EP1140056A2 - Die verwendung von hemmern des natrium-wasserstoff-austauschers zur herstellung eines medikaments zur verhinderung von altersbedingten organ-dysfunktionen, altersbedingten erkrankungen und zur lebensverlängerung - Google Patents

Die verwendung von hemmern des natrium-wasserstoff-austauschers zur herstellung eines medikaments zur verhinderung von altersbedingten organ-dysfunktionen, altersbedingten erkrankungen und zur lebensverlängerung

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Publication number
EP1140056A2
EP1140056A2 EP99959387A EP99959387A EP1140056A2 EP 1140056 A2 EP1140056 A2 EP 1140056A2 EP 99959387 A EP99959387 A EP 99959387A EP 99959387 A EP99959387 A EP 99959387A EP 1140056 A2 EP1140056 A2 EP 1140056A2
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EP
European Patent Office
Prior art keywords
alkyl
group
substituted
zero
hydrogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
EP99959387A
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German (de)
English (en)
French (fr)
Inventor
Wolfgang Linz
Hans-Jochen Lang
Bela Kelety
Peter Schmid
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanofi Aventis Deutschland GmbH
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Aventis Pharma Deutschland GmbH
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Publication date
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Publication of EP1140056A2 publication Critical patent/EP1140056A2/de
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • inhibitors of the sodium-hydrogen exchanger for the manufacture of a medicament for the prevention of age-related organ dysfunctions, age-related diseases and for the prolongation of life
  • the invention describes the use of inhibitors of the cellular sodium-hydrogen exchanger in human and veterinary medicine for the prevention of age-related functional disorders and dysfunctional changes in organs of the body and for the prevention of age-related diseases and for the prolongation of life while maintaining an improved quality of life.
  • NHE sodium / hydrogen exchanger
  • the important mechanism of action of the NHE inhibitors in acute ischemia is that they reduce the increased sodium ion influx which arises in acutely deficient tissue through activation of the NHE due to intracellular acidification. This will delay the situation of tissue sodium overload. Since sodium and calcium ion transport are coupled to one another in the heart tissue, this prevents the life-threatening calcium overload of the heart cells.
  • NHE inhibitors in addition to the protective effects against acute ischemic events and the subsequent equally acute reperfusion events, also have direct therapeutically utilizable effects against diseases and disorders of the entire mammalian organism, which were related to the phenomena of the chronic aging process and which are independent of acute deficient blood circulation and occur under normal, non-ischemic conditions.
  • NHE inhibitors diseases and disorders that are mainly caused by age-related changes in vital organs and their function and are becoming increasingly important in the aging organism.
  • Related diseases and disorders of organs and their functions act NHE inhibitors, such as Cariponde, through a cascade of primary and secondary mechanisms that have not yet been fully elucidated in their mechanism.
  • a life-prolonging and aging-protective effect could therefore not be expected for the NHE inhibitors or are predicted, quite apart from the fact that, to our knowledge, such pronounced and strong effects are not known by any at the moment
  • a class of active substances was shown in a comparable manner.
  • a life-prolonging effect with ACE inhibitors in particular with Ramip ⁇ l treatment, has recently been reported (Linz W, Jessen T, Becker RHA, Scholkens BA, Wiemer G Long-term ACE Inhibition doubles lifespan of hypertensive rats Circulation 1997, 96 3164 - 3172)
  • This life-prolonging effect only applies to hypertensive rats or organisms, which due to their high blood pressure have a shorter life expectancy compared to normotensive rats or organisms.
  • the life-prolonging effect of ACE inhibitors therefore only relates to high-pressure animals and can be Optimally, only achieve the lifespan of a normotensive organism.
  • ACE inhibitors Because the effect of ACE inhibitors is at least to a large extent caused by their hypotensive effects on high-pressure individuals, it was not surprising that ACE inhibitors lack lifelong effects on normotensive individuals Likewise, ACE inhibitors could not be observed to have comparable inhibitory effects on age-related organ damage or the development of cancer induced by the aging process.
  • age-related dysfunction Diseases related to age-related dysfunction, age-related wear and tear of organs are, for example, the insufficient responsiveness and reactivity of the blood vessels to contraction and relaxation reactions.
  • This age-related decrease in vascular responsiveness to constrictive and relaxing stimuli which are an essential process of the cardiovascular system and thus of life and health, can be significantly reduced or reduced by NHE inhibitors.
  • An important function and a measure for maintaining vascular responsiveness is the blockade or retardation of age-related progressive endothelial dysfunction, which can be reversed in a highly significant manner by NHE inhibitors.
  • An example of a further parameter that characterizes the aging process is the decrease in the contractility of the heart and the decrease in the adaptation of the heart to a required pumping power of the heart.
  • This reduced cardiac output as a result of the aging process is in most cases associated with a dysfunction of the heart, which is caused, among other things, by the incorporation of connective tissue into the heart tissue.
  • This connective tissue storage is characterized by an increase in the weight of the heart, by an increase in the heart and by a reduced heart function. It was surprising that such aging of the heart organ could be almost completely inhibited.
  • Inhibition of proliferation can be cured, but that the age-related incidence of cancer was prevented by NHE inhibitors and was significantly delayed. Particularly noteworthy is the finding that age-related diseases of all organs and not only certain forms of cancer are prevented or significantly delayed.
  • NHE inhibitors also makes it possible to combine these NHE inhibitors with other gerontologically active principles, measures, substances and natural substances, which are based on a different mechanism of action, such as active substance classes used in gerontological therapy, in addition to the sole use of active substances in humans and animals are in particular vitamins and antioxidative substances Since there is a correlation between caloric load or food intake and the aging process, the combination with dietary measures, e.g. with appetite suppressants, can also take place.
  • a combination with medications to lower blood pressure such as ACE inhibitors, angiotens receptor antagonists, diuretics, Ca +2 - Antagonists etc or with medication normalizing drugs such as cholesterol-lowering agents
  • Organs such as the heart, kidneys, skeletal muscles and eyes are examined histomorphologically
  • the surrogate parameters were determined after 30 months, a point in time when approximately 80% of the placebo group had died.
  • the lifelong treatment with Cariporid extended the life of the animals from 30 to 39 months. This life extension correlated with a delayed one
  • age-related cardiac hypertrophy that occurred in the placebo-treated animals was prevented by cariporid.
  • Cariporide significantly improved heart function compared to placebo hearts.
  • Age-related endothelial dysfunction was also significantly improved by the NHE inhibitor.
  • Age-related morphological organ changes, such as the incorporation of connective tissue in the aging heart muscle, age-related tubulo-interstitial lesions of the kidney, muscular dystrophy and retinal atrophy were drastically reduced or completely prevented by Cariporide.
  • the lifelong treatment of normotensive WKY rats with the NHE inhibitor cariporid extended the lifespan of the animals from 30 to 39 months. This extension of life span correlated with prevention of age-related left ventricular hypertrophy, cardiac and vascular dysfunction, and age-related changes in vital organs. In addition, the occurrence of all forms of age cancer was significantly delayed.
  • Blood pressure measurements were made using the tail plethysmography method. Events of death were recorded after they occurred.
  • the hearts were perfused according to the method described by Langendorff with an oxygen-saturated (95% 0 2 ⁇ -5% C0 2 ), non-circulating Krebs-Henseleit solution of the following composition (mmol / L): NaCl, 118; KCI, 4.7; CaCI 2 , 2.5; MgSO 4 , 1.6; NaHCO 3 , 24.9; KH 2 PO 4 , 1.2; Glucose, 5.5; Na pyruvate, 2.0, with a perfusion pressure of 60 mm Hg.
  • the left ventricular pressure and the heartbeat rate were measured via a balloon catheter.
  • the coronary blood flow was determined by means of an electromagnetic flow measuring head.
  • the aortic rings were placed under a passive tone of 4.9 mN. After an acclimatization period of one hour, the rings were contracted with potassium chloride (20 mmol / L). After reaching a plateau, acetylcholine was added to the bath in ascending concentrations of 10 " 8 , 10 " 7 , 10 “6 and 10 " 5 mol / L, which triggered an endothelium-dependent relaxation.
  • the placebo-treated WKY rats began to die after about 19 months due to age and all had died after 30 months of testing. In contrast, the maximum lifespan of the animals was extended to 39 months by caripid treatment, which corresponds to a life extension of 30% (Table 1).
  • kidney weights of both groups showed no significant difference between the groups with 332 ⁇ 6 mg / 100 mg body weight, while the spleen weights of the animals treated with cariporide were significantly below the placebo-treated group of WKY rats (303 ⁇ 12 versus 255 ⁇ 13 mg / 100g BW, p ⁇ 05)
  • Lactate ( ⁇ mol / min / g heart wwt) 14.3 ⁇ 1.3 2.5 ⁇ 0.13 *
  • LVP left ventricular pressure
  • dP / dtmax left ventricular contraction rate
  • CF coronary flow
  • CK creatine kinase in coronary effluate
  • LDH lactate dehydrogenase in the coronary effluate
  • Cariporide drastically reduced typical age-related histomorphological organ changes, such as connective tissue deposits in the heart muscle, muscular dystrophy, tubulo-interstitial damage to the kidney and retinal atrophy. In addition, no changes in the livers of these rats were found in comparison to control animals.
  • R (7) and R (8), identical or different, are H or (-CC 6 ) alkyl; or R (7) phenyl- (CH 2 ) m ; m 1-4; or R (7) phenyl which is unsubstituted or substituted with 1-2 substituents selected from the group consisting of fluorine, chlorine, methyl and methoxy; or R (7) and R (8) together form a straight-chain or branched (C4-C) chain, where the chain can additionally be interrupted by O, S or NR (9);
  • R (9) H or methyl
  • R (1) R (4) -SO m or R (5) R (6) N-SO 2 -; m zero, 1 or 2; R (4) and R (5)
  • Ci-C ⁇ -alkyl C 3 -C 6 alkenyl or -C n H 2n -R (7); n zero, 1, 2, 3 or 4;
  • R (7) C 5 -C 7 cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R (9); R (8) and R (9)
  • R (6) H or -CC 4 alkyl, or
  • R (5) and R (6) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by an O, S, NH, N-CH or N-benzyl;
  • R (10) H, Ci-Ce-alkyl, C 5 -C 7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl or -C n H 2n -R (12); n zero, 1, 2, 3 or 4;
  • R (12) phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R (9);
  • R (8) and R (9) are H or -CC 4 alkyl;
  • R (11) is hydrogen or -CC 3 alkyl; or
  • R (10) and R (11) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by O, S, NH, N-CH 3 or N-benzyl;
  • R (3) is defined as R (1), or d-Ce-alkyl, nitro, cyano, trifluoromethyl, F, Cl, Br, J or -XR (10);
  • R (10) is H, Ci-Ce-alkyl, C 5 -C 7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl or -C n H 2 nR (12); n zero to 4; R (12) phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R (9); R (8) and R (9) H or -CC 4 alkyl;
  • R (7) H or -CC 3 alkyl, or
  • R (6) H, Ci-Ce-alkyl, C 5 -C 7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl, - (CH 2 ) rr, CpF 2 p +1 or -C n H 2 nR (8); m zero or 1; P 1-3; n zero to 4;
  • R (8) phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (9) R (10); R (9) and R (10)
  • R (6) and R (7) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by an O, S, NH, N-CH 3 or N-benzyl;
  • R (2) and R (4) the same or different, R (11) -SO q - or R (12) R (13) N-S0 -; q zero - 2;
  • R (11) -CC 4 alkyl which is unsubstituted or carries phenyl as a substituent, phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR ( 9) R (10); R (9) and R (10)
  • R (12) and R (13) are defined as R (6) and R (7); or one of the two radicals R (2) or R (4)
  • R (1) Hydrogen or as defined by R (1); R (5) H, methyl, F, Cl or methoxy, and their pharmaceutically acceptable salts;
  • R (1) or R (2) is an amino group -NR (3) R (4);
  • R (3) and R (4), identical or different, are H, Ci-Ce-alkyl or C 3 -C -cycloalkyl; or
  • R (5) H or lower alkyl; the other substituent R (1) or R (2)
  • R (1) R (4) -SO m or R (5) R (6) N-SO 2 -; m zero, 1 or 2;
  • Ci-C ⁇ -alkyl C 3 -C 6 alkenyl or -C n H 2 nR (7); n zero, 1, 2, 3 or 4;
  • R (7) C 5 -C 7 cycloalkyl or phenyl which is unsubstituted or substituted by 1-3
  • R (6) H or -CC 4 alkyl; or R (5) and R (6) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by an O, S, NH, N-CH 3 or N-benzyl;
  • R (12) (C 3 -C 8 ) cycloalkyl;
  • R (13) is hydrogen or methyl, or
  • R (3) is defined as R (2); and wherein the aromatic substituents R (2) or R (3) are unsubstituted or with 1-3 substituents from the groups F, Cl, CF 3 , (-CC 4 ) alkyl, alkoxy, or NR (10) R (11) are substituted by R (10) and R (1 1) in the meaning of H or (dC 4 ) alkyl; and their pharmaceutically acceptable salts.
