Ortho-substituted benzoylguanidines, including composition and methods of using them

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.