Diacyl-substituted guanidines, a process for their preparation, their use as medicament or diagnostic aid, and medicament containing them

Abstract

Diacyl-substituted guanidines, a process for their preparation, their use as medicament or diagnostic aid, and medicament containing them. Diacyl-substituted guanidines of the formula I are described where X(1) and X(2) are T1 is zero, 1, 2, 3 or 4, R(A) and R(B) are hydrogen, Hal, CN, OR(106), (O) (cyclo)—(fluoro)alkyl, NR(107)R(108), phenyl or benzyl, or T2a and T2b are, independently of each other, zero, 1 or 2, where the double bond can be in the E or Z configuration; or X(1) and X(2) are as are the pharmaceutically tolerated salts thereof. They are outstandingly suitable for use as antiarrhythmic pharmaceuticals possessing a cardioprotective component for the prophylaxis and treatment of infarction and for the treatment of angina pectoris, in connection with which they also inhibit or strongly reduce, in a preventive manner, the pathophysiological processes associated with the genesis of ischemically induced damage, in particular associated with the elicitation of ischemically induced cardiac arrhythmias. On account of their protective effects against pathological hypoxic and ischemic situations, the compounds of the formula I according to the invention can, as a consequence of inhibiting the cellular Na + /H + exchange mechanism, be used as pharmaceuticals for treating all acute or chronic damage elicited by ischemia, or diseases induced primarily or secondarily thereby.

1 . A diacyl-substituted guanidine of the formula I  
       
         
           
           
               
               
           
         
       
       in which: 
 X(1) and X(2) are  
                     
 T1 is zero, 1, 2, 3 or 4,  
 R(A) and R(B) are, independently, 
 hydrogen, F, Cl, Br, I, CN, OR(106), (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, O zk (CH 2 ) zl C zm F 2zm+1 , NR(107)R(108), phenyl or benzyl, 
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(109)R(110),  
 R(109) and R(110) being 
 hydrogen, (C 3 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 
 
 zl is zero, 1, 2, 3 or 4,  
 zk is zero or 1,  
 zm is 1, 2, 3, 4, 5, 6, 7 or 8,  
 R(106) is 
 hydrogen, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-perfluoroalkyl, (C 3 -C 8 )-alkenyl, (C 3 -C 8 )-cycloalkyl, phenyl or benzyl, 
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy  
 and NR(111)R(112),  
 R(111) and R(112) being 
 hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 
 
 R(107) and R(108) are, independently of each other, defined as R(106),  
 or  
 R(107) and R(108) are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl,  
 or  
 X(1) and X(2) are  
                     
 T2a and T2b are, independently of each other, zero, 1 or 2,  
 where the double bond can have the E or Z configuration;  
 or  
 X(1) and X(2) are  
                     
 T3 is zero, 1 or 2,  
 U, YY and Z are, independently of each other, C or N, 
 where U, YY and Z can carry the following number of substituents:  
                                     Bonded to a double   Number of permitted     U, YY or Z   bond in the ring   substituents           C   yes   1     C   no   2     N   yes   0     N   no   1                                         
 R(D) is hydrogen, (C 1 -C 8 )-alkyl or (C 1 -C 8 )-perfluoroalkyl, R(U1), R(U2), R(Y1), R(Y2), R(Z1) and R(Z2) are, independently of each other,  
 
 hydrogen, F, Cl, Br, I, CN, OR(114), (C 1 -C 8 )-alkyl, (C 3 -C 8 )-cycloalkyl, O zka (CH 2 ) zla C zma F 2zma+1 ,  
 NR(115)R(116), phenyl or benzyl, 
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(117)R(118), 
 R(117) and R(118) being hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 
 zka is zero or 1,  
 zla is zero, 1, 2, 3 or 4,  
 zma is 1, 2, 3, 4, 5, 6, 7 or 8,  
 R(114) is hydrogen, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-perfluoroalkyl, (C 3 -C 8 )-alkenyl, (C 3 -C 8 )-cycloalkyl, phenyl or benzyl, 
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and  
 NR(119)R(120),  
 R(119) and R(120) being hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 R(115) and R(116) are, independently of each other, defined as R(114),  
 or  
 R(115) and R(116) 
 are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl,  
 
 where, however, the constitution U is nitrogen (N), YY is nitrogen (N) and Z is carbon (C) is excepted,  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 hydrogen, F, Cl, Br, I, —C≡N, X zoa —(CH 2 ) zpa —(C zqa F 2zqa+1 ), R(110a)-SO zbm , R(110b)R(110c)N—CO, R(111a)-CO— or R(112a)R(113a)N—SO 2 —, 
 where the perfluoroalkyl group is straight-chain or branched,  
 
