Patent IL-120358-A (IL)
Title: Ortho-substituted benzoylguanidines, process for their preparation and pharmaceutical or diagnostic compositions comprising them
IPC: C07C279/22
Filed: 1997-03-03
Abstract: Antiarrhythmic, cardioprotective ortho-substituted benzoylguanidines of the formula in which: R(1) is H, F, Cl, Br, I, CN, NO2, alkyl, having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkoxy having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, cycloalkoxy having 3, 4, 5, 6, 7 or 8 carbon atoms or Xa- (CH2)b-(CF2)c-CF3; X is oxygen or NR(5), a is zero or 1; 801 ט' באייר התשס" ב - April 21, 2002 b is zero, 1 or 2; c is zero, 1, 2 or 3; R(5) is H, alkyl having 1, 2, 3 or 4 carbon atoms or -C2H2dR(6); d is zero, 1, 2, 3 or 4; R(6) is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenylyl or naphthyl, where the aromatic radicals phenyl, biphenylyl or naphthyl are unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(7)R(8); R(7) and R(8) are, independently, H or alkyl having 1, 2, 3 or 4 carbon atoms; R(1) is-SR(10), -OR(10) or -CR(10)R(11)R(12); R(10) is CfH2f-cycloalkyl having 3, 4, 5, 6, 7 or carbon atoms in the cycloalkyl ring, or phenyl, where phenyl is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino and dimethylamino; f is zero, 1 or 2; R(11) and R(12) are, independently of each other, defined as R(1), or hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or R(1) is phenyl, naphthyl, biphenylyl or heteroaryl having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, with the latter being linked by a C atom of the ring, which are in each case unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxyl, amino, methylamino and dimethylamino, or R(1) is -SR(13), -OR(13), -NHR(13), -NR(13)R(14), -CHR(13)R(15), -C[R(15)R(16)OH], -C:CR(18), -C[R(19)]=CHR (18) or -[C R(20) R (21)]k- (CO}-[CR(22)R(23)1-R(24), k is zero, 1, 2, 3 or 4; l is zero, 1, 2, 3 or 4; R(13) and R(14) are, identically or differently, -(CH2)g-(CHOH)h-(CH2)i-(CHOH)j-R(17) or -(CH2)g-O-(CH2-CH2O)h-R(24); R(17) is hdyrogen or methyl, 802 ט' באייר התשס" ב - April 21, 2002 g, h and i are, identically or differently, zero, 1, 2, 3 or 4; with the proviso that when R(13) and R(14) are (CH2)g,-O-(CH2-CH2O)h-R24, g and h are not zero, j is 1, 2, 3, or 4; R(15) and R(16) are, identically of differently, hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, or are, together with the carbon atom carrying them, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; R(18) is phenyl, which is unsubstituted or substituted by 1 - 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(25)R(26); R(25) and R(26) are H or alkyl haivng 1, 2, 3, or 4 carbon atoms; or R(18) is heteroaryl having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, or R(18) is heteroaryl having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, which is unsubstituted or substituted as phenyl; or R(18) is alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms, which is unsubstituted or substituted by 1-3 OH; or R(18) is cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; R(19), R(20), R(21), R(22) and R(23) are, identically or differently, hydrogen or methyl; R(24) is H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or -CmH2m-R(18); m is 1, 2, 3 or 4; one of the two substituents R(2) and R(3) is hydroxyl; and the other of the subsitutents R(2) and R(3) in each case is defined as R(1); R(4) is alkyl having 1, 2, 3 or 4 carbon atoms; alkoxy having 1, 2, 3 or 4 carbon atoms, F, Cl, Br, I or -(CH2)n-(CH2)o-CF3; n is zero or 1; o is zero or 1; with the proviso that when R(13) and R(14) are (CH2)g-O-(CH2-CH2O)h-R24, g and h are not zero, and the pharmaceutically tolerated salts thereof.