  • R (4) and R (5) are the same or different, H or Ci-ds-alky !; or R (4) phenyl- (CH 2 ) m -; m 1, 2, 3 or 4, or R (4) phenyl which is unsubstituted or carries one or two substituents selected from the group consisting of fluorine, chlorine, methyl and methoxy, or
  • R (4) and R (5) together form a straight-chain or branched C 4 -C chain, where the chain can additionally be interrupted by O, S or NR (6), R (6) H or methyl, or R (4 ) and R (5) together with the nitrogen atom to which they are attached, a dihydroindole, tetrahydroquinoline or tetrahydroisoquinoline system, n zero, 1 or 2, and their pharmaceutically acceptable salts
  • R (1) is hydrogen, alkyl, cycloalkyl, arylalkyl, alkenyl, substituted aminoalkyl or an aryl or heteroarylnng, the rings being unsubstituted or substituted by 1-3 groups selected from the group consisting of halogen, nitro, amino, mono (non-alkylkyl ) am ⁇ no D ⁇ (n ⁇ ederalkyl) am ⁇ no, lower alkyl, lower alkoxy benzyloxy phenoxy, hydroxy trifluoromethyl, R (2) hydrogen, halogen, alkyl, or aryl, which is unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, nitro, amino, mono (n ⁇ ederalkyl) am ⁇ no, D ⁇ (n ⁇ ederalkyl) am ⁇ no, lower alkyl, lower alkoxy , Benzyloxy, phenoxy, hydroxy,
  • G -N C ⁇ [NR (3) R (4)] [N (R5) R (6)] ⁇ X (2), X (3) and X (4) independently of one another hydrogen, halogen, nitro, amino , Alkyl, sulfonamide, mono (n ⁇ ederalkyl) am ⁇ no, D ⁇ (n ⁇ ederalkyl) am ⁇ no, lower alkyl, benzyloxy, hydroxy,
  • X hydrogen, oxygen, sulfur or NR (7),
  • R (7) hydrogen alkyl cycloalkyl arylalkyl alkenyl substituted aminoalkyl or an aryl or heteroaryl ring, which rings are unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, amino,
  • R (4) and R (5) (-CC 8 ) alkyl, (C 3 -C 6 ) alkenyl, -C n H 2n -R (7) or CF 3 ; n zero, 1, 2, 3 or 4;
  • R (7) (C 3 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R ( 9);
  • R (10) and R (11) are the same or different
  • R (16), R (17), R (18), R (19) and R (20) are hydrogen or (dC 3 ) alkyl;
  • R (3) is defined as R (1), or R (3) (d-Ce) alkyl or -XR (22);
  • X is oxygen, S or NR (16);
  • R (16) H or (-CC 3 ) alkyl; or R (22) and R (16) together have 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 (22) is defined as R (14); and their pharmaceutically acceptable salts.
  • R (22) is defined as R (14); and their pharmaceutically acceptable salts.
  • R (7) (C 3 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R ( 9); R (8) and R (9)
  • R (5) and R (6) together have 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 (2) (-CC 9 ) heteroaryl which is linked via C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy , Amino, methylamino and dimethylamino; or
  • R (11) and R (12) independently of one another are defined as R (10) or hydrogen or (Ci-C 4 ) -alkyl;
  • R (3) is defined as R (1), or (d-Ce) alkyl or -XR (13); X is oxygen, S, or NR (14); R (14) h or (-C-C 3 ) alkyl; R (13) H, (-C-Ce) alkyl, (C 3 -C 8 ) cycloalkyl or -C b H 2b -R (15); b zero, 1, 2, 3 or 4; or R (13) and R (14) together have 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 (15) phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R (9); R (8) and R (9) H or (-CC) alkyl; and their pharmaceutically acceptable salts;
  • R (1), R (2), R (3) or R (4) an amino group -NR (5) [C n H 2n -R (6)];
  • R (5) is hydrogen or C ( ⁇ -6) alkyl; n zero, 1, 2, 3 or 4;
  • R (6) H or C (1-) alkyl; wherein a CH 2 group can be replaced by 1 S atom or a group NR (7);
  • R (7) hydrogen, methyl or ethyl
  • R (6) C (3-8) cycloalkyl or phenyl which is unsubstituted or 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, methyl, methoxy,
  • R (5) and R (6) together with the nitrogen atom form a 5-, 6- or 7-membered ring in which 1 C atom can be replaced by oxygen, S or NR (10); R (10) H, C ( ⁇ - 3 ) alkyl or benzyl; and the other substituents R (1), R (2), R (3), R (4):
  • X is oxygen or NR (12);
  • R (12) H or C ( ⁇ -3) alkyl;
  • R (11) hydrogen, C ( ⁇ -6) alkyl, C (3 -8) cycloalkyl or phenyl, which is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, CH 3 , CH 3 -O- and NR (13) R (14);
  • R (13) and R (14) are H, methyl or ethyl; and their pharmaceutically acceptable salts.
  • X is oxygen, S or NR (6); R (4) and R (5) the same or different, H, (-CC 8 ) alkyl, (C 3 -C 6 ) alkenyl or n zero, 1, 2, 3 or 4;
  • R (8) and R (9) together have 4 or 5 methylene groups, one of which
  • CH 2 group can be replaced by oxygen, S, NH, N-CH 3 or N-benzyl; R (3) H, F, Cl, Br, I, (-C-C 6 ) alkyl or -WR (8) as defined for R (2), and their pharmaceutically acceptable salts; (93 / F 054 - NZ 250 919, EP-OS 612 723) m) benzoylguanidines of the formula I.
  • R (4) C p F 2p + ⁇ ; p 1, 2 or 3 if n is zero or 1; or R (4) (C 3 -C 2 ) -Cyctoalkyl, phenyl, pyridyl, quinolyl or isoquinolyl, where the aromatic and heteroaromatic ring systems are unsubstituted or substituted with a substituent selected from the group consisting of F, Cl, CF 3 , methyl , Methoxy and NR (5) R (6); R (5) and R (6) are hydrogen or (Ci -C 4 ) alkyl; or one of the substituents R (1), R (2) or R (3) -C ⁇ CR (5) or -C [R (6)] CR (5); R (5) phenyl, that is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy, hydroxy, amino, methylamino and dimethylamin
  • R (5) (-CC 6 ) alkyl which is unsubstituted or substituted with 1-3 OH; or
  • R (6) is hydrogen or methyl; as well as their pharmacologically acceptable salts;
  • X is oxygen, S or NR (14); m zero, 1 or 2; o zero or 1; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6;
  • R (8) (C 3 -C 7 ) cycloalkyl or phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (9) R ( 10);
  • R (6) H Hoder (-C-C 4 ) alkyl; or R (6) and R (7) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by oxygen, S, NH, N-CH 3 or N-benzyl;
  • Y is oxygen, -S- or -NR (12) -;
  • R (11) and R (12) are hydrogen or (-CC 3 ) alkyl; h zero or 1; i, j and k independently zero, 1, 2, 3 or 4; however, h, i and k are not simultaneously zero, PCT / EP99 / 09621
  • R (3) is defined as R (1), or (-C 6 ) -alkyl or -XR (13); X is oxygen, S or NR (14);
  • R (14) H or (-CC 3 ) alkyl
  • R (13) H, (d-Ce) alkyl, (C 3 -C 8 ) cycloalkyl or -C b H 2b -R (15); b zero, 1, 2, 3 or 4; or R (13) and R (14) together 4 or 5 methylene groups, where a CH 2 group can be replaced by oxygen, S, NH, N-CH 3 or N-benzyl;
  • R (4) is hydrogen, -OR (16) or -NR (16) R (17); R (16) and R (17) independently of hydrogen or (-CC 3 ) alkyl; and their pharmaceutically acceptable salts; (HOE 93 / F 154 - EP-OS 628 543, NZ 260681) p) Benzoylguanidines of the formula I.
  • R (12) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, the aromatics being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (13) R (14);
  • R (8) H, (-CC 4 ) alkyl or (-C-C) -perfluoroalkyl; or R (7) and R (8) together have 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 (2) defined as R (1), or H, F, Cl, Br, I, CN, NO 2 , (-C-C 8 ) alkyl, (C ⁇ -C 8 ) - perfluoroalkyl, (C 3 -C 8 ) alkenyl or -C n H 2n R (15); n zero, 1, 2, 3, 4;
  • R (19) and R (20) independently of one another as R (18) defines or hydrogen, (dC 4 ) - alkyl or (-C-C 4 ) perfluoroalkyl, or
  • R (21) (C ⁇ -C8) alkyl, (C ⁇ -C8) -perfluoroalkyl, (C 3 -C 8) -alkenyl, -C n H 2n -R (24), n is zero, 1, 2, 3 or 4, R (24) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , Methyl, methoxy and NR (27) R (28), R (27) and R (28)
  • R (29) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, the aromatics being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (30) R (31), R (30) and R (31) H, (-CC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; R (23) H, (dC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; or
  • R (22) and R (23) together have 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 (2) R (33) X-;
  • R (36) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and
  • R (34) H, (-CC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl;
  • R (35) defines like R (33); or
  • R (51) is hydrogen or methyl; u 1, 2, 3 or 4; v zero, 1, 2, 3 or 4; p, q, r the same or different zero, 1, 2, 3 or 4; t 1, 2, 3 or 4;
  • R (42) and R (43), the same or different, are hydrogen or (-CC 6 ) -alkyl; or
  • R (45) is phenyl which is unsubstituted or substituted with 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (52) R (53); R (52) and R (53) are H or (-CC 4 ) alkyl, or
  • R (45) (-CC 6 ) alkyl which is unsubstituted or substituted with 1-3 OH;
  • Y is oxygen, S or N-R (58);
  • R (56) and R (57) the same or different H, (-CC 8 ) alkyl, (C 3 -C 6 ) alkenyl or
  • R (59) (C 5 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methoxy and (C1-C 4 ) alkyl; or
  • R (56) and R (57) together have 4 or 5 methylene groups, one of which is CH 2 -
  • Group can be replaced by oxygen, S, NH, N-CH 3 or N-benzyl;
  • R (58) is defined as R (56) or amidine;
  • R (3), R (4) and R (5) are independently defined as R (1) or R (2); and their pharmaceutically acceptable salts;
  • X is oxygen, -S- or NR (14); m zero, 1 or 2; o zero or 1; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6;
  • R (8) (C 3 -C 7 ) cycloalkyl, phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (9) R ( 10); R (9) and R (10)
  • R (6) hydrogen; R (7) hydrogen or (-CC 4 ) alkyl; or R (6) and R (7) together have 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 (2) R (11) (-CC 9 ) heteroaryl, which is linked via C or N and which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , Methoxy, hydroxy, amino, methylamino, dimethylamino and benzyl; Y is oxygen, -S- or NR (12);
  • R (14) H or (dC 3 ) alkyl
  • R (4) is hydrogen, -OR (16), -NR (16) R (17) or C r F 2r + 1 ;
  • R (16) and R (17) independently are hydrogen or (dC 3 ) alkyl; r 1, 2, 3 or 4; and their pharmaceutically acceptable salts;
  • R (9) H, methyl, ethyl, W oxygen or NR (10); R (10) H or methyl; y zero or 1; or R (8) CmF 2 m + ⁇ ; m 1 to 3; or R (8) 1- or 2-naphthyl, pyridyl, quinolyl or isoquinolyl;
  • R (13) H or (dC 4 ) alkyl; R (7) hydrogen, (-C-C ⁇ o) alkyl, (C 2 -do) alkenyl or R (8) -C n H 2n - and their pharmaceutically acceptable salts; (HOE 93 / F 236 - EP-OS 638 548, NZ 264 216) s) Benzoylguanidines of the formula I.
