CZ20004797A3 - Combined preparation of compounds exhibiting anti-infectious activity and inhibiting metabolic path of 2-C-methylerythrose-4, and lipid metabolism inhibitors - Google Patents

Abstract

Combined preparation containing at least the active substances one anti-infective compound that inhibits the pathway 2-C-methylerythrosa-4-metabolism, and at least one fat metabolism inhibitor. Combined preparation applied to infectious processes, especially human infections and the animal and the herbicide in plants. It turns out that the emergence resistance is relative to the individual preparations u combined preparation is greatly reduced.

Description

Combination of anti-infectious compounds that inhibit the 2-C-methylerythrosy-4 pathway and lipid metabolism inhibitors

Technical field t

BACKGROUND OF THE INVENTION The present invention relates to anti-infectious compounds which inhibit the pathway of 2-methylmethylthrosa-4-metabolism, as well as their salts and esters and fat metabolism inhibitors, and their simultaneous, separate or staggered use for the prophylaxis and therapy of infectious processes in plants, humans and animals and their use as a herbicide. Combined preparations according to the invention are particularly suitable for therapeutic and prophylactic treatment of infections or protozoal ^R metazoan parasites, fungi, bacteria or viruses but also as herbicides.

BACKGROUND OF THE INVENTION

The potency of various phosphororganic compounds as drugs is already known. Thus, for example, the antimicrobial activity of aminohydrocarbylphosphonic acid derivatives against bacteria in humans and animals and against fungi in plants is described (DE 27 33 658 A1, US 4 143 135, US 4 182 758 and US 4 206 156, US 4 994 447, US 4 888,330, 4,210,635, 3,955,958, 4,196,193, 4,268,503, 4,330,529, 5,189,030, 3,764,677, 3,764,676). Further, the substances of this group are described as herbicides (U.S. Pat. No. 4,693,742, U.S. Pat. No. 5,002,602, U.S. Pat. No. 4,131,448, U.S. Pat. No. 3,977,860, U.S. Pat. No. 4,062,669), as algocides (U.S. Pat. No. 3,887,353). US 4 127 401, US 4 120 668, US 3 961 934, US 4 431 438, US 3 853 530, US 4 205 977, US 4 025 332, US 3 894 861) and as dyes production reagents (US 4 051 175).

The use of, for example, aminohydrocarbylphosphonic acid derivatives in combating bacterial infections has proved to be very difficult. Many of the bacteria that are responsible for outpatient infections and infections that have been acquired during the clinical stay are not susceptible to therapy with this group. This includes bacteria of the genus Staphylococcus, especially Staphylococcus aureus. This skin embryo is a threat to patients staying in clinics. Another study, including phase IIa of the Applicant of DE 27 33 658, showed a very rapid generation of the resistance of the initially sensitive germs. Therefore, these derivatives have not been used in clinical practice.

Furthermore, the use of bisphosphonic acids and certain derivatives thereof in medicaments is already known. To date, the microbiostatic activity of bisphosphonic acids (DE 3 611 522), their efficacy in calcium and phosphate metabolic disorders (DE 2 534 390, DE 2 534 391, DE 3 334 211, DE 3 434 667, DE 2 745 083) ), cytostatic activity (DE 3 425 812), their lipid lowering activity (Arzneimittelforschung, 43, 759-62) and their ability to stimulate immune cells (WO 97/38 696).

Antimicrobial activity against bacteria and foscarnet activity against viruses have been described for phosphonochlorine. Furthermore, the potency of fosaminammonium and N, N-dimethyl- (hydroxy-2-oxo-2-methoxyethyl) phosphonamide as a herbicide has been reported.

The use of fat metabolism inhibitors has long been a recognized and widely used principle of treatment. These inhibitors are used to reduce the risk of cardiovascular disease due to hyperlipidemia. The pharmacotherapy of these hyperlipidemia generally consists in regulating the intake and regulating the synthesis of fat or, in particular, cholesterol. Cholesterol synthesis is generally controlled by the enzyme β-hydroxymethylglutaryl-CoA-reductase (HMG-CoA-Reductase). Cholesterol synthesis itself is generally greater than food intake. [Berthold] K., von Bregmann, K., Dtsch. Copper. Wochenschr. 121, p. 729 (1996); Richter W.O., Fortschr. copper. 114, pp. 177, 193],

Anion exchangers and βsitosterol are known to regulate intake of fats from the gastrointestinal tract. Anion exchangers include cholestyramine and colestipol. They resorb bile acids and thereby interrupt enterohepatic re-transport and thus affect the distinct increase in stool sterols. β-Sitosterol is a plant sterol, structurally related to cholesterol. It suppresses the absorption of cholesterol from food by the intestinal mucosa.

Furthermore, nicotinic acid and its derivatives, clofibrates and their derivatives, and probucol have been used in the regulation of fat metabolism or prevention of subsequent hyperlipidemia diseases. Nicotinic acids and nicotinic acid derivatives lead to a reduction in fatty acids, triglycerides and cholesterol. The mechanism is not yet known. Clofibrinic acid ethyl ester, clofibrate and derivatives as well as analogues lead to a decrease in cholesterol, the mechanism of action is also unknown. The mechanism of action of probucol is also not elucidated.

HMG-CoA synthetase inhibitors (US 50 64 856, US 47 51 237), HMG-CoA reductase inhibitors (US 38 18 080, US 39 83 140,

US 40 49 495, US 41 37 322, US 42 55 444, US 41 98 425, US 42 31 938, US 43 75 475, US 43 46 227, US 44 106 29, US 44 447 84, US 44 50 171, US 45 54 359, US 49 201 09, EP 0065835A1, EP 0142146A2, GB 15 86 152, US 33 75 475, GB 21 62 179A, EP 164698A, WO 8402903, WO 8401231, WO 8603448A, US 46 81 893, US 46 45,858, US 52,368,946, US 55 06,262, US 50 25,017, US 48 47 271, US 46 22 338, US 49 04 646, US 48 73 345, US 55 93 971, US 52 60 305, US 52 02 327, US 49 40 727, US 52 72 166, US 53 85 932, US 54 61 039, US 55 56 990, US 55 61 143, US 55 63 128), squalene synthetase inhibitors, in particular pyrophosphates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethylphosphonic acid derivatives, phosphinylformyl derivatives, phosphonocarboxy derivatives, phosphonosulfonic acid derivatives, which are also known in part as pharmaceutical and cosmetic agents for regulating the metabolism of calcium and phosphates (DE 25 34 390, DE 25 34 391, DE 33 34 211, DE 34 34 667; DE 2 No. 7 45 083, U.S. Pat. No. 52 12 814, U.S. Pat. No. 52 54 544, U.S. Pat. No. 54 70 845, U.S. Pat. No. 50 25 003, U.S. Pat. No. 55 34 532, U.S. Pat. No. 48 71 721, WO 92 15 579, US 51 35 935, WO 92 12 160, WO 92 12 159, WO 92 12 158, WO 92 12 157, WO 92 12 156, US 52 73 969, US 53 95 846, US 54 41 946, US 54 51 596, US 54 55 260, US 55 63 128, US 52 No. 02 327, US 49 04 646) and other cholesterol synthesis inhibitors (US 56 61 145, US 57 44 467), the assignment of which is not clarified. HMG-CoA reductase inhibitors competitively suppress the cholesterol synthesis rate determining enzyme, HMG-CoA reductase. They have up to 2000-fold higher affinity for the enzyme than the HMG-CoA substrate. HMG-CoA reductase leads to the conversion of HMG-CoA to mevalonate, which, besides cholesterol, isopentenyladenine as well as farnesylpyrophosphate, a precursor of dolichol and ubiquinone, are formed. Bacteria, fungi and parasites that possess HMG-CoA reductase produce isopentenyl diphosphates via an acetate / mevalonate pathway that is inhibited by HMG-CoA reductase inhibitors.

Early discovered inhibitors were isolated from Penicillium (mevastatin) and Aspergillus (lovastatin) fungi. Side chain modification led to simvastatin, a further development from mevastatin to pravastatin. Meanwhile, a fully synthetic enzyme inhibitor (fluvastatin), a mevalonlactone derivative of the fluorophenyl substituted indole ring, has become available.

Efforts have been made in the past to deploy these substances for application in combating infectious diseases. In particular, attempts have been made to inhibit the growth of plants, fungi, parasites, bacteria and viruses by the use of HMG-CoAinhibitors. HMG-CoA synthetase and HMG-CoA reductase inhibitors inhibit the acetate pathway in many bacteria, fungi and parasites4

mevalonate (US 50 26 554, US 50 64 856, US 49 20 111, US 49 20 113). However, many bacteria, such as Escherichia coli, show no inhibition by HMG-CoAreductase inhibitors. This is probably because these bacteria have an alternative pathway for metabolism. Indeed, Escherichia coli has been shown to be absent from the acetate-mevalonate pathway and the existence of another pathway [Rohmer M. et al., Biochem. J., 295, 517 (1993); Lois E. M. et al., Proc. Nati. Acad. Sci. USA, 95, 2105 (1998)].

So far no alternative route of metabolism has been known for parasites. However, the Applicant has succeeded in proving an alternative metabolism pathway for parasites, the so-called 1-desoxyxylulose-5-phosphate or 2-methylmethylthrosa-4-phosphate pathway. Studies with HMG-CoA reductase inhibitors on parasites gave different results depending on the parasites. Thus, with high doses of lovastatin, no killing of bilharziosis agents is achieved, whereas in malaria agents killing is achieved in vitro but not in vivo. Also, agents of sleeping sickness cannot be completely inhibited by HMG-CoA reductase inhibitors. Similar attempts to suppress virus reproduction show that virus-infected cells lose the suppressive effect of HMG-CoA reductase inhibitors.

Also squalene synthetase inhibitors such as aminobisphosphonates have been successfully tested as amoebic dysentery inhibitors. The killing efficiency was shown to be low. Similar experiments with Toxoplasmas also did not give any satisfactory results. In addition, squalene epoxidase inhibitors have also been developed as fungicides (US 47 82 059).

The principle of the invention

It is therefore an object of the invention to provide a composition which can be applied against infectious processes in humans, animals and plants and as a herbicide, and in which the emergence of resistance in plants, viruses, fungi, parasites and bacteria can be substantially reduced.

Surprisingly, it has been discovered that combinations of anti-infectious compounds that suppress the pathway of 2-C-methylerythrosa-4-metabolism with fat synthesis inhibitors, particularly cholesterol synthesis, particularly HMG-CoA reductase and squalene synthetase inhibitors, increase the breadth and effectiveness of therapy and prophylaxis of infections . In a marvelous way, the combination shows a strong reduction in the resistance to the deployed compounds, which is generally the biggest problem in the use of a group of fat metabolism inhibitor compounds.

• · · ♦ · · · · · · · · · «·« · · · · · · · · · ·· ···

Combinations of anti-infectious compounds that suppress the pathway of 2-C-methylerythrosa-4-metabolism and fat metabolism inhibitors are useful for the therapeutic and prophylactic treatment of infections in plants, and in particular in humans and animals, particularly infections caused by parasites, bacteria, fungi and viruses, and as a herbicide in plants.

The combination preparations of the invention comprise at least one anti-infectious compound which inhibits the pathway of 2-C-methylerythrosa-4-metabolism and / or its ester and / or its salts. This includes, in general, pharmaceutically acceptable salts, esters, salts of such esters, or, in turn, compounds which upon application give the compounds of the invention as metabolic or degradation products, also called precursors.

In the following, groups of substances that, in combination with fat metabolism inhibitors, show excellent results in the therapy and prophylactic treatment of infections will be described below.

Anti-infectious groups of compounds can be determined according to a procedure in which proteins that are involved in the pathway of 2-C-methylerythrosa-4 metabolism, or derivatives thereof, are contacted with the active compounds of interest and the active compounds selected to inhibit these proteins or derivatives are selected. . The procedure is known to the person skilled in the art.

I. Combined preparations of fat metabolism inhibitors with aminohydrocarbylphosphonic acid derivatives

Aminohydrocarbylphosphonic acid derivatives as well as their preparation are described in detail in DE-A1-2733658 and PCT / EP99 / 02462.

The aminohydrocarbylphosphonic acid derivatives correspond to the general formula (I):

N, N-Aj-P-R 3 (O ^R l ² R | 4 wherein Rn and R12 may be the same or different and are selected from the group consisting of H, OH, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl,

unsubstituted unsubstituted substituted and unsubstituted aralkyl and substituted and unsubstituted heterocyclic radicals,

R 13 and R 14 are selected from the group consisting of substituted and unsubstituted alkyl of 1 to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of 1 to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted aralkyl. unsubstituted alkenyl of 1 to 26 carbon atoms, substituted and alkynyl of 1 to 26 carbon atoms, substituted and cycloalkyl, substituted and unsubstituted heterocyclic radicals, halogen, X | ₃ and X | ₄ ,

X ₁ and X ₁₄ may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1 -C 26 alkyl, substituted and unsubstituted C 1 -C 26 hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl of 1 to 26 carbon atoms, substituted and unsubstituted alkynyl of 1 to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, a cation of an organic and inorganic base, in particular a metal of the first second or third major groups of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids; and

A 1 represents an alkylene residue, an alkenylene residue or a hydroxyalkylene residue, or corresponds to the following formula (IA):

B | 1 (B) | 3 ^ 5 B || 7 B | ⁹ θ | 1 ~ - ( --2 ^- - C | 3 C | 4 " C | 5 (IA) ♦ B | 2 (B) | 4 ^B | 6 η 8 B | io

wherein one or more carbon atoms selected from C _(3, C | ₄ C | ₅ together with their substituents may also be omitted and at least one of the existing substituent to Β ι · Bio is C3-8-cycloalkyl- (9) - an alkyl group, wherein both the C 3-8 -cycloalkyl group and the (C 0-6) -alkyl group may have one or more double bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen atoms,

and wherein both cycloalkyl and alkyl may be substituted with hydroxy, halogen, amino, oxo groups with branched and unbranched C 1-6 alkyl. C ₉ alkyl and _{second 9} alkenyl groups, wherein the C 1-8 alkyl and the C 2-9 alkenyl groups may be substituted by hydrogen, hydroxy, amino, halogen and oxo and the remaining existing substituents B 1 to B 1 | ₁₀ are selected from the group consisting of hydrogen, hydroxy, halo, amino, C _"26 alkyl radicals, C. ₂ 6-alkoxy radicals, Ci. _The 2-6-alkoxy-C 1-6 -alkyl radicals, or both substituents on one C-atom, together form an oxo group, wherein each C 1-6 alkyl radical and each C 1-6 alkyl radical form an oxo group. _The 6-alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups.

According to the invention, the fat metabolism inhibitor is not an aminohydrocarbylphosphonic acid derivative of formula (I) when the aminohydrocarbylphosphonic acid derivative is used as an anti-infective compound.

In addition, the invention also includes pharmaceutically acceptable salts, esters and ester salts.

In place of R11, OXh is preferred, in place of R13 is OX13 and in place of R _w is OX1 ₄ , wherein X 11 is selected from the group consisting of hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocyclic radicals, and R 12, X 13. X 4 and A 1 have the same meaning as in formula (I).

Carbon chain A | is preferred with three carbon atoms.

Preference is also given to compounds in which the carbon chain Ai in formula (IA) consists of four carbon atoms C 1, C 1, C 1, C 1, C 1, C 1, C 1, C 1, C 1, C 3. ₂ , C | ₃ , Cm and B17 or B1 ₈ or both are hydroxy. In this case, they are for R 1 ₃ and R 14, methylene groups are also preferred.

It is further preferred that Bh and B 1 ₂ together formed an oxo group. In this case, the carbon chain consists of A 1 of four carbon atoms Ch, C 1 ₂ , C13 ₄ .

It is further preferred that Bjz and Big together form an oxo group. In this case, the carbon chain consists of A 1 also from four carbon atoms Ch, C 1 ₂ , C ₁₃ , C _{13 4} .

The carbon chain preferably consists of 5 carbon atoms, _CH, C _2, C _{i3, C] 4,} C _i5 wherein Bn B | ₂ together form an oxo group and at least one substituent B 1 ₉ or Bho is hydroxy or B 1 ₉ or Bno together form an oxo group.

Also suitable are substances in which the sulfonic or sulfonyl group is in place of the phosphonic acid or phosphinic acid group or the phosphinoyl group:

O

-S — r _{| 3} (ib)

II. Combined preparations of fat metabolism inhibitors with bisphosphonic acid derivatives

As bisphosphonic acids and derivatives thereof, those having the general formula are used

ΪΗ

X || ₃ O - PC - P - ox _u1 (II),

Θ || 4θ A || OX || 2 i

^K || 2 where

Xih, X112. Xii3, Xii4, which may be the same or different with. selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, and substituted and unsubstituted heterocyclic radicals, metals of the first, second and third main groups of the periodic system, such as Na, K, Ca, Mg, Al as well as substituted and unsubstituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids,

Au, which may also be omitted, may be selected from the group consisting of alkylene, alkenylene and hydroxyalkylene,

R 11, R 12 may be the same or different and are selected from the group consisting of H, OH, -NH ₂ , substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, and substituted and an unsubstituted heterocyclic radical and -SR 11 ₃ , Cl and -NR ₁₁ R 8 ₄ , where

·············································

R ₁₁ , R 11 may be the same or different and are selected from the group consisting of H, OH, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, and substituted and unsubstituted heterocyclic moiety and their pharmaceutically acceptable salts, esters, as well as ester salts or compounds which, when administered, form the administered compounds as metabolism or degradation products.

Particular preference is given to bisphosphonic acid derivatives of formula II in which Xin, Xii2> Xii3, Xii4> which can be the same or different are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, and substituted and unsubstituted heterocyclic radicals, metals of the first 1, 2 and 3 main groups of the periodic system, such as Na, K, substituted and unsubstituted ammonium and ammonium compounds derived from ethylenediamine or amino acids,

And which may also be omitted, is selected from the group consisting of alkyl, (CH ₂₎ 6, in particular (CH ₂₎ 5 and amidino,

Rim is selected from the group consisting of H, OH, NH ₂ , -CH ₃ and

R ₁₁ is selected from the group consisting of -NH ₂ , -n

-N \ ^ N

Particularly preferred are bisphosphonates selected from the group consisting of amino-hydroxy-methylidene-bisphosphonic acid, 2-amino-1-hydroxyethylidene-1,1-bisphosphonic acid, 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid, 4-amino- 1-hydroxybutylidene-1,1-bisphosphonic acid, 6-amino-1-hydroxyhexylylidene-1,1-bisphosphonic acid, amidinomethylene-bisphosphonic acid, 3-methylpentylamino-1-hydroxypropylidene-1,1-bisphosphonic acid, 2- (3-pyridinyl) ) -1-hydroxyethylidene-1,1-bisphosphonic acid, 1-hydroxy-2- (imidazol-1-yl) -ethylidene-1,1-bisphosphonic acid, Cycloheptylaminomethylenediphosphonic acid, 4-chlorophenylthiomethylene-1,1-bisphosphonic acid, as well as derivatives thereof.