 X is hydrogen, S or NR(114a),  
 zoa is zero or 1, 
 R(114a) being H or (C 1 -C 3 )-alkyl,  
 
 zbm is zero, 1 or 2,  
 zpa is zero, 1, 2, 3 or 4,  
 zqa is 1, 2, 3, 4, 5, 6, 7 or 8,  
 R(110a), R(110b), R(111a) and R(112a) are, independently, 
 (C 1 -C 8 )-alkyl, (C 3 -C 8 )-alkenyl, —C zn H 2zn —R(115a) or (C 1 -C 8 )-perfluoroalkyl,  
 zn is zero, 1, 2, 3 or 4,  
 
 R(115a) is 
 (C 3 -C 8 )-cycloalkyl, phenyl, biphenylyl or naphthyl, 
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(116a)R(117a),  
 R(116a) and R(117a) being hydrogen, (C 1 -C 4 )-perfluoroalkyl or (C 1 -C 4 )-alkyl,  
 
 
 
 or  
 R(110b), R(111a) and R(112a) are also hydrogen,  
 R(110c) and R(113a) are, independently, hydrogen, (C 1 -C 4 )-perfluoroalkyl or (C 1 -C 4 )-alkyl,  
 or  
 R(110b) and R(110c) and also R(112a) and R(113a) are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, sulfur, NH, N—CH 3  or N-benzyl,  
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 (C 1 -C 8 )-alkyl, —C zal H 2zal R(118a) or (C 3 -C 8 )-alkenyl,  
 zal is zero, 1, 2, 3 or 4,  
 R(118a) is 
 (C 3 -C 8 )-cycloalkyl, phenyl, biphenylyl or naphthyl, 
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy or NR(119a)R(119b),  
 R(119a) and R(119b) being hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 (C 1 -C 9 )-heteroaryl which is linked via C or N and which is unsubstituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino,  
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 —C≡C—R(193),  
 R(193) is 
 phenyl which is not substituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy or NR(194)R(195),  
 R(194) and R(195) being hydrogen or CH 3 ,  
 
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 —Y-para-C 6 H 4 —(CO) zh —(CHOH) zi —(CH 2 ) zj —(CHOH) zk —R(123),  
 —Y-meta-C 6 H 4 —(CO) zad —(CHOH) zae —(CH 2 ) zaf —(CHOH) zag —R(124)  
 or  
 —Y-ortho-C 6 H 4 —(CO) zah —(CHOH) zao —(CH 2 ) zap —(CHOH) zak —R(125),  
 Y is oxygen, —S— or —NR(122d)-,  
 zh, zad and zah are, independently, 
 zero or 1,  
 
 zi, zj, zk, zae, zaf, zag, zao, zap and zak are, independently, 
 zero, 1, 2, 3 or 4,  
 
 where, however, in each case, 
 zh, zi and zk are not simultaneously zero,  
 zad, zae and zag are not simultaneously zero,  
 zah, zao and zak are not simultaneously zero,  
 
 R(123), R(124), R(125) and R(122d) are, independently, hydrogen or (C 1 -C 3 )-alkyl,  
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 SR(129), —OR(130), —NR(131)R(132) or —CR(133)R(134)R(135),  
 R(129), R(130), R(131) and R(133), are, independently, 
 —C zab H 2zab —(C 1 -C 9 )-heteroaryl which is unsubstituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino,  
 zab is zero, 1 or 2,  
 
