SK19612000A3 - COMBINED PREPARATION OF ANTI-INFECTIOUSLY ACTIVE COMPOUNDS WHICHì (54) INHIBIT THE 2-C-METHYLERYTHROSE-4 METABOLIC PATHWAY, ANDì (54) INHIBITORS OF LIPID METABOLISM - Google Patents

Abstract

The invention relates to a combined preparation which, as an active ingredient, contains at least one anti-infectiously active compound that inhibits the 2-C-methylerythrose-4 metabolic pathway, and which contains at least one lipid metabolism inhibitor. The combined preparation is used in infectious processes, especially in infections in humans and animals and as a herbicide in plants. It is shown that the build-up of resistance against the inventive combined preparation is largely reduced compared to the build-up of resistance against the individual components.

Description

Technical field

The invention relates to a combination preparation of anti-infectious compounds which inhibit the metabolic pathway of 2-C-methylerythrose-4 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 as well as their use as herbicides. The fat metabolism inhibitors of the present invention are particularly useful for the therapeutic and prophylactic treatment of infections with single-cell or multi-cell parasites, fungi, bacteria or viruses, but also as herbicides.

BACKGROUND OF THE INVENTION

The suitability of various organophosphorus compounds as well as their esters and salts of pharmaceutical compositions is already known. 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). Other substances of these groups 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 algicides (U.S. Pat. No. 3,887,353), plant growth regulators. 127,401, 4,120,668, 3,961,934, 4,431,438, 3,853,530, 4,205,977, 4,025,332, 3,894,861) and as pigments production reagents (US 4,051,175) .

The use of, for example, aminohydrocarbylphosphonic acid derivatives in controlling bacterial infections has proved to be very complicated. Many of the bacteria that are responsible for outpatient infections and infections acquired during the clinical stay are not susceptible to therapy with this group. This includes bacteria of the genus Staphylococcus, in particular the species Staphylococcus aureus. This skin bacterium poses a threat to patients who are hospitalized in clinics. Other studies, including the phase IIa study of the Applicant of DE 27 33 658, have shown a very rapid generation of resistance to originally susceptible bacteria. Therefore, these derivatives have not been used in clinical practice.

Bisphosphonic acid (DE 3 61 1 522), their efficacy in calcium and phosphate metabolism disorders (DE 2 534 390, DE 2 534 391, DE 3 334 211, DE 3 434 667, DE 2 745 083), cytostatic activity (DE No. 3,425,812), their lipid lowering activity (Arzneimittelforschung, 43, 759-62) and their ability to stimulate immune responses of cells (WO 97/38 696).

Antimicrobial activity against bacteria and v

for phoscarnetic activity against viruses. In addition, the potency of fosamine-ammonium 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 administered to reduce the risk of cardiac and vascular disease caused by hyperlipidemia. The pharmacotherapy of these hyperlipidemias generally consists in regulating the intake and regulating the synthesis of fats or, in particular, cholesterol. In general, cholesterol synthesis is controlled by the enzyme β-hydroxymethylglutaryl-CoAreductase (HMG-CoA-Reductase). The actual synthesis of cholesterol is usually greater than food intake. [Berthold HK, von Bregmann K, Dtsch. Med. Wochenschr. 121, p. 729 (1996); Richter W.O., Fortschr. med. 114, p.177, 193],

Anionic exchangers and β-sitosterol are known to control intestinal fat intake. Ion exchangers include cholestyramine and colestipol. They absorb bile acids and thereby interrupt enterohepatic re-transport and thereby cause a significant increase in stool sterols, β-sitosterol is a plant sterol,

tours related to cholesterol. It suppresses the absorption of cholesterol from food in the intestinal mucosa.

Furthermore, nicotinic acids and their derivatives, clofibrates and their derivatives, and probucol have found their use in regulating fat metabolism or preventing subsequent diseases of hyperlipidemia. 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. Also, the mechanism of action of probucol is 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

938, US 43 75 475, US 43 46 227, US 44 106 29, US 44 447 84, US 4450

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, U.S. Pat. No. 46 45 858, U.S. Pat. No. 52 36 946, U.S. Pat. No. 55 06 262, U.S. Pat

U.S. Pat. No. 25,017, U.S. Pat. No. 48 47 271, U.S. Pat. No. 46 22 338, U.S. Pat. No. 49 04 646, U.S. Pat. No. 48 73 345, U.S. Pat

971, US 52 60 305, US 52 02 327, US 49 40 727, US 52 72 166, US 5385

932, US 54 61 039, US 55 56 990, US 55 61 143, US 55 63 128), squalene synthetase inhibitors, especially pyrophosphates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethylphosphonic acid derivatives, phosphinylformyl derivatives, phosphonocarboxy derivatives, acid derivatives phosphonosulfone, which are also partly known as pharmaceutical and cosmetic agents in the regulation of calcium and phosphate metabolism (DE 25 34 390, DE 25 34 391, DE 33 34 21 1, DE 34 34 667, DE 27 45 083, US 52 12 814 US 52 54 544, US 54 70 845, US 50 25 003, US 55 34 532, US 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 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 elucidated. HMG-CoA reductase inhibitors competitively inhibit the enzyme that determines the rate of cholesterol synthesis, HMG-CoA reductase. They have up to 20,000 times the a4 ·· ···· enzyme finite 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, precursor of dolichol and ubiquinone, an orginate. Bacteria, fungi and parasites that possess HMG-CoAreductase produce isopentenyl diphosphates via an acetate / mevalonate pathway that is inhibited by HMG-CoA reductase inhibitors.

The first inhibitors discovered were isolated from the fungi Penicillium (mevastatin) and Aspergillus (lovastatin). Modification of the side chain led to simvastatin, a further development from mevastatin to pravastatin. Meanwhile, a fully synthetic enzyme inhibitor (fluvastatin), a mevalone lactone derivative of the fluorophenyl substituted indole ring, has become available.

There have been efforts in the past to use these substances to control infectious diseases. In particular, attempts have been made to inhibit the growth of plants, fungi, parasites, bacteria and viruses by the use of HMGCoA inhibitors. HMG-CoA synthetase and HMG-CoA reductase inhibitors inhibit the acetate / mevalonate pathway in many bacteria, fungi, and parasites (US 50 26 554, US 50 64 856, US 49 20 111, US 49 20 113). Of course, many bacteria, such as Escherichia coli, show no inhibition by the HMG-CoA reductase inhibitor. This is probably because these bacteria have an alternative pathway for metabolism. Indeed, the absence of an acetate / mevalonate metabolic pathway and the existence of another metabolic pathway have been demonstrated in Escherichia coli [Rohmer M. et al., Biochem. J., 295, p. 517 (1993); Lois E. M. et al., Proc. Natl. Acad. Sci. USA, 95, p. 2105 (1998)].

To date, no alternative metabolic pathway has been known for parasites. However, the Applicant has been able to demonstrate an alternative metabolic pathway for parasites, the so-called 1-deoxyxylulose-5-phosphate or 2-C-methylerythrose-4-phosphate pathway. Studies with HMG-CoA reductase inhibitors on parasites gave different results depending on the parasites. For example, with high doses of lovastatin, no killing of schistosomiasis agents is achieved, while malaria agents are killed in vitro but not in vivo. Similarly, agents of sleeping sickness cannot be completely inhibited by HMG-CoA reductase inhibitors. Similar attempts to suppress the proliferation of viruses show that virus-infected cells lose the inhibitory 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. Similarly, toxoplasmosis experiments did not give any satisfactory results. Furthermore, squalene monooxygenase inhibitors have also been developed as fungicides (US 47 82 059).

SUMMARY OF THE INVENTION

SUMMARY OF THE INVENTION It is therefore an object of the present 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.

Combinations of anti-infectious compounds that inhibit the 2-C-methylerythrose-4 metabolic pathway with fat synthesis inhibitors, particularly cholesterol synthesis, particularly HMG-CoA reductase and squalene synthetase inhibitors, have been found to increase the breadth and effectiveness of therapy and prophylaxis of infections. . Surprisingly, the combination exhibits a strong reduction in the resistance to the deployed compounds, which is generally the greatest problem in the use of a group of fat metabolism inhibitor compounds.

Combined preparations of anti-infectious compounds that inhibit the metabolic pathway of 2-C-methylerythrose-4 and fat metabolism inhibitors are useful for the therapeutic and prophylactic treatment of infections in plants and especially 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 that inhibits the 2-methylerythrose-4 metabolic pathway and / or its ester and / or salts thereof. This generally includes pharmaceutically acceptable salts, esters, salts of such an ester, or compounds which upon application provide the compounds of the invention as metabolism or degradation products, also called precursors.

Substance families which, 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 participate in the 2-Cyclylerythrose-4 pathway or derivatives thereof are contacted with the active compounds of interest and those which 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:

And N?

