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US 6,399,824 B1Granted
Substituted cinnamic, acid guanidides, process for their preparation, their use as a medicament, and medicament comprising them
AssigneeAventis Pharma Deutschland GmbH
InventorsArmin Hofmeister, Max Hropot, Uwe Heinelt, Markus Bleich, Hans-Jochen Lang
Life of this patent
Estimating the term…
Abstract
Substituted cinnamic acid guanidides, process for their preparation, their use as a medicament or diagnostic, and medicament comprising them. Compounds of the formula I which may be obtained by reaction of a compound II with guanidine.
Claims15
A compound of the formula I,
- in which:
- at least one of R(1), R(2), R(3), R(4) and R(5) is —Xa—Yb—Ln—U;
- X is CR(16)R(17), O, S or NR(18);
- where R(16), R(7) and R(18) independently of one another are H or an alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- a is zero or1;
- Y is alkylene having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkylene-T having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms in the alkylene group, T, or T-alkylene having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms in the alkylene group;
- where T is NR(20), phenylene, O or S, where the phenylene is not substituted or is substituted by 1-3 substituents chosen from F, Cl, CF3, methyl, methoxy and NR(21)R(22);
- where R(20), R(21) and R(22) independently of one another are H or an alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- b is zero or 1;
- L is O, S, NR(23) or CkH2k;
- where k is 1, 2, 3, 4, 5, 6, 7 or 8;
- where R(23) is H or an alkyl group having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- n is zero or 1;
- U is
- or a nitrogen-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, which is substituted by an —SO2NR(30)R(31)-group;
- where R(30) and R(31) independently of one another are H or an alkyl group having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms,
- where in the alkyl group, independently of one another, one or more CH2 groups can be replaced by O, NR(35), C═O, S or C═S;
- where R(35) is H or alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- or
- R(30) and R(31) independently of one another are H, an alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, where the alkyl is chosen from partially fluorinated alkyls and completely fluorinated alkyls, (C3-C8)-cycloalkyl, phenyl-(C1-C4)-alkyl or (C3-C8)-cycloalkyl-(C1-C4)-alkyl,
- where in the alkyl or in the cycloalkyl ring, independently of one another, one or more CH2 groups can be replaced by O, NR(35), C═O, S or C═S;
- or
- R(30) and R(31) together are 4 or 5 methylene groups,
- where, independently of one another, one or more CH2 groups can be replaced by O, NR(35), C═O, S or C═S;
- or
- R(31) and R(35) together are 4 or 5 methylene groups;
- R(32), R(33) and R(34) independently of one another are H, F, Cl, Br, I, (C1-C4)-alkyl, partially fluorinated (C1-C4)-alkyl, completely fluorinated (C1-C4)-alkyl, O—(C1-C4)-alkyl, partially fluorinated O—(C1-C4)-alkyl, completely fluorinated O—(C1-C4)-alkyl, NO2, or NR(28)R(29);
- where R(28) and R(29) independently of one another are H or an alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- where the N-containing heterocycles are N- or C-bridged and are unsubstituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(36)R(37);
- R(36) and R(37) independently of one another are H, an alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinateds, and completely fluorinated alkyls, or benzyl;
- and the remaining substituents of R(1), R(2), R(3), R(4) and R(5) independently of one another are H, F, Cl, Br, I, SO2NH2, SO2CH3, NO2, NR(24)R(25), CN, unsubstituted (C1-C8)-alkyl, partially fluorinated (C1-C8)-alkyl, completely fluorinated (C1-C8)-alkyl, unsubstituted O—(C1-C8)-alkyl, partially fluorinated O—(C1-C8)-alkyl, completely fluorinated O—(C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C4)-alkyl or phenyl-(C1-C4)-alkyl,
- where the phenyl is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(11)R(12);
- R(11), R(12), R(24) and R(25) independently of one another are H or an alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- R(6) and R(7) independently of one another are H, F, Cl, Br, I, CN, an alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls, and completely fluorinated alkyls, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl,
- where the phenyl is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR(14)R(15);
- R(14) and R(15) independently of one another are H or an alkyl having 1, 2, 3 or 4 carbon atoms, where the alkyl is chosen from unsubstituted alkyls, partially fluorinated alkyls and completely fluorinated alkyls;
- or a pharmaceutically tolerable salt thereof, in any stereoisomeric form, or a mixture of any such compounds in any ratio.
34 more elements
Dependencies are inferred from the claim text.