 R(132), R(134) and R(135) are, independently of each other, 
 defined as R(129), or hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 —W-para-(C 6 H 4 )—R(196), —W-meta-(C 6 H 4 )—R(197) or —W-ortho-(C 6 H 4 )—R(198),  
 R(196), R(197) and R(198) are, independently, 
 (C 1 -C 9 )-heteroaryl which is linked via C or N and which is unsubstituted or is substituted by 1 to 3 substituents from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino, dimethylamino and benzyl,  
 
 W is oxygen, S or NR(136)-, 
 R(136) being hydrogen or (C 1 -C 4 )-alkyl,  
 
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 R(146)X(1a)-,  
 X(1a) is oxygen, S, NR(147), (D=O)A- or  
 NR(148)C=MN(*)R(149)-, 
 M is oxygen or sulfur,  
 A is oxygen or NR(150), and  
 D is C or SO,  
 
 R(146) is (C 1 -C 8 )-alkyl, (C 3 -C 8 )-alkenyl, (CH 2 ) zbz —C zdz F 2zdz+1  or —C zxa H 2zxa —R(151) 
 zbz is zero or 1,  
 zdz is 1, 2, 3, 4, 5, 6 or 7,  
 zxa is zero, 1, 2, 3 or 4,  
 R(151) is 
 (C 3 -C 8 )-cycloalkyl, phenyl, biphenylyl or naphthyl,  
 where the aromatic radicals are not substituted or are substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(152)R(153),  
 R(152) and R(153) being hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 R(147), R(148) and R(150) are, independently, hydrogen, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-perfluoroalkyl,  
 
 R(149) is defined as R(146),  
 
 or  
 R(146) and R(147), or R(146) and R(148), respectively, are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, sulfur, NH, N—CH 3  or N-benzyl, where A and N(*) are bonded to the phenyl nucleus of the alkanoyl parent substance,  
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 —SR(164), —OR(165), —NHR(166), —NR(167)R(168), —CHR(169)R(170), —CR(154)R(155)OH, —C≡CR(156),  
 —CR(158)=CR(157) or —[CR(159)R(160)] zt -(C≡O)—[(CR(161)R(162)] zv -R(163),  
 R(164), R(165), R(166), R(167) and R(169) are identical or different and are 
 —(CH 2 ) zy —(CHOH) zz —(CH 2 ) zaa —(CHOH) zt —R(171)  
 or  
 —(CH 2 ) zab —(CH 2 —CH 2 O) zac —R(172)  
 R(171) and R(172) being hydrogen or methyl,  
 
 zu is 1, 2, 3 or 4,  
 zv is zero, 1, 2, 3 or 4, 
 zy, zz, zaa, zab and zac are identical or different and are 
 zero, 1, 2, 3 or 4,  
 
 zt is 1, 2, 3 or 4,  
 
 R(168), R(170), R(154) and R(155) are identical or different and are hydrogen or (C 1 -C 6 )-alkyl,  
 or  
 R(169) and R(170), or R(154) and R(155), respectively, are, together with the carbon atom carrying them, a (C 3 -C 8 )-cycloalkyl,  
 R(163) 
 is hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 8 )-cycloalkyl or —C zeb H 2zeb —R(173),  
 zeb is zero, 1, 2, 3 or 4,  
 
 R(156), R(157) and R(173) are, independently, phenyl which is unsubstituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(174)R(175), 
 R(174) and R(175) being hydrogen or (C 1 -C 4 )-alkyl,  
 
 or  
 R(156), R(157) and R(173) are, independently, 
 (C 1 -C 9 )-heteroaryl which is unsubstituted or is substituted as phenyl,  
 
 R(158), R(159), R(160), R(161) and R(162) are hydrogen or methyl,  
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 R(176)-NH—SO 2 —,  
 R(176) is R(177)R(178)N—(C═Y′)—, 
 Y, is oxygen, S or N—R(179),  
 R(177) and R(178) are identical or different and are 
 hydrogen, (C 1 -C 8 )-alkyl, (C 3 -C 6 )-alkenyl or —C zfa H 2zfa —R(180)  
 zfa is zero, 1, 2, 3 or 4,  
 R(180) is (C 5 -C 7 )-cycloalkyl or phenyl which is unsubstituted or substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methoxy or (C 1 -C 4 )-alkyl,  
 
 or  
 R(177) and R(178) 
 are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, sulfur, NH, N—CH 3  or N-benzyl,  
 