When the anti-infective compound is a bisphosphonic acid derivative, no bisphosphonic acid derivative is a metabolic inhibitor.

III. Combination preparations of inhibitors of fat metabolism with phosphorous compounds having a keto group

These compounds are described in detail in DE-A-198 31 637.2.

The compounds of the invention correspond to the general formula (III):

^R 11 ^{H A} ||| 1 ^C - ^A ||| 2-PR ||| 4 (III) ^R ||| 3

Run is selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cyclo aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OXim, wherein Xim is selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkenyl, substituted and unsubstituted substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, silyl, substituted and unsubstituted aryl; a substituted heterocyclic radical, an organic and inorganic base cation, in particular a metal of the first second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds,

Rum and Rih3 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen and OXw4 and OXw3, wherein Xm4 and X1113 are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted aryl , substituted and unsubstituted cycloalkyl, silyl, substituted and unsubstituted heterocyclic radicals, an organic and inorganic base cation, in particular a metal of the first second or third main group salts of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids; and

A1111 and Aih2, one or both of which may be omitted, are the same or different and represent an alkylene, alkenylene, oxo, hydroxy or oxo-hydroxyalkylene radical, with Am ₂ preferably being omitted.

The invention also includes pharmaceutically acceptable salts, amides, esters, and ester salts.

The phosphonic acid derivatives of the present invention have proven to be particularly suitable. In this case, for Rhi ₄ OXnw and for Rm ₃ 0Xm3, with Run, Xn14, X1113, A1111 and A1112 having the same meaning as in formula (III).

Particularly preferred phosphonic acid derivatives are chloroacetylphosphonic acid (phosphonochlorine), phosphoric acid (foscarnet), phosphonoacetic acid, N, N-dimethyl (1-hydroxy-2-oxo-2-methoxyethyl) phosphonamide and 2-hydroxy-2-hydroxymethyl- 3-oxo-butylphosphonic acid (phosphonothrixine) and ammonium ethylcarbamoylphosphonate (fosamin-ammonium).

IV. Combined preparations of fat metabolism inhibitors with phosphorous compounds having at least one ether group or a keto group

The compounds of the invention correspond to the general formula (IV):

· M o o o o o o o o o o o o ^o \ \ o \ \ \ \ \ \ ||

N-Biv-P-Riva

R iw I

Riv4 in which R | _V 1 and Riv 2 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen, OX | _The IA 0X | V2 with Xivi and Xiv2 may be the same or different and are selected from the group consisting of hydrogen, from substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals,

Biv is selected from the group consisting of an ether group (IVA) —A 1 _V 1-OA | _{In the} 2-C- (IVA)

With Aivi and A _V 2, of which _V 2 may also be omitted, they are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, keto (IVB)

O

II Z X

-A | V3-CA | _V 4 - (IVB) wherein Aiv 3 and Aiv 4, of which one or both may be omitted, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · and 5- and 6-membered cyclic, especially heterocyclic, compounds which, in addition to carbon, contain at least one heteroatom as part of the ring, wherein the heteroatom is selected from the group consisting of oxygen and nitrogen,

Riv 3 and Riv 4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl of up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, halogen, OXiv3 and OXiv4, or Xiv3 and X4 may be the same and is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl of up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of up to 26 carbon atoms, substituted and unsubstituted aryl, su substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, a cation of an organic or inorganic base, in particular third major groups of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids and their pharmaceutically acceptable salts, esters and amides and ester salts.

Particular preference is given to compounds having the formula (IVC)

ϊ Í

Ό-C-P-OXiv3

H OX | _V 4 (ivc) where

Riv 2 is selected from the group consisting of acetyl and formyl,

Aivi is selected from the group consisting of methylene, ethylene, ethenylene, hydroxyethylene, 2-hydroxypropylene, and 2-hydroxypropylene; · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

And Xiv4 are the same or different and are selected from the group consisting of sodium, potassium, methyl, ethyl.

Preferably, the -Aivi-O-C (XY) chain is an oxygen atom and two or three carbon atoms (substituents not included). Particularly preferred are two carbon atoms.

Particularly preferred ether compounds are those from the group consisting of [(N-formyl-N-hydroxylamino) -methoxy] -methylphosphonic acid disodium salt, [(N-acetyl-N-hydroxylamino) -methoxy] -methylphosphonic acid disodium salt, [2- (N-Formyl-N-hydroxylamino) -ethenoxy] -methylphosphonic acid disodium salt, [2- (N-Acetyl-N-hydroxylamino) -ethenoxy] methylphosphonic acid disodium salt, [3- (N) disodium salt -formyl-N-hydroxylamino) -2-hydroxypropoxy] -methylphosphonic acid, [3- (N-acetyl-N-hydroxylamino) -2-hydroxypropoxy] -methylphosphonic acid disodium salt.

Further preferred are compounds corresponding to formula (IVD)

HIM.

Riv ^

Aiv3 -—C-Αιν »

-0XIV3 (| ED)

0XIV4 whereby

Riv 2 is selected from the group consisting of acetyl and formyl,

Aiv 3 is selected from the group consisting of methylene, ethylene, ethenylene, hydroxymethylene, hydroxyethylene, 2-hydroxypropylene, Aiv 4 is removed or is methylene, and Xiv 3 and Xiv 4 are the same or different and are selected from the group consisting of metal first, second or third groups of the natural system, in particular sodium, potassium, methyl and ethyl.

Preferably, the -Aivi-O-Aiv2- chain consists of two to four carbon atoms (substituents not included), with three carbon atoms being particularly preferred.

Among these compounds, the disodium salt of 2- (N-formyl-N-hydroxylamino) -1-oxoethylphosphonic acid, the disodium salt of 2- (N-acetyl-N-), has proved to be particularly preferred.

hydroxylamino) -1-oxoethylphosphonic, disodná salt acid 3- (N-formyl-N-) hydroxylamino) -1-oxopropylphosphonic, disodná salt acid 3- (N-acetyl-N-) hydroxylamino) -1-oxopropylphosphonic, disodná salt acid 3- (N-formyl-N-)

hydroxylamino) -1-oxo-2-propenylphosphonic acid, 3- (N-acetyl-Nhydroxylamino) -1-oxo-2-propenylphosphonic acid disodium salt, 4- (N-formyl-N15) disodium salt • r · »·· • * Hydroxylamino) -1-oxo-3-hydroxybutylphosphonic acid, 4- (N-acetyl-Nhydroxylamino) -1-oxo-3-hydroxybutylphosphonic acid disodium salt , 3- (N-formyl-Nhydroxylamino) -2-oxopropylphosphonic acid disodium salt, 3- (N-acetyl-Nhydroxylamino) -2-oxopropylphosphonic acid disodium salt, 4- (N-formyl-Nhydroxylamino) -3- disodium salt oxo-2-hydroxy-2-methylbutylphosphonic acid, 4- (Nacetyl-N-hydroxylamino) -3-oxo-2-hydroxy-2-methylpropylphosphonic acid disodium salt, 4- (N-formyl-N-hydroxylamino) disodium salt - 3-oxo-2-hydroxy-2- (hydroxymethyl) -butylphosphonic acid and 4- (N-acetyl-N-hydroxylamino) -3-oxo-2-hydroxy-2 (hydroxymethyl) -propylphosphonic acid disodium salt.

For cyclic compounds, the amino group and the phosphorus atom may be bonded to any C-ring atoms. However, compounds in which they are bonded on two atoms which are separated only by another atom are preferred. In the case of heterocyclic compounds, the two atoms are preferably separated from one another by a heteroatom.

The following compounds are particularly preferred:

(IVE)

CX) X | V3

OXivt IVG

Substances in which the sulfonic or sulfonyl group is instead of phosphonic acid or phosphinic acid or phosphinoyl are also suitable:

S— Riv3 (VII)

V. Combination preparations of inhibitors of fat metabolism with phosphorous compounds having at least one hydroxyl group

The compounds of the invention correspond to the general formula (V):

Ϊ?

Bv Avi Č —Av2 P — OXvs (A)

OH OXv4 where

Aiv3 and A14, one or both of which may be omitted, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene and in particular carbon chain -AvrCH0H-Av2- consisting of 2 to 5 carbon atoms atoms, most preferably from 3 to 4 carbon atoms.

B _v is selected from the group consisting of the remainder of formula (VA)

R _V 1 -C (VA) wherein R _V 1 is selected from the group consisting of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted or unsubstituted heterocyclic radical and halogen, radical of formula (VB)

Ry2 r _V3

HO-C-C-

RV4 OH wherein Rv2, Rv3 and Rv4 are the same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic and halogen, and a radical of formula (VC) of Rv5

R _V-6 of alpha (VC)

Rv7 wherein Rvs, Rv6 and Rvz are the same or different and are selected from the group consisting of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted or unsubstituted heterocyclic radical and halogen, wherein Xv3 or Xv4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted an esubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, organic and inorganic base cations, in particular metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids and their pharmaceutically acceptable salts, esters and amides and ester salts.

In particular, Rvi in formula (VA) is methyl.

In formula (VB), in particular, Rv2 and Rv4 are hydrogen and Rv3 are methyl.

In particular, in formula (VC), R 18 is methyl, R 18 is selected from the group consisting of H, OH and methyl, and R 18 is hydroxy.

Particularly preferred are compounds which correspond to the formula

H

—0XV3 (VD)

H

H

Ixv4 whereby

Av 2 is unbranched hydroxyalkylene of one to three carbon atoms and X v 3 and X v 4 are the same or different and are selected from the group consisting of hydrogen, a metal of the first, second or third main groups of the periodic system, especially sodium, potassium and methyl, ethyl.

Among these compounds, 3,4-dihydroxy-5-oxo-hexylphosphonic acid disodium salt, 1,2,3,4-tetrahydroxy-5-oxohexylphosphonic acid disodium salt, 2,3,4-trihydroxy acid disodium salt have proven to be particularly preferred. -5-oxo-hexylphosphonic acid, 1,2,3-trihydroxy-4-oxo-pentylphosphonic acid disodium salt, and 2,3-dihydroxy-4-oxo-pentylphosphonic acid disodium salt.

Particularly preferred are also compounds which correspond to the formula

HIM-'

—OXvs (VE) ixv4 whereby

Av 2 is an unsaturated hydroxyalkylene of one to three carbon atoms and

_In X 3 and X _V4 are the same or different and are selected from the group consisting of hydrogen, metal of the first, second or third main group of the periodic system, especially sodium, potassium, and methyl, ethyl.

Of these compounds, 3,4,5-trihydroxy-4-methylpentylphosphonic acid disodium, 2,3,4,5-tetrahydroxy4-methylpentylphosphonic acid disodium, 1,3,4,5-tetrahydroxy disodium salt have proven to be particularly preferred. -4-methylpentylphosphonic acid, 1,2,3,4,5-pentahydroxy-4-methylpentylphosphonic acid disodium salt.

Particularly preferred are also compounds which correspond to the formula, whereby

Av 2 is unbranched hydroxyalkylene of one to three carbon atoms and X _V 3 and X _V 4 are the same or different and are selected from the group consisting of hydrogen, a metal of the first, second or third main groups of the periodic system, in particular sodium, potassium and methyl, ethyl.

Among these compounds, 3,4-dihydroxy-4-methyl-5-oxo-pentylphosphonic acid disodium salt, 2,3,4-trihydroxy-4-methyl-5-oxo-pentylphosphonic acid disodium salt, 1,2 sodium disodium salt has proven to be particularly preferred. 3-trihydroxy-4-methyl-5-oxopentylphosphonic acid, 2-monohydroxy-3-methyl-4-oxo-butylphosphonic acid disodium salt, and 1,2-dihydroxy-3-methyl-4-oxo-butylphosphonic acid disodium salt.

VI. Combined preparations of fat metabolism inhibitors with phosphorous or organic sulfur compounds having an amine or an imine group

The phosphororganic compounds of the invention correspond to the general formula (VI):

fí

Bvi — p —— Rvi 3 (vi)

RvN unsubstituted unsubstituted

Rvi3 and R _V I4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of 2 to 26 carbon atoms, substituted and cycloalkyl, substituted and unsubstituted heterocyclic radicals, halogen, OXvi3 and OXvi4.

Xvi3 and Xvi4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl of up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of organic and inorganic bases, in particular metals of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids; and

Bv is selected from the group consisting of (VIA)

Rvi \

AVI (VIA)

Rvi2 and Groups (VIB)

RVI ¹ -N = A / r (VIB) wherein Av 1 is selected from the group consisting of alkylene amine, alkenylene amine, hydroxyalkylenamine, wherein the nitrogen atom is found in the chain linking the phosphorus atom to the nitrogen atom of the group R 1 A

R 1 / N-N or groups

Rvi ² 'wherein Rvu and Rvi2 in group (VIA) are the same or different and Rvu and Rvi2 for group (VIA) and Rvu for group (VIB) are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted or unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OXvh and 0Xvi2, wherein X _V on Xvi2 may be the same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, and pharmaceutically acceptable salts, esters and amides, and ester salts thereof.

Preferred as A _V i is an amino group in which the nitrogen atom is not terminated. Preferably connects and _V, nitrogen and phosphorus atom three atoms (without substituents).

Particularly preferred are compounds which correspond to formula (VI)

Rvik / N-AVI

Rvi2 ^Z

Rvi 3

0XVI4 at which point

Rvu, Rvi2, Rvi3 and Xvw are defined as for formula (VI) and Avi is selected from the group consisting of C-N-C, C = N-C, C-N = C, wherein the carbon atoms may be substituted with hydroxy or alkyl groups of up to 7 carbon atoms.

Preferred are Rvu as hydroxy, Rvi2 is selected from the group consisting of acetyl and formyl, Rv is selected from the group consisting of hydrogen, methyl, ethyl, hexadecanyl, octadecanyl, and Xvi3 and Xvi3 and Xvi4 are selected from the group consisting of: · · · · · · · · · · · · · · · · · · · · · · · · · · , methyl, ethyl, hexadecanyl and octadecanyl, and if both exist, they may be the same or different.

Further preferred are compounds having the formula (VID)

O

Rvu-N = Avi-p-R 1 / (3) (VID) ox 1/4, whereby

Rvu, Rvi2, Rvi3 and Xvi4 are defined as for formula (I) and A is selected from the group consisting of C-N-C, C = N-C, C-N = C, wherein the carbon atoms may be substituted with hydroxy or alkyl of up to 7 carbon atoms.

Particularly preferred is I tear selected from the group consisting of acetyl and formyl, and Rvi3 from the group consisting of hydrogen, methyl, ethyl, hexadecyl, octadecyl and 0Xvi3 Xvi3 and X and _V | ₄ are selected from the group consisting of hydrogen, sodium, potassium, methyl, ethyl, hexadecanyl and octadecanyl, and if both exist, they may be the same or different.

VII. Combination preparations of inhibitors of fat metabolism with phosphorous compounds having a nitrogen heterocycle

The phosphororganic compounds used according to the invention correspond to the general formula (VII):

O

Rvil 1-AVI | 1 — pR _V || 3

RVII4 (in ») in which

Avii selected from the group consisting of (C-i_ ₉₎ -alkylene radical, which may have one or more double bonds and may be substituted with hydroxy, halo, amino, oxo groups with branched or unbranched Ci.g-alkyl and C ₂ -9 -alkenyl, wherein C1-9alkylskupiny and _C-2 .g alkenyl may be substituted with hydrogen, hydroxyl, amino, halogen and oxo, -COC- -CNC- and wherein the carbon atoms -C23

O-C- and -C-N-C- may be substituted by alkyl of up to 7 carbon atoms or hydroxy, or

Avii corresponds to the following formula (VIIA):

Bvm Bvil3 BVI | BVII7 BVI | 9 Cviii— - Exercise 2 - I - CVII3— I -CVII4- AND CVI | 5 - AND BVII2 BVII4 Bvn 6 Bvi | 8 Bvil ¹⁰

wherein one or more carbon atoms selected from the group _C II3, II4 _V C, Cviis, together with their substituents may also be omitted and at least one existing substituents B, _V m to _V B C Mo _{third 8} -cycloalkyl- (C ₀ -9) -alkyl, wherein the C as _{the third The} cycloalkyl group and the C 0-6 alkyl group may contain one or more double bonds and one or two of the carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, and wherein both the cycloalkyl group and the alkyl group may be substituted by hydroxy, halogen, amino, oxo with branched or unbranched C2-9-C1.9alkylskupinami and alkenyl wherein said Ci.g -alkyl and C ₂ -galkenylskupiny may be substituted by hydrogen, hydroxy, amino, halo and oxo, and the remaining substituents BVM to existing Bymojsou selected from hydrogen, hydroxy, halogen, amino, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, or both substituents on one carbon atom together form an oxo group, wherein each C 1-6 -alkyl radical and each C 1-6 -alkoxy radical it may be branched or unbranched, saturated or unsaturated with one or more double bonds and may be substituted by hydroxy, halogen, amino and oxo groups, where

Rvu is selected from the group consisting of 5- and 6-membered heterocycles with one or two nitrogen, oxygen or sulfur ring atoms, wherein the heterocycle may be saturated or unsaturated with one or more double and triple bonds and may be substituted with hydroxy, halogen , amino, oxo and branched or unbranched alkyl and Ci.g-C2-g-alkenyl, wherein Ci.g -alkyl and C ₂ -9 -alkenyl groups may be saturated or unsaturated with one or more double or triple bonds and may be

substituted with hydrogen, hydroxy, halo, amino and oxo, wherein R _V ii 3 and R _v 4 are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 -alkyl, hydroxy-C 1-6 -alkyl; -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyl, substituted and unsubstituted C 1-6 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted 4-O, substituted and unsubstituted 4-heterocyclic, ,whereas

Xvii3 and Xvii4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C ₂ -C 6 -alkyl, substituted and unsubstituted hydroxy-C 26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-4 alkenyl, substituted and unsubstituted C 1-2 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of the organic and inorganic bases, in particular of the metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids and their pharmaceutically acceptable salts, esters and amides and ester salts.

If there are two heteroatoms in the heterocycle Rvm, then, for example, an oxygen atom and a nitrogen atom may naturally also be mixed.