  • X is oxygen or S;
  • R (6) is hydrogen, (C ⁇ -C8) alkyl, (C ⁇ -C8) -perfluoroalkyl, (C 3 -C 8) -alkenyl or -C n H 2n -R (9); n zero, 1, 2, 3 or 4;
  • R (9) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (10) R (11); R (10) and R (11)
  • R (7) hydrogen, (dC 8 ) alkyl, (dC 8 ) perfluoroalkyl, (C 3 -C 8 ) alkenyl or -C 0 H 2 oR (12); o zero, 1, 2, 3 or 4;
  • R (12) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, the aromatics being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (13) R (14); R (13) and R (14)
  • R (8) defines like R (7); or R (7) and R (8) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by oxygen, S, NH, N-CH 3 or N-benzyl; the remaining substituents R (2), R (3), R (4), R (5) or R (1), R (2), R (4), R (5) or R (1), R (2), R (3), R (5) independently of one another hydrogen, F, Cl, Br, I, -Ot a (-C-C ⁇ ) alkyl, -O tb (C 3 - C 8 ) alkenyl,
  • R (18) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (19) R (20);
  • R (21) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, the aromatics being unsubstituted or substituted by 1-3 substituents from the group F, Cl, CF 3 , methyl, methoxy or NR (22 ) R (23), R (22) and R (23) are hydrogen, (-CC 4 ) alkyl or (C1-C4) - perfluoroalkyl; R (17) hydrogen, (dC 8 ) alkyl, (dC 8 ) perfluoroalkyl, (C 3 -C 8 ) alkenyl, - C r H 2r -R (24); r zero, 1, 2, 3 or 4;
  • R (24) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (25) R (26);
  • T1 zero, 1, 2, 3 or 4;
  • R (A) and R (B) independently is hydrogen, F, Cl, Br, I, CN, OR (106), (C ⁇ -C8) alkyl, (C 3 -C 8) - cycloalkyl, NR (107) R (108), phenyl or benzyl, the aromatics being unsubstituted or 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) are hydrogen, (-CC 4 ) -alkyl or (dC 4 ) -perfluoroalkyl; zl zero, 1, 2, 3 or 4; zk zero or 1; zm 1, 2, 3, 4, 5, 6, 7 or 8; R (106) is hydrogen, (C ⁇ -C8) alkyl, (C ⁇ -C8) -perfluoroalkyl, (C 3 -C 8) -alkenyl, (C 3 -
  • R (107) and R (108) are independently defined as R (106), or
  • R (107) and R (108) together have 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
  • T2a and T2b independently of one another zero, 1 or 2; wherein the double bond can be (E) - or (Z) -configured; or X (1) and X (2)
  • T3 zero, 1 or 2;
  • U, YY and Z independently of one another are C or N, where U, YY, Z can carry the following number of substituents:
  • R (D) hydrogen, (dC 8 ) alkyl or (-C-C 8 ) perfluoroalkyl, R (U1), R (U2), R (Y1), R (Y2), R (Z1), R (Z2 ) independently of one another hydrogen, F, Cl, Br, I, CN, OR (114), (dC 8 ) -alkyl, (C 3 -C 8 ) -cycloalkyl, O zka (CH 2 ) 2 iaCz m aF2zma + ⁇ , NR (1 15) R (1 16), phenyl or benzyl, the aromatics being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy, NR (117) R (118), R (117) and R (118) hydrogen, (-CC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl, zka zero or 1
  • R (115) and R (116) are independently defined as R (114); or
  • R (110a), R (110b), R (111 a) and R (112a) independently (C ⁇ -C 8 ) alkyl, (C 3 -C 8 ) alkenyl, -C Z nH 2 zn-R (115a ) or (Ci-C 8 ) perfluoroalkyl; zn zero, 1, 2, 3 or 4;
  • R (110c) and R (113a) independently of hydrogen, (-CC) perfluoroalkyl or (-C-C 4 ) alkyl; or
  • R (110b) and R (110c) as well as R (112a) and R (113a) 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), R (105) independently of one another (-CC 8 ) alkyl, -C Za iH 22a iR (118a) or (C 3 -C 8 ) alkenyl, zal zero, 1, 2, 3 or 4;
  • R (118a) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy or NR (119a) R (119b); R (1 19a) and R (119b)
  • Phenyl which is unsubstituted or substituted with 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy or NR (194) R (195); R (194) and R (195)
  • Y-ortho-CeH 4 - (CO) zah - (CHOH) zao - (CH 2 ) Z a p - (CHOH) Z a k -R (125); Y is oxygen, -S- or -NR (122d) -; zh, zad, zah independently zero or 1; zi, zj, zk, zae, zaf, zag, zao, zap and zak independently zero, 1, 2, 3 or 4; however, each 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, R (123), R (124), R (125) and R (122d) are independently hydrogen or (-C-C 3 ) alkyl; or R (101), R (102), R (103), R (104) and R (105) independently of one another SR (129), -OR (130), -
  • R (132), R (134) and R (135) independently of one another as R (129) defined or hydrogen, (C 1 - C 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; or R (101), R (102), R (103), R (104) and R (105) independently of one another -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) independently (-C-C 9 ) heteroaryl, which is linked via C or N and which is unsubstituted or substituted with 1 to 3 substituents from the group consisting of F, Cl , CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino, dimethylamino and benzyl; W oxygen, S or NR (136) -; R (136)
  • R (101), R (102), R (103), R (104) and R (105) independently of one another R (146) X (1 a) -; X (1 a)
  • R (146) and R (147) or R (146) and R (148) together have 4 or 5 methylene groups, of which one CH group can be replaced by oxygen, sulfur, NH, N-CH 3 or N-benzyl; wherein A and N w are bonded to the phenyl core of the alkanoyl base body; or
  • R (168), R (170), R (154), R (155), the same or different, are hydrogen or (-CC6) -alkyl, or
  • R (156), R (157) and R (173) are independently phenyl which is unsubstituted or substituted with 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (174) R (175 ); R (174) and R (175) are hydrogen or (-CC 4 ) alkyl; or R (156), R (157) and R (173) independently (-C-Cg) heteroaryl, which is unsubstituted or substituted like 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), R (105) independently of one another R (176) -NH-SO 2 -; R (176)
  • R (177) R (178) N- (C Y ') -; Y 'is oxygen, S or NR (179); R (177) and R (178) the same or different hydrogen, (-CC 8 ) alkyl, (C 3 -Ce) alkenyl or -C Z f a H 22fa -R (180); zfa zero, 1, 2, 3 or 4; R (180) (C 5 -C) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methoxy or (-C-C 4 ) alkyl; or
  • R (177) and R (178) together have 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 the same as amidine, or R (101), R (102), R (103), R (104), R (105) independently of one another NR (184a) R (185), OR (184b), SR (184c) or -C znx H 2znx -R (184d); znx zero, 1, 2, 3 or 4;
  • R (184a), R (184b), R (184c), R (185) independently of one another hydrogen, (-CC 8 ) alkyl, (-C -8 ) - perfluoroalkyl or (CH 2 ) zao -R (184g); zao zero, 1, 2, 3 or 4; 184g (C 3 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (184u) R (184v); R (184u) and R (184v) hydrogen or -CC 4 alkyl; or R (184a) and R (185) together 4 or 5 methyl groups, of which one CH 2 group can be replaced by oxygen, sulfur, NH, N-CH 3 or N-benzyl; and their pharmaceutically acceptable salts; (HOE 93 / F 254 - EP-OS 640 5
  • X is oxygen, S or NR (5); a zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3;
  • R (5) H, (-CC 4 ) alkyl or -C d H 2 R (6); d zero, 1, 2, 3 or 4; R (6) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (7) R (8);
  • R (7) and R (8) independently H or (-CC 4 ) alkyl; or
  • R (11) and R (12) independently of one another are defined as R (10) or hydrogen or (Ci-C 4 ) -alkyl; or R (1) phenyl, naphthyl, biphenyiyl or (d-Cg) heteroaryl, the latter linked via C or N, and which are unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; or
  • R (17) is hydrogen or methyl; - (CH 2 ) g -O- (CH 2 -CH 2 O) h -R (24), g, h, i identical or different zero, 1, 2, 3 or 4; j 1, 2, 3 or 4;
  • R (15) and R (16), the same or different, are hydrogen, (-CC6) -alkyl or together with the carbon atom carrying them a (C 3 -C 8 ) -cycloalkyl; R (18) phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (25) R (26); R (25) and R (26) H or (-CC 4 ) alkyl; or R (18) (-C-Cg) heteroaryl which is unsubstituted or substituted like phenyl; or R (18) (Ci-d-alkyl which is unsubstituted or substituted by 1 to 3 OH; or
  • R (18) (C 3 -C 8 ) cycloalkyl;
  • R (19), R (20), R (21), R (22) and R (23) are hydrogen or methyl;
  • k zero, 1, 2, 3 or 4;
  • R (2) and R (3) are independently defined as R (1);
  • R (7) and R (8) are independently defined as R (6);
  • R (B) is independently defined as R (A); X 1, 2 or 3;
  • R (2), R (3), R (4) and R (5) are independently defined as R (1); but under the condition that at least one of the substituents R (1), R (2), R (3), R (4), R (5), R (A) and R (B) has an -Ot (CH2) d C e F 2 e + ⁇ or an O r (CH 2 ) aC F 2b + ⁇ group, and their pharmaceutically acceptable salts;
  • HA SO m O or NR (5); m zero, 1 or 2;
  • R (5) is hydrogen, (d-Cs) alkyl or -C at H 2 a m R (81); at zero, 1 or 2;
  • R (81) (C 3 -C 8 ) -cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and
  • NR (82) R (83); R (82) and R (83) H or CH 3 ; or R (81) (-CC 9 ) heteroaryl, which is linked via C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, Hydroxy, amino, methylamino and dimethylamino; one of the two substituents R (1) and R (2) -CO-N C (NH 2 ) 2 ; and each other
  • R (3) and R (4) independently of one another hydrogen, F, Cl, Br, I, -C ⁇ N, X- (CH 2 ) p - (C q -F2 q + ⁇ ), R (8) -SO bm , R (9) R (10) N-CO, R (11) -CO- or R (12) R (13) N-SO 2 -, where the perfluoroalkyl group is straight-chain or branched, X is oxygen, S or NR (14) ; R (14) H or (-CC 3 ) alkyl; bm zero, 1 or 2; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6;