 R(179) is defined as R(177) or is amidine,  
 
 
 or  
 R(101), R(102), R(103), R(104) and R(105) are, independently of each other, 
 NR(184a)R(185), OR(184b), SR(184c) or —C znx H 2znx —R(184d),  
 znx is zero, 1, 2, 3 or 4,  
 R(184d) 
 is (C 3 -C 7 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(116k)R(117k), 
 R(116k) and R(117k) being hydrogen or (C 1 -C 4 )-alkyl,  
 
 
 
 R(184a), R(184b), R(184c) and R(185) are, independently of each other, 
 hydrogen, (C 1 -C 8 )-alkyl, (C 1 -C 8 )-perfluoroalkyl or (CH 2 ) zao —R(184g), 
 zao is zero, 1, 2, 3 or 4,  
 184g is (C 3 -C 7 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(184u)R(184v), 
 R(184u) and R(184v) being hydrogen or (C 1 -C 4 )-alkyl,  
 or  
 R(184a) and R(185) are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, sulfur, NH, N—CH 3  or N-benzyl,  
 and also pharmaceutically tolerated salts thereof,  
 where, however, the following compounds are excepted:  
                     
 and  
 where, additionally, the compounds are excepted in which the radicals R(1) to R(5) are combined as follows:  
                                                             R(101)   R(102)   R(103)   R(104)   R(105)   R(105)   R(104)   R(103)   R(102)   R(101)     [X(1)]   [X(1)]   [X(1)]   [X(1)]   [X(1)]   [X(2)]   [X(2)]   [X(2)]   [X(2)]   [X(2)]           H   Cl   Cl   H   H   H   H   Cl   Cl   H     H   H   NH 2     H   H   H   H   NH 2     H   H     H   H   H   H   H   H   H   H   H   H     Cl   H   H   H   H   H   H   H   H   Cl     H   H   Cl   H   H   H   H   Cl   H   H     H   H   CH 3     H   H   H   H   CH 3     H   H     H   H   NH 2     H   H   H   H   H   H   H     H   H   Cl   H   H   H   H   H   H   H     H   H   CH 3     H   H   H   H   H   H   H                                              
 
 
 
 
     
     
         2 . A compound of the formula I as claimed in  claim 1 , wherein X(1) is identical to X(2)  
       and wherein the remaining substituents are defined as in  claim 1 .  
     
     
         3 . A compound of the formula I as claimed in  claim 1 , wherein: 
 X(1) and X(2) are                          T1 is zero or 2,    R(A) and R(B) are, independently, 
 hydrogen, F, Cl, CN, OR(106), (C 1 -C 4 )-alkyl, (C 5 -C 6 )-cycloalkyl, CF 3  or NR(107)R(108),  
 R(106) 
 is hydrogen, (C 1 -C 4 )-alkyl, CF 3 , phenyl or benzyl, where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(111)R(112),  
 R(111) and R(112) being hydrogen, CH 3  or CF 3 ,  
 
 R(107) and R(108) are, independently of each other, defined as R(106),  
 or  
 R(107) and R(108) are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl,  
   or    X(1) is                          where the double bond can be in the E or Z configuration,    or    X(1) is                          U, YY and Z are, independently of each other, C or N; 
 with, however, the restriction that only one of the positions U, YY and Z can be nitrogen;  
 where  
   U, YY and Z can carry the following number of substituents:                                    U, YY   Bonded to a double   Number of permit-     or Z   bond in the ring   ted substituents           C   yes   1     C   no   2     N   yes   0     N   no   1                                           R(D) is hydrogen,    R(U1), R(U2), R(Y1), R(Y2), R(Z1) and R(Z2) are, independently of each other, 
 hydrogen, F, Cl, CN, OR(114), CH 3 , CF 3  or NR(115)R(116)  
 R(114) 
 is hydrogen, (C 1 -C 4 )-alkyl, CF 3 , phenyl or benzyl, where the aromatic radicals are not substituted or are substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(119)R(120),  
 R(119) and R(120) being hydrogen, CH 3  or CF 3 ,  
 
