carbon atom, carrying R 2  and R 3 ), -N(R 20e )-Z-, -N(R 20f )S(O) 2 -Z-, -S(O) 2 N(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 R 4  group); J is C 1-6 alkylene, possibly broken by a -S(O) 2 N(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 1-4 alkylene, possibly broken by a -N(R 20i )S(O) 2 - or -S(O) 2 N(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 1-6 alkyl; 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 2-4 alkylene, possibly broken or ending with O, N(H) or N(C 1-6 alkyl) group; R 20b  is H or C 1-6 alkyl; R 20c -R 20j  in each case when used in the given description of the invention independently represents H or C 1-6 alkyl; or R 20g  and R 20i  independently represent C 1-6 alkyl, substituted with 3,5-dimethylisoxazolyl; G is CH; R 4  is one or more possible substitutes selected from cyano, halogen, C 1-4 alkyl and C 1-6 alkoxy, possibly substituted with one or more hanogen and a R 4  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 2-4 alkylene; broken or ending with O or N(H) or a N(C 1-6 alkyl) group; R 41 -R 46  independently represent H; where each phenyl group is possibly substituted with one or more substitutes selected from halogen, cyano, C 1-6 alkyl and C 1-6 alkoxy (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