Preferred as R vm is a nitrogen-containing heterocycle, with particular preference being given to substituted or unsubstituted pyridine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrazole, and most preferably are

Preferably, the phosphororganic compound corresponds to formula (VIIC) O

RviM — Avii — P — Rviis (VIIC)

0XVII4

wherein R _V h 3 is preferably hydrogen, methyl, ethyl or an amide moiety and X _V H 4 is selected from the group consisting of hydrogen, sodium, potassium, methyl, ethyl, and a compound of formula (VIID) is particularly preferred

Rviii — Avii — P — OXvns (VIID)

0XVII4

Substances in which the sulfonic or sulfonyl group is instead of phosphonic acid or phosphinic acid or phosphinoyl are also suitable:

Ϊ,

-S-RVII3 (viie) δ

Vlil. Combined preparation of fat metabolism inhibitors with phosphonomic acid derivatives

The compounds are described in WO 98/16537.

The phosphororganic compounds used according to the invention correspond to the general formula (VIII):

wherein the wavy line indicates a bond having either a or β configuration, n is 0 or 1 in which

Rvmu is selected from the group consisting of substituted and unsubstituted C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, substituted and unsubstituted C 1-6 -alkyl. Unsubstituted aryl, substituted and unsubstituted acyl · nes ub ub ub ub ub ub ub ub ub ub ub substitu ub ub ub nes ub substitu nes nes substituted or unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyl, substituted and unsubstituted C 1-6 -alkenyl; 6alkinylu _2, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen aOXvmii wherein

XVIII is selected from the group consisting of hydrogen, substituted and unsubstituted C ₁ _ 6 alkyl _2, substituted and unsubstituted hydroxyl-C ₂ 6 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 2-6 -alkenyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, organic and inorganic base cations, especially metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds which derived from ethylenediamine or amino acids; and

R iim is selected from the group consisting of C 1-4 -alkyl radicals, C 2-24 -alkenyl radicals, C 2-24 -alkenyl poly radicals having 2 to 6 double bonds, C 2-24 -alkynyl radicals, C 3-8 -cycloalkyl radicals, C ₃ - 8-cycloalkyl-C 1. ₂ 4-alkyl radicals and C 1-6 -alkoxy-C 1-6 alkyl radicals,

R 2, R 2, 13, and R 11, 14 are independently selected from the group consisting of hydrogen, halogen, amino, acetylamino, azido, and XR 11n 6, wherein X is O or S and R 11w 6 is selected from the group consisting of hydrogen, branched or unbranched Cu- alkyl radicals and C 2-4 alkenyl radicals, wherein both the C 1-4 alkyl radicals and the C 2-4 alkenyl radicals may be optionally substituted by hydrogen, amino-, halogen- or 0x0-, or

Rvni2, Rviii3 and Rviii4 together with the respective geminal hydrogen group give an oxo group,

Rviii5 is selected from the group consisting of hydrogen, C1-24-alkyl, C3-8-cycloalkyl, Ar (C1-24-alkyl), aryl, acyl, heterocyclic, halogen, all of which may be branched or unbranched and may be optionally substituted by hydroxy-, amino-, halogen- or oxo- groups and may contain 2-6 double or triple bonds or is an R 5 -phenyl radical of formula VIIIA or VIIIB,

• · • · • • · • • · • · • · • · • · • ···· • · • • • »· • · • • • • · • · · ···· • · • ·

whereas

Rviii 3 Rviii are the same or different and bound at two arbitrary positions of the phenyl ring and in this case are independently selected from the group consisting of hydrogen, halogens, C 1-6. ₄ -alkyl radicals, CM-alkoxy radicals, radical formyl, acetyl, propionyl or butyryl residue formyloxy, acetoxy, propionyloxy, butyryloxy, _C2 -5-alkoxycarbonyl radicals, which all may be branched or unbranched or Rvni7 and Rviiis together may form an unbranched saturated alkylene chain of 3 to 4 carbon atoms that is bonded to adjacent positions, e.g., the 2,3-position or 3,4-position of the phenyl ring, or R ₇ and R 8 together form a methylenedioxy radical, A 1-ethylenedioxy radical or a 1,2-ethylenedioxy radical which are bonded to the 2,3- or 3,4-position of the phenyl ring, or

Rviiis is selected from the group consisting RviiigCOOCHRviino- Rvii.9OCOOCHRv.1no- and wherein R _V M ₉ is selected from the group consisting of Cl. _6- alkyl residues, C ₂ . ₆ alkenyl radicals, C _2, 6-alkynyl radicals, C _{3rd 8} -cycloalkyl residues, C ₃ . ₈ cycloalkyl-C _1-6 -alkyl radicals; _6- alkoxy-Ci. _6- alkyl radicals, wherein all radicals may be branched or unbranched and optionally substituted by hydroxy, amino, halogen or oxo-;

R 10 is a branched or unbranched C 1-4 alkyl moiety, and wherein the configurations of the substituents R _v m _2t R _v h _3i Rviim and R vn 10 OOCPO (OH) OCH ₂ - v (VIII), when n is 1, are independently D-gluco, L -gluco, D-galacto, L-galacto, D-manno, L-manno, D-talo, L-talo, D-allo, L-allo, D-altro, L-altro, D-gulo, L-gulo, D -ido or L-ido, or the configuration of the substituents R ₂ , R ₃ and R ₅ OOCPO (OH) OCH ₂ - in I are independently Dribo, L-ribo, D-arabino, L-arabino, D-xylo, L-xylo , D-lyxo, L-lyxo when n is 0.

The α-configuration of the glycosidic bond is preferred for the compounds of the invention.

Preferred compounds of formula (VIIIa) are those wherein R vm is selected from the group consisting of C ₉ . ₂ 4-alkyl radicals, C ₉ . _24- alkenyl radicals, C ₉ . ₂₄ alcapolyene residues containing 2 to 6 double bonds, C ₉ . ₂₄ -alkynyl radicals, C ₃ .8 cycloalkyl-C _6-2 4 -alkyl radicals, C ₁₂ -C ₈ -alkoxy -i ₂ - alkyl radicals, which in this ♦ • · ·· ··

Případě · podle · · · • · · · případě případě případě případě případě případě mohou mohou případě mohou mohou mohou případě případě případě případě mohou mohou mohou případě branched or unbranched and may be substituted with hydrogen, amino, halogen or oxo.

It is particularly preferred to use those compounds wherein R vim is selected from the group consisting of an n-tetradecyl residue, an n-octadecyl residue, a trans-9-octadecen-1-yl residue, a cis-9-octadecen-1-yl residue . In this case, as RVHi ₂ Rviii3, vii favorisována hydroxy. Preferably Rvms is hydrogen, formyl or acetyl. In addition, 1 is preferred as n, and the D-gluco configuration for Rvni2, Rvu13, Rviim and Rvii15OOCPO (OH) OCH2Rvimi is preferably OXviiih with Xviiih = hydrogen.

IX Combined preparation of fat metabolism inhibitors with heterocyclic phosphonomic acid derivatives

The phosphororganic compounds of the invention are described in WO 98/16537 and correspond to formula (IX):

whereas

Rixi is selected from the group consisting of substituted and unsubstituted C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic, halogen and OXix, wherein:

Xixii is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 -alkyl, substituted and unsubstituted hydroxy-C 1-6 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyl, substituted and unsubstituted aryl. unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted A heterocyclic radical, a silyl, an organic and inorganic base cation, in particular a metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids and wherein:

Rixi θ Rix2 are each independently selected from the group consisting of C · ^ alkyl radicals, C ₃ _ ₈ -cykloalkylových residues C _{3rd 8} -cycloalkyl-C ₁ . ₂ 4-alkyl radicals, C ₁ _ ₂₄ -alkoxylových radicals, C ₁ _ ₂ 4-alkylthio-residues C _1st C ₂₄ -alkoxy _{first 24} alkyl radicals, C - ^ - C ^ alkylthio alkyl radicals, acyl radicals, aryl radicals, aralkyl radicals, heterocyclic radicals, halogen and hydrogen, and each a C ₂₄ alkyl radical and a C an alkoxy radical may be branched or unbranched, and saturated or unsaturated with 2 to 6 double bonds and optionally substituted by hydroxy-, amino-, mercapto-, halogen-, oxo- or C- groups. ₂₄ alkoxy radicals, C ^ alkylcarbonyloxy radicals, CR. ^ - alkoxycarbonyloxy radicals, _{C1. 24} -alkylthio radicals, C ^ -alkylkarbonylthio radicals, C ₂₄ -alkylaminovými radicals, di- (C _2.1 4-alkyl) amino radicals, C. ^ - alkylkarbonylaminovými radicals, C ^^ - alkyl-ICV ₂₄ -alkylcarbonyl) amino radicals, C ^ -alkoxykarbonylaminovými · radicals or C ^ alkyl (C ₁ _ ₂₄ alkoxycarbonyl) amino radicals, wherein each aralkyl radical, heterocyclic radical, alkyl radical C ^ C ^ and an alkoxy radical may be branched or unbranched, saturated or unsaturated with 2 to 6 double or triple bonds, or wherein R 1 -CH-CH-R 3 forms part of a C ₄ -C ₈ -carbon ring which may optionally be substituted by hydroxy-, mercapto-, amino-, halogen- , oxo or C 1-6 -alkyl radicals, C 1-6 -alkoxy radicals, C ₁ . _24- alkylthio radicals, Ct. ₂₄ alkylamino radicals, C 1 -C 4 -alkyl amino radicals, C 1 -C 4 -alkylcarbonyl radicals, C 1 -C 4 -alkylcarbonyloxy radicals, C 1 -C 3 -alkoxycarbonyloxy radicals, C 1 -C ₂₄ -alkyloxycarbonyloxy radicals; ₂₄ alkylcarbonylthio radicals, or C ₁ .2 ₄ - ^ lkylkarbonylaminovými radicals, C-alkyl-IC-alkylcarbonyl) amino radicals, wherein each C - ^ - alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 or wherein R _(X10 is a branched or unbranched alkyl moiety, and wherein R ₁ -CH ₁ -CH-CH-R 1 _{X 2} forms part of a furanose or pyranose ring of a sugar, e.g. D-ribose, D-arabinose, D-xylose, D -lyxoses, D-glucose, D-galactose, D-mannose, D-talose, D-allose, D-altrose, D-gulose, D-idose, or the corresponding L-isomer, wherein the hydroxyl groups may always be optionally

• · ·· • ·· «· ·· • · ·· · • • ···· • « • • • · · • · • • • • · ··· · ·· ···· ·· ··

radicals substituted by hydrogen, amino, azido, oxo, mercapto, or C ^ -alkoxyzbytky, C ₁ _ ₂ 4 -alkylthio radicals, C - ^ - alkylamino radicals, di- (C _1.2 4 -alkyl) amino residues, C _d . ₂ 4-alkylcarbonyloxy radicals, C ^ -alkylkarbonylthio radicals, C - ^ - alkylkarbonylaminozbytky, C ₁ _ ₂₄ -alkyl- (C ^ -alkylkarbonylJamino radicals, wherein each C-alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 double bonds, and their pharmaceutically acceptable salts, esters and amides, and ester salts, as well as their optical isomers.

Rixi θ Rix2 may particularly each independently selected from the group consisting of carboxyl radicals, carboxamido radicals, aryl radicals, aryloxycarbonyl radicals, aryl-C - ^ - alkyl radicals, C ₂₄ -alkoxykarbonyloxy radicals, Ο · ,. ₂₄ alkylaminocarbonyl radicals, di- / Cv ^ -alkyljaminokarbonylové radicals, C ^^ aryl-alkoxycarbonyl radicals, aryl-C ^ -alkylaminokarbonylové radicals, C.,. ₂ C4alkylcarbonyloxy- (C _4.1) alkylmethoxykarbonylové radicals, C ^^ alkoxykarbonyloxymethoxykarbonylové radicals, C ₁ _ ₂₄ -alkoxycarbonyloxy- (C ₁ _ ₄ alkyl) methoxycarbonyl radicals, each a C ₂₄ -alkyl radical may be branched or unbranched, saturated or unsaturated with 2 to 6 double bonds and each C ₁₄ -alkyl radical and C 1-4 -alkoxy radical may be branched or unbranched and saturated or unsaturated and each aryl radical of formula IXA

wherein R 1 _X3 and R1 | _{X 4} are the same or different and are each independently selected from the group consisting of hydrogen, halogen, C 1-4 -alkyl radicals, C 1-4 -alkoxy radicals, formyl, acetyl, propionyl or butyryl radicals, formyloxy-, acetoxy-, propionyloxy-, butyryloxy-. θ 1-4 -alkoxycarbonyl radicals, all of which may be branched or unbranched, or R, _{X 3} and R 1 _{X 4} together form an unbranched saturated alkylene chain having 3 to 4 carbon atoms, which is bonded to adjacent positions in the phenyl ring, or R 1 | _{X 3} and R 1, _{X 4} together form a methylenedioxy radical, 1,1-ethylenedenedioxy radical or 1,2-ethylenedioxy radical which are bonded to adjacent positions of the phenyl ring.

Preference is given to using compounds in which R 1, _{X 1} and R, _{X 2} in this case are independently selected from the group consisting of hydrogen, hydroxy, formyl, acetyl and methyl, wherein the methyl radical may optionally be substituted by hydroxy or mercapto or C _1-2 4-alkoxy radicals, C ₂₄ alkylcarbonyloxy radicals, C 24 alkylthio groups or C ₂ 4-alkylcarbonylthio radicals, whereby Ci-24-alkyl and Ci-24-alkoxy groups may be branched or unbranched, saturated or or unsaturated with 1 to 6 double bonds.

Particularly preferred as Rixi is a methyl radical which may be optionally substituted by hydroxy or mercapto or C 1-4 -alkoxy radicals, C 1-6. ₂₄ -alkyl-alkylcarbonyloxy radicals, C-24-alkylthio radicals, or C1-24alkylkarbonylthio radicals, wherein C. ₂ 4-alkyl groups and C ₂₄ alkoxy groups may be branched or unbranched, saturated or unsaturated or having 1-6 double bonds, and Rix ₂ is hydrogen.

Particularly good results have been obtained with compounds in which Rix 1 and R 1 _{X 2 are} independently selected from the group consisting of hydrogen and an n-octadecylmethyl radical, wherein Rix 1 is preferably an n-octadecylmethyl radical and R ₂ hydrogen. Particular advantages are obtained when the compound has the (R) configuration.

Preferably, Rix 1 is OXix with Xixn = hydrogen.

X. Combined preparation of fat metabolism inhibitors with hydroxyaminooxocarbyl derivatives

The hydroxyaminooxocarbyl derivatives used according to the invention correspond to the general formula (X):

^H0 \!

N-R _X 2 (X)

Rxi in which

R xi is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-8 alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted or unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen and ΟΧχι, wherein:

Xxi is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-8 alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, wherein Rx2 is selected from the group consisting of C1-26-alkyl radicals, C1-26alkoxy radicals, C1-26-alkoxy -C 1-6 -alkyl radicals, C 3-8 -cycloalkyl- (Co-26) alkyl radicals, wherein one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, each C 3-26 -alkyl radical and each C3_26-alkoxy radical can be branched or unbranched and each C 3 ₈ -cycloalkyl radical, each _C2 -26-alkyl residue and each C ₂ -26-alkoxy radical may be saturated or unsaturated with one or more double bonds and C each _{third The 8-} cycloalkyl radical, each C 1-6 -alkyl radical and each C 1-6 -alkoxy radical may be substituted with a hydroxy-, amino-, halogen and oxo- or carbyl group CORx3, wherein Rx3 is selected from the group consisting of substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and 0Χχ 3, wherein Χχ 3 is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 -alkyl, substituted and unsubstituted hydroxy-C 1-6 -alkyl, substituted and unsubstituted aryl, substituted unsubstituted aralkyl, substituted and unsubstituted substituted C 1-6 -alkenyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, cation of an organic and inorganic base, in particular a metal of the first, second or third group of the Periodic System, ammonium, substituted ammonium and ammonium compounds which are derived from ethylene amine or amino acids.

• · • ®

Rx2 is preferably a carboxyl group -COOH, wherein R _{X 1} is a branched or unbranched C _M-alkyl, particularly isopropyl group is preferred; as well as their pharmaceutically acceptable salts, esters and amides.

Preferred are the carboxylic acid salts in which H is replaced by the metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium, or ammonium compounds which are derived from ethylene amine or amino acids. Ie. they consist of salts of hydroxyaminooxocarbylcarboxylic acid derivatives with organic or inorganic bases (eg sodium salt, potassium salt, calcium salt, aluminum salt, ammonium salt, magnesium salt, triethylammonium salt, ethanolamine salt, dicyclohexylamine salt, ethylenediamine salt, N salt , N'-dibenzylethylenediamine, etc.) as well as amino acids (e.g., arginine salt, aspartic acid salt, glutamic acid salt, etc.) and the like.

Preferably, esters can also be formed on the carboxyl group. Suitable examples for such esters include suitable mono- and diesters, and preferred examples for such esters include alkyl esters (e.g., hexadecyl ester, octadecyl ester, etc.)

XI. Combined preparation of fat metabolism inhibitors with phosphorous compounds containing either two phosphoryloxy groups or one phosphoryloxy group and one suifoxy group

The phosphororganic compounds used according to the invention correspond to the general formula (XI):

RXI2 ixi4 wherein Z _x) is a phosphorus atom or a sulfur atom, and wherein _X is unbranched C ₂ .g alkylene chain substituents, which are identical or different and are selected from the group consisting of hydrogen, hydroxy, halo, amino and oxo, C.,. 26 alkyl radicals, 0 ^ 26 alkoxy radicals, C ₁ _ ₂₆ alkoxy-C ₁ "26-alkylamino or _{C3. 8} -cykloalkyi- (C _{0th g)} -alkyl groups, wherein each 0 ^ 26 alkyl residue and each C ·, ^ alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double • • · · bonds and it may be substituted with hydroxy, halogen, amino and oxo groups and as C ₃ . ₈ -cycloalkyl and C _{0th 9-} C ₃ alkyl. ₈ -cycloalkyl- (C _{0th 9)} alkyl groups may have one or more double bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur, and wherein both the cycloalkyl group and the alkyl group may also be substituted with hydroxy, halogen, -, amino, oxo groups with branched or unbranched C ^ and C ₂ galkylskupinami .9-alkenyl wherein said alkyl and Ci.g-c _{2. The} alkenyl groups may be substituted with hydrogen, hydroxy-, amino-, halogen- and oxo groups in which R ₁ , R _1, and R ₁ , ₂ are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-4 alkyl. g-alkyl, substituted and unsubstituted hydroxy-C 1-8 -alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-4 alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted , substituted and unsubstituted heterocyclic radical, halogen, OX _XM and OX _{X 12} , wherein X _xh and X _X | ₂ are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-8 -alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkyl; ₁ _ ₉ -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and. unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, in which R _X | ₃ and R _xw are the same or different and are selected from the group consisting of substituted and unsubstituted C 1-4 -alkyl, hydroxy-C 1-4 -alkyl. _26- alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted Cf. ₂₆ alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic, halogen, OX _X | ₃ and OX _X | ₄ , wherein

Mohouχΐ3 θ Χχΐ4 may be the same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-4 alkyl, substituted and unsubstituted hydroxy-C-]. _26- alkyl, substituted and unsubstituted aryl, " unsubstituted " aryl, and " unsubstituted "aryl; Substituted and unsubstituted aralkyl, substituted and unsubstituted C1-6alkyl; ₂ 6 alkenyls, substituted and unsubstituted C ₂₆ alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, a cation of organic and inorganic base, in particular the metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids and their pharmaceutically acceptable salts, esters and amides and ester salts.

