Claims
- 1. A benzoylguanidine of the formula I ##STR4## in which: R(1) is H, F, Cl, Br, I, CN, NO.sub.2, (C.sub.1 -C.sub.8)-alkyl, (C.sub.3 -C.sub.8)-cycloalkyl or X.sub.a --(CH.sub.2).sub.b --(CF.sub.2).sub.c --CF.sub.3,
- X is oxygen, S or NR(5),
- a is zero or 1,
- b is zero, 1 or 2,
- c is zero, 1, 2 or 3,
- R(5) is H, (C.sub.1 -C.sub.4)-alkyl or --C.sub.d H.sub.2d R(6),
- d is zero, 1, 2, 3 or 4,
- R(6) is (C.sub.3 -C.sub.8)-cycloalkyl, phenyl, biphenylyl or naphthyl, where the phenyl, biphenyl or naphthyl radicals are not substituted or are substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3, methyl, methoxy and NR(7)R(8), with R(7) and R(8) being, independently, H or (C.sub.1 -C.sub.4)-alkyl, or
- R(1) is --SR(10), --OR(10) or --CR(10O)R(11)R(12),
- R(10) is --C.sub.f H.sub.2f --(C.sub.3 -C.sub.8)-cycloalkyl, --(C.sub.1 -C.sub.9)-heteroaryl or phenyl, where the heteroaryl or phenyl system is unsubstituted or is substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dirnethylamino,
- f is zero, 1 or 2,
- R(11) and (R12), independently of each other, are defined as R(10) or are hydrogen or (C.sub.1 -C.sub.4)-alkyl, 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 are substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino, or
- (R1) is --SR(13), --OR(13), --NHR(13), --NR(13)R(14), --CHR(13)R(15), --C[R(15)R(16)]OH, --C.tbd.CR(18), --C[R(19)].dbd.CR(18), --[CR(20)R(21)].sub.k --(CO)--[CR(22)R(23)R(24)].sub.1
- R(13) and R(14), identically or differently, are --(CH.sub.2).sub.g --(CHOH).sub.h --(CH.sub.2).sub.i --(CHOH).sub.j --R(17),
- R(17) is hydrogen, methyl or --(CH.sub.2).sub.g --O--(CH.sub.2 --CH.sub.2 O).sub.h --R(24),
- g, h and i, identically or differently, are zero, 1, 2, 3 or 4,
- j is 1, 2, 3 or 4,
- R(15) and R(16), identically or differently, are
- hydrogen, (C.sub.1 -C.sub.8)-alkyl or, together with the carbon atom carrying them, a (C.sub.3 -C.sub.8)-cyclo-alkyl,
- R(18) is phenyl,
- which is unsubstituted or is substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3 methyl, methoxy and NR(25)R(26) with R(25) and R(26) being H or (C.sub.1 -C.sub.4)-alkyl, or
- R(18) is (C.sub.1 -C.sub.8)-heteroaryl,
- which is unsubstituted or is substituted as phenyl, or
- R(18) is (C.sub.1 -C.sub.6)-alkyl,
- which is unsubstituted or is substituted by 1 to 3 OH, or
- R(18) is (C.sub.3 -C.sub.8,)-cycloalkyl, and
- R(19), R(20), R(21), R(22) and R(23) are hydrogen or methyl,
- k is zero, 1, 2, 3 or 4,
- l is zero, 1, 2, 3 or 4,
- R(24) is H, (C.sub.1 -C.sub.6)-allcyl, (C.sub.3 -C.sub.8,)-cycloalkyl
- or --C.sub.m H.sub.2m --R(18),
- m is 1, 2, 3 or 4,
- R(2) and R(3) are defined as R(1), and
- R(4) is (C.sub.1 -C.sub.3)-alkyl, F, Cl Br, I, CN or --(CH.sub.2).sub.n --(CF.sub.2).sub.o --CF.sub.3,
- with the proviso that the compound ortho-chlorobenzoylguanidine hydrochloride is excluded,
- n is zero or 1,
- o is zero, 1 or 2,
- or a pharmaceutically tolerated salt thereof.