R | 2

wherein R 11 and R 12 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, substituted and unsubstituted aralkyl, and substituted and unsubstituted heterocyclic Rest,

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. Substituted hydroxyalkyl of 1 to 26 carbon atoms, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or 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, halogen, X13 and X14,

X 13 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 or 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 first, second or third main metal 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 1A:

(IA) wherein one or more carbon atoms selected from C13, C14, C15, together with their substituents, may also be absent and at least one of the existing substituents B1 to B10 is C3-8-cycloalkyl- (C0-9) -alkyl using as a _C3-.8 cycloalkyl group as well (-9 C ₀₎ alkyl can have one ··· ·· or more double bonds and one or two carbon atoms of the cycloalkyl groups may be replaced with N, O or S, and wherein such cycloalkyl as well as alkyl may be substituted with hydroxy, halogen, amino, branched and unbranched oxo groups of C 1-9 -alkyl and C 2-9 -alkenyl, wherein the C 1-9 -alkyl and C 2-9 -alkenyl groups may be substituted by hydrogen, hydroxy , amino, halogen and oxo and the remaining existing substituents Bn to Bno are selected from the group consisting of hydrogen, hydroxy, halogen, amino, C 1-6 -alkyl radicals, C 1-6 alkoxy radicals , C 1-6 -alkoxy-C 1-6 -alkyl radicals or both substituents on one C-atom together form an oxo group, wherein each C 1-6 -alkyl group is an oxo group. _The 2-6-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 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 antiinfective-acting compound.

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

Preferably, R 11 is OX 11, R 13 is O 14, and R 14 is O 14, 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 an unsubstituted heterocyclic radical and R 12, X 13, X 14 and A 1 have the same meaning as in formula I.

Preferably, the carbon chain A 1 consists of three carbon atoms.

Also preferred are compounds in which the carbon chain A 1 in the formula

IA consists of four carbon atoms Cn, C12, C13, C14 and B17 or Big or both are hydroxy. In this case, methylene groups are also preferred for R 13 and R ₁₄ .

······························································································ · ··· ·· ···· ·· ·· ·· ··· in

It is further preferred that Bn and B12 together form an oxo group. In this case, the carbon chain in Ai consists of four carbon atoms Ch, C12, C13, C14.

It is further preferred that Bp and Bis together form an oxo group. In this case, the carbon chain in Ai also consists of four carbon atoms Cn, C12, C13, C14.

The carbon chain is preferably formed with 5 carbon atoms Cn, C12,

C13, C14, C15, wherein Bn and B12 together form an oxo group and at least one substituent of B19 or Bno is hydroxy or B19 and Bno together form an oxo group, respectively.

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

—R | 3 (ib) o

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

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

·· ·· ·· ····

·· ···· • · · • · · · ·· ·· where

And X112, Xii3, X114, 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, and substituted and unsubstituted heterocyclic radicals. , the metals of the first main groups 1, 2 and 3 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 absent, may be selected from the group consisting of alkylene, alkenylene and hydroxyalkylene,

R 11i, R 112 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 radical and -SR113, C1 and -NR113R114, wherein

R113, R11 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 and their pharmaceutically acceptable salts, esters, as well as ester salts or compounds which when administered form the compounds to be administered as metabolism or degradation products.

Particularly preferred are bisphosphonic acid derivatives of formula II, wherein βπ, X112, X113, X114, 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, and substituted and unsubstituted heterocyclic radicals, metals of the first main group 1, 2, and 3 of the periodic system ············ As Na, K, substituted and unsubstituted ammonium and ammonium compounds which are derived from ethylenediamine; or amino acids,

Au, which may also be absent, is selected from the group consisting of alkyl, (CH ₂ ) 0-6, especially (CH ₂ ) 1-5, and amidino,

R 11 is selected from the group consisting of H, OH, NH ₂ , -CH 3 and

R 12 is selected from the group consisting of -NH ₂ ,

(2) 4-CH ₃

Particularly preferred are bisphosphonates selected from the group consisting of amino-hydroxymethylidene-bisphosphonic acid, 2-amino-1-hydroxyethylidene-1,1-bisphosphonic acid, 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid, acid 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid, 6-amino-1-hydroxyhexylylidene-1,1-bisphosphonic acid, amidinomethylenebisphosphonic acid, 3-methylpenthylamino-1-hydroxypropylidene-1,1bisphosphonic acid, 2- ( 3-pyridinyl) -1-hydroxy-ethylidene-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 antiinfective compound is a bisphosphonic acid derivative, no bisphosphonic acid derivative is a metabolic inhibitor.

III. Combined preparations of fat metabolism inhibitors with organophosphorus compounds containing a keto group

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

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

The following compounds of the invention correspond to formula III:

^R II | 1 Α _{ν | 1} i ---- Α _{| Μ} 2 ---- '---- R _{||| 4} (m). R ||| 3 in which

Rome 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 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 alkenyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkenyl; substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, silyl, substituted and an unsubstituted 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,

R 14 and R 14 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 and unsubstituted cycloalkyl, substituted and unsubstituted-13; - - - - - - - - - - - - - - - - - Aralkyl, substituted and unsubstituted heterocyclic radical, halogen, and OX114 and OX1113, wherein X1114 and X1113 are selected from the group consisting of < RTI ID = 0.0 > which consists of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted an cycloalkyl, silyl, substituted and unsubstituted 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 derived from ethylenediamine or amino acids, and

Anii and A1112, one or both of which may be absent, are the same or different and represent an alkylene moiety, an alkenylene moiety, an oxo group, a hydroxy group or an oxo-hydroxyalkylene moiety, wherein Aim is preferably absent.

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

The phosphonic acid derivatives according to the invention have proved to be particularly suitable. In this case, Rnuje 0Xni4 and Rhi the 0Xni3 _3, the R1111, X1114, X1113, Aim and Am ₂ are as defined in formula (III).

Particularly preferred phosphonic acid derivatives are chloroacetylphosphonic acid (phosphonochloro), phosphonomic acid (foscarnet), phosphonoacetic acid, N, N-dimethyl (1-hydroxy-2-oxo-2-methoxyethyl) phosphonamide and 2-hydroxy-2-hydroxymethyl- 3-oxo-butylphosphonic (phosphonotrixin) and ammonium ethylcarbamoyl phosphonate (fosamin-ammonium).

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

The following compounds of the invention correspond to formula IV:

(IV) · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

wherein Riv 1 and Riv 2 are the same or different and 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 , substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen, OXivi and OXiv2, wherein Xivi and Xiv2 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted alkenyl; substituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals,

Biv is selected from the group consisting of ether group IVA (IVA)

Z wherein Ajvi and Aiv2, of which Aiv2 may also be absent, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene,

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

keto group IVB

--- A | ------ A V3 | V4 --- (IVB) where Aiv3 and AI _in 4 of them may be one or also both absent are the same or different and are selected from the group consisting of an alkylene radical, an alkenylene radical and a hydroxyalkylene radical, and a 5- and 6-membered cyclic, in particular heterocyclic, compounds which, in addition to carbon, contain at least one heteroatom as part of the ring, the heteroatom being selected from 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 XIV4 and XIV4 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 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 radical, silyl, the organic and cationic organic cation , the second or third major group 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.

Particularly preferred are compounds which correspond to formula IVC

---- OXix / 3 (ivc)

H ÔXiv4 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

Xiv 3 and Xiv 4 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 (without substituents). In particular, two carbon atoms are preferred.

Of the ether compounds, particularly preferred are 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) etenoxy] -methylphosphonic acid, [2- (N-acetyl-Nhydroxylamino) etenoxy] methylphosphonic acid disodium salt, [3- (N-formyl-Nhydroxylamino) -2-hydroxypropoxy] methyl disodium salt phosphonic acid, [3 (N-acetyl-N-hydroxylamino) -2-hydroxypropoxy] methylphosphonic acid disodium salt.

Further preferred are compounds that correspond to the formula IVD.

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

HO

IV3 --- C — AlV * - P — 0XIV3 (ivd)

R | V2

0XIV4 where

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

Ajv3 is selected from the group consisting of methylene, ethylene, ethenylene, hydroxymethylene, hydroxyethylene, 2-hydroxypropylene, Aiv4 may also be absent or methylene, and Xiv3 and Xiv4 are the same or different and are selected from the group consisting of metal first, second or a third major group of the periodic system, in particular sodium, potassium methyl and ethyl.