  • R (8), R (9), R (11) and R (12) independently (dC 8 ) alkyl, (C 3 -C 6 ) alkenyl, -C n H 2n -R (15), CF 3 ; n zero, 1, 2, 3 or 4; R (15) (C 3 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy or NR (16) R ( 17); R (16) and R (17)
  • R (9), R (11) and R (12) H; R (10) and R (13) are independently H or (-CC 4 ) alkyl; or R (9) and R (10) and R (12) and R (13) 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 can, or R (3) and R (4) independently of one another (-C-C ⁇ ) -alkyl or -C a ⁇ H 2a ⁇ R (18); al zero, 1 or 2; R (18) (C 3 -C 8 ) cycloalkyl or phenyl; which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (19) R (20); R (19) and R (20) H or CH 3 ; or R (3) and R (4) independently of one another (-CC 9 ) heteroaryl which is linked via C or N and which is unsubstitute
  • Y is oxygen, -S- or -NR (22) -; h, ad, ah independently zero or 1; i, j, k, ae, af, ag, ao, ap and ak independently zero, 1, 2, 3, 4, but with h, i and k not simultaneously zero, ad, ae and ag not simultaneously zero and ah , ao and ak are not simultaneously zero, R (23), R (24) R (25) and R (22) independently of one another hydrogen or (-CC) alkyl; or
  • R (3) and R (4) independently of one another hydrogen, F, Cl, Br, I, CN, (-CC 8 ) alkyl, (-C-C 8 ) - perfluoroalkyl, (C 3 -C 8 ) alkenyl or -C 8 H 2g R (26); g zero, 1, 2, 3 or 4; R (26) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (27) R (28); R (27) and R (28) H, (-CC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; or R (3) and R (4) independently of one another SR (29), -OR (30), -NR (31) R (32) or
  • R (29), R (30), R (31) and R (33) independently -C a H 2a - (-C ⁇ -C9) heteroaryl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; a zero, 1 or 2;
  • R (32), R (34) and R (35) independently of one another are defined as R (29) or hydrogen, (C ⁇ -C 4 ) -
  • R (96), R (97) and R (98) independently (-C-C 9 ) heteroaryl, which is linked via C or N and which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino, dimethylamino or benzyl;
  • R (3) and R (4) independently of one another R (37) -SO cm or R (38) R (39) N-S0 2 -; cm 1 or 2;
  • R (37) (-C-Cs) -alkyl, (C ⁇ -C 8 ) -perfluoroalkyl, (C 3 -C 8 ) -alkenyl or -C 3 H 2s R (40); s zero, 1, 2, 3 or 4;
  • R (40) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, the aromatics being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and
  • R (39) H, (dC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; R (39) H, (-CC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; or R (38) and R (39) together have 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 (3) and R (4) independently of one another R (46) X (1) -;
  • R (46) (-C-C ⁇ ) alkyl, (C 3 -C 8 ) alkenyl, (CH 2 ) C d F 2d + ⁇ or -C x H 2x -R (51); b zero or 1; d 1, 2, 3, 4, 5, 6 or 7; x zero, 1, 2, 3 or 4;
  • R (51) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and
  • R (47), R (48) and R (50) independently of hydrogen, (-CC 4 ) alkyl or (C 1 -C 4) - perfluoroalkyl;
  • R (64), R (65), R (66), R (67) and R (69) the same or different - (CH 2 ) y- (CHOH) z - (CH 2 ) aa - (CH 2 O) rR (71) or - (CH 2 ) a b -O- (CH 2 -CH 2 O) ac-R (72),
  • R (71) and R (72) are hydrogen or methyl; u 1, 2, 3 or 4; v zero, 1, 2, 3 or 4; y, z, aa the same or different zero, 1, 2, 3 or 4; t 1, 2, 3 or 4;
  • R (68), R (70), R (54) and R (55) the same or different hydrogen, (-C-C ⁇ ) -alkyl; or R (69) and R (70) or R (54) and R (55) together with the carbon atom carrying them a (C 3 -C 8 ) cycloalkyl; R (63)
  • R (56), R (57) and R (73) independently phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (74) R ( 75);
  • R (56), R (57) and R (73) independently (-C-Cg) heteroaryl, which is unsubstituted or substituted like phenyl;
  • R (58), R (59), R (60), R (61) and R (62) are hydrogen or methyl, or R (3) and R (4) independently of one another R (76) -NH-SO 2 - ;
  • R (76) R (77) R (78) N- (C Y ') -; Y 'is oxygen, S or NR (79);
  • R (80) (C 5 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methoxy and (-C-C) alkyl; or R (77) and R (78) 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 (79) is defined as R (77) or the same as amidine, or
  • R (84) and R (85) independently of one another H, (-CC 4 ) alkyl, or together 4 or 5 methylene groups, one of which is a CH 2 group by oxygen, S, NH, N-CH 3 or N- Benzyl can be replaced, or one or two of which
  • CH2 groups can be replaced by CH-CdmH 2 m + ⁇ , and their pharmaceutically acceptable salts,
  • T, U, V, W, X, Y and Z are independently nitrogen or carbon, but with the restriction that X and Z are not nitrogen at the same time and that T, U, V, W, X, Y and Z do not carry a substituent if they are nitrogen and that no more than four of them are nitrogen at the same time,
  • R (3), R (4), R (5), R (6) and R (7) independently of one another hydrogen, F, Cl, Br, I, -CDN, Xk- (CH2) p - (C q F 2q + ⁇ ), R (10a) -SO bm , R (10b) R (10c) N-CO, R (11) -CO- or R (12) R (13) N-SO 2 -, the perfluoroalkyl group being straight-chain or is branched; X is oxygen, S or NR (14);
  • R (14) H or (-CC 3 ) alkyl; bm zero, 1 or 2; p zero, 1 or 2; k zero or 1; q 1, 2, 3, 4, 5 or 6;
  • R (10a), R (10b), R (11) and R (12) independently of one another (-CC 8 ) alkyl, (C 3 -C 6 ) alkenyl, -C n H 2 nR (15) or (C ⁇ -C 8 ) perfluoroalkyl; n zero, 1, 2, 3 or 4; R (15) (C 3 -C) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (16) R (17th ); R (16) and R (17) H or -CC 4 alkyl; or R (10b), R (11) and R (12)
  • R (10c) and R (13) independently of one another hydrogen or (-CC 4 ) alkyl; or R (10b) and R (10c) as well as R (12) and R (13) 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 (3), R (4), R (5), R (6) and R (7) independently of one another (-C-C 8 ) -alkyl, -C a ⁇ H 2a ⁇ R (18) or (C3-C 8 ) alkenyl; al zero, 1 or 2;
  • R (18) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3,
  • Y is oxygen, -S- or -NR (22) -; h, ad, ah independently of one another zero or 1; i, j, k, ae, af, ag, ao, ap and ak independently of one another zero, 1, 2, 3 or 4; However, where h, i and k are not simultaneously zero, ad, ae and ag are not simultaneously zero and ah, ao and ak are not simultaneously zero, R (23), R (24), R (25) and R (22) are independent each other is hydrogen or (dC 3 ) alkyl; or R (3), R (4), R (5), R (6) and R (7) independently of one another SR (29), -OR (30), -NR (31) R (32) or
  • R (29), R (30), R (31) and R (33) independently of one another -C a H 2a - (-C-C 9 ) heteroaryl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; a zero, 1 or 2;
  • R (32), R (34) and R (35) independently of one another as R (29) defined or hydrogen, (C1-C4) -
  • R (96), R (97) and R (98) independently of one another (-CC 9 ) heteroaryl which is linked via C or N and which is unsubstituted or substituted by 1 to 3
  • R (51) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (52) R (53); R (52) and R (53)
  • R (71) and R (72) independently of one another are hydrogen or methyl; u 1, 2, 3 or 4; v zero, 1, 2, 3 or 4; y, z, aa the same or different
  • R (68), R (70), R (54) and R (55), the same or different, are hydrogen or (-CC 6 ) -alkyl; or
  • R (69) and R (70) or R (54) and R (55) together with the carbon atom carrying them are a (C 3 -C 8 ) cycloalkyl;
  • R (56), R (57) and R (73) independently Phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (74) R (75), R (74) and R (75) hydrogen or ( C ⁇ -C) alkyl, or R (56), R (57) and R (73) independently
  • R (77) and R (78) the same or different, hydrogen, (-CC 8 ) -alkyl, (C3-C 6 ) -alkenyl or -C f H 2f -R (80), f zero, 1, 2, 3 or 4, R (80) (C 5 -C) cycloalkyl or phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methoxy and (C 1 - C 4 ) Alkyl, or R (77) and R (78) 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 (79) as defined in R (77) or the same as amidine, or
  • R (3), R (4), R (5), R (6) and R (7) independently of one another NR (84a) R (85), OR (84b), SR (84c) or
  • R (84d) (C 3 -C) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (16) R (17) ; R (16) and R (17) are hydrogen, or -CC 4 alkyl;
  • R (84a) R (84b) R (84c) and R (85) independently of one another hydrogen, (C ⁇ -C8) alkyl, (C ⁇ -C8) - perfluoroalkyl, or (CH 2) ax -R (84g) ; ax zero, 1, 2, 3 or 4; R (84g) (C 3 -C) cycloalkyl or phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (84u) R (84v ); R (84u) and R (84v) hydrogen or -CC 4 alkyl; or R (84a) and R (85) 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 their pharmaceutically acceptable salts;
  • R (6) perfluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, which is straight-chain or branched;
  • R (2) and R (3) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3 or 4 carbon atoms.
  • R (4) and R (5) independently of one another are hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, Br, I, CN, OR (7), NR (8) R (9) or - ( CH 2 ) n - (CF 2 ) 0 -CF 3 ; R (7), R (8) and R (9) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms.
