Patent IL-121590-A (IL)
Title: Phenyl-substituted alkenylcarboxylic acid guanidines, process for their preparation, and pharmaceutical compositions containing them
IPC: C07C279/22
Filed: 1997-08-21
Abstract: Anti-arrhythmic cardioprotective phenyl-substituted alkenylcarboxylic acid guanidides of the formula in which: T is 1083 י" ב בסיון התשס" ב - May 23, 2002 R(A) is hydrogen, F, Cl, Br, I, CN, O, OR(6), (C1-C4)-alkyl, Or(CH2)aCbF2b+1, (C3-C8)-cycloalkyl or NR(7)R(8) r is zero or 1; a is zero, 1, 2, 3 or 4;b is 1, 2, 3 or 4; R(6) is (C1-C4)-alkyl, (C1-C4)-perfluoroalkyl, (C3-C6)-alkenyl, C3-C8)-cycloalkyl, phenyl or benzyl, the phenyl nucleus not being substituted or being substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(9)R(10); R(9) and R(10) are H, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl; R(7) and R(8) independently of one another are defined as R(6); or R(7) and R(8) together are 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R(B) R(C) and R(D) independently are defined as R(A); x is zero, 1 or 2; y is zero, 1 or 2; R(F) is hydrogen, F, Cl, Br, I, CN, OR(12), (C1-C8)-alkyl, Op(CH2)fCgF2g+1, (C3-C8)-cycloalkyl or (C1-C9)-heteroaryl; p is zero or 1; f is zero, 1, 2, 3 or 4; g is 1, 2, 3, 4, 5, 6, 7 or 8; R(12) is (C1-C8)-alkyl, (C1-C4)-perfluoroalkyl, (C3-C8)-alkenyl, (C3-C8)-cycloalkyl, phenyl or benzyl the phenyl nucleus not being substituted or being substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(13)R(14); R(13) and R(14) are H, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl; R(E) is defined as R(F); R(1) is defined as T; or R(1) is hydrogen, -OkCmH2m+1, -On(CH2)pCqF2q+1, F, Cl, Br, I, CN, -(C=O)-, N=C(NH2)2, -SOrR(17), -SOr2NR(31)R(32); -Ou(CH2)vC6H5, -Ou2-(C1-C9)- heteroaryl is -Su2-(C1-C9)-heteroaryl; k is zero or 1; m is zero, 1, 2, 3, 4, 5, 6, 7 or 8; n is zero or 1; p is zero, 1, 2, 3 or 4; q is 1, 2, 3, 4, 5, 6, 7 or 8; r is zero, 1, 2; R(17) is (C1-C8)-alkyl; u is zero or 1; r2 is zero, 1 or 2; R(31) and R(32) independently of one another hydrogen, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl; or R(31) and R(32) together 4 or 5 methylene groups one of which can be replaced by oxygen, S, NH, N-CH3 or N-Benzyl; u2 is zero or 1; v is zero, 1, 2, 3 or 4; the phenyl nucleus not being substituted or being substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, -(CH2)wNR(21)R(22), NR(18)R(19) and (C1-C9)-heteroaryl; R(18), R(19), R(21) and R(22) independently of one another are (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl; w is 1, 2, 3 or 4; the heterocycle of the (C1-C9)-heteroaryl being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl or methoxy; R(2), R(3), R(4) and R(5) independently of one another are defined as R(1), or R(1) and R(2) or R(2) and R(3) in each case together are -CH-CH=CH-CH-, which is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy- (CH2)w2NR(24)R(25) and NR(26)R(27); R(24), R(25), R(26) and R(27) are H, (C1-C4)-alkyl or (C1-C4)-perfluoroalkyl; w2 is 1, 2, 3 or 4; the radical T being present in the molecule at least twice, but only three times at most; or their pharmaceutically tolerable salts. 1084 י" ב בסיון התשס" ב - May 23, 2002