 R(115) and R(116) are, independently of each other, defined as R(114),  
 or  
 R(115) and R(116) 
 are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl,  
 
   R(101) 
 is hydrogen, F, Cl, CH 3 , OH, NH 2  or CF 3 ,  
   R(102) 
 is hydrogen, F, Cl, Br, —C≡N, —C zqa F 2zqa CF 3 , R(110a)-SO 2 R(110b)R(110c)N—CO—, R(111a)-CO— or  
   R(112a)R(113a)N—SO 2 —,    R(110a), R(110b), R(111a) and R(112a) are, independently, 
 (C 1 -C 4 )-alkyl, (C 3 -C 4 )-alkenyl, —C zn H 2zn —R(115a)  
 or CF 3 ,  
 zn is zero or 1,  
 zqa is zero, 1, 2, 3, 4 or 5,  
 R(115a) 
 is (C 3 -C 6 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-2 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(116a)R(117a), 
 R(116a) and R(117a) being hydrogen or methyl,  
 or  
 R(110b), R(111a) and R(112a) are also hydrogen,  
 R(110c) and R(113a) are, independently, hydrogen or methyl,  
 
 
   R(103) 
 is —Y-para-C 6 H 4 —(CO) zh —(CHOH) zi —(CH 2 ) zj —(CHOH) zk —R(123),  
 —Y-meta-C 6 H 4 —(CO) zad —(CHOH) zae —(CH 2 ) zaf —(CHOH) zag —R(124) or  
 —Y-ortho-C 6 H 4 —(CO) zah —(CHOH) zao —(CH 2 ) zap —(CHOH) zak —R(125),  
 Y is oxygen, S or —NR(83),  
 R(123), R(124), R(125) and R(83) are, independently, hydrogen or methyl, 
 zh, zad and zah are, independently, 
 zero or 1,  
 
 zi, zk, zae, zag, zao and zak are, independently, 
 zero, 1, 2 or 3,3  
 
 zj, zaf and zap are, independently, 
 zero or 1,  
 
 where, however, in each case, zh, zi and zk are not simultaneously zero, 
 zad, zae and zag are not simultaneously zero  
 and  
 zah, zao and zak are not simultaneously zero,  
 or  
 
 
   R(103) is hydrogen, F, Cl, Br, CN, (C 1 -C 8 )-alkyl, CF 3 , (C 3 -C 8 )-alkenyl or —C zal H 2zal R(118a), 
 zal is zero, 1 or 2,  
 R(118a) is (C 3 -C 6 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and 
 NR(119a)R(119b),  
 R(119a) and R(119b) being hydrogen or CH 3 ,  
 
   or    R(103) 
 is (C 1 -C 9 )-heteroaryl which is linked via C or N and which is unsubstituted or is substituted by 1-2 substituents from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino,  
   or    R(103) 
 is —W-para-(C 6 H 4 )—R(196), —W-meta-(C 6 H 4 )—R(197) or —W-ortho-(C 6 H 4 )—R(198),  
 R(196), R(197) and R(198) are, independently, pyrrolyl, imidazolyl, pyrazolyl or pyridyl which in each case is unsubstituted or substituted by 1 to 2 radicals selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, dimethylamino and benzyl,  
 W is oxygen, —S— or NR(136)—,  
 R(136) being hydrogen or methyl,  
   or    R(103) is 
 —SR (129), —OR (130), —NR (131)R(132) or —CR(133)R(134)R(135),  
 R(129), R(130), R(131) and R(133) are, independently of each other, 
 —C zab H 2zab —(C 1 -C 9 )-heteroaryl which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino, 
 zab is zero or 1,  
 
 
 R(132), R(134) and R(135) are, independently of each other, 
 hydrogen or CH 3 ,  
 
   or    R(103) is 
 R(110a)-SO 2  or R(112a)R(113a)N—SO 2 —,  
 R(110a) is 
 (C 1 -C 4 )-alkyl, CF 3 , (C 3 -C 4 )-alkenyl or —C zn H 2zn —R(115a),  
 zn is zero or 1,  
 
