Claims
- 1. A benzoylguanidine of the formula I ##STR6## in which: R(1) is hydrogen, F, Cl, Br, I, CN, NO.sub.2,OH, (C.sub.1 -C.sub.8)-alkyl, (C.sub.3 -C.sub.8)-cycloalkyl, O.sub.a --(CH.sub.2).sub.b --(CF.sub.2).sub.c --CF.sub.3 ;
- a is zero or 1;
- b is zero, 1 or 2;
- c is zero, 1, 2 or 3; or
- R(1) is R(5)-SO.sub.m or R(6)R(7)N--SO.sub.2 --;
- m is zero, 1 or 2;
- R(5) and R(6) independently of one another are (C.sub.1 -C.sub.8)-alkyl, (C.sub.3 -C.sub.6)-alkenyl, CF.sub.3 or --C.sub.n H.sub.2n --R(8);
- n is zero, 1, 2, 3 or 4;
- R(7) is hydrogen or (C.sub.1 -C.sub.4)-alkyl;
- R(8) is (C.sub.3 -C.sub.7)-cycloalkyl or phenyl,
- which is not substituted or is substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, methyl, methoxy and NR(9)R(10);
- R(9) and R(10) independently of one another are hydrogen or (C.sub.1 -C.sub.4)-alkyl; or
- R(6) is H;
- or R(6) and R(7) together are 4 or 5 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, S, NH, N--CH.sub.3 or N-benzyl, or
- R(1) is --SR(11), --OR(11) or --CR(11)R(12)R(13);
- R(11) is --C.sub.p H.sub.2p --(C.sub.3 -C.sub.8)-cycloalkyl, --(C.sub.1 -C.sub.9)-heteroaryl or phenyl,
- the aromatic systems being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- R(12) and R(13) independently of one another are defined as R(11) or are hydrogen or (C.sub.1 -C.sub.4)-alkyl;
- p is zero, 1 or 2; or
- R(1) is phenyl, naphthyl, biphenylyl or (C.sub.1 -C.sub.9)-heteroaryl, the latter linked via C or N,
- which are unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- R (2) is --CF.sub.2 R(14), --CF[R(15)][R(16)], --CF[(CF.sub.2).sub.q CF.sub.3)][R(15)], --C[(CF.sub.2).sub.r --CF.sub.3 ] .dbd.CR(15)R(16);
- R(14) is (C.sub.1 -C.sub.4)-alkyl or (C.sub.3 -C.sub.6)-cycloalkyl;
- R(15) and R(16) independently of one another are hydrogen or (C.sub.1 -C.sub.4)-alkyl;
- q is zero, 1 or 2;
- r is zero, 1 or 2;
- R(3) is defined as R(1);
- R(4) is hydrogen, (C.sub.1 -C.sub.3)-alkyl, F, Cl, Br, I, CN or --(CH.sub.2).sub.s --(CF.sub.2).sub.t --CF.sub.3 ;
- s is zero or 1;
- t is zero, 1 or 2;
- or a pharmaceutically tolerable salt thereof.
- 2. A compound of the formula I as claimed in claim 1, wherein:
- R(1) is H, F, Cl, Br, CN, (C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.6)-cycloalkyl, O.sub.a --(CF.sub.2).sub.c --CF.sub.3 ;
- a is zero or 1;
- c is zero, 1, 2 or 3; or
- R(1) is R(5)-SO.sub.m or R(6)R(7)N--SO.sub.2 --;
- m is zero, 1 or 2;
- R(5) and (R6) independently of one another are (C.sub.1 -C.sub.4)-alkyl, (C.sub.3 -C.sub.6)-alkenyl, CF.sub.3 or --C.sub.n H.sub.2n --R(8);
- n is zero or 1;
- R(7) is hydrogen or (C.sub.1 -C.sub.4)-alkyl;
- R(8) is (C.sub.3 -C.sub.6)-cycloalkyl or phenyl,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, methyl, methoxy and NR(9)R(10);
- R(9) and R(10) are hydrogen or (C.sub.1 -C.sub.4)-alkyl; or
- R(6) is hydrogen; or
- R(6) and R(7) together are 4 or 5 methylene groups, of which one CH.sub.2 group can be replaced by oxygen, S, NH, N--CH.sub.3 or N-benzyl, or
- R(1) is --OR(11);
- R(11) is --C.sub.f H.sub.2f --(C.sub.3 -C.sub.6)-cycloalkyl, --(C.sub.1 -C.sub.9)-heteroaryl or phenyl,
- the aromatic systems being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- f is zero or 1; or
- R(1) is phenyl, naphthyl, biphenylyl or (C.sub.1 -C.sub.9)-heteroaryl, the latter linked via C or N, and which are unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- R(2) is --CF.sub.2 R (14), --CF[R(15)][R(16)], --CF[(CF.sub.2).sub.q --CF.sub.3)][R(15)], --C[(CF.sub.2).sub.r --CF.sub.3 ].dbd.CR(15)R(16);
- R(14) is (C.sub.1 -C.sub.4)-alkyl or (C.sub.3 -C.sub.6)-cycloalkyl;
- R(15) and R(16) independently of one another are hydrogen or (C.sub.1 -C.sub.4) alkyl;
- q is zero, 1 or 2;
- r is zero, 1 or 2;
- R(3) is defined as R(1);
- R(4) is H, C.sub.1 -C.sub.3)-alkyl, F, Cl, Br, CN or CF.sub.3 ;
- or a pharmaceutically tolerable salt thereof.