Preferably, the -Aivi-O-Aiv2- chain is comprised of two to four carbon atoms (not including substituents), 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-hydroxylamino) -1-oxoethylphosphonic acid, the disodium salt of the acid has proven to be particularly preferred. 3- (N-formyl-N-hydroxylamino) -1-oxopropylphosphonic acid, disodium salt of 3- (N-acetyl-N-hydroxylamino) -1-oxopropylphosphonic acid, disodium salt

3- (N-formyl-N-hydroxylamino) -1-oxo-2-propenylphosphonic acid, 3- (N-acetyl-N-hydroxylamino) -1-oxo-2-propenylphosphonic acid disodium, 4- (N) disodium salt -formyl-N-hydroxylamino) -1-oxo-3-hydroxybutylphosphonic acid, 4- (N-acetyl-N-hydroxylamino) -1-oxo-3-hydroxybutylphosphonic acid disodium salt, 3- (N-formyl-N) disodium salt -hydroxylamino) 2-oxopropylphosphonic acid, 3- (N-acetyl-N-hydroxylamino) -2-oxopropylphosphonic acid disodium salt, 4- (N-formyl-N-hydroxylamino) -3oxo-2-hydroxy-2-methylbutylphosphonic acid disodium salt , 4- (N-acetyl-N9) disodium salt

9999

9999 hydroxylamino) -3-oxo-2-hydroxy-2-methylpropylphosphonic acid, 4- (N-formyl-N-hydroxylamino) -3-oxo-2-hydroxy-2- (hydroxymethyl) -butylphosphonic acid disodium salt and disodium 4- (N-acetyl-N-hydroxylamino) -3-oxo-2-hydroxy-2- (hydroxymethyl) -propylphosphonic acid salt.

For cyclic compounds, the amino group and the phosphorus atom can be bonded to any C-ring atoms. However, compounds in which they are bonded at two atoms which are separated only by another atom are preferred. In heterocyclic compounds, the two atoms are most preferably separated by a heteroatom.

The following compounds are particularly preferred:

(IVF)

(IVH)

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

S-R | V3 (VIIE)

V. Combined preparations of fat metabolism inhibitors with organophosphorus compounds containing at least one hydroxyl group

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

bv

Avi-C --- A \ / 2

OH

--Ϊ-OXV3

OXV4 (V) where

Aiv 3 and Au, of which one or both may be absent, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, and in particular carbon chain -Avi-CHOHAv2- consisting of 2 to 5 carbon atoms , most preferably from 3 to 4 carbon atoms.

Bv is selected from the group consisting of VA

wherein Rvi 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 and unsubstituted aralkyl, substituted or unsubstituted heterocyclic radical and halogen, radical of formula VB

R 1/2 Rv3

HO - C - C--

(VB) wherein Rv2, 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 and unsubstituted heterocyclic and halogen, and the radical of formula VC

(VC) wherein R vs, R v and R v7 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, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted or unsubstituted heterocyclic radical and halogen, and wherein Xv3 or Xv4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted 21;

Unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of the organic and inorganic bases, in particular the 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.

Rvi in formula VA is primarily methyl.

In formula VB are preferably Rv and Rv ₂ H ₄ Rv3 a methyl group.

In the formula VC, in particular, R8 is methyl, Rve is selected from the group consisting of H, OH and methyl, and R11 is hydroxy.

Particularly preferred are compounds having the formula VD

while

Av2 is a straight-chain hydroxyalkylene having one to three carbon atoms and a

Xv3 and Xv4 are the same or different and are selected from the group consisting of hydrogen, a metal of the first, second or third main group of the periodic system, in particular sodium, potassium and methyl, ethyl.

Among these compounds, the disodium salt of 3,4-dihydroxy-5-oxo-hexylphosphonic acid, the disodium salt of 1,2,3,4-tetrahydroxy-5-oxo-hexylphosphonic acid, the disodium salt of 2,3,4- trihydroxy-5-oxo-hexylphosphonic acid, 1,2,3-trihydroxy-4-oxo22 disodium salt ·· ····

pentylphosphonic acid and 2,3-dihydroxy-4-oxopentylphosphonic acid disodium salt.

Especially preferred are compounds which correspond to the formula VE

--0XV3

XV4 (Ve) where

Av2 is a straight-chain hydroxyalkylene having one to three carbon atoms and a

Xv3 and Xv4 are the same or different and are selected from the group consisting of hydrogen, a metal of the first, second or third main group of the periodic system, in particular sodium, potassium and methyl, ethyl.

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

Especially preferred are compounds which correspond to the formula VF

(VF) where

Av2 is a straight-chain hydroxyalkylene of one to three carbon atoms and ···········

· .. · * .. · ·. · ···

Xv3 and Xv4 are the same or different and are selected from the group consisting of hydrogen, a metal of the first, second or third main group of the periodic system, in particular sodium, potassium and methyl, ethyl.

Among these compounds, the disodium salt of 3,4-dihydroxy-4-methyl-5-oxo-pentylphosphonic acid, the disodium salt, has proven to be particularly advantageous.

2,3,4-trihydroxy-4-methyl-5-oxo-pentylphosphonic acid, 1,2,3-trihydroxy-4-methyl-5-oxo-pentylphosphonic acid disodium, 2-monohydroxy-3-methyl-4-oxo-disodium salt butylphosphonic acid and 1,2-dihydroxy-3-methyl-4-oxo-butylphosphonic acid disodium salt.

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

The organophosphorus compounds of the invention correspond to the general formula

VI:

BV) --- Ϊ --- R _V | 3 (VI)

RVK

Rvi3 and Rvi4 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 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, halogen, OXvn and OXv4 ··· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

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, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids; and

Bvi is selected from the group consisting of VIA

Rvik ysl — Avi

RvP ^Z (VIA) and Group VIB

RVI ¹ - N

Ay | (vib) wherein Av 1 is selected from the group consisting of alkylene amine, alkenylene amine, hydroxyalkylene amine, wherein the nitrogen atom is in the chain linking the phosphorous atom to the nitrogen atom of the group

or R 1 / N 1 = N ⁼⁼⁼ wherein Rvn and Rvi2 in group VIA are the same or different and Rvn and Rvi2 for group VIA and Rvn 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 acyl, substituted and unsubstituted acyl, substituted and unsubstituted unsubstituted heterocyclic radical, halogen, OXvn and OXvi2, wherein Xvn and Xvi2 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 alkenyl, substituted and unsubstituted alkenyl; Alki substituted, unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic moieties, and pharmaceutically acceptable salts, esters, amides, and ester salts thereof.

Preferred as Av 1 is an amino group in which the nitrogen atom is not terminated. Preferably, Av 1 combines nitrogen and phosphorus atom with three atoms (without substituents).

Particularly preferred are compounds which correspond to formula VI

(VI) mov.

while

Rvn, Rvi2, Rvi3 and Xvi4 are defined as for formula (VI) and A _V i is selected from the group consisting of CNC, C = NC, CN = C, wherein the carbon atoms may be substituted with hydroxy or alkyl groups of up to 7 carbon atoms26 ·· ····

Preferred are Rvn as hydroxy, Rvi2 is selected from the group consisting of acetyl and formyl, Rvi3 is selected from the group consisting of hydrogen, methyl, ethyl, hexadecanyl, octadecanyl and OXvi3 and Xvi3 and Xvi4 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.

Further preferred are compounds which correspond to the formula VID 1

Ryji --- N = A \ /!! --- --- Ryp (yiD)

0Xy | 4 where

Rvn, Rvi2, Rvb 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.

More preferably Rvn is selected from the group consisting of acetyl and formyl and Rvi3 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 hydrogen, sodium, potassium, methyl, ethyl, hexadecanes and * if both exist, they may be the same or different.

F

VII. Combined preparations of fat metabolism inhibitors with organophosphorus compounds containing a nitrogen heterocycle

The organophosphorus compounds used according to the invention correspond to the general formula VII:

·· ····

Ο

Rvm Avi --- | --- 1 --- J RVI | 3

Rvi | 4 (VII) in which:

Avn is selected from the group consisting of a (C 1-9) -alkylene radical which may have one or more double bonds and may be substituted by hydroxy, halogen, amino, oxo groups with branched or unbranched C 1-9 -alkyl and C 2-9 -alkenyl groups wherein the C 1-9 alkyl and C 2-9 -alkenyl groups may be substituted by hydrogen, hydroxy-, amino-, halogen- and 0x0-, -COC- and -CNC- groups, wherein the -COC- and -CNC- carbon atoms may be substituted alkyl of up to 7 carbon atoms or hydroxy;

Avn corresponds to the following formula VIIA:

(VIIA) wherein one or more of the carbon atoms selected from Cvii3, Cvii4, Cvii5 together with their substituents may also be omitted and at least one of the existing substituents Bviii to Bvino is a C 3-8 -cycloalkyl- (C 0 -C 9) -alkyl group, wherein both the C 3-8 -cycloalkyl group and the C 3-9 -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 hydroxy, halo, amino, branched or unbranched oxo groups of C 1-9 -alkyl and C 2-9 -alkenyl, wherein the C 1-9 -alkyl and C 2-9 -alkenyl may be substituted with hydrogen, hydroxy, amino, halo and halo; ···· xo groups and the remaining existing substituents Bvm to B wine are selected from the group consisting of hydrogen, hydroxy, halo, amino, Ci.26-alkyl radicals, C 26 -alkoxy radicals, C. _The 6-alkoxy-C 1-6 -alkyl radicals, or both substituents on one carbon atom together, form an oxo group, each C 1-6 alkyl being substituted by an oxo group. _The 2-6-alkyl radical and each C 1-6 -alkoxy radical may be branched or unbranched, saturated or unsaturated with one or more double bonds and may be substituted by hydroxy, halogen, amino and oxo, wherein VII is selected from the group consisting of 5- and 6-membered heterocycles with one or two nitrogen, oxygen or sulfur atoms in the ring, the heterocycle may be saturated or unsaturated with one or more double and triple bonds and may be substituted by hydroxy, halogen, amino, oxo and branched or unbranched C 1-9 -alkyl and C 2-9 -alkenyl groups, wherein the C 1-9 -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 groups wherein Rvin and Rvii 4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 -alkyl, hydroxy-C 1-6 -alkyl. 26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted or unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-6-alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted, substituted, unsubstituted, 0Xvii3 and 0Xvii4, whereby

Xvii3 and Xvii4 may be the same or different and are 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 C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, cation · · · · · · · · · · Or a third organic and inorganic base, in particular a metal the first, second 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; and amides and ester salts.