 R(115a) is 
 (C 3 -C 6 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and 
 NR(116a)R(117a),  
 R(116a) and R(117a) being hydrogen or CH 3 ,  
 
 
 R(112a) is 
 hydrogen, (C 1 -C 4 )-alkyl, CF 3 , (C 3 -C 4 )-alkenyl or —C za H 2za —R(115a),  
 za is zero or 1,  
 
 R(115a) is 
 (C 3 -C 6 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and 
 NR(116a)R(117a),  
 R(116a) and R(117a) being hydrogen or CH 3 ,  
 
 
 R(113a) is 
 hydrogen or CH 3 ,  
 
 or  
 R(112a) and R(113a) are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl,  
   or    R(103) is 
 R(146)X(1a)-,  
 X(1a) is oxygen, S, NR(147), (C═O)A- or  
 NR(148)C=MN(%)R(149)-, 
 M is oxygen, and  
 A is oxygen or NR(150),  
 R(146) and R(147) are, independently, hydrogen, (C 1 -C 6 )-alkyl, (C 3 -C 4 )-alkenyl,  
 (CH 2 ) zbz C zdz F 2zdz+1  or C zxa H 2zxa —R(151), 
 zbz is zero or 1,  
 zdz is 1, 2, 3, 4, 5, 6 or 7,  
 zxa is zero or 1,  
 
 
 R(151) 
 is (C 3 -C 6 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy or NR(152)R(153),  
 R(152) and R(153) being hydrogen or CH 3 ,  
 
 R(148) 
 is hydrogen or (C 1 -C 4 )-alkyl,  
 
 R(149) is defined as R(146),  
 or  
 20 R(146) and R(147), or R(146) and R(148), respectively, are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl,  
 where A and N(*) are bonded to the phenyl nucleus of the benzoylguanidine parent substance,  
   or    R(103) 
 is —SR(164), —OR(165), —NHR(166), —NR(167)R(168), —CHR(169)R(170), —[CR(154)R(155)OH], —C≡CR(156), —CR(158)=CR(157) or  
 —[CR(159)R(160a)] zz -(CO)-[CR(161)R(162)] zv -R(163),  
 R(164), R(165), R(166), R(167) and R(169) are identical or different and are 
 —(CH 2 ) zy —(CHOH) zz —(CH 2 ) zaa —(CHOH) zt —R(171) or  
 —(CH 2 ) zab —O—(CH 2 —CH 2 O) zac —R(172),  
 
 R(171) and R(172) are hydrogen or methyl, 
 zu is 1 or 2,  
 zv is zero, 1 or 2,  
 zy, zz, zaa, zab and zac are identical or different and are  
 zero, 1 or 2,  
 
 zt is 1, 2 or 3,  
 R(168), R(170), R(154) and R(155) are identical or different and are 
 hydrogen or methyl,  
 
 or  
 R(169) and R(170), or R(154) and R(155), respectively, together with the carbon atom carrying them, are a (C 3 -C 6 )-cycloalkyl,  
 R(163) is 
 hydrogen, (C 1 -C 4 )-alkyl, (C 3 -C 6 )-cycloalkyl or  
 —C zeb H 2zeb —R(173),  
 zeb is zero, 1 or 2,  
 
 R(156), R(157) and R(173) are, independently of each other, 
 phenyl which is unsubstituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and  
 NR(174)R(175), 
 R(174) and R(175) being hydrogen or CH 3 ,  
 
 
 or  
 R(156), R(157) and R(173) are, independently of each other, 
 (C 1 -C 9 )-heteroaryl which is unsubstituted or is substituted as phenyl,  
 
 R(158), R(159), R(160), R(161) and R(162) are hydrogen or methyl,  
   or    R(103) 
 is R(176)-NH—SO 2 —,  
   R(176) 
 is R(177)R(178)N—(C═Y′)—,  
 Y′ is oxygen, S or N—R(179),  
 R(177) and R(178) are identical or different and are hydrogen, (C 1 -C 4 )-alkyl, (C 3 -C 4 )-alkenyl or —C zfa H 2zfa —R(180), 
 zfa is zero or 1,  
 