For Αχι, a C 3-8 -alkyl chain is preferred.

Particularly preferred are compounds in which R _{X1 2} is methyl and Z _{X 1} , R _X n, R _X 13, R xm are as defined above, wherein R _X n is preferably substituted with hydroxyl at the C-atom adjacent to the heteroatom and compounds wherein R _X | ₂ represents a hydroxy group, where Z and _X, R _X n, _X and R ₃ RXW are defined as above, and R h, _X is preferably an acyl group, particularly preferably a formyl, acetyl, propionyl or butyryl.

Preference is also given to compounds having the following structures:

· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ^Η ΐ.

Rxi 1-ΖΧΙ-C-C — C-C — P-Rxi 3 (XID),

RX | 2

RXI4

RX1-Zxi — C-C — C-C — P-Rxi 3 (XIE),

OH _{? ? H} Hp

Rxii-Zxi-C-C-C-C-P Rxi 3 (XIF),

Rx | 2

RXI4

RX 1 ' ^h ' n

- Zxi — C — C — C — C — P-RX13 (XIG) a

RXI2

OH

C-C-C-P-Rxi 3

RX14 (XIH).

XII. Combined preparation of fat metabolism inhibitors with 3-isoxazolidinones and hydroxylamino acids

These compounds are described in U.S. Patent 4,405,357.

Compounds of the invention which are contained in medicaments correspond to the general formula (XII):

.:. :

ŽípxiH

-N-O-RXII3 (XII);

Αχιι is selected from the group consisting of hydrogen, substituted and unsubstituted Ci-28-alkyl radicals, substituted and unsubstituted alkoxy- _(C0 -28) -alkyl, substituted and unsubstituted cykloalkyI- (Co-28) alkyl, substituted and unsubstituted cycloalkoxy- (Co-28) -alkyl groups, substituted and unsubstituted amino- (Co-28) -alkyl groups, substituted and unsubstituted thio- (Co-28) -alkyl groups, and substituted or unsubstituted acyl- (Co-28) -alkyl residues and halogen, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical, each acyl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms ry,

Rxii3 is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted alkoxy- (C 0-6) alkyl groups, substituted and unsubstituted C 3-14 -cycloalkyl- (C 0-6) -alkyl groups, substituted and unsubstituted cycloalkoxy- (Co-26) -alkyl groups, substituted and unsubstituted amino- (Co-26) -alkyl groups, substituted and unsubstituted silyl- (Co-26) -alkyl groups, substituted and unsubstituted thio- (Co-26) -alkyl groups, wherein each the alkyl radical and each alkoxy radical may be branched or unbranched, and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen atoms, oxygen or sulfur, or a carbon chain of two C-atoms in Axn with R _X h ₃ forms a ring thereby by forming an isoxazolidone ring and

Rxii4 is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted acyl radicals, and substituted and unsubstituted cycloalkyl- (C 0-6) alkyl groups, wherein each alkyl radical and each acyl radical may be: · · · · ·

and each alkyl radical, each acyl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms.

Αχιι preferably corresponds to formula (XIIA)

RX | 5 RXI | 1

Rxi | 6-C-C- (XIIA) |

I I

Rxi | 7 Rx || 2 where

R xm θ R xii2 are the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, substituted and unsubstituted amino radicals, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, and substituted and unsubstituted cycloalkyl- (C _{0 -)} . ₍₂₆ ) -alkyl groups, wherein each alkyl radical and each alkoxy radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl radical may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of cycloalkyl the groups may be replaced by nitrogen, oxygen or sulfur atoms,

Rxii5. Rxii6 Rxii7 θ j ^sou same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl- (C _{0 "26)} -alkyl, substituted and unsubstituted cykloalkoxy- (C _{0th 26)} -alkyl, substituted and unsubstituted alkoxy- (C _{0th 26)} -alkyl, substituted and unsubstituted amino groups, substituted and unsubstituted thio- (C ₀ _ ₂₆₎ alkyl and substituted or unsubstituted acyl radicals, wherein each alkyl the radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced nitrogen, oxygen or sulfur atoms, whereas

R _X h5 alternatively with Rxm can also form a circle and • · ·· ···· · ·

R _X ii ₃ and R _X || 7 may have a single carbon-oxygen bond by forming a ring structure.

The invention also includes pharmaceutically acceptable salts, esters and ester salts.

Preferably, R _{XN 1} and R _X h _{2 are the} same or different and are selected from the group consisting of substituted or unsubstituted alkyl groups, most preferably C ₁ -C ₄ -alkyl groups.

_XN3 R is preferably selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, most preferably _{Ci-C 4} -alkyl, substituted and unsubstituted aromatic C ₇ -C ₁₄ -alkyl, pyranyl group and t-butyldimethylsilyl group, and

-CR _X || 8 where

_X II R ₈ is selected from the group consisting of substituted and unsubstituted, most preferably halogen-substituted alkyl groups, substituted and unsubstituted cycloalkyl (C _{0 2} _ 6) -aíí <yl, substituted and unsubstituted amino groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted phenoxy, substituted and unsubstituted alkylthio, substituted and unsubstituted aromatic cycloalkylthio groups, most preferably one unsubstituted or substituted halogen-, methyl-, methoxy-, nitro-, amino- or CF ₃ -groups.

R x 114 is preferably selected from the group consisting of hydrogen, substituted alkyl radicals, substituted and unsubstituted phenyl radicals, and

whereas

_X n is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl radicals and phenyl radicals and Y _X n is selected from the group consisting of hydrogen, halogen, C 1 -C ₄ -alkyl radicals, nitro radicals, methoxy radicals, methylenedioxy wherein n is 0 or 1,

R _{7 X} j II, ^E is preferably selected from the group consisting of hydrogen and halo, or R _{@ 3} and R n _X || ₇ show a single carbon-oxygen bond in that a ring structure is formed.

···· · *

Particularly preferred are compounds wherein R xm and R xn ₂ are independently selected from the group consisting of methyl and ethyl,

Rxiis and Rxiie are independently selected from the group consisting of hydrogen, chloro, bromo and methoxy.

Particularly preferred are compounds in which Rxiw is

wherein Z is selected from the group consisting of 2-chloro, 2-bromo, 2-fluoro, and Y is selected from the group consisting of 4-chloro, 4-bromo, 4-fluoro, 5-fluoro- and 4,5-methylenedioxy, wherein n is 0 or 1.

It particularly prefers compounds in which _X RXM and R ₂ are H, methyl, and Rxh3 Rxh7 are hydrogen or contain a carbon-oxygen bond and form a ring structure.

Examples of preferred compounds are 3-chloro-N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N -hydroxy-N-phenyl-2,2-dimethylpropanamide, N- (2-bromophenyl) methyl-3-chloro-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N-hydroxy-2,2-dimethylN- (2-methylphenyl) methylpropanamide, 3-chloro-N-hydroxy-2,2-N-trimethyl-propanamide, 3-chloro-N-hydroxy-2,2-dimethyl-N- (phenylmethyl) propanamide, 3-chloro- N- (2,4-dichlorophenylmethyl) -N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N- (2-chlorophenyl) methyl-N-methoxy-2,2-dimethylpropanamide, 3,3-dichloro-N- ( 2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N- (2-fluorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-bromo-N- (2-chlorophenyl) methyl- N-hydroxy-2,2-dimethylpropanamide, N-benzyloxy-3-chloro-N- (2-chlorophenyl) methyl-2,2-dimethylpropanamide, N-acetoxy-3-chloro-N- (2-chlorophenyl) methyl- 2,2-dimethylpropanamide, N-chloroacetoxy-3-chloro-N- (2-chlorophenyl) methyl-2,2-dimethylpropanamide, 2- (2-chlorophenyl) meth yl-4,4-dimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenyl-3-isoxazolidinone, 2- (2-bromophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, 4,4-dimethyl-2 - (2-methylphenyl) methyl-3-isoxazolidinone, 2,4-trimethyl

ΛΑ · · · · ···

4ι ··· · ♦ · ····· ·· ·

3-isoxazolidinone, 4,4-dimethyl-2-phenylmethyl-3-isoxazolidinone, 2- (2,4-dichlorophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, 5-chloro-2- (2-chlorophenyl) methyl-4,4-dimethyl-3 isoxazolidinone, 2- (2-chlorophenyl) -methyl-5-methoxy-4,4-dimethyl-3-isoxazolidinone, 2- (2-fluorophenyl) methyl-4,4-dimethyl-3 -isoxazolidinone, N- [2- (2-chlorophenyl) methyl] -N, 3-dihydroxy-2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N ( methylaminocarbonyloxy) propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(tetra hydropyranyl) oxy] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] - 2,2-dimethyl-N- [dimethyl (1,1-dimethylsilyl) oxy] propanamide, 3-acetoxy-N - [(2-chlorophenoxy) methyl] -N-hydroxy-2,2-dimethylpropanamide, 2 - [(2 -chloro-4-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-5-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2- ( (2,4,5-trichlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-6 fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2- [ (2-chlorophenyl) methyl] -5-ethoxy 4,4-dim ethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-phenylamino-3 isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-hydroxy-4,4-dimethyl -3-isoxazolidinone, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(phenylamino) carbonyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N- (phenoxycarbonyloxy) propanamide, 3 chloro-N - [(2-chlorophenyl) methyl] -N-ethoxycarbonyloxy-2,2-dimethylpropanamide, N benzyloxy-3,3-dichloro-N- [ (2-chlorophenyl) methyl] -2,2-dimethylpropanamide, N - [(2 bromophenyl) methyl] -3,3-dichloro-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N - [(2 chlorophenyl) methyl] -N- (4-nitrobenzoyloxy) -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(2-methylphenyl) carbonyloxy] propanamide, 3-chloro-N-dichloro-acetoxy-N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(4-methylphenyl) sulfonyloxy] propanamide, 3-chloro-N - [(2 chlorophenyl) methyl] -2,2-dimethyl-N - [(1,1-dimethylethyl) carbonyloxy] propanamide, 3 chloro- N - [(2-chlorophenyl) methyl 2-chloro-N - [(2,2,2-trichloroethoxy) carbonyloxy] -N - [(2-chlorophenyl) methyl] -2,3-dimethyl-N - [(ethylthiocarbonyl) oxy] propanamide -dimethylpropanamide, 3-chloro-N - ((2-chlorophenyl) aminocarbonyloxy)] - N - [(2-chlorophenyl) methyl] -2,2 dimethylpropanamide, 3-chloro-N - [(4-chlorophenyl) aminocarbonyloxy)] N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N (phenylmethoxy) propanamide, 3-chloro -N - [(2,4-dichlorophenoxy) acetoxyl] -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2 -dimethyl-N [(3-trifluoromethyl) benzoyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2 dimethyl-N - [(4-methylphenyl) aminocarbonyloxy)] propanamide, 3-chloro -N - [(2-chlorophenyl) methyl] -N - [(3,4-dichlorophenyl) aminocarbonyloxy)] - 2,2-dimethylpropanamide, 3-chloro-N (3-Chloro-2,2-dimethyl-1-oxopropoxy) -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide 3-bromo-N - [(2-bromophenyl) methyl] -N-hydroxy -2,2-dimethylpropanamide, 3-chloro-N [(2-chlorophenyl) methyl] -N - [(2-fluoromethyl) aminocarbonyloxy] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(4-methoxyphenyl) aminocarbonyloxy] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(3-trifluoromethylphenyl) aminocarbonyloxy] -2, 2-dimethylpropanamide, 3-bromo-N - [(2-chlorophenyl) methyl] -N- (methylaminocarbonyloxy) -2,2-dimethylpropanamide, 3-bromo-N- (2-chloroacetoxy) -N - [(2 3-chloro-N- [2,5-dichloro-formylamino) benzoyloxy] -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-bromo -N - [(2-bromophenyl) methyl] -N-2-chloroacetoxy-2,2-dimethylpropanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N (methylcarbonyloxy) -2,2-dimethylpropane -amide, 3-bromo-N - [(2-bromophenyl) methyl] -N - [(2-chlorophenyl) aminocarbonyloxy] -2,2-dimethylpropanamide, 2 - [(2-chlorophenyl) methyl] -N- hydroxy-2,2-dimethyl-3-methylthio-propanamide, 3-phenylcarbonyloxy-N - [(2-chlorophenyl) methyl] -N-hydroxy-2,2-dimethylpropanamide, 2 - [(4-chlorophenyl) methyl] - 4,4-dimethyl-3-is oxazolidinone, 2 - [(3,4-dichlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-yl acetate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-yl-benzoate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-yl-dichloroacetate, 2 - [( chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-yl-phenylcarbamate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-ylmethylcarbamate, 2 - [(2-chloro- 4-cyanophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 [(2-chloro-5-methoxyphenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-4-methoxyphenyl) (methyl) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2,4-difluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(4-bromo-2-chlorophenyl) methyl] - 4,4-dimethyl-3-isoxazolidinone, 2 - [(2-bromo-4-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(6-chloro-1,3-benzdioxol-5-yl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-phenoxy-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4, 4-Dimethyl-5- (1-methylethoxy) -3- isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5 (phenylmethoxy) -3-isoxazolidinone, 2 - [(2-bromophenyl) methyl] -5-chloro-4,4-dimethyl- -3-isoxazolidinone, 2 - [(2,5-dichlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-propoxy-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] 4,4-dimethyl-5- (2-propenyloxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2-propynyloxy) - 3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2-methoxyethoxy) -3-isoxazolidinone, 2 - [(4-fluoro-2-iodophenyl) methyl] -4 4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-cyclopentoxy-4,4-dimethyl-3-isoxazolidinone,

2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (4-nitrophenoxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-cyclopropylmethoxy-4,4- dimethyl-3-isoxazolidinone, 2 - [(2-bromophenyl) methyl] -4,4-dimethyl-5- (2-propinoxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (3-butinoxy) ) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (2-butinoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] - 5- (3-butenoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-pentoxy-4,4-dimethyl-3-isoxazolidinone, 2 [(2-chlorophenyl) methyl] 5-hexoxy-4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (1-methylpropoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2- chlorophenyl) methyl] -5 (3-methyl-3-butenoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenylmethyl) -5-butoxy-4,4-dimethyl-3-isoxazolidinone, 2- [ (2-chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone.

XIII. Combined preparation of fat metabolism inhibitors with thiadiazole derivatives

The thiadiazole derivatives used according to the invention correspond to the general formula (XIII):

Rxih2 Rxiii3

wherein n is an integer from 0 to 4, and wherein

Rxx, Rxiii2, Rxiiis, Rxiii4, Rxiiis and Rxine are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted and unsubstituted acyl radicals, substituted and unsubstituted cycloalkyl groups. (Co-26) -alkyl radicals, substituted and unsubstituted cycloalkyl (Co-26) -alkoxy radicals and halogen, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each acyl radical , each alkoxy radical and each cycloalkyl- (C 0-6) -alkyl group may be saturated or unsaturated with one or more double or triple bonds, and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms.

· * ·· · · · · ·

For R xm -j, COOC ₂ H ₅ is preferred.

Further preferred are compounds wherein R _X m ₂ to R _X m ₆ are selected from the group consisting of hydrogen and halogen, especially chlorine.

In addition, 1 or 2 is preferred for n.

XIV. Combined preparation of inhibitors of fat metabolism with heterocycle with one nitrogen and oxygen

The compounds of the invention which are contained in medicaments correspond to the general formula (XIV):

Rxiv3

where Y _X | _W is C - ^ - alkenyl, which is substituted by R _{x) at} ^r i xiv2 ^and optionally R _X ^Ar xiv4 IV3. whereas

R _X and R _X IVI iv8 are the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl- (C _{0 2} _ 6) -alkyl, substituted cykloalkoxy- and unsubstituted (C _{0th 2} 6) -alkyl, substituted and unsubstituted alkoxy- (C _{0 "26)} -alkyl, substituted and unsubstituted amino groups and substituted and unsubstituted thio- (C ₀ _ ₂₆₎ alkyl, substituted and unsubstituted sulfonyl - (C _{0th 26)} -alkyl, substituted and unsubstituted sulfinyl- (C ₀ _ ₂₆₎ alkyl and substituted and unsubstituted acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl the residue, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more d and / or one or two carbon atoms of cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms; and

R _X ivi3 and R _X ivu are defined as R _x , vi ^{to R} xivs. or taken together form an oxo group, after which Z _XfV is a phosphororganic group ···

-RXIV9

Rxivio wherein Rxiv9 and Rxivio are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted (C1-26) alkyl, substituted and unsubstituted hydroxy- (C1-26) alkyl, substituted and unsubstituted cycloalkyl- ( C 0-6 alkyl-substituted and unsubstituted acyl, halogen, ΟΧχινθ or ΟΧχινιο, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical, each acyl radical and each the cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, wherein X _X iv9 or Χχινιο may be the same or different and selected from the group; which consists of hydrogen, substituted and unsubstituted (C1-26) alkyl groups, substituted and unsubstituted hydroxy (C1-26) alkyl groups, substituted and unsubstituted cycloalkyl- (C0-26) -alkyl groups, substituted and unsubstituted acyl, silyl, cations of organic and inorganic bases, in particular of metal of the first, second or third / groups of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical, and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, or wherein Ζχιν is an amino group

-N-Rxivn

XIV12 wherein Rxivn Rxivi2 and are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl- (Co-26) -alkyl, substituted and unsubstituted cykloalkoxy- (C ₂ _ ₀ 6 ) -alkyl, substituted and unsubstituted alkoxy- (C _{0th 2} 6) -alkyl, and substituted or unsubstituted acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy the radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, wherein

Βχιν is selected from the group consisting of substituted and unsubstituted C ₁ .26 ^_a lkenylenové groups, wherein one C atom may be replaced by an oxygen atom and one C-atom by a sulfur atom, or two C atoms may be replaced by each and Sheterocyklem the alkenylene moiety may be branched or unbranched and saturated or unsaturated with one or more double or triple bonds and substituted with one or more hydroxy, halogen or oxo groups.

^R xivi 3 and ^R xivi 4 together preferably form an oxo group at the α-position to the nitrogen atom.

For Υχιν, a methylene group, preferably substituted by two methyl groups, is preferred.