  • R (6) (-C 8 ) alkyl, (C 4 ) perfluoroalkyl, (C 3 -C 8 ) alkenyl, (C 3 -C 8 ) cycloalkyl, phenyl or benzyl; the aromatics being unsubstituted or substituted by 1-3 substituents from the group consisting of F, Cl, CF 3 ,
  • R (7) and R (8) are independently defined as R (6); or R (7) and R (8) together have 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 (B) is independently defined as R (A); X is zero, 1 or 2; Y is zero, 1 or 2; R (C) hydrogen, F, Cl, Br, I, CN, OR (12), (-C-C 8 ) alkyl, Op (CH 2 ) f C g F 2 g +1 or (C 3 - C 8 ) Cycloalkyl; p zero or 1; f zero, 1, 2, 3 or 4; g 1, 2, 3, 4, 5, 6, 7 or 8;
  • R (2), R (3), R (4) and R (5) are independently defined as R (1); but under the condition that at least one of the substituents R (A), R (B), R (C), R (D), R (1), R (2), R (4) or R (5) is one O r (CH 2 ) a C b F 2b + ⁇ -, Op (CH 2 ) f CgF 2g + ⁇ - or O t (CH 2 ) d C e F 2 e + ⁇ group and R (3) no O t ( Is CH 2 ) d C e F 2e + ⁇ group; and their pharmaceutically acceptable salts; (HOE 94 / F 182 - EP-OS 690 048, NZ 272 449) ac) Ortho-amino-substituted benzoylguanidines of the formula
  • R (50) and R (6) independently of one another hydrogen, (-CC 8 ) alkyl or (-C-C 8 ) - perfluoroalkyl; R (2), R (3), R (4) and R (5) independently of one another R (10) -SO a -, R (11) R (12) N-CO-, R (13) -CO- or R (14) R (15) N-SO 2 -; a zero, 1 or 2,
  • R (16) (C 3 -C 7 ) -cycloalkyl, phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl,
  • CF 3 methyl, methoxy or NR (17) R (18); R (17) and R (18) independently of one another H, CF 3 or (-CC 4) alkyl; or R (11), R (12), and also R (14) and R (15) together 4 or 5 methylene groups, of which one CH 2 group is replaced by oxygen, S, NH, N-CH 3 or N-benzyl can be; or R (11), R (12), R (14) and R (15) independently of one another are hydrogen; or
  • R (2), R (3), R (4) and R (5) independently of one another SR (21), -OR (22), -NR (23) R (24) or
  • Methylamino and dimethylamino; b zero, 1 or 2; R (24), R (26) and R (27) independently of one another hydrogen, (-CC 4 ) alkyl or (C1-C4) - perfluoroalkyl; or R (2), R (3), R (4) and R (5) independently of one another hydrogen, F, Cl, Br, I, CN, - (Xa) dg -C da H 2 da + ⁇ , - ( Xb) h- (CH 2 ) db-CdeF 2 d ⁇ + ⁇ , (C 3 -C 8 ) alkenyl or -C d fH 2df R (30); (Xa) O, S or NR (33);
  • R (2), R (3), R (4) and R (5) independently of one another NR (40) R (41) or - (Xe) - (CH 2 ) eb R (45); R (40) and R (41) independently of one another are hydrogen, (-C-C ⁇ ) -alkyl, (C ⁇ -C ⁇ ) - perfluoroalkyl or (CH 2 ) e -R (42); e zero, 1, 2, 3 or 4; R (42)
  • R (43) and R (44) independently of one another H, CF 3 or (-C-C) alkyl; or
  • R (40) and R (41) together have 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 (47) H, (-CC 4 ) alkyl or (-C-C 4 ) perfluoroalkyl; eb zero, 1, 2, 3 or 4;
  • R (45) (C 3 -C) cycloalkyl, phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy, NR (50) R (51 ) and - (Xfa) - (CH 2 ) ed - (Xfb) R (46);
  • R (46) H, (-CC 4 ) alkyl or (-C-C) perfluoroalkyl; R (48), R (49), R (50) and R (51) independently of one another H or (dC 4 ) -alkyl or (C1-C4) -
  • R (3) and R (4) cannot be hydrogen, and their pharmaceutically acceptable salts;
  • one of the three substituents R (1), R (2) and R (3) (-CC) heteroaryl-N-oxide which is linked via C or N and which is unsubstituted or substituted by 1-3 Substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; or one of the three substituents R (1), R (2) and R (3)
  • R (11) and R (12) independently defined as R (10), hydrogen or (dC 4 ) alkyl; and the other substituents R (1), R (2) and R (3) independently of one another (-CC 8 ) alkyl, (C 2 -C 8 ) alkenyl or -C m H 2m R (14); m zero, 1 or 2;
  • R (14) (C 3 -C 8 ) cycloalkyl or phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (15) R ( 16), R (15) and R (16)
  • R (1), R (2) and R (3) independently of one another are hydrogen, F, Cl, Br, I, -C ⁇ N, X- (CH 2 ) p - (C q F 2q + ⁇ ), R (22) -SO u , R (23) R (24) N-CO, R (25) -CO- or R (26) R (27) N-SO 2 -, the perfluoroalkyl group being straight-chain or branched;
  • X is a bond, oxygen, S or NR (28); u zero, 1 or 2; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6;
  • R (22), R (23), R (25) and R (26) independently (-CC 8 ) alkyl, (C 2 -C 6 ) alkenyl, -C n H 2n -R (29) or CF 3 ; n zero, 1, 2, 3 or 4;
  • R (28) is hydrogen or (dC 3 ) alkyl;
  • R (30) and R (31) are hydrogen or CC 4 alkyl, or R (23),
  • R (25) and R (26) are also hydrogen;
  • R (24) and R (27) independently of one another hydrogen or (-CC 4 ) alkyl; or
  • R (23) and R (24) and R (26) and R (27) together have 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 the other substituents R (1), R (2) and R (3) independently of one another OR (35) or NR (35) R (36); R (35) and R (36) independently of one another are hydrogen or (CrC ⁇ J-alkyl; or R (35) and R (36) together 4-7 methylene groups, one of which is a CH 2 group by oxygen, S, NH, N- CH 3 or N-benzyl can be replaced, R (4) and R (5) independently of one another hydrogen, (CC 4 ) -alkyl, F, Cl, -OR (32), -
  • R (32), R (33) and R (34) independently of one another hydrogen or (-CC 3 ) alkyl; r 1, 2, 3 or 4; and their pharmaceutically acceptable salts;
  • R (1) hydrogen, F, Cl, Br, I, CN, NO 2 , OH, (-C-C 8 ) alkyl, (C 3 -C 8 ) cycloalkyl, O a - (CH 2 ) b - ( CF 2 ) c -CF 3 ; a zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3; or
  • R (1) R (5) -SO m or R (6) R (7) N-SO 2 -; m zero, 1 or 2; R (5) and R (6) independently of one another (-C-C ⁇ ) alkyl, (C 3 -C 6 ) alkenyl, CF 3 or -C n H 2n -R (8); n zero, 1, 2, 3 or 4;
  • R (7) is hydrogen or (C -C 4 ) alkyl; R (8) (C 3 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl,
  • R (12), R (13) independently of one another are defined as R (11) or hydrogen or (C 1 -C 4) alkyl; p zero, 1 or 2; or
  • R (2) -CF 2 R (14), -CF [R (15)] [R (16)], -CF [(CF 2 ) q -CF 3 )] [R (15)], -C [ (CF 2 ) r -CF 3 ] CR (15) R (16);
  • R (15) and R (16) independently of one another hydrogen or (-CC 4 ) alkyl
  • R (3) is defined as R (1);
  • R hydrogen, (-C-C 3 ) alkyl, F, Cl, Br, I, CN, - (CH 2 ) s - (CF 2 ) t-CF 3 ; s zero or 1; t zero, 1 or 2; and their pharmaceutically acceptable salts; (HOE 94 / F 267 - EP-OS 700 899, NZ 272 947) ae) Benzoylguanidines of the formula I
  • R (9) is hydrogen or - (-C-C 4 ) alkyl; R (7) -OR (10) or -NR (10) R (11); R (10) and R (11) independently of one another hydrogen, - (-C 8 ) alkyl, - (-C 8 ) alkanoyl, - (-C 8 ) alkoxycarbonyl, benzyl, benzyloxycarbonyl; or
  • Y ' is oxygen, -S- or -NR (20); R (18) and R (19) independently of one another hydrogen, - (-C-C 8 ) alkyl, - (C 3 -Ce) alkenyl or - (CH 2 ) tR (21); t zero, 1, 2, 3 or 4;
  • Perfluoroalkyl group is straight-chain or branched;
  • X is a bond, oxygen, -S- or -NR (28); u zero, 1 or 2; p zero, 1 or 2; q 1, 2, 3, 4, 5 or 6;
  • R (22), R (23), R (25) and R (26) independently of one another - (-CC 8 ) alkyl, - (C 3 -C 6 ) alkenyl, - (CH 2 ) n -R (29) or -CF 3 ; n zero, 1, 2, 3 or 4;
  • R (28) is hydrogen or - (dC 3 ) alkyl; R (29) - (C 3 -C 7 ) -cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF 3 , methyl, methoxy and -NR (30 ) R (31);
  • R (23), R (25) and R (26) are hydrogen;
  • R (24) and R (27) independently of one another are hydrogen or - (dC 4 ) -alkyl; or
  • R (23) and R (24) and R (26) and R (27) together have 4 or 5 methylene groups, of which one CH 2 group is replaced by oxygen, -S-, -NH-, - N-CH 3 or - N-benzyl can be replaced; or the respective other radicals R (1), R (2) and R (3) independently of one another -OR (35) or -NR (35) R (36); R (35) and R (36) independently of one another are hydrogen or - (dC 6 ) -alkyl; or R (35) and R (36) together 4-7 methylene groups, of which one CH 2 group can be replaced by oxygen, -S-, -NH-, -N-CH 3 or -N-benzyl;
  • R (4) and R (5) independently of one another hydrogen, - (-CC) -alkyl, F, Cl, -OR (32), -
  • R (2) is defined as R (1), or H, OH, F, Cl, Br, I, CN, NO 2 , (-C-C 8 ) alkyl, (dC 8 ) - perfluoroalkyl, (C 3 -C 8 ) alkenyl or -C n H 2n R (15); n zero, 1, 2, 3 or 4;
  • R (19) and R (20) independently of one another are defined as R (18) or hydrogen, (dC 4 ) -alkyl or (-C-C 4 ) -perfluoroalkyl; or
  • R (2) R (21) -SO m or R (22) R (23) N-S0 2 -; m 1 or 2;
  • R (21) (-C 8 ) alkyl, (-C 8 ) perfluoroalkyl, (C 3 -C 8 ) alkenyl or -C n H 2n -R (24); n zero, 1, 2, 3 or 4;
  • R (24) (C 3 -C 8 ) cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and
  • R (29) (C 3 -C 8 ) -cycloalkyl, phenyl, biphenyiyl or naphthyl, where the aromatics are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl,
  • R (23) is hydrogen, (-CC) alkyl or (-C-C 4 ) perfluoroalkyl; or
  • R (22) and R (23) together have 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 (2) R (33) X-;
  • R (34) hydrogen, (-C-C 4 ) -alkyl or (-C-C 4 ) -perfluoroalkyl, R (35) defined as R (33), or R (33) and R (34) 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 l * ! are bound to the phenyl core of the benzoylguanidine base body, or
  • R (2) -SR (40), -OR (40), -NHR (40), -NR (40) R (41), -CHR (40) R (42), -CR (42) R (43 ) OH, -C ⁇ CR (45), -CR (46) CR (45) or - [CR (47) R (48)] U -CO- [C (R49) R (50)] V -R (44 ), R (40) and R (41) independently of one another - (CH 2 ) p - (CHOH) q - (CH 2 ) r - (CHOH) t -R (51) or - (CH 2 ) p -O- (CH 2 -CH 2 0) q -R (51), R (51) hydrogen or methyl, u 1, 2, 3 or 4, v zero, 1, 2, 3 or 4, p, q and r independently of one another Zero, 1, 2, 3 or 4, t 1, 2 3 or 4,
  • R (42) and R (43) independently of one another hydrogen or (-CC 6 ) alkyl; or R (42) and R (43) together with the carbon atom carrying them are a (C 3 -C 8 ) cycloalkyl;
  • R (44) hydrogen, (-CC 6 ) alkyl, (C 3 -C 8 ) cycloalkyl, -C e H 2e -R (45); e zero, 1, 2, 3 or 4;
  • R (45) phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl,
  • R (56) and R (57) independently of one another hydrogen, (-CC 8 ) alkyl, (C 3 -Ce) alkenyl or -C f H 2f -R (59); f zero, 1, 2, 3 or 4;
  • R (59) (C 5 -C 7 ) cycloalkyl, phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methoxy and (-C-C 4 ) alkyl; or R (56) and R (57) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl;
  • R (58) is defined as R (56) or the same as amidine;
  • R (3), R (4) and R (5) are defined independently of one another as R (1) or R (2), but at least one of the substituents R (2), R (3), R (4) and R (5) must be equal to
  • NR (11) can be replaced, or
  • R (6) a basic heteroaromatic ring system with 1-9 C atoms; AC b H 2b ; b 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; wherein in group C b H 2b one or two methylene groups are selected by one of the groupings from the group consisting of -O-, -CO-, -CH [OR (20)] -, -SO m -, -NR (20) -, -NR (20) -CO-, -NR (20) -CO-NH-, -NR (20) -CO-NH-SO 2 -
  • R (19) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms
  • R (20) is hydrogen or methyl
  • B is a phenylene or naphthylene radical
  • R (12) and R (13) independently of one another are hydrogen, methyl, F, Cl, Br, J, CF3 or -SO w -R (14); R (14) methyl or NR (15) R (16); R (15) and R (16) independently of one another are hydrogen or alkyl having 1, 2,
  • R (21) is hydrogen or methyl; m zero, 1 or 2; and the other substituents R (1) and R (2) and R (3) independently of one another hydrogen, F, Cl, Br, J, -CN, - (-C-C 8 ) alkyl, - (C 2 -
  • R (17) is hydrogen, cycloalkyl having 3, 5 or 6 carbon atoms or C k F 2 ⁇ + ⁇ -; k 1, 2 or 3, or R (17) pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl , Br, I, -CN, (C 2 -C 8 ) alkanoyl, (C 2 -C 8 ) alkoxycarbonyl, formyl, carboxy, -CF 3 , methyl and methoxy; or
  • R (4) and R (5) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -OR (32), -NR (33) R (34) or -C r F 2r + ⁇ ;
  • R (32), R (33) and R (34) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms; r 1, 2, 3 or 4; and their pharmacologically acceptable salts;
  • R (1) and R (2) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10
  • R (12) and R (13) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms.