- 2. A compound of the formula I as claimed in claim 1, wherein:
- R(1) is H, F, Cl, Br, CN, NO.sub.2, (C.sub.1 -C.sub.8)-alkyl, (C.sub.3 -C.sub.8)-cycloalkyl or X.sub.a --(CF.sub.2).sub.c --CF.sub.3,
- X is oxygen or S,
- a is zero or 1,
- c is zero, 1, 2 or 3, or
- R(1) is --SR(10) or --OR(10),
- R(10) is --C.sub.f H.sub.2f --(C.sub.3 -C.sub.6)-cycloalkyl,--(C.sub.1 -C.sub.9)-heteroaryl or phenyl, where the --(C.sub.1 -C.sub.9)-heteroaryl or phenyl system is unsubstituted or is substituted by 1 to 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)-heteroanyl, the latter linked via C or N, and which are unsubstituted or are substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino, or
- (R1) is --SR(13), --OR(13), --NHR(13), --NR(13)R(14), --C.tbd.--CR(18), --C[R(19)].dbd.CR(18),
- R(13) and R(14), identically or differently, are --(CH.sub.2).sub.g --(CHOH).sub.h --(CH.sub.2).sub.i --(CHOH).sub.j --R(17),
- R(17) is hydrogen, methyl or --(CH.sub.2).sub.g --O--(CH.sub.2 --CH.sub.2 O).sub.h --R(24),
- g, h and i, identically or differently, are zero, 1 or 2,
- is 1 or 2,
- R(18) is phenyl, which is unsubstituted or is substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3, methyl, methoxy and NR(25)R(26) with R(25) and R(26) being H or (C.sub.1 -C.sub.4)-alkyl, or
- R(18) is (C.sub.1 -C.sub.9)-heteroaryl, which is unsubstituted or is substituted as phenyl, or
- R(18) is (C.sub.1 -C.sub.6)-alkyl,
- which is unsubstituted or is substituted by 1 to 3 OH, or
- R(18) is (C.sub.3 -C.sub.8)-cycloalkyl, and
- R(19) is hydrogen or methyl,
- R(2) and R(3) are defined as R(1), and
- R (4) is (C.sub.1 -C.sub.2)-alkyl, F, Cl Br, CN or --(CH.sub.2).sub.n --(CF.sub.2).sub.o --CF.sub.3,
- with the proviso that the compound ortho-chlorobenzoylguanidine hydrochloride is excluded,
- n is zero or 1,
- o is zero or 1,
- or a pharmaceutically tolerated salt thereof.
- 3. A compound of the formula I as claimed in claim 1, wherein:
- R(1) is H, F, Cl, (C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.6)-cycloalkyl or X.sub.a --(CF.sub.2).sub.2 --CF.sub.3,
- X is oxygen,
- a is zero or 1,
- c is zero or 1, or
- R(1) is --SR(10) or --OR(10),
- R(10) is (C.sub.4 -C.sub.6,)-cycloalkyl, quinolyl, isoquinolyl, pyridyl or phenyl, which is unsubstituted or is substituted by 1 to 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 phenyl, quinolyl, isoquinolyl, pyridyl or imidazolyl, bonded via C or N, which are unsubstituted or are substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF.sub.3, CH.sub.3, methoxy, hydroxyl, amino, methylamino and dimethylamino, or
- (R1) is --C.tbd.CR(18),
- R(18) is phenyl or (C.sub.5 -C.sub.6)-cycloalkyl,
- R(2) and R(3) are defined as R(1), and
- R(4) is methyl, F, Cl or CF.sub.3,
- with the proviso that the compound ortho-chlorobenzoylgiuanidine hydrochloride is excluded,
- or a pharmaceutically tolerated salt thereof.
- 4. A process for preparing a compound I as claimed in claim 1, which process comprises reacting
- a compound of the formula II ##STR5## in which R(1) to R(4) have the meanings given in claim 1 and L is a leaving group which is able to be nucleophilically substituted with guanidine.
- 5. A composition for treating arrhythmias, comprising an effective amount of a compound of formula (I) according to claim 1, together with a pharmaceutically acceptable carrier.
- 6. A method of treating arrhythmias, comprising administering to a host in need thereof an effective amount of a compound of formula (I) according to claim 1.
- 7. A composition for treating or preventing cardiac infarction, comprising an effective amount of a compound of formula (I) according to claim 1, together with a pharmaceutically acceptable carrier.
- 8. A method of treating or preventing cardiac infarction, comprising administering to a host in need thereof an effective amount of a compound of formula (I) according to claim 1.
- 9. A composition for treating or preventing angina pectoris, comprising an effective amount of a compound of formula (I) according to claim 1, together with a pharmaceutically acceptable carrier.
- 10. A method of treating or preventing angina pectoris, comprising administering to a host in need thereof an effective amount of a compound of formula (I) according to claim 1.
- 11. A composition for treating or preventing ischemic conditions of the heart, comprising an effective amount of a compound of formula (I) according to claim 1, together with a pharmaceutically acceptable carrier.
- 12. A method of treating or preventing ischemic conditions of the heart, comprising administering to a host in need thereof an effective amount of a compound of formula (I) according to claim 1.
Priority Claims (1)
Number |
Date |
Country |
Kind |
43 28 869 |
Aug 1993 |
DEX |
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Parent Case Info
This application is a continuation of Ser. No. 08/657,434, filed Jun. 3, 1996, now abandoned, which is a continuation of Ser. No. 08/449,262, filed May 24, 1995, now abandoned, which is a continuation of Ser. No. 08/294,798, filed Aug. 25, 1994, now abandoned.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3780027 |
Cragoe et al. |
Dec 1973 |
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5091394 |
Englert et al. |
Feb 1992 |
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5516805 |
Lang et al. |
May 1996 |
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Foreign Referenced Citations (2)
Number |
Date |
Country |
0556673 |
Aug 1993 |
EPX |
0556674A1 |
Aug 1993 |
EPX |
Non-Patent Literature Citations (3)
Entry |
Mildner et al., "Inhibition of Urease by Some Triazole, Urea, and Guanidine Derivatives," Croatica Chemica Acta, 46(1):79-82 (1974). |
Englert et al II, Chemical Abstracts, vol. 115, #71158m (1991). |
Lang et al II, Chemical Abstracts, vol. 119, #270818j (1993). |
Continuations (3)
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Parent |
657434 |
Jun 1996 |
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Parent |
449262 |
May 1995 |
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Parent |
294798 |
Aug 1994 |
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