Preference is further given to compounds in which as B _{X 1 V} is an ether group (XIVA)

-Axivi-O-Αχιν2- (XIVA) with A _X | _{V1 is} omitted or is a (C 1-8) -alkylene residue and

A _X IV2 omitted or is selected from the group consisting of (C ^ gj-alkylene radicals, sulfur, and (C _3.8) -heterocycle, which has at least one sulfur atom. As A _X | _V IA and _X, v2 a methylene group is particularly preferred.

Also preferred are compounds in which B _{X 1 V} represents keto group (XIVB)

O

-Αχιν3-C-Αχιν4- (XI VB) with A _X | _V 3 and A _X | _{V 4} , one or both of which may be omitted, are the same or different and are selected from the group consisting of (C 1-8) -alkylene residues, wherein all (C ₁₉ ) -alkylene residues may be branched or unbranched; Or contain one or more double bonds or be substituted by a hydroxy or a halogen group, it is preferred that A _X | _{V3 is} omitted and A _X | V4 represents a methylene or ethylene group.

Furthermore, for B _X | _In preference 2-hydroxy propylene group.

Rxivg θ Rxivio are preferably OX _XIV9 and OX _X | _V10 , where X _x , _V9 or

They may be the same or different and selected from the group consisting of the metal of the first, second or third main group of the periodic system, in particular sodium and potassium and methyl, ethyl.

The peculiarities of the above definitions and suitable examples are given in the following:

Acyl is a substituent derived from an acid, such as an organic carboxylic acid, such as carbonic acid, carbamic acid, or each of the aforementioned corresponding thioacids or imidic acids, or organic sulfonic acids, which acids include the respective organic, aromatic and / or heterocyclic groups such as carbamoyl or carbamimidoyl.

Suitable examples for these acyl groups are given in the following.

Aliphatic acyl groups denote acyl residues derived from aliphatic acids and include the following:

alkanoyl (eg, formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, etc.);

alkenoyl (e.g., acryloyl, methacryloyl, crotonoyl, etc.); alkylthioalkanoyl (eg, methylthioacetyl, ethylthioacetyl, etc.); alkanesulfonyl (e.g., mesyl, ethanesulfonyl, propanesulfonyl, etc.); alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, etc.); alkylcarbamoyl (eg, methylcarbamoyl, etc.);

(N-alkyl) -thiocarbamoyl (e.g., (N-methyl) -thiocarbamoyl, etc.); alkylcarbamimidoyl (e.g. methylcarbamimidoyl etc.); oxalo;

alkoxalyl (eg, methoxalyl, ethoxalyl, propoxalyl, etc.).

In the above examples of aliphatic acyl groups, the aliphatic hydrocarbon moiety, in particular the alkyl group and the carbohydrate moiety, may be aliphatic. an alkane radical, optionally having one or more suitable substituents such as amino, halogen (e.g., fluorine, chlorine, bromine, etc.), hydroxy,

hydroxyimino, carboxy, alkoxy (e.g. methoxy, ethoxy, propoxy etc.), alkoxycarbonyl, acylamino (e.g. benzyloxycarbonylamino etc.), acyloxy (e.g. acetoxy, benzyloxy etc.) and the like; preferred aliphatic acyl radicals with such substituents include, for example, amino, carboxy, amino and carboxy, halogen, acylamino or the like substituted alkanoyls.

Aromatic acyl radicals are those which are derived from an acid with a substituted or unsubstituted aryl group, and may include phenyl, tolyl, xylyl, naphthyl and the like as an aryl group; suitable examples are given in the following:

aroyl (e.g., benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl, etc.); aralkanoyl (eg, phenylacetyl, etc.); aralkenoyl (eg cinnamoyl etc.); aryloxyalkanoyl (eg, phenoxyacetyl, etc.); arylthioalkanoyl (eg, phenylthioacetyl, etc.); arylaminoalkanoyl (eg, N-phenylglycyl, etc.);

arensulfonyl (e.g. benzenesulfonyl, tosyl and toluenesulfonyl, naphthalenesulfonyl, etc.);

aryloxycarbonyl (eg, phenoxycarbonyl, naphthyloxycarbonyl, etc.); aralkoxycarbonyl (e.g. benzyloxycarbonyl, etc.); arylcarbamoyl (eg, phenylcarbamoyl, naphthylcarbamoyl, etc.); arylglyoxyloyl (e.g., phenylglyoxyloyl etc.).

In the above examples of aromatic acyl radicals, the aromatic hydrocarbon moiety (especially the aryl moiety) and / or the aliphatic hydrocarbon moiety (especially the alkane moiety) may optionally have one or more suitable substituents, such as those already mentioned as suitable substituents for the alkyl group and the alkyl group, respectively. alkane residue. Particularly and by way of example, preferred aromatic acyl radicals with particular substituents include halogen- and hydroxy- or halogen- and acyloxy-substituted aroyl and hydroxy-, hydroxyimino-, dihaloalkanoyloxyimino-substituted aralkanoyl as well as arylthiocarbamoyl (e.g. phenylthiocarbamoyl, etc.); arylcarbamimidoyl (e.g., phenylcarbamimidoyl, etc.).

As heterocyclic acyl radical is meant an acyl radical which is derived from an acid having a heterocyclic group; it belongs to this:

heterocyclic carbonyl wherein the heterocyclic radical is an aromatic or aliphatic 5- to 6-membered heterocycle with at least one nitrogen, oxygen and sulfur heteroatom (e.g., thiophenyl, furoyl, pyrrolecarbonyl, nicotinoyl, etc.);

heterocycle-alkanoyl in which the heterocyclic radical is an aromatic or aliphatic 5- to 6-membered heterocycle and has at least one heteroatom selected from nitrogen, oxygen and sulfur (e.g., thiophenylacetyl, furylacetyl, imidazolylpropionyl, tetrazolyl, 2- (2-amino-4-) thiazolyl) -2-methoxyiminoacetyl etc.) and the like.

In the above examples for heterocyclic acyl radicals, the heterocycle and / or the aliphatic hydrocarbon moiety may optionally have one or more suitable substituents such as those listed as suitable for alkyl and alkane groups.

Alkyl, unless otherwise defined, is an alkyl residue of up to 9 carbon atoms, straight or branched chain such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like.

Alkenyl, unless otherwise defined, includes alkenyl groups of up to 9 carbon atoms, straight or branched chain such as vinyl, propenyl (e.g., 1-propenyl, 2-propenyl), 1-methylpropenyl, 2-methylpropenyl, butenyl, 2-ethylpropenyl, pentenyl, hexenyl.

Alkynyl, unless otherwise defined, includes alkenyl groups of up to 9 carbon atoms, straight or branched.

In particular, cycloalkyl represents optionally substituted C3-C7-cycloalkyl; suitable substituents include, but are not limited to, alkyl, alkoxy, (e.g., methoxy, ethoxy, etc.), halogen (e.g., fluorine, chlorine, bromine, etc.), nitro, and the like.

Aryl is an aromatic hydrocarbon radical such as phenyl, naphthyl, etc., which may optionally have one or more suitable substituents such as alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc.), nitro and the like .

Aralkyl includes mono-, di-, triphenyl-alkyls such as benzyl, phenethyl, benzhydryl, trityl and the like, wherein the aromatic moiety may optionally have one or more suitable substituents such as alkoxy (e.g. methoxy, ethoxy, etc.), halogen (e.g. fluorine, chlorine, bromine, etc.), nitro and the like.

Alkylene includes straight or branched chain alkylene groups having up to 9 carbon atoms and can be represented by the formula - (C _n H ₂ n) - in which n is an integer from 1 to 9 such as methylene, ethylene, trimethylene, methylethylene,

• · • 9 9 • · • • • · • · • · • • • • · · · · • · « 9 · « • · «· · · • ·· • • ···· • ♦ · •

tetramethylene, 1-methyltrimethylene, 2-ethylethylene, pentamethylene, 2-methyltetramethylene, isopropylethylene, hexamethylene and the like; preferred alkylene radicals have up to 4 carbon atoms, and especially 3 radicals such as trimethylene are preferred.

Alkenylene includes straight or branched chain alkenylene groups having up to 9 carbon atoms and can be represented by the formula - (CnH ₂ n-2) - in which n is an integer from 1 to 9 such as vinylene, propenylene, (e.g., 1-propenylene, 2-propenylene), 1-methylpropenylene, 2-methylpropenylene, butenylene, 2-ethylpropenylene, pentenylene, hexenylene; particularly preferably the alkenylene radical may have up to 5 carbon atoms and in particular 3 carbon atoms such as e.g.

1- Propenylene.

The hydroxyalkylene may include straight or branched chain alkylene radicals having up to 9 carbon atoms, wherein one or more selected carbon atoms are substituted with a hydroxy group; These residues may be represented by the formula - (C _n H ₂ NZ) _(OH) -, wherein n is an integer of 1 to 9 and z is an integer which determines the application of <n. Suitable examples of such hydroxyalkenylenové groups include hydroxymethylene, hydroxyethylene (e.g., 1-hydroxyethylene and 2-hydroxyethylene), hydroxytrimethylene (e.g., 1-hydroxytrimethylene,

2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-methyltrimethylene, 2-hydroxy-2-hydroxytrimethylene; Particularly preferred is a lower hydroxyalkylene of up to 4 carbon atoms, and especially one having 3 carbon atoms such as 2-hydroxytrimethylene.

Alkyleneamines include straight or branched chain alkylenamine groups having up to 9 carbon atoms and may be represented by the formula - (C _n H ₂ n) -N- (C _m H _{2 m} ) - in which n and _m may be the same or different and are whole a number from 0 to 9 and is 1 < n + m &lt; 9, such as methyleneamine, ethyleneamine, dimethyleneamine, trimethyleneamine, methyleneethyleneamine, tetramethyleneamine, 1-methyltrimethyleneamine, 2-ethylethylenamine, ethyl-4-methylenamine, pentamethylenamine, 2-methyltetramethylenamine, isopropylethylenamine, hexamethylenamine and the like; preferred alkylene amine residues have 2 carbon atoms that are terminal. Dimethylenamine is particularly preferred. Hydrogen atoms can also be replaced by substituents, such as halogen radicals.

Alkylenimine includes straight or branched chain alkylenimine groups having up to 9 carbon atoms and can be represented by the formula - (C _n H ₂ ni) = N- (C _m H _{2 m} ) - or - (C _n H _{2 n} ) -N = (C _m H2 _m- i) -, in which n and m may be the same or different and are an integer from 0 to 9 and are subject to 1 <n + m 9 9, such as methyleneimine, ethyleneimine, dimethyleneimine, trimethyleneimine, methylenethyleneimine tetramethyleneimine, 1-methyltrimethyleneimine, 2-ethylethyleneimine, ethylene methyleneimine, pentamethyleneimine, 2-methyltetramethyleneimine, isopropylethyleneimine, hexamethyleneimine and the like; preferred alkyleneimine residues have 2 carbon atoms that are terminal. Dimethyleneimine is particularly preferred. Hydrogen atoms can also be replaced by substituents, such as halogen radicals.

Alkenyleneamine includes straight or branched chained or branched-chain alkenyl groups having up to 9 carbon atoms and can be represented by the formula - (C _n H ₂ n-2) -N- (C _m H 2 _m -2) -; - (C _o H2o) -N- (C _m H _{2 m} -2) -; - (C _n H 2 _n -2) -N (C _o H ₂ o) - in which n and m can be the same or different and are an integer from 2 to 9 and n + m is £ 9 and o is a number between 0 and 7 and is + n <9, such as vinylenamine, methylenvinylenamine, divinylenamine, propenylenamine (eg 1-propenylenamine, 2propenylenamine), methylenepropenylenamine, 1-methylpropenylenamine, 2-methylpropenylenamine, butenylenamine, 2-ethylenepropenylamine, pentlenene, like them. Hydrogen atoms can also be replaced by substituents, such as halogen radicals.

Alkenyleneimine includes straight or branched chain alkenyleneimine groups having up to 9 carbon atoms and may be represented by the formula - (C _n H 2 _n -3) = N- (C m H ₂ m-2) -; - (C _o H2o-i) = N- (C _m H ₂ m-2) -; - (C ₁₁ H ₂ n-3) = N (CoH ₂ O) ·; - (Cn H2n-2) ⁼ N- (C m H 2m-3) ^_; “(CoH2O) ⁼ N- (CmH2m-3) ^- ; (C11H2n-2) ⁼ N- (CoH2o-1) ^- ; In which n and m are the same or different and are an integer from 2 to 9 and for which n + m < 9 and o is a number between 0 and 7 and o + n £ 9, such as vinylenimine, methylenvinylenimine, ethylenvinylenimine, propenylenimine ( such as 1-propenyleneimine, 2-propenyleneimine), methylene-propenyleneimine, 1-methyl-propenyleneimine, 2-methylpropenyleneimine, butenyleneimine, 2-ethylene-propenyleneimine, pentenyleneimine, hexenyienimine, vinylmethyleneimine and the like. Hydrogen atoms can also be replaced by substituents, such as halogen radicals.

Hydroxyalkyleneamines may include straight or branched chain alkenylene radicals having up to 9 carbon atoms, wherein 4 &apos;

OZ- at least one selected carbon atom is substituted with a hydroxy group and these residues can be represented by the formula - (CnH ₂ nz) (OH) _of -N- (C _m H2m- y) (OH) y in which n and m are the same or different and are an integer from 0 to 9, and for them 1 <n + m <9, az and y are the same or different and are an integer for which Suitable examples for such hydroxyalkyleneamino groups include hydroxymethyleneamine, hydroxyethyleneamine (e.g., 1-hydroxyethylenamine and 2-hydroxyethylenamine), hydroxytrimethylenamine (e.g., 1-hydroxytrimethylenamine, 2-hydroxytrimethylenamine, 3-hydroxytrimethylenamine), e.g. 2-hydroxy-2-methyltrimethyleneamine, hydroxypentamethyleneamine (eg 2-hydroxypentamethyleneamine), hydroxyhexamethyleneamine (eg 2-hydroxyhexamethyleneamine), methylenehydroxymethyleneamine, methylenehydroxyethyleneamine and the like. Particularly preferred is a lower hydroxyalkyleneamine having two carbon atoms and one nitrogen atom, both of which are terminal. Hydrogen atoms can also be replaced by substituents, such as halogen radicals.

Hydroxyalkylenimine may include straight or branched chain alkenylene radicals having up to 9 carbon atoms, with at least one selected carbon atom being substituted by hydroxy, and these radicals may be represented by the formulas

- (CnH _2n -Z) _(OH) = N- (C _m H _{2 m} .y) (OH) y - (C _n H ₂ Nzi) _(OH) -N = (C _m H _{2 m} .y) (OH) y where n and m are the same or different and are an integer from 0 to 9 and 1 £ n + m £ 9, az and y are the same or different and are an integer for which 0 ^ z ^ n-1 Suitable examples for such hydroxyalkyleneimino groups include hydroxymethyleneimine, hydroxyethyleneimine (e.g., 1-hydroxyethyleneimine and 2-hydroxyethyleneimine), hydroxytrimethyleneimine (e.g., 1-hydroxytrimethyleneimine, 2hydroxytrimethyleneimine, 3-hydroxytrimethyleneimine), 2-hydroxy-tetramethyleneimine), 2-hydroxy-2-methyltrimethyleneimine, hydroxypentamethyleneimine (eg 2-hydroxypentamethyleneimine), hydroxyhexamethyleneimine (eg 2-hydroxyhexamethyleneimine), methylenehydroxymethyleneimine, methylenehydroxyethyleneimine and the like. Particularly preferred is a lower hydroxyalkylenimine having two carbon atoms and one nitrogen atom, both of which stand at the end. Hydrogen atoms can also be replaced by substituents, such as halogen radicals.

♦ · • · · »·« · • • 9 • • «· • • · · • 9 • 9 • 9 • 9 • • • · • 9 9 9 • 9 «» · * • · 9 9 • ♦ 999

Five-membered and six-membered cyclic compounds which may represent B1 _V , may be aromatic or aliphatic and substituted, for example, with alkyl groups of up to 7 carbon atoms and hydroxy groups.

Five-membered and six-membered heterocyclic compounds, which may represent R vim and R _v ih 2 as well as R xi and R x ₂ and contain as one or two nitrogen or oxygen or sulfur atoms besides carbon, may be saturated or unsaturated.

The alkoxy radical, unless otherwise defined, is an alkoxy radical of up to 26 carbon atoms, straight chained or branched such as methoxy, ethoxy, etc. It may be substituted by hydroxy, aminohalo, oxo and alkoxy radicals such as methoxy, ethoxy.

Alkoxy- (C 0-6) -alkyl groups are alkoxy radicals which can be attached to the backbone via an alkyl radical. Alkyl and alkoxy groups are defined as above.

Cycloalkyl- (C 0-6) -alkyl radicals are cyclic compounds having 3 to 8 carbon atoms, which, unless otherwise defined, are attached to the backbone via an alkylene radical. The alkylene radical may be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloalkyl radical are, inter alia, alkoxy radicals, alkyl radicals, hydroxyl radicals, halobenzyl radicals, amino radicals, oxo radicals. Cycloalkyl groups can also be aromatic with the appropriate number of double bonds. be aryl- (C 0-6) -alkyl radicals (e.g. phenyl-, pyridyl-, naphthyl- etc.). Particularly aromatic cyclic compounds may further contain substituents such as nitro, CF 3 and phenyl radicals.

Cycloalkoxy- (C 0-6) -alkyl groups are cyclic compounds having 3 to 8 carbon atoms, which are bonded to the backbone directly via oxygen or via an alkylene residue. The alkylene radical may be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloalkyl radical are, inter alia, alkoxy radicals (also alkylenedioxy radicals such as methylenedioxy-), alkyl radicals, hydroxyl radicals, halogen radicals, amino radicals, oxo radicals. Cycloalkyl groups may also be multicyclic and aromatic with the appropriate number of double bonds (e.g., phenoxy, pyridoxy, naphthoxy, etc.). Particularly aromatic cyclic compounds may further contain substituents such as nitro, CF ₃ and phenyl radicals.

• · · · · · · · · · · ·

The amino radicals may, for example, be substituted with alkyl radicals or cycloalkyl- (C _{0 26} ) -alkyl radicals as defined above.

Amino- _{(C0. 2} 6) -alkyl are amino radicals, which can be attached to the backbone via an alkyl residue. Alkyl and amino groups are as defined above.

For example, the silyl radicals may be substituted with alkyl radicals or cycloalkyl- (C _{0 26} ) -alkyl radicals as defined above.

Silyl- (C _{0 26} ) -alkyl groups are silyl radicals which can be attached to the backbone via an alkyl radical. Alkyl and silyl groups are defined as above.