  • alkynyl with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms alkylaryl with 1, 2, 3 or 4 carbon atoms in the alkyl group
  • alkenyl aryl with 2, 3, 4 , 5, 6, 7, 8, 9 or 10 carbon atoms in the alkenyl group, alkynyl aryl with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms in the alkynyl group C 1 -C 4- alkyl-substituted aryl, dC 4 -alkyl heteroaryl, -C-C -alkenyl heteroaryl, aminoalkyl-aryl with 1, 2, 3 or 4 C-
  • R (7), R (8), R (9) and R (10) independently of one another are hydrogen, alkyl, cycloalkyl, aryl, alkylaryl; or R (8) and R (9) together form part of a 5, 6 or 7-membered heterocyclic ring; A absent or a non-toxic organic or mineral acid.
  • R (96) R (97); R (96) and R (97) independently of one another are hydrogen or -CH 3 ;
  • Y is a bond, CH 2 , oxygen, -S- or -NR (9);
  • R (9) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
  • R (8) SO a [NR (98)] b NR (99) R (10); a 1 or 2; b 0 or 1; a + b 2; R (98), R (99) and R (10) independently of one another hydrogen, - (-C ⁇ -Cs) -alkyl, benzyl, - (C 2 -C 8 ) -alkylene-NR (11) R (12), ( C 2 -C 8 ) Alkylene NR (13) - (C 2 -C 8 ) Alkylene NR (37) R (38) or (C 0 -C 8 ) Alkylene CR (39) R (40 ) - CR (41) R (42) (C 0 -C 8 ) alkylene NR (43) R (44); R (11), R (12), R (13), R (37), R (38), R (43) and R (44) independently of one another hydrogen, - (-C-C 8 ) alkyl or benzyl; R (39), R (40), R
  • R (99) and R (10) together have 4-6 methylene groups, of which one CH 2 group can be replaced by oxygen, -S-, -NH-, -N-CH 3 or -N-benzyl; or
  • R (8) SO a [NR (98)] b NR (95) -C [ NR (94)] - NR (93)
  • R (92); R (92), R (93), R (94) and R (95) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or R (1), R (2) and R (3) independently of one another pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CN, (C 2 -C 8 ) -
  • Alkanoyl (C 2 -C 8 ) alkoxycarbonyl, formyl, carboxy, -CF 3 , methyl, methoxy; or
  • R (1), R (2) and R (3) independently of one another hydrogen, - (-C-C 8 ) alkyl, - (C 2 -Cs) alkenyl or
  • R (23), R (24) independently of one another hydrogen, - (-C 8 ) -alkyl or benzyl; k zero, 1, 2, 3 or 4; or R (1), R (2) and R (3) independently of one another (Ci-CgJ-heteroaryl, which is linked via C or N and which is unsubstituted or substituted with 1-3 substituents from the group F, Cl, CF. 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; or
  • R (26) and R (27) independently of one another as R (25) defines or hydrogen or (-C-C 4 ) alkyl, or R (1), R (2) and R (3) independently of one another (C ⁇ -Cg ) -Heteroaryl-N-oxide, which is linked via C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; or
  • R (1), R (2) and R (3) independently of one another -SR (28), -OR (28), -NR (28) R (29) or
  • R (28) -C 8 H 2g - (-CC) heteroaryl-N-oxide which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, Hydroxy, amino, methylamino and dimethylamino; g zero, 1 or 2;
  • R (1), R (2) and R (3) independently of one another hydrogen, F, Cl, Br, I, -C ⁇ N, T- (CH 2 ) h - (CiF 2i + ⁇ ), R (31) SO ⁇ -, R (32) R (33) N-CO-, R (34) -CO- or R (45) R (46) N-SO 2 , the perfluoroalkyl group being straight-chain or branched; T is a bond, oxygen, -S- or -NR (47);
  • I zero, 1 or 2; h zero, 1 or 2; i 1, 2, 3, 4, 5 or 6;
  • R (31), R (32), R (34) and R (45) independently of one another - (-CC 8 ) alkyl, - (C 3 -C 6 ) alkenyl, (CH 2 ) n R (48) or -CF 3 ; n zero, 1, 2, 3 or 4;
  • R (47) is hydrogen or alkyl having 1, 2 or 3 carbon atoms; R (48) - (C 3 -C 7 ) cycloalkyl or phenyl, which is unsubstituted or substituted by 1-3
  • R (32), R (34) and R (45) are hydrogen;
  • R (33) and R (46) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or R (32) and R (33) and R (45) and R (46) together 5 or 6 methylene groups, one of which is a CH 2 group by oxygen, -S-, -NH-, -NCH 3 or -N -Benzyl can be replaced; or
  • R (1), R (2) and R (3) independently of one another R (51) -A-G-D-;
  • R (51) is a basic protonatable residue, i.e. an amino group
  • R (52), R (53), R (54) and R (55) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms.
  • R (51) is a basic heteroaromatic ring system with 1 - 9 C atoms;
  • A is a group C e H 2e ; e zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; in the group C e H 2e a carbon atom through one of the groupings -
  • R (57) is hydrogen or methyl;
  • G is a phenylene radical,
  • R (58) and R (59) independently of one another hydrogen, methyl, methoxy, F, Cl, Br, J, CF 3 or -SO S -R (60);
  • R (61) and R (62) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; D -CH v -E w -; v zero, 1, 2, 3 or 4;
  • R (64) alkyl with 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms;
  • R (65) and R (66) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; q zero, 1 or 2; p zero, 1 or 2; or
  • R (1), R (2) and R (3) independently of one another -OR (67) or -NR (67) R (68); R (67) and R (68) independently of one another are hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; or R (67) and R (68) together 4, 5, 6 or 7 methylene groups, of which one CH 2 group is replaced by oxygen, -S-, SO 2 , -NH-, -NCH 3 or -N-benzyl can be;
  • R (4) and R (5) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -OR (69), -NR (70) R (71) or ; R (69), R (70) and R (71) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms.
  • R (6) and R (7) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; X is oxygen or NR (72);
  • R (72) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; and their pharmaceutically acceptable salts; (HOE 95 / F 115 - EP 744 397, NZ 286 622) ak) Alkenylcarboxylic acid guanidides of the formula which carry fluorophenyl groups
  • R (6) is hydrogen, (-CC 8 ) -alkyl, (C 3 -C 8 ) -cycloalkyl or phenyl, the phenyl group being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (9) R (10); R (9) and R (10)
  • R (7) is independently defined as R (6);
  • R (1), R (2), R (3), R (4) and R (5) independently of one another are hydrogen or F; however, at least one of the radicals R (1), R (2), R (3), R (4) and R (5) must be fluorine; and their pharmaceutically acceptable salts; (HOE 95 / F 167 - NZ 299 015) al) benzoylguanidines of the formula I
  • R (1) R (4) -SO m or R (5) R (6) N-SO 2 -; m 1 or 2; R (4) and R (5) independently of one another alkyl with 1,2,3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl with 3, 4, 5 or 6 carbon atoms, CF 3 or -C n H 2n -R (7); n zero, 1,2, 3 or 4; R (6) is H or alkyl having 1, 2, 3 or 4 carbon atoms;
  • R (7) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (8) R (9); R (8) and R (9)
  • R (5) is also hydrogen; or R (5) and R (6) together have 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 (3) is hydrogen or is independently defined as R (1); and their pharmaceutically acceptable salts; (HOE 95 / F 173 - NZ 299 052) am) Substituted cinnamic acid guanidides of the formula I.
  • R (16), R (17) and R (18) independently of one another are H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; a zero or 1;
  • R (24) and R (25) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms; or R (24) and R (25) together 4 or 5 methyl groups, of which one CH 2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, the N-containing heterocycles N- or Are C-bridged and are not substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (27) R (28); R (23), R (27) and R (28) independently of one another are H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms, and the respective other substituents R (1), R (2), R (3), R (4) and R (5) independently of one another H, F, Cl, Br, I, CN
  • R (12); R (11) and R (12) independently of one another are H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; R (6) and R (7) independently of one another are hydrogen, F, Cl, Br, I, CN, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, or phenyl which is unsubstituted or substituted with 1 - 3 substituents selected from the group consisting of F, Cl, CF 3 , methyl,
  • R (15); R (14) and R (15) independently of one another are H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; and their pharmaceutically acceptable salts;
  • R (7) is hydrogen or methyl
  • R (8) and R (9) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl which is unsubstituted or substituted is selected with 1-3 substituents on the group consisting of F, Cl, CF 3 , methyl and methoxy; or the other substituents R (1), R (2) and R (3) independently of one another phenyl, C6H 5 - (dC) -alkyl, naphthyl, biphenyiyl,
  • Quinolinyl isoquinolinyl or imidazolyl, with quinolinyl, isoquinolinyl or imidazolyl being bonded via C or N, and with phenyl, C 6 H5- (C 1 -C 4 ) alkyl, naphthyl, biphenyiyl, quinolinyl, isoquinolinyl and imidazolyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; or the other substituents R (1), R (2) and R (3) independently of one another SR (10), -OR (10), -CR (10) R (11) R (12);
  • R (11) and R (12) independently of one another are defined as R (10), hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
  • R (4) and R (5) independently of one another are hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, Br, I, CN, OR (13), NR (14)
  • R (13), R (14) and R (15) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; n zero or 1; o zero, 1 or 2; as well as their pharmacologically acceptable salts;
  • At least one of the three substituents R (1), R (2) and R (3) is a benzoylguanidine
  • NH 2 which is unsubstituted or substituted in the phenyl part with 1-4 radicals selected from the group consisting of alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl having 2, 3, 4, 5, 6 , 7 or 8 carbon atoms, - (CH 2 ) m - R (14), F, Cl, Br, I, -C ⁇ N, CF 3 , R (22) SO 2 -, R (23) R (24) N-CO-, R (25) - CO-, R (26) R (27) N-SO 2 , -OR (35), -SR (35) or -NR (35) R (36); m zero, 1 or 2; R (14)
  • R (16); R (15) and R (16) independently of one another are hydrogen or -CH 3 ; R (22), R (23), R (25) and R (26) independently of one another alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-
  • R (24) and R (27) independently of one another are hydrogen or alkyl having 1, 2, 3 or
  • R (6) and R (7) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms
  • R (32) and R (33) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (35) Ci-Cg-heteroaryl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF, CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino; and the other substituents R (1), R (2) and R (3) independently of one another are alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms,
  • R (8); R (7) and R (8) independently of one another are hydrogen or alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms
  • R (2) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or -S0 2 R (9)
  • R (9) independently as R (1) defined
  • R (3) is hydrogen, -SR (25), -OR (25), -NR (25) R (26) or -CR (25) R (26) R (27);
  • R (25) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , CH 3 , methoxy, hydroxy, amino, methylamino and dimethylamino, or R (25)
  • R (26) and R (27) independently of one another are defined as R (25) or are hydrogen or alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms
  • R (4) is hydrogen, F Cl, Br, I, OH, -C ⁇ N, CF 3 , alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 carbon atoms Atoms or - (CH 2 ) m R (14), m zero, 1 or 2, R (14) - (C 3 -C 8 ) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF 3 , methyl, methoxy and -NR (15) R (16),
  • R (15) and R (16) independently of one another are hydrogen or -CH 3
  • R (5) and R (6) are independently of one another hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -OR ( 32), -NR (33) R (34) or CF 3 ,
  • R (32), R (33) and R (34) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms, and also their pharmaceutically acceptable salts, (HOE 95 / F 269 K - EP-OS 774 458) aq) benzenedicarboxylic acid diguanidides of the formula I.