If there are two heteroatoms in the Rvn heterocycle, then mixed, e.g. an oxygen atom and a nitrogen atom.

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

or

Preferably, the organophosphorus compound corresponds to formula VIIC

ABOUT

RVI | Avil 1 ---- ---- ---- P RVI | 3

OXviK (VIIC) wherein Rvii3 is preferably hydrogen, methyl, ethyl or an amide residue and Xvii4 is selected from the group consisting of hydrogen, sodium, potassium, methyl, ethyl, and a particularly preferred compound of formula VIID

0XVII4 ·· ····

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

S ---- RVII3

ABOUT

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

The compounds are described in WO 98/16537.

The organophosphorus compounds used according to the invention correspond to the general formula VIII:

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

Rvmii is selected from the group which consists of substituted and unsubstituted Ci-26-alkyl, hydroxy-C ₂ 6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and 31 ·· ·· ·· ···· · · · · · · · · · · · · · · · · · · · · ·

Or unsubstituted aralkyl, substituted and unsubstituted C 1-6 alkenyl, substituted and unsubstituted C 1-6 alkenyl. ₂ 6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and OXvimi, wherein

Xviiiu 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 alkyl. ₂ 6 alkenyl, substituted and unsubstituted C |. ₂ 6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids and

R iim is selected from the group consisting of C 1-6. ₂ 4-alkylzvyškov C _{2nd 2} 4alkenylzvyškov, C2-24-alkapolyenylzvyškov comprising 2-6 double bonds, C ₂ -24-alkinylzvyškov, cykloalkylzvyškov C 3-8, C 3-8 cycloalkyl C1.24alkylzvyškov CI.I a _{2-alkoxy-Ci.i2} -alkyl radicals,

Rviii2> Rvni3 and Rvni4 are independently selected from the group consisting of hydrogen, halogen, amino, acetylamino, azido, and XRvIII10, wherein X is O or S and Rvni6 is selected from the group consisting of hydrogen, branched or unbranched C1 . ₄ -alkyl radicals and the C ₂ -4-alkenyl radicals, such as the C-4-alkyl radicals, and C2.4alkenylové radicals may be optionally substituted by hydrogen, amino, halo, or 0x0- or

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

Rvíns is selected from the group consisting of hydrogen, Ci-24-alkyl, _C3 8-cycloalkyl, N (C]. _2-4 alkyl) groups, aryl groups, acyl groups, heterocyclic radicals, halogen, wherein any the radicals may be branched or unbranched and optionally substituted by groups

··· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · , halogen- or oxo-, and may contain 2-6 double or triple bonds or Rviiis is a phenyl moiety of formula VIIIA or VIIIB

(Viii)

VIII8 (VIIIB) wherein Rviii7 and Rviiis 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 1-4 -alkyl radicals, C 1-4 -alkoxy radicals, radical formyl, acetyl, propionyl or butyryl, formyloxy- radical, the acetoxy, propionyloxy, butyryloxy-, _{C2-s-alkoxycarbonyl} radicals, which all may be branched or unbranched or RVNNO and R VIII may be taken together to form a saturated straight chain alkylene of 3 to 4 carbon atoms, which is bonded to adjacent positions, e.g. The 2,3-position or the 3,4-position of the phenyl ring or R 7 and R 8 together form a methylenedioxy radical, 1,1-ethylidenedioxy radical or 1,2-ethylenedioxy radical which are bonded to the 2,3- or 3-radical, The 4-position of the phenyl ring; or

R VIII are selected from the group consisting of a Rviii9COOCHRviiiio- Rviii90COOCHRviiiio- wherein Rvni9 is selected from the group consisting of Ci.e-alkylamino, C2-6-alkenyl radicals, C ₂ -6-alkynyl radicals, C _3. 8-cycloalkyl radicals, C 3-8 -cycloalkyl-C 1-6 -alkyl radicals, and C 1-6 -alkoxy-C 1-6 alkyl radicals, all of which may be branched or unbranched and optionally substituted by hydroxy-, amino-, halogen- or oxo- and

R 10 is branched or unbranched Ci. ₄ -alkyl radical, and wherein the substituents Rvni2, Rviib, R VIII and Rvni5OOCPO (OH) OCH2 in (VIII) where n is 1, are independently D-gluco, L-gluco, ··· ·· ·· · · ·

D-galacto, L-galacto, D-mano, L-mano, D-talo, L-talo, D-alo, L-alo, D-altro, L-altro, D-gulo, L-gulo, D- ido or L-ido, or R 2, R 3 and substituent configurations

R 5 OOCPO (OH) OCH 2 - in I are independently D-ribo, L-ribo, D-arabino, L-arabino, Dxylo, 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 (VIII) are those wherein Rvin is selected from the group consisting of C 9-24 -alkyl residues, C 9. ₂ 4-alkenyl radicals, C9.24alkapolyénové radicals, comprising 2-6 double bonds, -C. ₂ 4-alkynyl radicals, _C3 8-cycloalkyl-C 6. ₂ 4-alkyl radicals, and C ₂ -C ₈ -alkoxy .i2- alkyl radicals, which in this case may optionally be branched or unbranched and may be substituted by hydrogen radicals, amino radicals, halogen or oxo moieties.

Particularly preferred is the use of 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, a hydroxy group is preferred as Rviii2, Rviib, Rviii4. Rviii5 is preferably hydrogen, formyl or acetyl. In addition, L and the D-glucose configuration are preferred as n for the Rviin, Rv113, Rv114 and Rv115OOCPO (OH) OCH2- substituents. Preferably, Rviiiii represents OXVIH11 with XviII11 = hydrogen.

IX. Combined preparation of fat metabolism inhibitors with heterocyclic phosphonic acid derivatives

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

·· ····

··· w

(I / V * '* ¹ (IX)

while

Rixn 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 OXIXn, wherein:

Xixn is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 -alkyl, substituted and unsubstituted hydroxyC 1-6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of 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 which are derived from ethylenediamine or amino acids and wherein

Rix 1 and Rix 2 are each independently selected from the group consisting of C 1-24 alkyl, C 3-8 -cycloalkyl radicals, C 3-8 -cycloalkyl-C 1-24alkyl radicals, C 1-4 -alkoxy radicals, C 1-4 -alkylthio-residues, C1 .24alkoxy-C1-24-alkyl radicals, C1-4alkoxy; ₂ 4 -alkylthio-C. ₂ 4-alkyl radicals, acyl radicals, aryl radicals, aralkyl radicals, heterocyclic radicals, halogen and hydrogen and each C 1. _The 4-alkyl radical and the C 24-24 -alkoxy radical may be branched or unbranched and saturated or unsaturated with up to 6 double bonds and optionally substituted by hydroxy-, amino-, mercapto-, halogen-, oxo- or C1-24-alkoxy radicals, C1-4alkoxy; 24-alkylcarbonyloxy radicals, C 1-4 -alkoxycarbonyloxy radicals, C 1,24-alkylthio radicals, C 1-4 -alkylcarbonylthio radicals, C 1-4 -alkylamino radicals, di (C 1-24-alkyl) amine radicals, C 1-24- alkylcarbonylamino radicals, C 24 -alkyl- (Ci.24-alkylcarbonyl) amino radicals, C1.24alkoxykarbonyl-amino residue or C _2-alkyl-4 (C-24 alkoxycarbonylamino radicals, wherein each aralkyl radical, heterocyclic radical, C The -24-alkyl moiety and the C 1-24-alkoxy moiety may be branched or unbranched, saturated or unsaturated with 2 to 6 double or triple bonds, or wherein Rix-CH-CH-Rix2 forms part of a C4-C8-carbon ring which may optionally be substituted by hydroxy-, mercapto-, amino-, halogen-, oxo- or C1-24-alkyl radicals, C1-24-alkoxy radicals, C1-24-alkylthio-radicals, C1-24-alkylamino radicals, di (C1-C4) -alkyl radicals; (C1-4-alkylcarbonyl) C1-24 alkylcarbonyloxy, C1-24 alkoxycarbonyloxy, C1-4alkylcarbonylthio or C1-24 alkylcarbonylamino, C1-4 alkylcarbonyloxy; 24-alkyl- (C _1-4 -alkylcarbonyl) amino-residues, wherein each C 1-4 -alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 double bonds, or wherein Rixio is branched or unbranched C 1-4 alkyl and wherein Rixi-CH-CH-Rix2 forms part of a furan or pyran ring of a sugar, e.g. D-ribose, D-arabinose, D-xylose, D-lyxose, D-glucose, D-galactose, D-mannose, D-talose, D-alose, D-altrose, D-gulose, D-idose or the corresponding L-isomers wherein the hydroxy groups may each be optionally substituted radicals by hydrogen, amino, azido, 0x0-, mercapto, or C 24 alkoxy radicals, C 24 alkylthio radicals, 2alkyl ₄ -alkylaminozvyškami, di ( Ci-24-alkyl) amino radicals, C 24 alkylcarbonyloxy radicals, C1.24alkylkarbonyltio-radicals, C-24-alkylcarbonylamino radicals, 2alkyl ₄ alkyl- (C 24-alkylcarbonyl) amino radicals, wherein each C 1-4 -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.