Thio- (C ₀ _ ₂₆₎ alkyl may be substituted with the above defined alkyl radicals or cykloaIkyl- (Co_26) -alkylzbytky. (C ₀ _ ₂₆₎ alkyl groups are alkylene radicals having a straight or branched chain such as methylene, ethylene, propylene, isopropylene, butylene, isobutylene, tert-butylene, pentylene, hexylene and the like. They may contain double or triple bonds and may be substituted by, for example, hydroxy, amino, halogeno (e.g. fluorine, bromine, chlorine), oxo and alkoxy radicals, such as methoxy, ethoxy.

Most preferably the radicals may X ₍₃ to X _VN3 and X | _{4 TO} X n ₄ as Ryms, Rixh, X, _X i _4, Xih ^and X '2 are selected to form the esters to phosphonic or sulphonyl. Suitable examples mono and diesters are encompassed for the esters of the compounds used in the invention, and preferred examples of such esters include alkyl esters (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, hexyl, etc.);

aralkyl esters (benzyl, phenethyl, benzhydryl, trityl, etc.); aryl esters (eg, phenyl ester, tolyl ester, naphthyl ester, etc.); aroylalkyl esters (eg, phenacylester); and silyl esters (e.g., trihalogensilyl-, dialkyldihalogensilyl-, alkyltrihalogensilyl-, dialkylarylhalogensilyl-, trialkoxyhalogensilyl-, dialkylaralkylhalogensilyl-, dialkoxydihalogensilyl-, trialkoxyhalogensilyl-ester etc.).

For the upper esters, the alkane and / or arene moiety may optionally have at least one suitable substituent such as halogen, alkoxy, hydroxy, nitro or the like.

X, 3 to X _V || ₃ and X | ₄ to X _V ii4 as well as X _X | ₃ and X _xw , X | _M and Xn ₂ are preferably the metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium or ammonium compounds derived from ethylenediamine. c * · · *

GG ® ® and «wv # ·» · * ·· · * <- · *> · <<

or amino acids. Ie. salts of ammonium phosphonic acid derivatives with organic or inorganic bases are formed (eg sodium salt, potassium salt, calcium salt, aluminum salt, magnesium salt, triethylammonium salt, ethanolamine salt, dicyclohexylammonium salt, ethylenediamine salt, N, N 'salt dibenzylethylenediamine, etc.), as well as salts with amino acids (e.g., arginine salt, aspartic acid salt, glutamic acid salt, etc.) and the like.

The compounds according to the invention of formulas (I) to (XIV) allow the occurrence of spatial isomers, for example, for those containing double bonds or chiral groups of substituents R or A or B or Y or Z or X. pure substances as well as mixtures thereof.

Pharmaceutically acceptable salts of the aminohydrophosphonic acid derivatives include those which form the compounds of the invention in their protonated form as the ammonium salt of inorganic or organic acids such as hydrochloric acid, sulfuric acid, citric acid, maleic acid, fumaric acid, tartaric acid, p-toluenesulfonic acid.

Also particularly suitable are the salts formed by a suitable selection of X ₃ (X ₁₃ to X _V3 ) and X ₄ (X ₁₄ to X V ₄ ), as well as X 4 | _M and X _H2 as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylammonium salt, dicyclohexylammonium salt and as amino acid salts such as arginine, aspartic acid salt, glutamic acid salt.

The combination preparations of the invention comprise one or more fat metabolism inhibitors. Both inhibitors that regulate fat intake and inhibitors that regulate fat synthesis may be employed. Such inhibitors include anion exchangers, preferably cholestyramine and colestipol, β-sitosterine, nicotinic acids and derivatives thereof such as nicotinyl alcohol, clofibrates and derivatives thereof such as clofibrinic acid ethyl ester, as well as analogues thereof such as bezafibrate, fenofibrate and gemfibrozil and probucol.

Inhibitors that regulate fat synthesis include HMG-CoA synthetase inhibitors. HMG-CoA-reductase inhibitors, preferably lovastatin, mevastatin, simvastatin, fluvastatin, atorvastatin, pravastatin and cerivastatin, squalene synthetase inhibitors, preferably pyrophosphates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethisphosphonic acid derivatives, phosphinylformylderivers, phosphinylformyldererivatives phosphinylmethyphosphonic acids, squalene epoxidase inhibitors and other cholesterol synthesis inhibitors.

Preferred are HMG-CoA reductase inhibitors and squalene synthetase inhibitors.

Of the bisphosphonates, clodronate, etidronate, pamidronate, ibandronate, alendronate, zoiedronate, risedronate, tiludronate and cimadronate are particularly preferred.

The infectious compounds and their esters, as well as their salts, exhibit potent cytoxic activity against monocellular and multicellular parasites, fungi, bacteria and viruses infected with simultaneous, separate or staggered use with fat metabolism inhibitors. The compounds of the invention are useful for the treatment of infectious diseases caused in humans and animals by parasites, fungi, bacteria or viruses. The compounds are also suitable for use in preventing these diseases.

The combined preparations are effective against unicellular parasites (protozoa) in particular against agents of malaria and sleeping sickness, as well as Chagas disease, toxoplasmosis, amoebic dysenteria, leishmaniases, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcocosseis, coccureboscosis, acanthameboscosis, akantlerebose .

They are therefore particularly suitable for the prophylaxis of malaria and for the prophylaxis of sleeping sickness, as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniosis, trichomoniasis, pneumocystoses, balantidiosis, cryptosporidiosis, sarcocystoses, acanthameboses, coccidiosis, coccidiosis and naeglerosis.

The combined preparations are particularly useful against the following bacteria: Bacteria of the family Propionibacteriaceae, in particular the genus Propionibacterium, in particular the species Propionibacterium acnes; bacteria of the family Actinomycetaceae, in particular genus Actinomyces; bacteria of the genus Corynebacterium, in particular Corynebacterium diphteriae and Corynebacterium pseudotuberculosis species; bacteria of the family Mycobacteriaceae, genus Mycobacterium, in particular species Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium; bacteria of the family Chlamydiaceae, in particular Chlamydia trachomatis and Chlamydia psittaci; bacteria of the genus Listeria in particular Listeria monocytogenes; Erysipelthrix rhusiopathiae; bacteria of the genus Clostridium; Yersinia bacteria, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia entrocolitica and Yersinia ruckeri; bacteria of the family Mycoplasmataceae, genera Mycoplasma and Ureoplasma, in particular Mycoplasma pneumoniae; Brucella; Bordetella; bacteria of the family Neiseríaceae, in particular genera Neisseria and Moraxela, in particular Neisseria species

meningitides, Neisseria gonorrhoeae and Moraxela bovis; bacteria of the family Vibrionaceae, in particular genera Vibrio, Aeromonas, Plesiomonas and Photobacterium, in particular Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas; Campylobacter bacteria, in particular Campylobacter jejuni, Campylobacter coli and Campylobacter fetus species; Helicobacter species, in particular Helicobacter pylori species; bacteria of the family Spirochaetaceae and Leptospiraceae, in particular of the genera Treponema, Borrelia and Leptospira, in particular Borrelia burgdorferi; bacteria of the genus Actinobacillus; bacteria of the family Legionellaceae, genus Legionella; bacteria of the family Rickettsiaceae and family Bartonellaceae; Nocardia and Rhodococcus bacteria; bacteria of the genus Dermatophilus; bacteria of the family Pseudomonadaceae, in particular of the genera Pseudomonas and Xanthomonas; bacteria of the family Enterobacteriaceae, in particular of the genera Escherichia, Klebsiella, Proteus, Providencia, Salmonella, Serratia and Shigella; bacteria of the family Pasteurellaceae, in particular of the genus Haemophilus; bacteria of the family Micrococcaceae, in particular of the genera Micrococcus and Staphylococcus; bacteria of the family Streptococcaceae, in particular of the genera Streptococcus and Enterococcus, and bacteria of the family Bacillaceae, in particular of the genera Bacillus and Clostridium.

Thus, the combination preparations of the invention are suitable for the treatment of diphtheria, Acne vulgaris, listerios, animal robins, gangrene in man and animals, paragonimosis in man and animals, tuberculosis in man and animals, leprosy and other mycobacterios in man and animals, paratuberculosis in animals , plague, mesenteric lymphadenitis and pseudotuberculosis in humans and animals, cholera, legionnaires' disease, borreliosis in humans and animals, leptospirosis in humans and animals, syphilis, Campylobacterenteritis in humans and animals, Moraxella-keratoconjunctivitis and animal serositis, brucellosis in animals and humans, anthrax in humans and animals, actinomycosis in humans and animals, streptotrichos, psittacosis / ornithoses in animals and Q-fever and Ehrlichiosis.

It is also beneficial to treat Helicobacter eradication in gastric and intestinal ulcers.

For the treatment of the aforementioned diseases, other combinations with another antibiotic may be employed. Isoniazide, rifampicin, ethambutol, pyrazinamide, streptomycin, protionamide and dapson are particularly suitable for the treatment of tuberculosis in combination preparations with second antiinfectives.

The combination preparations according to the invention can further be used especially in infections with the following viruses: Parvoviridae: parvoviruses, dependoviruses, densoviruses; Adenoviridae: adenoviruses, mastadenoviruses, aviadenoviruses; Papovaviridae: papovaviruses, especially papillomaviruses (so-called wart viruses), polyomaviruses, in particular JC-virus, BK-virus and miopapovaviruses; Herpesviridae: all herpesviruses, particularly Herpessimplex viruses, varicela / zoster viruses, human cytomegalovirus, Epstein-Barr viruses, all human herpesviruses, human herpesvirus 6, human herpesvirus 7, human herpesvirus 8; Poxviridae: smallpox viruses, orthopox-, parapox-, molluscumcontagiosum-virus, aviviruses, capriviruses, leporipoxviruses; all primary hepatotropic viruses, hepatitis-viruses: hepatitis-A-viruses, hepatitis-B-viruses, hepatitis-C-viruses, hepatitis-D-viruses, hepatitis-E-viruses, hepatitis-F-viruses, hepatitis-G-viruses; hepadnaviruses: all hepatitisviruses. Hepatitis-B-viruses, hepatitis-D-viruses; Picornaviridae: picomaviruses, all enteroviruses, all polioviruses, all coxsackieviruses, all echoviruses, all rhinoviruses, hepatitis-A-virus, aftoviruses; Calciviridae: hepatitis-E viruses; Reoviridae: reoviruses, orbiviruses, rotaviruses; Togaviridae: togaviruses, alphaviruses, rubiviruses, pestiviruses, Rubellavirus; Flaviridae: flaviviruses, FSME-virus, hepatitis-C-virus; Orthomyxoviridae: all influenza viruses; Paramyxoviridae: paramyxoviruses, morbillivirus, pneumovirus, masernvirus, mumpsvirus; Rhabdoviridae; rhabdoviruses, rabiesvirus, lyssavirus, viscular stomatitisvirus; Coronaviridae: coronaviruses; Bunyaviridae; bunyaviruses, nairovirus, flebovirus, uukuvirus, hantavirus; Arenaviridae: arenaviruses, lymphocytic choriomeningitis virus; Retroviridae: retroviruses, all HTL-viruses, human T-cell leukemia virus, oncornaviruses, spumaviruses, lentiviruses, all H1-viruses; Filoviridae: Marburg- and Ebola-virus, slow virus infections, prions; oncoviruses, leukemia viruses.

The preparations according to the invention are thus suitable for combating the following viral infections:

eradication of papilloma viruses for the prophylaxis of tumors, particularly genital tumors caused by papillomaviruses in humans. Eradication of JC-viruses and BK-viruses, eradication of herpesviruses, eradication of human herpesviruses 8 for the treatment of Kaposi-sarcoma, eradication of cytomegalitic viruses before transplantation, eradication of Epstein-Barr viruses prior to transplantation for prophylaxis of tumors associated with EpsteinBarr virus prophylaxis of liver tumors and liver cirrhosis, eradication of coxsackieviruses in cardiomyopathies, eradication of coxsackieviruses in patients with diabetes mellitus, eradication of immunodeficiency viruses in humans and animals, treatment of concomitant infections in patients with AIDS, treatment of inflammations of the respiratory tract, viral origin, pharyngitis, bronchitis, pneumonia), sensory organs (keratoconjunctivitis), nervous system ··· (poliomyelitis, meningoencephalitis, encephalitis, subacute sclerosing panencephalitis, SSPE, p progressive multifocal leukoencephalopathy, lymphocytic choriomeningitis), stomach and intestinal tract (stomatitis, gingivostomatitis, esophagitis, gastritis, gastroenteritis, diarrhea), liver and bile system (hepatitis, cholangitis, lymphoma, hepatocelulosis) hepatocellular , genital organs (mumpsorchitis), skin (warts, dermatitis, Herpes labialis, fever blisters, Herpes zoster, shingles), mucous membranes (papillomas, conjunctivapapilomas, hyperplasia, dysplasia), heart and vascular blood system, endocarditis, myocarditis, arteritis, arteritis ), kidney and urinary tract, genital organs (anogenital lesions, warts, genital warts, pointed condylomas, dysplasia, papillomas, cervical dysplasia, condyloma acuminata, epidermodysplasia verruciformis), musculoskeletal system (myositis, myalgia) arthropods, Colorado-tick fever, dengue-syndrome, haemorrhagic fever, early summer meningoencephalitis (FSME) and yellow fever.

The compositions are suitable for combination with other compositions having antiviral properties.

Compounds of the invention, which generally include pharmaceutically acceptable salts, esters, salts of such esters, or even compounds which upon application provide compounds of the invention as metabolic or degradation products, also called. prodrugs may be prepared for administration in any suitable form analogous to known antiinfective agents (mixed with a non-toxic pharmaceutically acceptable carrier).

The combination preparation of the invention may be administered in conjunction with non-toxic, inert, pharmaceutically acceptable carriers. This includes solid, semi-solid or liquid diluents, fillers and formulation aids of any kind.

Tablets, coated tablets, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays may be mentioned as pharmaceutical preparations. Tablets, dragees, capsules, pills, and granules may contain the active ingredients in addition to conventional carriers such as (a) fillers and extenders, eg starches, milk sugar, raw sugar, glucose, mannitol and silicic acid, (b) binders, eg carboxymethylcellulose, (c) humectants such as glycerol, (d) blowing agents such as agar-agar, calcium carbonate, sodium carbonate, (e) dissolution retardants such as alginates, gelatin, polyvinylpyrrolidone, (c) humectants such as glycerol, paraffin, (f) resorption accelerators such as ammonium compounds, (g) wetting agents such as cetyl alcohol, glycerol monostearate, (h) adsorbents such as kaolin and bentonite, and (i) antiadhesives such as talc, calcium and magnesium stearate and solids polyethylene glycols or mixtures of the substances mentioned under (a) to (i). The compounds of the invention may further be incorporated into other carrier materials such as plastics (plastic strips for local therapy), collagen or bone cement.

Tablets, dragees, capsules, pills, and granules may optionally be provided with a repeating agent comprising coatings and coatings, and may also be formulated so as to deliver the active ingredients only or preferentially in a certain part of the intestinal tract, possibly elongated, polymeric substances and waxes.

Alternatively, the active compounds may also exist in microencapsulated form with one or more of the above-mentioned carriers.

Suppositories may contain, in addition to the active ingredients, customary, water-soluble or water-insoluble carriers such as polyethylene glycols, fats such as cocoa butter and higher esters (e.g. C 14 -alcohol with C 16 -fatty acid) or mixtures thereof.

Ointments, pastes, creams and gels may contain, in addition to the active ingredients, conventional carriers such as animal and vegetable fats, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc, zinc oxide or mixtures thereof.

Powders and sprays may contain, in addition to the active ingredients, conventional carriers, for example, milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures thereof. Sprays can additionally contain conventional expellers such as chlorofluorocarbons.

The solutions and emulsions may contain, in addition to the active compounds, customary carriers such as solvents, solubilizers and emulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, especially cotton oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan fatty acid esters or mixtures thereof.

999999 · 9 9 99 · * • · 999 «9 · θΊ *** * ·· · ** · · * · *

For parenteral administration, solutions and emulsions may also be available in sterile and blood-isotonic form.

The suspensions may contain, in addition to the active compounds, conventional carriers such as liquid diluents, e.g. water, ethanol, propylene glycol, suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitan esters and sorbitan esters, microciiptaline cellulose, aluminum hydroxide, bentonite, agar-agar and tragacanth.

The active compound (s) of the formulas (I) to (XIV) in the abovementioned pharmaceutical preparations should preferably be present in a concentration of from about 0.1 to 99.5% by weight, in particular from about 0.5 to 95% by weight of the total mixture. . The ratio between the individual substances to be combined in this case depends on the individual active substance. Thus, the active substances are usually administered at a dose of 0.1 mg / kg body weight per day (ibandronate and alendronate), 0.5 mg / kg body weight per day (mevastatin, simvastatin, pravastatin, fluvastatin), 10 mg / kg body weight per day (mem. dronate).

In addition to the compounds of formulas (I) to (XIV) and fat metabolism inhibitors, the aforementioned pharmaceutical preparations may also contain other pharmaceutically active substances, such as antiviral, antiparasitic, antifungal or antibacterial agents.

Thus, the combination preparations of the invention may further comprise sulphonamide, sulphadoxin, artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, priaziquantil, nicamidine, nicamidine, nicamidine, nicamidine, nicamidine, nicamidine, nicamidine, piperazine, pyrivinum, metrifonate, oxamnichin, bithionol or suramine or more of these substances.

Preferably, lovastatin, atorvastatin, simvastatin, mevastatin, pravastatin and fluvastatin are orally administered, with pravastatin and fluvastatin being administered in active form.

In both human and veterinary medicine, it is generally preferred to administer the active compound (s) of formula (I) and (V) to achieve the desired effects in a total amount of from about 0.5 to about 600, in particular 1 to 200 mg / kg body weight. weight in 24 hours, optionally in the form of multiple individual doses. A single dose contains the active compound (s) in particular in amounts of from about 0.5 to about 200, in particular from 1 to 60 mg / kg of body weight. However, it may be desirable

• · • · · * · · · ♦ ♦ · • · • · • • · ♦ * · «♦ »·» * • · · • · «· ♦ ♦ · · • »· · · · · ♦

Depending on the type and body weight of the patient being treated, the type and severity of the disease, the type of preparation and the application of the medicament, as well as the time period or time period, respectively. the interval at which administration takes place.

In order to obtain the desired effects, it has proven advantageous to administer fat metabolism inhibitors in the dosage ranges known for the treatment of fat metabolism disorders and calcium and phosphate management. These are total amounts of from about 0.005 to about 200, in particular 0.01 to 100 mg / kg of body weight per 24 hours, optionally in the form of multiple doses. A single dose contains the active compound (s) (fat metabolism inhibitors) in particular in amounts of from about 0.002 to about 50, in particular 0.1 to 10 mg / kg body weight. However, it may be desirable to deviate from the listed dosages, depending on the type and body weight of the patient being treated, the type and severity of the disease, the type of preparation and the drug being administered, as well as the time period and time. the interval at which administration takes place. Thus, aminobisphosphonates have to be taken into account that their resorbability is very low. This property is an advantage in intestinal involvement (for example in the case of amoebic dysentery). Here, oral doses of pamldronate of up to 10 mg / kg body weight are administered. Dosages up to 2 mg / kg body weight are generally sufficient for injection.