  • R (2) and R (4) independently of one another R (22) -SO 2 -, R (23) R (24) N-CO-, R (28) -CO- or
  • R (29) R (30) N-SO 2 , R (22) and R (28) independently of one another methyl or -CF 3 , R (23), R (24), R (29) and R (30) independently from each other hydrogen or methyl, or R (2) and R (4) independently of one another -OR (35) or -NR (35) R (36), R (35) and R (36) independently of one another hydrogen or alkyl with 1 2 , 3, 4, 5 or 6
  • R (25) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF. 3 , CH 3 ,
  • R (26) and R (27) independently of one another as R (25) defined or hydrogen or alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms , R (5) alkyl with 1, 2, 3 or 4 carbon atoms, F, Cl, Br, I, X- (CH 2 ) y -CF 3 or phenyl, which is unsubstituted or substituted with 1-3 substituents from the group consisting of F and Cl, -CF 3 , methyl, methoxy and -NR (6) R (7); R (6) and R (7) independently of one another are hydrogen or -CH 3 ; X is a bond or oxygen; y zero, 1 or 2; and their pharmaceutically acceptable salts;
  • one of the radicals R (1), R (2), R (3) and R (5) -CO-N C (NH 2 ) 2 ; and the respective other radicals R (1), R (2), R (3) and R (5): R (1) and R (5) independently of one another hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms , F, Cl, -OR (32), -NR (33) R (34) or CF 3 ;
  • R (32), R (33) and R (34) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
  • R (36), R (35) and R (36) independently of one another are hydrogen or alkyl having 1, 2, 3, 4, 5 or 6
  • R (25) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF. 3 , CH 3 ,
  • R (26) and R (27) independently of one another as R (25) defined or hydrogen or alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms , R (4) CF 3 , alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, - (C 3 -C 8 ) cycloalkyl or - (CH 2 ) m R (14); m 1 or 2;
  • R (15) and R (16) independently of one another are hydrogen or -CH 3 ; or
  • R (16); R (15) and R (16) independently of one another are hydrogen or CH 3 ; and their pharmaceutically acceptable salts;
  • one of the radicals R (1), R (2), R (3), R (4) and R (5) -CO-N C (NH 2 ) 2 ;
  • the other radicals R (1) and R (5) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -OR (32), -NR (33) R (34) or CF 3 ;
  • R (32), R (33) and R (34) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
  • the respective other radicals R (2) and R (4) independently of one another hydrogen, F, Cl, Br, I, OH, -CN, CF 3 , -CO-N C (NH 2 ) 2 , alkyl with 1, 2 , 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 carbon atoms or - (CH 2 ) m R (14), m zero, 1 or 2,
  • R (35) and R (36) together 4-7 methylene groups, of which one CH 2 group can be replaced by oxygen, -S-, -NH-, -NCH 3 or -N-benzyl; the other R (3)
  • R (25) is hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF. 3 , CH 3l methoxy, hydroxy, amino, methylamino and dimethylamino; or
  • the other radicals R (6) and R (10) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -OR (132), -NR (133) R (134) or CF 3 ;
  • R (132), R (133) and R (134) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; the respective other radicals R
  • R (122) and R (128) independently of one another are methyl or -CF 3 ;
  • R (123), R (124), R (129) and R (130) independently of one another are hydrogen or methyl; or the respective other radicals R (7) and R (9) independently of one another -OR (135) or -NR (135) R (136);
  • R (135) and R (136) independently of one another are hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; or R (135) and R (136) together 4-7 methylene groups, of which one CH 2 group can be replaced by oxygen, -S-, -NH-, -NCH 3 or -N-benzyl; the other R (8)
  • R (126) and R (127) independently of one another are defined as R (125) or are hydrogen or alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms;
  • a absent, -NR (11) -CO-, -NR (12) -CO-NR (13) -, -NR (17) -CO-NR (18) -SO 2 -, - NR (19) -S0 2 -, -S0 2 -NR (19) -SO 2 -, -SO 2 -NR (19) -CO-, -O-CO-NR (19) -SO 2 - or -CR (20) CR ( 21) -; R (11), R (12), R (13), R (17), R (18), R (19), R (20) and R (21) independently of one another are hydrogen or alkyl having 1, 2, 3 , 4, 5, 6, 7 or 8 carbon atoms
  • R (41) and R (42) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, perfluoroalkyl having 1, 2, 3 or 4 carbon atoms, or R (41) and R (42) 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; and the other substituents R (1), R (2) and R (3) independently of one another H, F, Cl, Br, I, CN, -O na -C ma H 2ma + ⁇ or - O ga C ra H 2ra R (10); na zero or 1; ma zero, 1,2, 3, 4, 5, 6, 7 or 8; ga zero or 1; ra zero, 1,2, 3 or 4; R (10) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms or phenyl, wherein the phenyl is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF
  • R (14) and R (15) independently of one another are H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; and their pharmaceutically acceptable salts; (HOE 96 / F 032 - EP-OS 791 577) au) Ortho-substituted benzoylguanidines of the formula I.
  • R (2) and R (3) independently of one another are hydrogen, Cl, Br, I, (C-
  • R (5) (C1 -C8) alkyl or -C d H 2d - (C3-C8) cycloalkyl; d zero, 1 or 2; where one of the two substituents R (2) and R (3) is always hydrogen, but not both substituents R (2) and R (3) are simultaneously hydrogen, and their pharmaceutically acceptable salts; (HOE 96 / F 042 - EP-OS 794 171) av) Benzoylguanidines of the formula I
  • X is oxygen, S, NR (5), a zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3;
  • R (5) H, alkyl having 1, 2, 3 or 4 carbon atoms or -C d H 2d R (6); d zero, 1, 2, 3 or 4;
  • R (6) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenyiyl or naphthyl, the aromatics phenyl, biphenyiyl or naphthyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of from F, Cl, CF3, methyl, methoxy and
  • NR (7) R (8); R (7) and R (8) independently are H or alkyl having 1, 2, 3 or 4 carbon atoms; or R (1) -SR (10), -OR (10) or -CR (10) R (1 1) R (12); PCT / EP99 / 09621
  • R (11) and R (12) independently of one another are defined as R (10) or hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (1) phenyl, naphthyl, biphenyiyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, the latter linked via a carbon or nitrogen atom of the ring, each of which is unsubstituted or are substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy,
  • R (13) and R (14) the same or different - (CH 2 ) g- (CHOH) n - (CH 2 ) i- (CHOH) jR (17) or - (CH 2 ) g-0- (CH2- CH 2 O) h -R (24);
  • R (17) is hydrogen or methyl, g, h and i, identical or different, are zero, 1, 2, 3 or 4; j 1, 2, 3 or 4; R (15) and R (16), identical or different, are hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, or together with the carbon atom carrying them cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; R (18)
  • Phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl,
  • R (19), R (20), R (21), R (22) and R (23), the same or different, are hydrogen or methyl;
  • R (2) and R (3) are defined as R (1); R (4) alkyl having 1, 2, 3 or 4 carbon atoms; and their pharmaceutically acceptable salts; (HOE 96 / F 043 - EP-OS 794 172) aw) Ortho-substituted benzoylguanidines of the formula
  • X is oxygen, S, NR (5), a zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3; R (5) H, alkyl having 1, 2, 3 or 4 carbon atoms or -C d H 2d R (6); d zero, 1, 2, 3 or 4;
  • R (6) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenyiyl or naphthyl, the aromatics phenyl, biphenyiyl or naphthyl not being substituted or substituted by
  • R (7) and R (8) independently represent H or alkyl with 1, 2, 3 or 4
  • R (11) and R (12) independently of one another are defined as R (10) or hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (1) phenyl, naphthyl, biphenyiyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, the latter linked via a carbon or nitrogen atom of the ring, each of which is unsubstituted or are substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy,
  • R (13) and R (14) the same or different - (CH2) g - (CHOH) h - (CH 2 ) r (CHOH) jR (17) or - (CH 2 ) gO- (CH2-CH 2 O) h -R (24);
  • R (17) is hydrogen or methyl, g, h and i, identical or different, are zero, 1, 2, 3 or 4; j 1, 2, 3 or 4; R (15) and R (16), identical or different, are hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, or together with the carbon atom carrying them cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; R (18)
  • Phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26);
  • R (19), R (20), R (21), R (22) and R (23), the same or different, are hydrogen or methyl;
  • R (2) and R (3) Hydroxyl; and the other of the substituents R (2) and R (3) is defined as R (1); R (4) alkyl having 1, 2, 3 or 4 carbon atoms; Alkoxy with 1, 2, 3 or 4 carbon atoms, F, Cl, Br, l or - (CH 2 ) n - (CF 2 ) 0 -CF 3 ; n zero or 1; o zero or 1; and their pharmaceutically acceptable salts.
  • HOE 96 / F 135 - EP-OS 810 207 ax) bis-ortho-substituted benzoylguanidines of the formula
  • R (1), R (2) and R (3) independently of one another are R (10) -SO a - or R (14) R (15) N-SO -, a is zero, 1 or 2,
  • R (10), R (14) and R (15) independently of one another alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms,
  • R (16) cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms or phenyl which is unsubstituted or substituted by 1-3
  • R (1), R (2) and R (3) independently of one another SR (21), -OR (22), -NR (23) R (24) or
  • R (21), R (22), R (23) and R (25) independently of one another -C b H - (-C-C 9 ) heteroaryl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of from F, Cl, CF 3 , CH 3 ,
  • R (24), R (26) and R (27) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (1), R (2) and R (3) independently of one another hydrogen, F, Cl, Br, I, CN, - (Xa) dg-Cd a H 2d a + ⁇ , -
  • R (33) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1,
  • R (34) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; ie zero or 1; since zero, 1,2, 3, 4, 5, 6, 7 or 8; db zero, 1,2, 3 or 4; de zero, 1,2, 3, 4, 5, 6 or 7; df zero, 1,2, 3 or 4;
  • R (30) cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenyiyl or
  • Naphthyl wherein the aromatics phenyl, biphenyiyl or naphthyl are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (31) R (32); R (31) and R (32)
  • R (1), R (2) and R (3) independently of one another NR (40) R (41) or - (Xe) - (CH 2 ) eb R (45);
  • R (40) and R (41) independently of one another are hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or (CH 2 ) e -R (42); e zero, 1, 2, 3 or 4;
  • R (42) cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms or phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (43) R (44); R (43) and R (44) independently of one another are hydrogen, CF 3 or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (40) and R (41) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by oxygen, sulfur, NH, N-CH 3 or N-benzyl; (Xe) oxygen, sulfur or NR (47);
  • R (47) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; eb zero, 1, 2, 3 or 4; R (45) cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms or phenyl which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy, NR (50) R (51) and - (Xfa) - (CH 2 ) ed - (Xfb) R (46);
  • Xfa CH 2 , oxygen, sulfur or NR (48); Xfb oxygen, sulfur or NR (49); R (48), R (49), R (50) and R (51) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; ed 1,2,3 or 4; R (46) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or
  • Perfluoroalkyl with 1, 2, 3 or 4 carbon atoms or R (1), R (2) and R (3) independently of one another -CHR (52) R (53); R (52) - (CH 2 ) g - (CHOH) h - (CH) i- (CHOH) k -R (54) or - (CH2) g -O- (CH 2 -CH 2 O) h-
  • R (54) is hydrogen or methyl; g, h, i the same or different zero, 1, 2, 3 or 4; k 1,2,3 or 4;
  • R (53) is hydrogen or alkyl with 1, 2, 3 or 4 carbon atoms; or R (1), R (2) and R (3) independently of one another -C (OH) R (55) R (56); R (55) and R (56), the same or different, are hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (55) and R (56) together cycloalkyl having 3, 4, 5 or 6 carbon atoms; or
  • R (55) -CH 2 OH; and R (4) and R (5) independently of one another alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms, OH, F, Cl, Br, I, CN, - O n - (CH2) o- (CF 2 ) p-CF3, n zero or 1, o zero, 1 or 2, p zero, 1 or 2, and their pharmaceutically acceptable salts
  • R2, R3, R4, R5, R6, R7 and R8 independently of one another H, F, Cl, Br, I, CN, NO 2 , CF 3 , C 2 F 5 or X a YZ,
  • R (10), R (11) and R (12) independently of one another are H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl having 3, 4, 5, 6 or 7 carbon atoms -Atoms, a zero or 1, Y alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH 2 groups, one of these CH 2 groups being represented by O, S, NR (13) or o- , p- or m-phenylene can be replaced, R (13) H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1,2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5 or 6 carbon atoms; b zero or 1; ZH, alkyl having
  • Z is an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the N-containing heterocycle being linked via N or C and being unsubstituted or substituted by 1-3 Substituents selected from the group consisting of F, Cl, Br, CF 3 , methyl, methoxy and NR (21) R (22), but in the event that R (4) is an alkoxy radical, at least one of the substituents R (2), R (3), R (5), R (6), R (7) and R (8) are not hydrogen; and their pharmaceutically acceptable salts
  • R1, R3, R4, R5, R6, R7 and R8 denotes XY a WZ or X ⁇ a WZ, XO, S, NR (10) or CR (11) R (12);
  • R (10), R (11) and R (12) independently of one another are H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl having 1, 2, 3 or 4 carbon atoms or
  • Cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms Y alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH 2 groups, one of these CH 2 groups can be replaced by O, S, NR (13) or o-, p- or m-phenylene; R (13) H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5 or 6 carbon atoms;
  • R (18) and R (19) independently of one another are H, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; or R (18) and R (19) together have 4 or 5 methylene groups, of which one CH 2 group can be replaced by oxygen, S, NH, N-CH 3 , N-benzyl or N- (p-chlorophenyl); R (20)
  • NR (30) C O or NR (30) SO 2 , whereby the linkage with the naphthalene ring takes place via the atom on the left;
  • Z 'C ( O) R (15), SO 2 R (15), an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the N - containing heterocycle is linked via N or C and is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF 3 , methyl, methoxy and NR (21) R (22); R (21) and R (22) independently of one another are H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms;
  • N C (NH 2 ) 2 , NR (18) R (19), N (CH 2 ) b NR (18) R (19) or OR (20); R (18) and R (19) independently of one another are H, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms.