In particular, Rix 1 and Rix 2 may each be independently selected from the group consisting of carboxyl residues, carboxamide residues, aryl residues, aryloxycarbonyl residues, aryl-C 1-24 -alkyl residues, C 1-24 -alkoxycarbonyloxy radicals, C 1-24 -alkylaminocarbonyl residues, di ( Ci-24-alkyl) aminocarbonyl moieties, aryl-C-24-alkoxycarbonyl radicals, aryl-C 24 alkylamino-carbonyl radicals, C 2 ₄ -alkylcarbonyloxy- (C ₄₎ alkylmetoxy-carbonyl radicals, C-24 alkoxycarbonyloxymethoxycarbonyl radicals, C1-24-alkoxycarbonyloxy (C1-4-alkyl) methoxycarbonyl radicals, wherein each C1-24-alkyl radical may be branched or unbranched, saturated or unsaturated with 2 to 6 double bonds, and each C1-6-alkyl; _{The 4-} alkyl radical and the C 1-4 -alkoxy radical may be branched or unbranched and saturated or unsaturated, and each aryl radical corresponds to formula IXA

(IXA) wherein Rix ₃ and Rix ₄ are the same or different and are each independently selected from the group consisting of hydrogen, halogen, C 1-6. _4- alkyl radicals, Ci. ₄ alkoxy radicals, formyl, acetyl, propionyl or butyryl radicals, formyloxy-, acetoxy-, propionyloxy-, butyryloxy-, C1-8 radicals; ₄ alkoxycarbonyl radicals, which all may be branched or unbranched or R1X3 and Rix ₄ together form a straight saturated alkylene chain having 3 to 4 carbon atoms, which is bonded to adjacent positions of the phenyl ring or Rix3 and Rix ₄ together form a methylenedioxy radical, 1 , A 1-ethylidenedioxy radical or a 1,2-ethylenedioxy radical which are bonded to adjacent positions of the phenyl ring.

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

· · ·

It is preferred to use compounds in which Rix ₁ and Rix ₂ in this case are independently selected from the group consisting of hydrogen, hydroxy, formyl, acetyl and methyl, wherein the methyl radical may be optionally substituted by hydroxy or mercapto or C 1. _{2 by} 4-alkoxy radicals, Ci. ₂ 4-alkylcarbonyloxy radicals, Ci. _{2 with} 4-alkylthio residues or C 1-6 alkyl; ₂ 4alkylkarbonyltio-radicals, the C]. _And 4-alkyl; _The 4-alkoxy groups may be branched or unbranched or saturated or unsaturated with 1 to 6 double bonds.

Particularly preferred as Rixn is a methyl radical which may be optionally substituted by hydroxy or mercapto or C 1. _{2 by} 4-alkoxy radicals, Ci. ₂ 4-alkylcarbonyloxy radicals, Ci. ₂ or 4-alkyltiozvyškami C]. _With 4-alkylcarbonylthio radicals wherein C 1. _And 4-alkyl groups; _The 4-alkoxy groups may be branched or unbranched or saturated or unsaturated with 1 to 6 double bonds, and Rix ₂ is a hydrogen radical.

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

R 1 xii preferably represents OXix with Xixn = hydrogen.

X. Combined preparation of fat metabolism inhibitors with hydroxyaminooxocarb (derivatives

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

RX2 (x) ·· ···· in which

R xi is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-8 -alkyl, substituted and unsubstituted hydroxy-C 1-6 alkyl. 9-alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted or unsubstituted aralkyl, substituted and unsubstituted Pričomχι, where

Xxi is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxyC 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, 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, C1-6-alkoxy radicals, -26-alkoxy-Ci-26-alkyl radicals, C3.8cykloalkyl- (Co. ₂ 6) -alkyl radicals, wherein one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur, each C3-26-alkyl the radical and each C3-26-alkoxy radical may be branched or unbranched and each C3-8-cycloalkyl radical shock, each C2. The 26-alkyl radical and each C 2-26 -alkoxy radical may be saturated or unsaturated with one or more double bonds and each C 3-8 -cycloalkyl radical, each C 1-6 -alkyl radical and each C 1-6 -alkoxy radical may be substituted hydroxy, amino, halogen, and oxo or carbyl group CORx3, wherein R _X3 is selected from the group consisting of substituted and unsubstituted C1-6-alkyl, hydroxy-C1-6-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aryl; unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1.26 ·, -, -, -, -, -, -, -, - Alkenyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic, halogen and 0Χχ3, with Χχ3 s and selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 -alkyl, substituted and unsubstituted hydroxy-C 1-6 alkyl. 26-alkyl, substituted and unsubstituted aryl, 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, silyl, cationic, cationic, cationic especially metal of the first, second or third main 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 Rxi is a branched or unbranched C1-4 -alkyl group, particularly preferably an isopropyl group; 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 group of the periodic system, ammonium, substituted ammonium or ammonium compounds which are derived from ethylene amine or amino acids. Similarly, salts of hydroxyamino-oxocarbylcarboxylic acid derivatives with organic or inorganic bases are formed (e.g., sodium salt, potassium salt, calcium salt, aluminum salt, magnesium salt, magnesium salt, triethylammonium salt, ethanolamine salt, dicyclohexylamine salt, ethylene salt, dicyclohexylamine salt). , a salt with N, N'-dibenzylethylenediamine, etc.) as well as amino acids (e.g., arginine salt, aspartic acid salt, glutamic acid salt, etc.) and the like.

Preferably, esters may 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 organophosphorus compounds containing either two phosphorous groups or one phosphorous group and one sulfoxy group

The organophosphorus compounds used according to the invention correspond to the general formula XI:

(XI) wherein Ζχι is a phosphorus or sulfur atom in which Αχι is an unbranched C2-9-alkylene chain with substituents that are the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen- , amino- and oxo-groups, C 1-6 alkyl radicals, C 1-6 alkoxy radicals, C 1-6 -alkoxy-C 1-26 -alkyl radicals or C 3-8 cycloalkyl- (C 0 -C 9) -alkyl groups, wherein each C The .26 alkyl radical and each C26 alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, halogen, amino and oxo groups and both C3-8cycloalkyl and Co2 groups. 9-alkyl _C3-.8 cycloalkyl (Co-9) the alkyl groups can 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 the cycloalkyl group as well alkylsku the pins may be substituted with hydroxy, halogen, amino, oxo groups with branched or unbranched C 1-9 -alkyl and C 2-9 -alkenyl groups, wherein the C 1-9 -alkyl and the C 2-9 -alkenyl groups may be substituted with hydrogen, hydroxyamino- , halogen- and oxo- groups in which R xn and R x 2 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1. ₉ -alkyl, substituted, and substituted .alpha.-substituted. Unsubstituted C 1-8 alkenyl, substituted and unsubstituted C 1-9 alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic, halogen, OXxh and aχη, wherein pričomχπ and Χχΐ2 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted o acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals in which R xb and R xu are the same or different and are selected from the group consisting of substituted and unsubstituted C 1-6 -alkyl, hydroxyCi-26 -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, substituted, unsubstituted, substituted, unsubstituted, and 0xX4, wherein

Χχπ and Χχΐ4 may be the same or different and are 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 C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of organic and inorganic bases, especially metal of the first, second or third main group of the periodic system ammonium, substituted ammonium, and ammonium compounds derived from ethylenediamine or amino acids; and e ·· ··· Their pharmaceutically acceptable salts, esters and amides and salts thereof. esters.

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

Particularly preferred are compounds, wherein R _X and ₂ is methyl and Ζχι, RXU, RXU, Rxi4 are defined as above, wherein RXII is preferably substituted with hydroxyl at the C-atom adjacent to a heteroatom, and those where xi ₂ is hydroxy wherein Ζχι, Rxn, xb, RXM are defined as above, wherein the R n _X is preferably acyl group, particularly preferably a formyl, acetyl, propionyl or butyryl.