Thus, in some cases it may be sufficient to start with less than the abovementioned amount of active substance, while in other cases the abovementioned amount of active substance must be exceeded. The determination of the appropriately required optimum amount can be determined according to the expert's knowledge.

The combination preparations of the invention may be administered to the animals at the usual concentrations and formulations together by feeding or feeding the animals. feed preparations or drinking water.

The combination preparations may be administered simultaneously, separately or in staggered fashion.

DETAILED DESCRIPTION OF THE INVENTION

Production of anti-infective agent

Preparations for injection 4 4 4 4 4 4 4 4 * 4

9 • 4 • 4 44 »(1) Required amount of sterile, anti-infective agent, 500 mg of 3- (N-acetyl-N-hydroxylamino) -propylphosphonic acid monosodium salt and 90 mg of 3-amino-1-hydroxypropylidene disodium salt The 1,1-bisphosphone was dispensed into vials or ampoules. The vials were hermetically sealed to eliminate bacteria. For injection, it is taken in 500 ml of physiological common salt solution and administered.

In substantially the same manner as described above under (1), other injectable preparations of antiinfective agents were made.

(2) 250 mg of 3- (N-formyl-N-hydroxylamino) -propylphosphonic acid monosodium salt and 90 mg of 3-methylpentylamino-1-hydroxypropylidene-1,1-bisphosphonic acid disodium salt were used as active ingredients for injection.

(3) 250 mg of 3- (N-formyl-N-hydroxylamino) -trans-1-propenylphosphonic acid monosodium salt and 90 mg of 3-amino-1-hydroxypropylidene-1,1- bisphosphonic.

Production of tablets

A suitable formulation for tablets was made with the following mixture:

3- (N-Formyl-N-hydroxylamino) -propylphosphonic acid monosodium salt 200 mg

Lovastatin 10 mg

Mannit 400 mg

Starch 50 mg

Magnesium stearate 10 mg

Production of capsules

3- (N-Formyl-N-hydroxylamino) -propylphosphonic acid monopotassium salt 300 mg

Simvastatin 10 mg

Magnesium stearate 15 mg

The above components were mixed and then foamed into hard gelatin capsules in the usual manner.

• 9 9 9 9 9 999 999 9

9

9 9 99 99 999

Claims (23)