   R(180) 
 is (C 5 -C 7 )-cycloalkyl or phenyl which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methoxy or methyl,  
 or  
 R(177) and R(178) are together 4 or 5 methylene groups of which one CH 2  group can be replaced by oxygen, S, NH, N—CH 3  or N-benzyl, 
 R(179) is defined as R(177),  
 
   R(104) 
 is hydrogen, CF 3  (C 1 -C 8 )-alkyl or —C zal H 2zal R(118a),  
 zal is zero or 1,  
 R(118a) 
 is (C 3 -C 6 )-cycloalkyl or phenyl which is not substituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(119a)R(119b),  
 R(119a) and R(119b) being hydrogen or CH 3 ,  
 
   or 
 R(104)  
 is quinolyl, isoquinolyl, pyrrolyl, pyridyl or imidazolyl which are linked via C or N and which are unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxyl, amino, methylamino and dimethylamino,  
   or    R(104) 
 is R(110a)-SO 2  or R(112a)R(113a)N—SO 2 —,  
 R(110a) 
 is (C 1 -C 4 )-alkyl or CF 3 ,  
 
 R(112a) 
 is hydrogen, (C 1 -C 4 )-alkyl, CF 3  or —C za H 2za —R(115a),  
 za is zero or 1,  
 
   R(115a) 
 is phenyl which is not substituted or is substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(116a)R(117a), 
 R(116a) and R(117a) being hydrogen or CH 3 ,  
 
 R(113a) 
 is hydrogen or CH 3 ,  
 
   or    R(104) 
 is —C≡CR(193),  
 R(193) 
 is phenyl which is unsubstituted or substituted by 1-2 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR(194)R(195),  
 R(194) and R(195) being hydrogen or CH 3 ,  
 
   R(105) 
 is hydrogen.  
   
     
     
         4 . A process for preparing a compound I as claimed in  claim 1 , wherein 
 a) two equivalents of the compounds of the formula II are reacted with one equivalent of the guanidine,                          where X(1) and X(2) have the given meaning and L is a leaving group which can readily be substituted nucleophilically, or    b) a compound of the formula Ia                          is reacted with a compound of the formula III                          with the participation of a base, where X(1) and X(2) have the given meaning and L is a leaving group which can readily be substituted nucleophilically,    and wherein conversion takes place, where appropriate, into a pharmaceutically tolerated salt.    
     
     
         5 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment of arrhythmias.  
     
     
         6 . A method for treating arrhythmias, wherein an effective quantity of a compound I as claimed in  claim 1  is treated with the customary additives and administered in a suitable form for administration.  
     
     
         7 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment or prophylaxis of cardiac infarction.  
     
     
         8 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment or prophylaxis of angina pectoris.  
     
     
         9 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment or prophylaxis of ischemic conditions of the heart.  
     
     
         10 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment or prophylaxis of ischemic conditions of the peripheral and central nervous system and of stroke.  
     
     
         11 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment or prophylaxis of ischemic conditions of peripheral organs and limbs.  
     
     
         12 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment of shock conditions.  
     
     
         13 . The use of a compound I as claimed in  claim 1  for preparing a medicament for employment in surgical operations and organ transplantations.  
     
     
         14 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the preservation and storage of transplants for surgical procedures.  
     
     
         15 . The use of a compound I as claimed in  claim 1  for preparing a medicament for the treatment of diseases in which cell proliferation represents a primary or secondary cause, and consequently its use as an anti-atherosclerotic agent, or as an agent against diabetic late complications, cancerous diseases, fibrotic diseases such as pulmonary fibrosis, hepatic fibrosis or renal fibrosis, and against hyperplasia of the prostate.  
     
     
         16 . The use of a compound I as claimed in  claim 1  for preparing a scientific tool for inhibiting the Na + /H +  exchanger and for diagnosing hypertension and proliferative diseases.  
     
     
         17 . A medicine containing an effective quantity of a compound I as claimed in  claim 1.