Preference is also given to compounds having the following structures:

OH

RXH

RXI4

R _Xi 2 (XIC), eeeeee ee eeee e · e

• e ······ e e ee ee

(XIF);

(XIG)

R XII-Ϊχι-Ϊ- -.- o 7Χ » (XIH). OH Rx | 4

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

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

The medicaments of the compounds according to the invention correspond to the general formula XII:

(XII) where

Αχιι is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-28 -alkyl residues, substituted and unsubstituted alkoxy- (C 0-28) -alkyl groups, substituted and unsubstituted cycloalkyl- (C 0-28) -alkyl groups, substituted and unsubstituted cycloalkoxy (C 0-28) -alkyl groups, substituted and unsubstituted amino- (C 0-28) -alkyl groups, substituted and unsubstituted thio- (C 0-28) -alkyl groups, and substituted or unsubstituted acyl- (C 0-28) -alkyl residues, and 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 radical may be saturated or unsaturated with one or more double or triple bonds and one or two cycloalkyl carbon atoms may be replaced by atoms nitrogen, oxygen or sulfur,

Rxin 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 26) -alkyl groups, substituted and unsubstituted cycloalkoxy- ( C 0-6 alkyl, substituted and unsubstituted amino- (C 0-26) -alkyl, substituted and unsubstituted silyl- (C 0-26) -alkyl, substituted and unsubstituted thio- (C 0-6) -alkyl groups, each 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 the one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur · · · · · · · · · · · · · · · · · · · · · · Or a carbon chain of two C-atoms in Αχπ with Rxm forms a ring by forms an isoxazolidone ring and

Rxx is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted acyl radicals, and substituted and unsubstituted cycloalkyl (C 0-26) -alkyl groups, wherein each alkyl radical and each acyl radical may be branched or unbranched, and each alkyl moiety, each acyl moiety, 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

Rxi | 5 RXI | 1 (XIIA) where

Rxiii and Rxin 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- (Co) radicals. - (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 the carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms,

Rxns, Rxiie and Rxin 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- (Co-26) 46 ·· ···· alkyl groups, substituted and unsubstituted cycloalkoxy- (Co-26) alkyl groups, substituted and unsubstituted alkoxy- (Co-26) -alkyl groups, substituted and unsubstituted amino groups, substituted and unsubstituted thio- (Co-26) -alkyl groups, and substituted or unsubstituted acyl groups 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 atoms of the cycloalkyl groups may be replaced by atoms nitrogen, oxygen or sulfur, whereby

Rxh5 alternatively with Rxm can also form a ring a

Rxm and Rxin can exhibit a single carbon-oxygen bond by forming a ring structure.

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

Preferably, R xm and R xh 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.

R xm is preferably selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, most preferably C 1 -C 4 -alkyl, substituted and unsubstituted aromatic C 7 -C 14 -alkyl, pyranyl and tert-butyldimethylsilyl and

RXII8 where

R xm is selected from the group consisting of substituted and unsubstituted, most preferably halogen substituted alkyl, substituted and unsubstituted cycloalkyl (C 0-6) -alkyl, substituted and unsubstituted amino groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted alkoxy groups, substituted and unsubstituted alkoxy groups unsubstituted phenoxy, substituted and unsubstituted alkylthio, substituted and unsubstituted aromatic cycloalkylthio, most preferably one unsubstituted or substituted halogen-, methyl-, methoxy-, nitro-, amino- or CF3-group.

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

while

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

Preferably, Rxin is selected from the group consisting of hydrogen and halogen, or Rxu3 and Rxin exhibit a single carbon-oxygen bond by forming a ring structure.

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

Rxii4 is

• BB BBB B B B B B B B B B

B B B B B B B B B B B

BBB B B B BBB

BB BBB BB BB BB BBB

Rx15 and Rx16 are independently selected from the group consisting of hydrogen, chlorine, bromine and methoxy.

Particularly preferred are compounds wherein R xiu 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.

Particular preference is then given to compounds in which Rxm and Rxm are methyl, Rxin and Rxin are hydrogen or contain a carbon-to-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-dimethyl-N - (2-methylphenyl) methylpropanamide, 3-chloro-N-hydroxy-2,2-Ntrimethyl-propanamide, 3-chloro-N-hydroxy-2,2-dimethyl-N- (phenylmethyl) propanamide, 3-chloro- N- (2,4-dichloro-phenylmethyl) -N-hydroxy-2,2-dimethylpropane-amide,

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-benzoyloxy-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) 2- (2-chlorophenyl) methyl-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-349-9 999 9 isoxazolidinone, 4,4-dimethyl-2 -phenylmethyl-3-isoxazolidinone, 2- (2,4-dichlorophenyl) methyl 1-4,4-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-isoxazolidine O, 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 - [(tetrahydropyranyl) oxy] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2 -di-methyl 1-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 1- 3-isoxazolidinone, 2 - [(2,4,5-trichlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-6-fluorophenyl) methyl] -4,4-dimethyl 1-3 -isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-ethoxy-4,4-dimethyl 1-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl 1-5 -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 1J-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-dichloroacetoxy-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] -2,2-dimethyl-N - [( ethylthiocarbonyl) oxy] propanamide, 3-chloro-N [(2,2,2-trichloroethoxy-) carbonyloxy] -N - [(2-chlorophenyl) methyl] -2,3-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) acetoxy] -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2 · 1 · ···· · · · · · · ·) · Chlorophenyl) methyl] -2,2-dimethyl- N - [(3-trifluoromethyl) benzoyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(4-methyl-phenyl) aminocarbonyl-oxy)] P ^R propanamides, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(3,4- (dichlorophenyl) aminocarbonyloxy)] - 2,2-dimethylpropanamide, 3-chloro-N- (3-chloro-2,2-dimethyl-loxopropoxy) -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-chloroacethoxy) -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N- [2,5-dichloro (formylamino) benzoyloxy] -N - [(2-chlorophenyl) methyl] -2,2-dimethyl-propanamide, 3-bromo-N - [(2-bromophenyl) -methyl] -N-2-chloroacethoxy-2,2-dimethyl-propanamide, 3-bromo-N - [(2-bromophenyl) methyl ] -N- (methylcarbonyl phenyloxy) -2,2-dimethylpropanamide,

3-bromo-N - [(2-bromophenyl) methyl] -N - [(2-chlorophenyl) aminocarbonyloxy] -2,2-dimethylpropanamide, 2 - [(2-chlorophenyl) methyl] -N-hydroxy-2,2 -dimethyl 1-3-methylthiopropanamide, 3-phenylcarbonyloxy-N - [(2-chlorophenyl) methyl] -N-hydroxy-

2,2-dimethylpropanamide, 2 - [(4-chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 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-isoxazolidinone-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-iso oxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-1-5- (1-methylethoxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl- 5- (phenylmethoxy) -3-isoxazolidinone, 2 - [(2-bromophenyl) methyl] -5-chloro-4,4-dimethyl 1-3-isoxazolidinone, 2 - [(2,5-dichlorophenyl) methyl] 51

4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-propoxy- • ΦΦ··φφ φ φφ φ φ φφ φφ φφ ···

3-isoxazolidinone, isoxazolidinone, isoxazolidinone,

2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2-propenyloxy) -3

2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2-propynyloxy) -3

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-butyloxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (2-butyloxy) -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-1-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-hexoxy-4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) 1-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:

in which n is an integer from 0 to 4 and in which n is an integer from 0 to 4 and in which n is an integer from 0 to 4 and in which n is an integer from 0 to 4 and in which n is an integer from 0 to 4 and ····· ·· ·· ·· ·

R 1 -X 1, R 1, R 1, R 3, R 3, R 3, R 4, R 5, R 5, R 5, R 5, R 5, R 5, R 5, R 5, R 5, R 5 and R 6 are identical or different and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted and unsubstituted acy substituted and unsubstituted cycloalkyl- (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 moiety, each acyl moiety, each alkoxy moiety, 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 groups may be replaced by nitrogen atoms , oxygen or sulfur ·

For R xnn, COOC 2 H 5 is preferred.