PATENT CLAIMS Combination composition comprising, as active substances, at least one anti-infectious compound which suppresses the pathway of 2C-methylerythrosa-4-metabolism and at least one fat metabolism inhibitor, wherein the fat metabolism inhibitor and the antiinfective are not identical. Combined preparation according to claim 1, characterized in that the fat metabolism inhibitors are selected from the group consisting of cholestyramine, βsitosterin, colestipol, probucol, nicotinic acid, nicotinyl alcohol, clofibrinic acid derivatives and clofibrinic acid analogs, HMG-CoA synthetase inhibitors , HMG-CoA reductase inhibitors, squalene synthetase inhibitors, and squalene epoxidase inhibitors. Combination preparation according to claim 2, characterized in that the fat metabolism inhibitors are squalene synthetase inhibitors, in particular pyrophosphates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethyphosphonic acid derivatives, phosphinylformyl derivatives, phosphonocarboxy derivatives, phosphonosulfonic acid derivatives, phosphinylmethylphosphonic acid derivatives. Combined preparation according to claim 2, characterized in that the fat metabolism inhibitors are HMG-CoA reductase inhibitors, in particular lovastatin, atorvastatin, mevastatin, simvastatin, fluvastatin, pravastatin and cerivastatin. Combined preparation according to claim 2, characterized in that the fat metabolism inhibitors are clofibrinic acid derivatives and analogues thereof, in particular gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate and clinofibrate. Combination preparation according to claim 2, characterized in that the fat metabolism inhibitors are bisphosphonic acid derivatives, in particular clodronic acid derivatives, etidronic acid derivatives, pamidronic acid derivatives, in particular pamidronate, ibandronic acid derivatives, in particular • · «· « »· • • · * · ·· · • • • · •> ··· • 9 • • • · • • · • • • 9 • • · · ·· ·· ♦ · ·· ibandronate, alendronic acid derivatives, in particular alendronate, zoledronic acid derivatives, in particular zoiedronate, risedronic acid derivatives, tiludronic acid derivatives and cimadronic acid derivatives. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one aminohydrocarbylphosphonic acid derivative of the general formula (I) as active substance: ^R <Ϊ _/ NA _j -P — R, s (I) ^R ' ² R, 4 substituted unsubstituted unsubstituted unsubstituted R _h and R i ₂ may be the same or different and is selected from the group consisting of H, OH, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, and substituted unsubstituted heterocyclic radicals, R ₁₃ and R 11 ₄ is selected from the group consisting of substituted and unsubstituted alkyl of 1 to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of 1 to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, and unsubstituted aralkyl, substituted and alkenyl of 1; up to 26 carbon atoms, substituted and cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, X, _3, and X ₁₄ , wherein: X ₁ and X ₁₄ may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1 -C 26 alkyl, substituted and unsubstituted C 1 -C 26 hydroxyalkyl, substituted and unsubstituted aryl, substituted unsubstituted aralkyl, substituted and unsubstituted alkenyl of 1 to 26 carbon atoms, substituted and unsubstituted alkynyl of 1 to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, a cation of an organic and inorganic base, in particular a metal third major groups of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids; and A | represents an alkylene residue, an alkenylene residue or a hydroxyalkylene residue, or corresponds to the following formula (IA): θ | 1 θ | 3 Bj | 5 Bj 7 ^ ιθ C | ·, C12 and C14 C15 0 A) J ₂ b ' _{| 4} B | 6? 8 4 10 wherein one or more carbon atoms selected from the group C 1-6; ₃ , C | ₄ , C | ₅ , together with their substituents, may also be omitted and at least one of the existing substituents B ₁ to B ₁₀ is C ₃ . ₈ -cycloalkyl- (C _{0th 9)} alkyl, wherein each C ₃ _ ₈ -cycloalkyl as well (Co_ ₉₎ -aikylskupina may have one or more double bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur, and both cycloalkyl and alkyl can be substituted by hydroxy, halogen, oxo groups with branched or unbranched C 1-6 alkyl and C ₂ . _And alkenyl groups, wherein the C-. C ₉ alkyl and _{second 9} alkenyl groups may be substituted by hydrogen, hydroxy, amino, halogen and oxo substituents and the remaining existing B-B _{n) 10} are selected from the group consisting of hydrogen, hydroxy, halogen, amino, 0 ^ 26alkylové radicals, C ^ -alkoxy residues, C ₁ . ₂ 6-alkoxy-C ₁ . _The 2-6-alkyl radicals or both substituents on one C-atom together form an oxo group, wherein each C 1-6 alkyl radical and each C 1-6 alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double bonds and it may be substituted by hydroxy, amino, halogen and oxo. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one bisphosphonic acid of the formula II as active substance. • 4 4 · • 4 44 • 4 • • • • · • • • 4 • 4444 • · « • 4 · • • • • • • • • ··· • 44 ♦ · • 4 · ϊ Μ Θ || 3θ — Ρ — C — ρ — ΟΧ ,,, Χ || 4θ Α || ΟΧ || 2 ^Κ || 2 (II). where Xin. Χιΐ2. Χιΐ3. Χιΐ4. which may be the same or different are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, metals first 1, 2 and 3 main groups of the periodic system, such as Na, K, Ca, Mg, Al, as well as substituted and unsubstituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids, A, which may also be omitted, may be selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, R 11, R 12 may be the same or different and are selected from the group consisting of H, OH, -NH ₂ , substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl and substituted and unsubstituted heterocyclic radicals and -SRh ₃ , Cl and -NRh ₃ Rh ₄ , wherein Rii3. R ₁₁ may be the same or different and is selected from the group consisting of H, OH, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, and substituted and unsubstituted heterocyclic radicals or a pharmaceutically acceptable salt, ester, or ester salt or compound thereof, which upon administration forms the compounds to be administered as metabolism or degradation products. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (III) as active substance: • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · R | _N1 n-Α _{| Ν} 2-Pr _{||| 4} (lil) R ||| 3 wherein Run is selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cyclo aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OXm-i, wherein Xnn is selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkenyl; , substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, silyl, substituted and unsubstituted a substituted heterocyclic radical, an organic and inorganic base cation, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds, Rome and R 1 H 3 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl , substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen and OXM ₄ and OXM _3, wherein Xm ₄ and Xm ₃ is selected from the group consisting of hydrogen, from substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, silyl, substituted and unsubstituted heterocyclic radicals, cations of organic and inorganic bases, especially the first metal • 9 99 9 « 99 9 99 9 9 9 9 9 9 9 9 9 • 999 • 9 9 • • · • • 9 9 9 9 • 9 • • 9 · 99 9 * 99 99 99 second or third major groups of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids; and Aim and A 1 H, from which one or both may be omitted, are the same or different and represent an alkylene residue, an alkenylene residue, an oxo group, a hydroxy group or an oxo-hydroxyalkylene residue. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (IV) as active substance: Riv / O Biv-P-Riv R1V4 (iv) wherein _R1V1 and R1 _{V 2} are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted acyl cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OX | _V ia OX | _V2 , where X | _V1 and X, _V2 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, B | _V is selected from the group consisting of an ether group (IVA) -A 1 _V 1-OA | _V 2-C— (IVA) ** · t t t t t t t t ** ** ** IV IV ** ** ** ** ** 4 where A _tV i θ A | _In the second ^of which two and _IV can also be omitted, the same or different and are selected from the group consisting of alkylene radical, alkenylene radical and a hydroxyalkylene radical, a keto group (IVB) • A | V3 O II -C A | _V 4 (IVB) unsubstituted unsubstituted wherein A 1 _V3 and A | _V4 , one or both of which may be omitted, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, and 5- and 6-membered cyclic, especially heterocyclic compounds containing, in addition to carbon, as at least one heteroatom part of the ring, wherein the heteroatom is selected from the group consisting of oxygen and nitrogen, Riv 3 and R 11 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl of up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl , substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and cycloalkyl, substituted and unsubstituted heterocyclic radicals, halogen, OX | _V3 and OX | _V4, wherein X, X and _V 3 | _{V 4} may be the same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl of up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl of up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted aralkyl. unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of organic and inorganic bases, in particular metals of the first, second or third main groups of the periodic system, ammonium , substituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids and their pharmaceutically acceptable salts, esters and amides, and ester salts. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one phosphonic acid derivative of the general formula (V) as active substance: Bv-Avi — C-Av2 P — 0Xv3 (V) OH OXv4 where A _{V 1} and A _{V 2} , one or both of which may be omitted, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, and in particular the carbon chain -A _V i -CHOH -Av 2 consisting of 2 up to 5 carbon atoms, preferably 3-4 carbon atoms, B _v is selected from the group consisting of the remainder of formula (VA)? Ryl-C- (VA) wherein R and _V is selected from the group consisting of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic and halogen, from the radical of formula (VB) Rv ² Rys Ho-C-C- (UK) RV4 UH wherein R _V2, RV3, and RV4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted or unsubstituted heterocyclic, halogen, and is selected from the radical of formula (VC) (j) Rv5 Rve-c-C- (VC) i R V7 wherein R _V5 , Rv6 ^and Rz8 are the same or different and selected from the group consisting of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl , substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic and halogen, and wherein X ₃ or X ₄ may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, organic and inorganic base cations, in particular metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids and their pharmaceutically acceptable salts, esters and amides and ester salts. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (VI) as active substance: · · —Νι — Ρ - r _V | 3 (VI) Rvi 4 where R _V | 3 and RVI ₄ are identical or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals _V , halogen and OX, halogen, OX3, O3 and OX3; OX _V | 4 X _V | ₃ and X _V i4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl having up to 26 carbon atoms, substituted and unsubstituted hydroxyalkyl having up to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl of up to 26 carbon atoms, substituted and unsubstituted alkynyl of up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of the organic and inorganic bases, especially the first, second or second metal third major groups of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids; and B _V | is selected from the group consisting of (VIA) Rvi ¹ Avi Rvi2 and Groups (VIB) Rvi ¹ —N = Avi (VIB) wherein A _Vi is selected from the group consisting of alkylene amine, alkenylene amine, hydroxyalkyleneamine , alkyleneimine radical alkenyleniminový radical and hydroxyalkyleniminový residue wherein the nitrogen atom is located in the chain which connects the phosphorus atom with the nitrogen atom ^R V | i dm_ η \ Ι_ or ^N -, and ^r V | 2 ^/ wherein the RVU and R _V | ₂ in group (VIA) are the same or different and R _V to R _V | ₂ for group (VIA) and R _VM for group (VIB) are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted or unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic, halogen, OX _V to OX _V | ₂ wherein X and X _{Vi1 V} | ₂ may be the same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted acyl cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, or pharmaceutically acceptable salts, esters and amides, and ester salts thereof. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (VII) as active substance: 9 9 9 9 O Rvm — Avm — p — r _V ii3 (villa) ' RVII4 in which A _V ii is selected from the group consisting of (C 1-6 alkyl), which may have one or more double bonds and may be substituted with hydroxy, halogen, amino, branched or unbranched C 1-6 alkyl and C ₂ oxo groups _9-alkenyl, wherein C and C ^ galkylskupiny _9.2 -alkenyl may be substituted with hydrogen, hydroxyl, amino, halogen and oxo, and -CNC- -COC-, wherein the carbon atoms -C? C- and -CNC- may be substituted with alkyl of up to 7 carbon atoms or hydroxy, or wherein A _V h corresponds to the following formula (VIIA): Bvi | BVII3 BVII5 BVII7 BVII9 - CVII1- - CVI | 2 - I “CVI | 3— T CVII4 AND “CVII5- T (VIIA) Bvil2 BVII4 BVII6 BVI | 8 Bvil ¹⁰ wherein one or more carbon atoms selected from the group _C n ₃ C _V II4, Cviisspolu with their substituents may also be omitted and at least one existing substituents B, _V m to _V B C Mo _{third 8} -cycloalkyl- (C _{0th 9)} -alkyl, wherein the C as _{the third 8} cycloalkyl, and C _0-.g alkyl group may contain one or more double bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur, and wherein both the cycloalkyl group and the alkyl group may be substituted with hydroxy, halo amino, branched or unbranched C 1-6 alkyl, and C _{2 -} . ₉ -alkenyl, wherein C ^ g alkyl-C and _{the second The} alkenyl groups may be substituted with hydrogen, hydroxy, halo, amino and oxo groups, and the remaining existing substituents B _{VN 1} to B _V n ₁₀ are selected from the group consisting of hydrogen, hydroxy, halo, amino, C 1-4 -alkyl, C 1-4 -alkyl. ₂₆ alkoxy radicals, C _{1st 2} 6 -alkoxy-C ₁ _ ₂₆ -alkyl residues or both substituents on one carbon atom together form an oxo group, wherein each C ^^ - alkyl • • · · · · · · · · ··· • »· · · · ······ · · · · · · • · · · · · · »9 ··· ·· ····» £ ·· "residue and each C ₁ _ _26, an alkoxy radical may be branched or unbranched , saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halogen and oxo groups in which R (11 _{) is} selected from the group consisting of 5- and 6-membered heterocycles with one or two nitrogen, oxygen or sulfur atoms in the ring, wherein the heterocycle may be saturated or unsaturated with one or more double or triple bonds and may be substituted hydroxy, halo, amino, oxo groups with branched or unbranched C ^ galkylskupinami and C _2-9 -alkenyl, which C ^ -alkyl, and c _{2. The} alkenyl groups may be saturated or unsaturated with one or more double or triple bonds and may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups in which: R _V ii ₃ and R _V h 4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-4 -alkyl, hydroxy-C 1-4 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted acyl unsubstituted aralkyl, substituted and unsubstituted C _{1st 26} -alkenyl, substituted and unsubstituted C ^ ₂ ealkinylu, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic residue, halogen, OX _V OX and _V H3 || ₄ , wherein X vn 3 and X _v ii 4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-4 alkyl, substituted and unsubstituted hydroxy-C 1-4 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-4 alkenyl, substituted and unsubstituted C 1-4 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of the organic and inorganic bases, in particular metal of the first, second or third main groups of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids; and pharmaceutically acceptable salts, esters and amides, and ester salts thereof. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the formula (IIIa) as active substance: wherein the wavy line indicates a bond having either _a or β configuration, n is 0 or 1 in which R 6 is selected from the group consisting of substituted and unsubstituted G ₁ . _26- alkyl, hydroxy-C-. ₂ 6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C. ₂ 6 -alkenyl, substituted and unsubstituted C ^ ₂ qalkinylu, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OXviiih. whereas Xviiih selected from the group consisting of hydrogen, substituted and unsubstituted C ^ -alkyl, substituted and unsubstituted hydroxy-C ·,. ^ Alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted-C ₂₆ -alkenyl i_ , substituted and unsubstituted C 1-8. _26- alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, organic and inorganic base cations, in particular metal of the first, second or third main groups of the Periodic System, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids and R iim is selected from the group consisting of C 1-6 -alkyl residues, C ₂ . ₂ 4-alkenyl radicals, c _{2. 24} -alcapolyene residues containing 2 to 6 double bonds, C ₂ . ₂₄ alkynyl residues, C ₃ . ₈ -cycloalkyl radicals, C ^ g-cycloalkyl-C ^^ - alkyl radicals and C ₁ _ ₁₂ alkoxy-C _{first 12} -alkyl radicals, Rvni2. R 11i 3 ^and R 11i 4 are each independently selected from the group consisting of hydrogen, halogen, amino, acetylamino, azido, and XRVu 6, wherein X is O or S and RVni 6 ^is selected ^{from the} group consisting of hydrogen, branched or unbranched C 1-4 alkyl radicals and C ₂ _ ₄ -alkenyl radicals, wherein each C-alkyl radicals, as well as c _{2. The 4-} alkenyl radicals may be optionally substituted by hydrogen, amino, halogen or oxo-, or Rviii2. Rviii3 ^and Rvni4 together with the respective geminal hydrogen group give an oxo group, J ^e Rviii5 selected from the group consisting of hydrogen, C ^ -alkyl groups, C _{3rd 8-} cycloalkyl, Ar / C 1-6 -alkyl, aryl, acyl, heterocyclic, halogen, all of which may be branched or unbranched and may optionally be substituted by hydroxy, amino, halogen or oxo- and may be contain 2-6 double and triple bonds, or R _V iii ₅ is a phenyl moiety of formula VIIIA or VIIIB, wherein R ₇ and _V iii Rviiis are the same or different and bonded to two arbitrary positions of the phenyl ring and are each independently selected from the group consisting of hydrogen, halogen, C ^ -alkyl radicals, C ^ -alkoxy radicals, radical formyl, acetyl, propionyl or butyryl residue formyloxy, acetoxy, propionyloxy, butyryloxy, c _{2. 5-} alkoxycarbonyl radicals, all of which may be branched or unbranched, or Rviuz ^θ Rvuie may together form an alkylene chain of 3 to 4 carbon atoms, which is bonded to adjacent positions, e.g. 2,3-positions or 3,4-positions of phenyl ring, or R _V θ ni7 IRST methylendioxyzbytek together form a 1,1-ethylidenedioxy-residue or a 1,2-ethylenedioxy residue, which are bonded at the 2,3- or 3,4-positions of the phenyl ring, or R _{VI 1.5} is selected from the group consisting of R _V mg COOCH R _V - and R _V , O O O COOCH R _at " ₁₁₀ ", wherein R _V iii ₉ is selected from the group consisting of C ₁ -C 5. _6- alkyl residues, C ₂ . ₆ alkenyl radicals, c _{2. 6-} alkynyl residues, C ₃ . ₈ -cycloalkyl residues, C ₃ . ₈ cycloalkyl-C 1-6 alkyl radicals and C ₁ . ₆ -alkoxy-C _{first 6-} alkyl radicals, all radicals being branched or unbranched and optionally substituted by hydroxy, amino, halogen or oxo- and Rvimo J ^e Ci.4 branched or unbranched alkyl radical, and wherein R _in configuration III ₂ Rvni3, ^and Rviiw RviiisOOCPO (OH) OCH2 in (VIII), when n is 1, are independently D-gluco, L D-galacto, L-galacto, D-manno, L-manno, D-talo, L-talo, D-allo, L-allo, D-altro, L-altro, D-gulo, L-gulo, D- ido or L-ido, or the configurations of Rvw2> RviH3 ^and Rvni5OOCPO (OH) OCH2- in (VIIIa) are independently D-ribo, L-ribo, D-arabino, L-arabino, D-xylo, L-xylo, D -lyxo, L-lyxo when n is 0. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (IX) as active substance: whereas R, _X1 is selected from the group consisting of substituted and unsubstituted C ^^ - alkyl, _hydroxy-C1 _26 ^_a lkylu, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted C ^ g- alkenyl, substituted and unsubstituted C ₁ _ ₂₆ -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OX | _X11 , whereby X, _X11 is selected from the group consisting of hydrogen, substituted and unsubstituted C ^ -alkyl, substituted and unsubstituted hydroxy-C ₁ _26alkylu, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C ₁ _ ₂₆ -alkenyl, »4 4 4 4 4 4 φ 4 4 φ 4 4 4 φ φ 4 4 4 4 4 4 4 4 φ »substituted and unsubstituted C ₁ _ ₂₆ -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, a cation of organic and inorganic base, in particular the metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds, which are derived from ethylenediamine or amino acids, wherein: Rix 1 and Rix 2 are now independently selected from the group consisting of Ο ·). ₂₄ alkyl radicals, C ₃ . ₈ -cycloalkyl residues, C ₃ . ₈ -cycloalkyl-C ₁ _ ₂₄ alkyl radicals, C ₁ _ ₂₄ -alkoxyiových radicals, C ₁ _ ₂₄ -alkylthio radicals, C. ^ - alkoxy-C ^^ - alkyl radicals, C ^ C ^ -alkylthio - alkyl radicals, acyl radicals, aryl radicals, aralkyl radicals, heterocyclic radicals, halogen and hydrogen, and any C ^ alkyl, and C., _ ₂₄ an alkoxy radical may be branched or unbranched and saturated or unsaturated with 2 to 6 double bonds, and optionally it may be substituted by hydroxy-, amino-, mercapto-, halogen-, oxo- or C- groups. ₂₄ alkoxy radicals, C 1-6 -alkylcarbonyloxy radicals, C 1-6 -alkoxycarbonyloxy radicals, C 1-6 -alkoxycarbonyloxy radicals, C 1-6 -alkoxycarbonyloxy radicals, C 1-6 -alkoxycarbonyloxy radicals; ₂₄ -alkylthio radicals, C ^ -alkylkarbonylthio radicals, C ^ -alkylaminovými radicals, di (Ci. ₂₄ alkyl) amino ^N ° vými radicals, C ^ -alkylkarbonylaminovými radicals, C-i ^ -alkyHC. _24- alkylcarbonyl) amino radicals, C ₁ . ₂₄ -alkoxycarbonylamino residues or nebo ·). _The alkyl moiety is an alkyl (C 1 -C ₂₄ -alkoxycarbonyl) amino radical, each aralkyl radical, a heterocyclic radical, a C 1-4 alkyl radical and a C 1-6 alkyl radical. _{The 24-} alkoxy radical may be branched or unbranched, saturated or unsaturated with 2 to 6 double or triple bonds, or wherein R 1 is C 1-6 -alkyloxy; _{X 1} -CH-CH-R 1 _{X 2} forms part of a C ₄ -C ₈ -carbon ring which may be optionally substituted by hydroxy-, mercapto-, amino-, halogen-, oxo or C 1-6 -alkyl radicals, C 1-6 -alkoxy radicals, C 1-6 -alkylthio-radicals, · C,. ^ alkylamino radicals, di (C. ₂₄ -alkyl) amino radicals, C., _ 2 ₄ -alkylkarbonylovými radicals C · ^ alkylcarbonyloxy radicals, C - ^ - alkoxycarbonyloxy radicals, C - ^ - alkylkarbonylthiozbytky or Ci. _24- alkylcarbonylamino radicals, wherein each C 1-6 alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 double bonds, or wherein R 10 _{X 10} is a branched or unbranched C _1-4 alkyl radical, and wherein: R 1 _X -CH-CH-R 1 _{X 2} forms part of the furanose or pyranose ring of a sugar, e.g. D-ribose, D-arabinose, D-xylose, D-lyxose, D-glucose, D-galactose, D-mannose, D-talose, D-allose, D-altrose , D-gulose, D-idose, or the corresponding L-isomers, said hydroxyl group may optionally be substituted by residues respectively hydrogen, amino, azido, oxo, mercapto, C, or _{the first 2} 4-alkoxy radicals, C₁₋₄ alkylthio radicals, C ₁ _ ₂ 4-alkylamino radicals, di- (C- |. ₂₄ -alkyl) amino radicals Ο · ,. _{24-alkylcarbonyloxy} radicals, C ^ -alkylkarbonylthio radicals, C - ^ - alkylkarbonylaminozbytky, _C1 _24-alkyl (C _1.24 alkylcarbonyl) amino radicals, wherein each C - ^ - alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 double bonds, and their pharmaceutically acceptable salts, esters and amides, and ester salts, as well as their optical isomers. Rix1 and Rix2 may in each case be independently selected, in particular, from the group consisting of carboxyl radicals, carboxamide radicals, aryl radicals, aryloxycarbonyl radicals, aryl-C1 -C4 -alkyl radicals, C1 -C4 -alkoxycarbonyloxy radicals, C1 -C4 -alkylaminocarbonyl radicals, C1-4 radicals; C 1-6 -alkylaminocarbonyl radicals, aryl-C 1-4 alkoxycarbonyl radicals, aryl-C 1-4 alkylaminocarbonyl radicals; ₂₄ alkylcarbonyloxy (C ₄₎ alkylmethoxykarbonylové residues -alkoxykarbonyloxymethoxykarbonylové C ₂₄ radicals, C ^^ - alkoxycarbonyloxy IC -alkylJmethoxykarbonylové radicals, wherein each C-alkyl radical may be branched or unbranched, saturated or unsaturated with 2 to 6 double bonds, and each C 1-4 -alkyl radical and the C 1-4 -alkoxy radical may be branched or unbranched and saturated or unsaturated and each aryl radical of formula IXA wherein: Rix3 Rix4 and are the same or different and each are independently selected from the group consisting of hydrogen, halogen, C _{1st 4-} alkyl radicals, C ₁ . ₄ -aikoxylové radicals radical formyl, acetyl, propionyl or butyryl residue formyloxy, acetoxy, propionyloxy, butyryloxy, C _{1st 4-} alkoxycarbonyl radicals, all of which may be branched or unbranched, or R1 | _{X 3} and R 4, _{X 4} taken together can form an unbranched, saturated C 3 -C 4 alkylene chain that is bonded to adjacent positions of the phenyl ring, or R, _X 3, and R 4; _{X 4} together form a methylenedioxy radical, 1,1-ethylenedenedioxy radical or 1,2-ethylenedioxy radical which are bonded to adjacent positions of the phenyl ring. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (X) as active substance: Rxi in which R _X1 is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-4 -alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted C 1-8 -alkyl. unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen and ΟΧχι, wherein: X _{x 1} is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-4 -alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted C 1-8 -alkyl. unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals in which R 1 is selected from the group consisting of C 1-6 alkyl radicals, C 1-6 alkoxy radicals, C ₁ . 26 ^- _{alkoxy-C1-.26} alkyl radicals, C _{3rd 8} -cycloalkyl- (C _{0th 2} 6) alkyl radicals, wherein one or two carbon atoms the cycloalkyl radicals may be replaced by nitrogen, oxygen or sulfur, each C _{3rd 26} -al keel residue and each C ₃ . _26, an alkoxy radical may be branched and unbranched and each a C ₃ _ ₈ cycloalkyl radical, each C _{2 '26} -alkyl residue and each C ₂ _ _26, an alkoxy group may be saturated or unsaturated with one or more double bonds and each _C3 . _{An 8-} cycloalkyl radical, each C ₁ . _{The 26-} alkyl radical and each C 1-6 -alkoxy radical may be substituted by hydroxy, amino, halogen and oxo- or carbyl groups COR _{X 3} , pQ · · 444 4 4 · OO 444 · 4 4 4 4 44 4 · 444 in which R _{X 3} is selected from the group consisting of substituted and unsubstituted C 1-4 -alkyl, hydroxy-C 1-4 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted acyl unsubstituted aralkyl, substituted and unsubstituted C _{1st 26-} alkenyl, substituted and unsubstituted C1-6alkyl; ₂₆ alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OX _X3, wherein _X3, X is selected from the group consisting of hydrogen, substituted and unsubstituted C ^ -alkyl, substituted and unsubstituted hydroxy-C ·,. ^ alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-4 alkenyl, substituted and unsubstituted C 1-4 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, organic and inorganic metal cations the first, second or third main groups of the periodic system, ammonium, substituted ammonium, and ammonium compounds that are derived from ethylene amine or amino acids. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (XI) as active substance: RX | 1-ΖΧΙ-Αχί-P-Rx | 3 (xi) » R x 12 i _x 4 in which Z _x is a phosphorus atom or a sulfur atom in which A _X) is an unbranched C ₂ chain. ₉ is -alkylene substituents which may the same or different and are selected from the group consisting of hydrogen, hydroxy, halo, amino and oxo, 0 ^ 26 alkyl radicals, _C-26 alkoxy radicals, C _{1st 26} -alkoxy ^and C ₁ _26- lkylových radicals or C ₃ _ ₈ cycloalkyl (C ₀ _ ₉₎ alkyl groups, wherein each C ^^ -alkyl radical and each C- |. _{The 26-} alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy-, amino-, halogen- and oxo-groups and as C ₃ . ₈ -cycloalkyl and C ₀ _ ₉ alkyl group of C ₃ _ ₈ -cykloalkyl84 • • · · · · • • ···· ·· · * · (C _{0th 9)} -Alkyl groups may comprise one or more double bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms and wherein both the cycloalkyl group and the alkyl group may be substituted by hydroxy-, halo-, amino- and oxo-groups with branched or unbranched C 1-6 -alkyl and C ₂ . _9- alkenyl, wherein C-1.9alkyl and C ₂ . _{The 9-} alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo groups in which R _1h and R ₁ , ₂ are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 g. -alkyl, substituted and unsubstituted hydroxy-C 1-8 -alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, ΟΧ _Χ η and OX _X | ₂ , wherein X _X to X _X | ₂ are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-8 -alkyl, substituted and unsubstituted C 1-8 -alkenyl, substituted and unsubstituted C 1-8 -alkyl; C 1-8 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals in which R _x , ₃ and R _X | ₄ are the same or different and are selected from the group consisting of substituted and unsubstituted C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-6 "26- ^{and an} LK yl, substituted and unsubstituted C ^ alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic residue, halogen, OX _X | ₃ and OX _X | _4, wherein X _x, X ₃ and _{X 4} may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C _{1st 26-} alkyl, substituted and unsubstituted hydroxy-C 1-4 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-8. ₂₆ -alkenyl, substituted and unsubstituted C _{1st 2S-} alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, organic and inorganic base cations, in particular metal of the first, second or third main groups of the Periodic System, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids , and their pharmaceutically acceptable salts, esters and amides, and ester salts. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (XII) as active substance; jj> fj ^ XII ³ Axn-C-N-O — Rxi | 3 (XII) 'where AXN is selected from the group consisting of hydrogen, substituted and unsubstituted C ^ -afkylových radicals, substituted and unsubstituted alkoxy- (Co _"28) -alkyl, substituted and unsubstituted cycloalkyl- (C ₀ .2 ₈₎ alkyl groups, substituted and cykloalkoxy- unsubstituted (C ₀ _ ₂₈₎ -alkyl, substituted and unsubstituted amino- (Co. ₂₈₎ -alkyl, substituted and unsubstituted thio- (C _{0. 28)} alkyl and substituted or unsubstituted acyl (C _{0. 28)} -alkyl radicals and halogen, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical, each acyl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of cycloalkyl groups may be replaced by nitrogen, oxygen sulfur or sulfur, _X R II ₃ ΐθ selected from the group consisting of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted alkoxy- _{(C0. 26)} alkyl, substituted and unsubstituted C3. ₁₄ -cycloalkyl- ₍₂ Co .. 6) -alkyl, substituted and unsubstituted cykloalkoxy- ₍₀ _ C ₂₆₎ -alkyl, substituted and unsubstituted amino- (C _{2 0} .. 6) -alkyl, substituted and unsubstituted silyl- ( C ₀ .26) -alkyl and substituted and unsubstituted thio- (C _{0th 26)} -alkyl, wherein each alkyl radical and each alkoxy radical can be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, or the carbon chain of the two C atoms in A _XN with R _XN3 forms a ring by forming an isoxazolidone ring, and R II _{X 4} is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted acyl radicals, and substituted and unsubstituted cycloalkyl- (C _{0 2} _ 6) alkyl, wherein each alkyl radical and each acyl radical may be branched or unbranched and each alkyl radical, each acyl radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (XIII) as active substance: wherein n is an integer from 0 to 4, and wherein ^R xim, ^R xiii2i, ^r xiii3. ^{r r} xiii4- xiiis XIIIa and ^R same or different and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted and unsubstituted acyl radicals, substituted and unsubstituted cycloalkyl- (C _{0th (26} ) -alkyl radicals, substituted and unsubstituted cycloalkyl (Co-26) -alkoxy radicals and halogen, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each acyl radical, each alkoxy radical and each cycloalkyl- (C _{0 26} ) -alkyl group may be saturated or unsaturated with one or more double or triple bonds, and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms. Combination preparation according to one of Claims 1 to 6, characterized in that it contains at least one compound of the general formula (XIV) as active substance: where Y _X | _V is C ^ -alkenylene which is substituted by substituents R and R _{X XiV1} IV2 3 optional substituents R _X | _V3 to R _X | _V 4, where Rxivi to Rxivgjsou same or different and selected from the group consisting of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl- (C _{0th 26)} -alkyl, substituted and unsubstituted cykloalkoxy- _(C0 _ ₂₆₎ -alkyl, substituted and unsubstituted alkoxy- (C ₀ _ ₂₆₎ -alkyl, substituted and unsubstituted amino groups and substituted and unsubstituted thio- (C ₀ _ ₂₆₎ -alkyl, substituted and unsubstituted sulfonyl- (C _{0th 26)} -alkyl, substituted and unsubstituted sulfinyl- (C _{0th 2} 6) -alkyl and substituted and unsubstituted acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double not or triple bonds and one or two carbon atoms of cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, and R xivi3 ^and R _X ivi4 are defined as R _{X1 In} 1 to Rxive. or together form an oxo group, wherein Z _x , _v is a phosphororganic group · <♦ · · · · · · · · · · · · · · · · · · · ··· ΐ -Ρ-Rxiv9 Rxivio where R _X | _GA Rxivio are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted (C _{R 26)} alkyl, substituted and unsubstituted hydroxy (C _{R 26)} alkyl, substituted and unsubstituted cycloalkyl- (Co. ₂ 6) -alkyl , substituted and unsubstituted acyl, halogen, OX _{X 1 In} g or OX _X | _V io. wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, wherein Χ _χ , _ν9 or X _x) vio may be the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted (C 1 -C ₂₆ ) -alkyl substituted and unsubstituted hydroxy- (C- | - ₂₆₎ -alkyl, substituted and unsubstituted cycloalkyl- (C ₀ .26) -alkyl, substituted and unsubstituted acyl, silyl, a cation of organic and inorganic base, in particular the metal of the first, second or third main group a periodic system, ammonium, substituted ammonium and ammonium compounds which are o each of the alkyl radicals, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, or wherein Z _X | _V is the amino group -N-Rxivii Where R _{X1 V} to R _X | _At 12 are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl- (C ₀ _ ₂₆₎ -alkyl radicals, substituted and • · ·· ·· · • * · · · · W · · · «· * * * * w w w w w * * * * w w w w w w w w w ··· cykloalkoxy- unsubstituted (C ₀ .26) -alkyl, substituted and unsubstituted alkoxy- (C _{0th 2} 6) alkyl and substituted or unsubstituted acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur, wherein Βχιν is selected from the group consisting of substituted and unsubstituted C ₁ .26 ^_a lkenylenové groups, wherein one C atom may be replaced by an oxygen atom and one C-atom by a sulfur atom, or two C atoms may be replaced by each and Sheterocyklem the alkenylene moiety may be branched or unbranched and saturated or unsaturated with one or more double or triple bonds and substituted with one or more hydroxy, halogen or oxo groups. Use of the combination preparations according to any one of the preceding claims for the therapeutic and prophylactic treatment of infectious processes in humans, animals and plants and as herbicides in plants. Use according to claim 21, characterized in that the infectious processes are caused by unicellular or multicellular parasites, fungi, bacteria or viruses. Use according to claim 21 or claim 22, characterized in that it is an infection process in humans or animals.