  • NH, N-CH 3 , N-benzyl or N- (p-chlorophenyl) can be replaced; b 2 or 3; R (20) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms ; or Z - if W is not O or NR (14) - NR (16) R (17);
  • Q alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH 2 groups, one of these CH 2 groups being replaced by 0, S, NR (68) or o-, p- or m-phenylene can be; R (68)
  • alkyl with 1, 2, 3, 4, 5, 6 or 7 carbon atoms, cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms, C ( 0) R (65), S0 2 R ( 65), NR (61) R (62) or phenyl, that is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF 3 , methyl, methoxy and NR (63) R (64); R (63) and R (64) independently of one another H, alkyl with 1, 2, 3 or 4 C-
  • R (65) N C (NH 2 ) 2 , NR (61) R (62) or OR (60);
  • R (61) and R (62) independently of one another are H, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; or
  • U is an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the N-containing heterocycle being linked via N or C and being unsubstituted or substituted by 1-3 Substituents selected from the group consisting of F, Cl, Br, CF 3 , methyl, methoxy and NR (63) R (64); however, at least one of the substituents R5, R6, R7 and R8 is not hydrogen; and their pharmaceutically acceptable salts.
  • R (6) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenyiyl or naphthyl, the aromatics phenyl, biphenyiyl or naphthyl not being substituted or substituted by
  • R (7) and R (8) independently represent H or alkyl with 1, 2, 3 or 4
  • R (11) and R (12) independently of one another are defined as R (10) or hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • R (13) and R (14) the same or different - (CH 2 ) g- (CHOH) h - (CH 2 ) j- (CHOH) kk -R (17) or - (CH 2 ) gO- (CH2- CH 2 O) h -R (24);
  • R (17) is hydrogen or methyl, g, h and i, identical or different, are zero, 1, 2, 3 or 4; kk 1, 2, 3 or 4; R (15) and R (16), identical or different, are hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, or together with the carbon atom carrying them, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms; R (18) phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl,
  • Methoxy and NR (25) R (26); R (25) and R (26) are H or alkyl having 1, 2, 3 or 4 carbon atoms; or
  • Cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms R (19), R (20), R (21), R (22) and R (23), the same or different, hydrogen or methyl, R ( 24) H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms or -C m H 2m -R (18), m 1, 2, 3 or 4, one of the two substituents R (2) and R (3) -O-CO-R (27),
  • R (1) R (13) -SO m or R (14) R (15) N-S ⁇ 2-; m 1 or 2;
  • R (13) alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl having 3, 4, 5, 6, 7 or 8 carbon atoms or -C n H 2n -R (16), n zero, 1, 2, 3 or 4;
  • R (16) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenyiyl or naphthyl, phenyl, biphenyiyl and naphthyl being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F.
  • R (25) and R (26) independently of one another are hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms;
  • R (14) is hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl with 3, 4, 5, 6, 7 or 8 carbon atoms or -C n H 2n -R (27), n zero, 1, 2, 3 or 4;
  • R (27) cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, phenyl, biphenyiyl or naphthyl, where phenyl, biphenyiyl and naphthyl are not substituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl,
  • Methoxy and NR (28) R (29), R (28) and R (29) independently of one another hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms
  • R (15) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms, or R (14) and R (15) together have 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, one of the substituents R (2) and R (3) is hydrogen; and the other substituent R (2) and R (3) -CHR (30) R (31); R (30) - (CH 2 ) g- (CHOH) n - (CH 2 )
  • R (24 and R (32) independently of one another are hydrogen or methyl, g, h, i, identical or different, zero, 1, 2, 3 or 4, k 1, 2, 3 or 4, or the other substituent R (2) and R (3) -C (OH) R (33) R (34), R (31), R (33) and R (34) the same or different hydrogen or alkyl with 1, 2, 3 or 4 C-
  • R (33) and R (34) together cycloalkyl having 3, 4, 5 or 6 carbon atoms; or
  • HOE 96 / F 202 bc) indanylidine acetylguanidines of the formula I.
  • Alkyl 2 or SO 2 -N (alkyl) (alkylaryl);
  • R7, R8, R9 and R10 independently of one another are H, alkyl, cycloalkyl, aryl, alkylaryl, or R8 and R9 together form part of an a 5-, 6- or 7-membered heterocyclic ring; or their pharmaceutically acceptable salts.
  • R (6) (-CC 4 ) -alkyl, (-C-C 4 ) -perfluoroalkyl, (C 3 -C 6 ) -alkenyl, (C 3 -C 8 ) -cycloalkyl, phenyl or benzyl, wherein the phenyl nucleus is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy and NR (9) R (10); R (9) and R (10) H, (-CC 4 ) alkyl or (dC 4 ) perfluoroalkyl;
  • R (7) and R (8) are independently defined as R (6); or R (7) and R (8) together have 4 or 5 methylene groups, one of which is CH 2 -
  • R (B), R (C) and R (D) are independently defined as R (A); x zero, 1 or 2; y zero, 1 or 2;
  • R (12) (C ⁇ -C8) alkyl, (C ⁇ -C4) perfluoroalkyl, (C 3 -C 8) -Aikenyl, (C 3 -C 8) - cycloalkyl, phenyl or benzyl, where the phenyl nucleus not is substituted or substituted 1 - 3 substituents selected from the group
  • R (E) is independently defined as R (F);
  • N C (NH 2 ) 2 -SO r R (17), -SO r2 NR (31) R (32), -Ou (CH 2 ) v C 6 H 5 , -O u2 - (C ⁇ -C 9 ) - Heteroaryl or -Su 2 - (-C-Cg) heteroaryl, k zero or 1; m zero, 1,2, 3, 4, 5, 6, 7 or 8; n zero or 1; p zero, 1, 2, 3 or 4; q 1, 2, 3, 4, 5, 6, 7 or 8; r zero, 1.2; r2 zero, 1.2;
  • R (31) andR (32) independently of one another are hydrogen, (dC 8 ) -alkyl or (-C-C 8 ) - perfluoroalkyl, or R (31) andR (32) together have 4 or 5 methylene groups, one of which is a CH2 group Oxygen, S, NH, N-CH3 or N-benzyl can be replaced;
  • R (18) R (19), R (21) and R (22) independently of one another (-C-C) alkyl or (C ⁇ -C) - perfluoroalkyl, w 1,2, 3 or 4, the heterocycle of (C ⁇ -C9) heteroaryl is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3 , methyl or methoxy, R (2) R (3), R (4) and R (5) defined independently of one another as R (1), or R (1) and R (2) or R (2) and R (3) in each case together -CH-CH CH-CH-, which is not substituted or substituted by 1 - 3 substituents selected from the group consisting of F, Cl, CF 3 , methyl, methoxy, - (CH 2 ) w2 NR (24) R (25) and NR (26) R (27); R (24), R (25), R (26) and R (27)

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EP99959387A 1998-12-23 1999-12-08 Die verwendung von hemmern des natrium-wasserstoff-austauschers zur herstellung eines medikaments zur verhinderung von altersbedingten organ-dysfunktionen, altersbedingten erkrankungen und zur lebensverlängerung Ceased EP1140056A2 (de)

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DE19859727A DE19859727A1 (de) 1998-12-23 1998-12-23 Die Verwendung von Hemmern des Natrium-Wasserstoff-Austauschers zur Herstellung eines Medikaments zur Verhinderung von altersbedingten Organ-Dysfunktionen, altersbedingten Erkrankungen zur Lebensverlängerung
DE19859727 1998-12-23
PCT/EP1999/009621 WO2000038661A2 (de) 1998-12-23 1999-12-08 Die verwendung von hemmern des natrium-wasserstoff-austauschers zur herstellung eines medikaments zur verhinderung von altersbedingten organ-dysfunktionen, altersbedingten erkrankungen und zur lebensverlängerung

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NZ534479A (en) * 2002-02-04 2006-03-31 Sanofi Aventis Deutschland Combination preparation of the sodium-hydrogen exchange inhibitor cariporide with ACE inhibitors for preventing heart failure and other age-related dysfunctions of organs, age-related diseases and for prolonging lifespan
US7375138B2 (en) * 2002-05-18 2008-05-20 Sanofi-Aventis Deutschland Gmbh Pentafluorosulfanylbenzoylguanidines, processes for their preparation, their use as medicaments or diagnostic aids, and medicaments comprising them
FR2840302B1 (fr) * 2002-06-03 2004-07-16 Aventis Pharma Sa Derives d'isoindolones, procede de preparation et intermediaire de ce procede a titre de medicaments et compositions pharmaceutiques les renfermant
US6878748B2 (en) 2002-06-13 2005-04-12 Aventis Pharma Deutschland Gmbh Fluorinated cycloalkyl-derivatized benzoylguanidines, process for their preparation, their uses as medicament, and medicament containing them
EP2617709B8 (en) * 2003-06-26 2022-12-21 Biotron Limited Guanidine derivatives as antiviral agents
US8017863B2 (en) * 2005-11-02 2011-09-13 The Regents Of The University Of Michigan Polymer wrapped carbon nanotube near-infrared photoactive devices
US8013240B2 (en) * 2005-11-02 2011-09-06 The Trustees Of Princeton University Organic photovoltaic cells utilizing ultrathin sensitizing layer
US7947897B2 (en) * 2005-11-02 2011-05-24 The Trustees Of Princeton University Organic photovoltaic cells utilizing ultrathin sensitizing layer
KR101042078B1 (ko) * 2009-01-13 2011-06-16 한국항공우주산업 주식회사 치공구 제작용 수평 측면 가공 치구
CN104103253B (zh) 2014-07-04 2016-08-17 京东方科技集团股份有限公司 发射电极扫描电路、阵列基板和显示装置

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