Further preferred are compounds wherein R xn 2 to R xm 2 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 medicaments of the compounds according to the invention correspond to the general formula XIV:

Rxiv3

XIV --- ZXIV

Wherein Υχιν is a C 1-3 -alkenyl group which is substituted with R xiv 1 and R xiv 2 and optionally R xiv 3 and R xiv 4, wherein:

Rxivi to Rxivi are the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl, substituted and unsubstituted cycloalkyl- (C 0-6) alkyl, substituted and unsubstituted cycloalkoxy- (Co-) (26) alkyl, substituted and unsubstituted alkoxy- (Co-26) -alkyl groups, substituted and unsubstituted amino groups, and substituted and unsubstituted thio- (Co-26) -alkyl groups, substituted and unsubstituted sulfonyl- (Co-26) -alkyl groups, substituted and unsubstituted sulfinyl- (C26) -alkyl groups 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 radical may be saturated or unsaturated with one or more double but or triple bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms; and

Rxivb and Rxívu are defined as Rxívi to Rxívs or together form an oxo group, with zaχιν being an organophosphorus group

Rxívio the Rxiv9 and Rxívio the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted (C1-26) alkyl groups, substituted and unsubstituted hydroxy- (C ₂ 6) alkyl groups, substituted and unsubstituted cycloalkyl- (C 0-6) -alkyl, substituted and unsubstituted acyl, halogen, ΟΧχινί 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 acyl radical; 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 pričomχιν9 or Χχινιο may be the same or different and selected from the group, k it consists of hydrogen, substituted and unsubstituted (C 1-2) alkyl, substituted and unsubstituted hydroxy (C _1-2 ) alkyl, substituted and unsubstituted cycloalkyl- (C 0-6) -alkyl, substituted and unsubstituted acyl, silyl, 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 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 groups may be replaced by nitrogen, oxygen or sulfur atoms, or o wherein Ζχιν is an amino group

N --- ---- RXIV

Wherein R xiv and R xivi 2 are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted cycloalkyl- (C 0-6) -alkyl, substituted and unsubstituted cycloalkoxy- (Co) -26) -alkyl, substituted and unsubstituted alkoxy- (C 0-6) -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 the 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, wherein Βχιν is selected from the group consisting of substituted and unsub • · ·· e · φ · St Ci st st st Ci Ci Ci Ci Ci Ci Ci Ci st Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci Ci alkenylene groups wherein one C-atom can be replaced by an oxygen atom and one C-atom by a sulfur atom or two C-atoms can be replaced by an S-heterocycle and wherein each alkenylene residue can be branched or unbranched and saturated or unsaturated with one or more double or triple bonds and substituted with one or more hydroxy, halo or oxo.

Rxivi3 and Rxivi4 together together preferably form an oxo group at the α-position to the nitrogen atom.

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

Preference is further given to compounds in which as the ether group XIVA is as well

--- Axivi --- O --- Axiv2 --- (XIVA) where Αχινι falls off or is a (C 1-9) -alkylene residue and

In addition, or is selected from the group consisting of (C 1-9) -alkylene residues, a sulfur atom and a (C 3-8) -heterocycle having at least one sulfur atom. The methylene group is particularly preferred as Αχινι and Αχιν2.

Also preferred are compounds in which ,χιν represents keto group XI VB

--- Αχιν3 ------ Axiv4 --- (XIVB) wherein Αχιν3 and Axjv4, one or both of which may be absent, are the same or different and are selected from the group consisting of (Ci.gj-). alkylene radicals wherein any (C-9) alkylene radicals may be branched or unbranched ····, or can contain one or more double bonds and may be substituted by hydroxy or halo group. it is preferred that the a and _X JV3 Void A _X and _V 4 both represent a methylene or ethylene group.

Further, a 2-hydroxypropylene group is preferred for B _X iv.

R _X iv9 and R xivio preferably represent 0Χχιν9 and ΟΧχινιο, wherein Χχιν9 or X _X ivio may be the same or different and selected from the group consisting of metal of the first, second or third main group of the periodic system, in particular sodium and potassium and methyl, ethyl .

The particularities of the above definitions and the appropriate examples are given as follows:

Acyl is a substituent that originates from an acid such as an organic carboxylic acid such as carbonic acid, carbamic acid or a single one of the foregoing corresponding thioacid or imidic acid or an organic sulfonic acid, which acids include appropriate aliphatic, aromatic and / or heterocyclic groups such as carbamoyl or carbamimidoyl.

Suitable examples for these acyl groups are given as follows.

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

Alkanoyl (e.g., formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, etc.);

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

alkylcarbamoyl (e.g., methylcarbamoyl, etc.); (N-alkyl) -thiocarbamoyl (e.g., (N-methyl) thiocarbamoyl, etc.);

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

Alkyl carbamimidoyl (e.g. methylcarbamimidoyl, etc.);

oxalo;

alkoxalyl (e.g., methoxalyl, etoxalyl, 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 are e.g. amino, carboxy, amino and carboxy, halogen, acylamino or the like substituted alkanoyls.

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

Aroyl (e.g., benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl, etc.); Aralkanoyl (e.g., phenylacetyl, etc.);

Aralkenoyl (e.g. cinamoyl etc);

Aryloxyalkanoyl (e.g. phenoxyacetyl etc.); Arythioalkanoyl (e.g., phenythioacetyl, etc.);

Arylaminoalkanoyl (e.g., N-phenylglycyl, etc.); Arenesulfonyl (e.g. benzenesulfonyl, tosyl and toluenesulfonyl, naphthalenesulfonyl, etc.);

Aryloxycarbonyl (e.g., phenoxycarbonyl, naphthyloxycarbonyl, etc.); Aralkoxycarbonyl (e.g. benzyloxycarbonyl, etc.);

Arylcarbamoyl (e.g., 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 of the aromatic acyl radicals. More suitable substituents than those already mentioned as suitable substituents for the alkyl group, respectively. alkane residue. Particularly and by way of example for preferred aromatic acyl radicals, 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);

arylcarbamimidoyl (e.g., phenylcarbamimidoyl, etc.).

A heterocyclic acyl radical is an acyl radical derived from an acid having a heterocyclic group; this includes:

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

heterocycloalkanoyl wherein the heterocyclic moiety is an aromatic or aliphatic 5- to 6-membered heterocycle and has at least one nitrogen, oxygen and sulfur heteroatom (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 indicated for alkyl and alkane groups.

Alkyl, unless otherwise defined, is an alkyl radical 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 with up to 9 carbon atoms, straight or branched chain such as e.g. 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.

Cycloalkyl is especially optionally substituted C 3 -C 7 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, benzydryl, 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-chain or branched 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 , 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 e.g. trimethylene.

Alkenylene includes straight or branched chain alkenylene groups having up to 9 carbon atoms and may be represented by the formula

- ( _Cn H _2n . ₂ ) -, wherein n is an integer from 1 to 9 such as e.g. vinylene, propenylene, (e.g., 1-propenylene, 2-propenylene), 1-methylpropenylene, 2-methylpropenylene, butenylene, 2-ethylpropenylene, pentenylene, hexenylene; in particular, al60 may be preferred to be able to be used in the following manner: a) 60.························································· The kenylene radical may have up to 5 carbon atoms and in particular 3 carbon atoms such as e.g. 1-propenylene.

Hydroxyalkylene may include straight or branched chain alkylene radicals having up to 9 carbon atoms, one or more selected carbon atoms being substituted with hydroxy; these residues may be represented by the formula

- (C _n H _{2 n} . ₂ ) (OH) _z - in which n is an integer from 1 to 9 and z is an integer for which z is <n. Suitable examples for such hydroxyalkenylene groups include hydroxymethylene, hydroxyethylene (e.g., 1-hydroxyethylene and 2-hydroxyethylene), hydroxytrimethylene (e.g., 1-hydroxytrimethylene, 2-hydroxytrimethylene and 3-hydroxytrimethylene), hydroxytetramethylene (e.g., 2-hydroxyytetramethylene). methyltrimethylene, hydroxypentamethylene (e.g. 2-hydroxy-pentamethylene), hydroxyhexamethylene (e.g. 2-hydroxyhexamethylene) and the like. Particularly preferred is a lower hydroxyalkylene of up to 4 carbon atoms and especially one having 3 carbon atoms such as e.g. 2-hydroxytrimethylene.

The alkylene amines include alkylénamínové a straight or branched chain which have up to 9 carbon atoms and may be represented by the formula - (C _n H _2LL) N (C _m H _2lI1) -, in which us are the same or different, are an integer from 0 to 9 and are 1 < n + m < 9, such as methyleneaminine, ethyleneaminine, dimethyleneaminine, trimethyleneaminine, methylenemethyleneaminine, tetramethyleneaminine, 1-methyltrimethyleneaminine, 2-ethylethyleneaminine, ethylenmethyleneaminine, pentamethylenethyleneamine, 2methylenethyleneaminine, im similar; preferred alkylene amine residues have 2 carbon atoms that are terminal. Dimethyleneamine 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 may be represented by the formula

999

- (C _n H _{2 n} -i) = N- (C _m H ₂ m) - or by the formula - (C _n H _{2 n} ) -N = (C _m H 2 _{m. I} ) -,

99 ·· • 9 · 9 • 99

9 * 9

99

99 ···· ·· ·

99

9 99

99 ··

In which n and m can be the same or different and are an integer from 0 to 9 and are 1 <n + m <9, such as methyleneimine, ethyleneimine, dimethyleneimine, trimethyleneimine, methylenethyleneimine, tetramethyleneimine, 1- methyltrimethylenimine, 2-ethylethylenimine, ethylenemethylenimine, pentamethylenimine, 2-methyltetraethylenimine, isopropylethylenimine, hexamethylenimine 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 chain alkenyleneamine groups having up to 9 carbon atoms and may be represented by the formula