- 3. A compound of the formula I as claimed in claim 1, wherein:
- R(1) is hydrogen, F, Cl, Br, (C.sub.1 -C.sub.4)-alkyl, (C.sub.5 -C.sub.6)-cycloalkyl, O.sub.a --(CF.sub.2).sub.c --CF.sub.3 ;
- a is zero or 1;
- c is zero or 1; or
- R(1) is R(5)-SO.sub.2 ;
- R(5) is (C.sub.1 -C.sub.4)-alkyl or CF.sub.3 ; or
- R(1) is --OR(11);
- R(11) is (C.sub.4 -C.sub.6)-cycloalkyl, quinolyl, isoquinolyl, pyridyl, in each case bonded via C or N, or phenyl,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino; or
- R(1) is quinolyl, isoquinolyl, pyridyl, in each case bonded via C or N,
- or phenyl,
- which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino;
- R(2) is --CF.sub.2 R(14), --CF[R(15)][R(16)], --CF(CF.sub.3)[R(15)], --C(CF.sub.3).dbd.CR(15)R(16);
- R(14) is (C.sub.1 -C.sub.4)-alkyl or (C.sub.3 -C.sub.6)-cycloalkyl;
- R(15) and R(16) independently of one another are hydrogen or (C.sub.1 -C.sub.4)-alkyl;
- R(3) is hydrogen, F, Cl, Br, I, --SO.sub.2 Me or CF.sub.3 ;
- R(4) is hydrogen, methyl, F, Cl or --CF.sub.3 ;
- or a pharmaceutically tolerable salt thereof.
- 4. A process for the preparation of a compound of the formula I as claimed in claim 1, which comprises reacting
- a compound of the formula II ##STR7## in which R(1) to R(4) have the meaning indicated in claim 1 and L is a leaving group which can readily be substituted nucleophilically, with guanidine.
- 5. A pharmaceutical composition comprising a compound of formula I as claimed in claim 1 together with a pharmaceutically acceptable carrier.
- 6. A method for the treatment of arrhythmias, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 7. A method for the treatment of cardiac infarction, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 8. A method for the treatment of angina pectoris, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 9. A method for the treatment of ischemic heart conditions, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 10. A method for the treatment of ischemic conditions of the peripheral and central nervous systems and of stroke, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 11. A method for the treatment of ischemic conditions of peripheral organs and members, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 12. A method for the treatment of states of shock, which comprises administering to a host in need of said treatment an effective amount of a compound of the formula I as claimed in claim 1.
- 13. A method for the preservation and storage of transplants for surgical interventions, which comprises treating said transplants with an effective amount of a compound of formula I as claimed in claim 1.
- 14. A diagnostic agent for the inhibition of the Na+/H+ exchanger and the diagnosis of hypertension and proliferative diseases, which comprises a compound of formula I as claimed in claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
44 32 105 |
Sep 1994 |
DEX |
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Parent Case Info
This is a continuation of application Ser. No. 08/525,095, filed Sep. 8, 1995, now U.S. Pat. No. 5,869,531, the entire contents of which are incorporated herein by reference.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3780027 |
Cragoe, Jr. et al. |
Dec 1973 |
|
5091394 |
Englert et al. |
Feb 1992 |
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5373024 |
Lang et al. |
Dec 1994 |
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Foreign Referenced Citations (3)
Number |
Date |
Country |
5522994 |
Aug 1994 |
AUX |
602 522 |
Jun 1994 |
EPX |
604 852 |
Jul 1994 |
EPX |
Non-Patent Literature Citations (2)
Entry |
Derwent Abstract of EP 602 522, 1994. |
Derwent Abstract of EP 604 852, 1994. |
Continuations (1)
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Number |
Date |
Country |
Parent |
525095 |
Sep 1995 |
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