- (C _n H _{2 n 2} ) -N- (C _m H _{2 m 2} ) -; - (C ₀ H2 _O) N (C _m H _{2m. 2)} -; - (C n H 2n-2) -N- ₍₂ COH O) -, in which us are the same or different and are an integer of 2-9 and m + n is valid <9, and that of from 0 to 7, and five-a n < 9, such as e.g. vinyleneamine, methylenevinyleneamine, divinyleneamine, propenyleneamine (e.g., 1-propenyleneamine, 2propenyleneamine), methylenepropenyleneamine, 1-methylpropenyleneamine, 2-methylpropenyleneamine, butenyleneamine, 2-ethylenepropenyleneamine, hexenylenemethylenamine, pentenyleneamine, pentenyleneamine, pentenyleneamine, pentenyleneamine, pentenyleneamine. 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 formulas

- (C _n H 2n-3) = N (C -2 _H2m) -; - (C _a H _2-ol) -N- (C _m H ₂ m-2) -; - (C _n H 2n-3) = N (COH ₂ O) -; (CnH _2n .2) -N- (C .3 _H2m) -; - (CoH ₂ O) = N- (C _m H _{2 m,} 3) -; - (C _n H _{2n. 2)} N- _{(2 °} C _a H .i) -;

wherein n and m are the same or different and are an integer from 2 to 9 and n + m < 9 and o is a number between 0 and 7 and o + n < 9, e.g. vinyleneimine, methylene-vinyleneimine, ethylene-vinyleneimine, propenyleneimine (eg 1-propenyleneimine, 2-propenyleneimine), methylene-propenyleneimine, 1-methylpropenyleneimine, 2-methylpropenyleneimine, butenyleneimine, 2-ethylene62 ········· Propenyleneimine, pentenyleneimine, hexenyleneimine, vinylmethyleneimine and the like. Hydrogen atoms can also be replaced by substituents such as halogen radicals.

The hydroxy alkylene may include alkenylene radicals, linear or branched, which contain up to 9 carbon atoms, wherein at least one selected carbon atom is substituted by a hydroxy group, and the radicals may be represented by formula (C _n H _{2n. Z) (OH)} - N- (C _m H _{2 m} . _Y ) (OH) _y in which n and m are the same or different and are an integer from 0 to 9 and are 1 <n + m <9, and az and u are the same or different and are an integer to which 0 <z <to 0 <y <may + z> 1 Suitable examples for such hydroxyalkyleneamines include hydroxymethyleneaminine, hydroxyethyleneaminine (e.g. 1-hydroxyethyleneaminine and 2-hydroxyethyleneaminine), hydroxytrimethyleneaminine (e.g. 1-hydroxytrimethyleneaminine, 2-hydroxytrimethyleneaminine, 3-hydroxytrimethyleneamine), hydroxytetramethyleneamine (e.g. 2-hydroxy-tetramethyleneamine), 2-hydroxy-2-methyltrimethyleneamine, hydroxy pentamethyleneamine (e.g. 2-hydroxypentamethyleneamine), hydroxyhexamethyleneamine (e.g. (hydroxyhydroxyethyleneamines), methylenehydroxymethyleneamines, methylenehydroxyethyleneamines and the like. Particularly preferred is a lower hydroxyalkylene amine having two carbon atoms and one nitrogen atom, both carbon atoms being 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, at least one selected carbon atom being substituted by hydroxy, and these radicals may be represented by formulas in which they are the same or different and are an integer from 0 to 9 and holds l <n + m <9, azays are the same or different and are an integer for which 0 <z <n-1 and 0 <y <m-1 and y + z> 1. Suitable examples for such

- (C _{2n II. Of. 1) (OH)} = N- (C _m H _{2 m. S)} (OH) _y - (C _n H _{2n. You} .I) _(OH) -N- ( C _m H _2m ( _y ) (OH) _y , · · hydroxy al al al al hydroxy hydroxy hydroxy hydroxy hydroxy hydroxy hydroxy hydroxy al al al hydroxy al hydroxy hydroxy al al hydroxy hydroxy al al al al al al - groups include hydroxymethylenimine, hydroxyethylenimine (e.g., 1-hydroxyethylenimine and 2-hydroxyethylenimine), hydroxytrimethyleneimine (e.g. 1-hydroxytrimethyleneimine, 2-hydroxytrimethyleneimine, 3-hydroxytrimethyleneimine), hydroxytetramethyleneimine (e.g. 2-hydroxyytetramethylethylamine) - e.g. such as 2-hydroxypentamethylenimine), hydroxyhexamethylenimine (e.g. 2-hydroxyhexamethylenimine), methylene hydroxymethylenimine, methylene hydroxyethylenimine 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.

The 5- and 6-membered cyclic compounds which may be Biv may be aromatic or aliphatic and substituted, for example, with alkyl groups having up to 7 carbon atoms and hydroxy groups.

A five and six membered compounds, which may represent a rvim Rviii2 well as xi and R _2, and comprise as a ring atom adjacent one or two nitrogen or oxygen or sulfur atoms, may be saturated or unsaturated.

The alkoxy radical, unless otherwise defined, is an alkoxy radical up to 26 straight-chain or branched alkoxy radicals such as methoxy, ethoxy, etc. '. It may be substituted by hydroxy, amino, halogen, oxo and alkoxy radicals such as methoxy, ethoxy.

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

Cycloalkyl- (C 0-26) -alkyl radicals are cyclic compounds having 3 to 8 carbon atoms, which, unless otherwise defined, are bonded to the parent skeleton via an alkylene residue. The alkylene moiety 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, halogen radicals, amino radicals, oxo radicals.

··································································· I · · · · ···················

Cycloalkyl groups can also be aromatic, with the appropriate number of double bonds. is 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 moiety. The alkylene moiety 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, oxides. Cycloalkyl groups may also be multicyclic and aromatic (e.g., phenoxy, pyridoxy, naphthoxy, etc.) with the appropriate number of double bonds. Particularly aromatic cyclic compounds may further contain substituents such as nitro, CF 3 and phenyl radicals.

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

Amino- (Co-26) -alkyl groups are amino radicals which can be attached to the basic skeleton via an alkyl radical. Alkyl and amino groups are as defined above.

The silyl moieties may be substituted for example by alkyl radicals or cycloalkyl- (Co ₂ 6) -alkyl radicals as defined above.

Silyl- (Co-26) -alkyl groups are silyl radicals which can be attached to the basic skeleton via an alkyl radical. Alkyl and silyl groups are defined as above.

Thio- (C 0-6) -alkyl groups may, for example, be substituted with alkyl radicals as defined above or cycloalkyl- (C 0-26) -alkyl radicals. (C20) -alkyl groups are straight-chain or branched alkylene radicals such as methylene, ethylene, propylene, isopropylene, butylene, isobutylene, tert-butylene, pentylene, hexylene and the like. They may contain double or triple bonds, and they may contain double or triple bonds, and they may contain double or triple bonds. * May be substituted, e.g. hydroxy, amino, halogen (e.g., fluorine, bromine, chlorine), oxo and alkoxy residues such as methoxy, ethoxy.

Most preferably, residues X13 to Xvii3 and X14 to Xvii4 as well as Rviiis, Rixii, Χχΐ4, ππ and X112 may be selected to form esters on the phosphonic or sulfonyl group. Suitable examples for the esters of the compounds of the invention include mono- and diesters, and preferred examples for such esters include alkyl esters (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, hexyl, etc.);

aralkyl esters (benzyl, phenethyl, benzhydryl, trityl, etc.); aryl esters (e.g., phenyl ester, tolyl ester, naphthyl ester, etc.);

aroylalkyl esters (e.g. phenacylester); and silyl esters (e.g., trihalosilyl-, dialkyldihalosilyl-, alkyltrihalosilyl-, dialkylarylhalo-silyl-, trialkoxyhalo-silyl-, dialkylaralkylhalo-silyl-, dialkoxydihalosilyl-, trialkoxyhaloglyl, etc.).

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

X13 to Xvii3 and X14 to Xvii4 as well as Xxb and Χχΐ4, Xni and X112 are preferably the metal of the first, second or third main group of the Periodic System, ammonium, substituted ammonium or ammonium compounds derived from ethylenediamine or amino acids. In other words, the ammonium salt compounds of phosphonic acid derivatives with organic or inorganic bases (e.g., sodium salt, potassium salt, calcium salt, aluminum salt, magnesium salt, triethylammonium salt, ethanolamine salt, dicyclohexylammonium salt, salt with ethylenediamine, salt with ethylenediamine, salt with ethylenediamine). dibenzyl-ethylenediamine, etc.) as well as amino acid salts (e.g., arginine salt, aspartic acid salt, glutamic acid salt, etc.) and the like.

································

I ***** · ·························

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 substituent groups R or A or B or Y or Z or X. The use of the compounds of the invention includes all spatial isomers as well as 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.

Particularly pharmaceutically suitable are salts formed by suitable selection of _X3 (X 13 to XV ₃₎ X 4 (X 14 to XV4) and xed and X 112 as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine, triethyl salt, dicyclohexylammonium salt and as salts with an amino acid such as arginine, salt with aspartic acid, salt with glutamic acid.

The combination preparations of the invention comprise one or more fat metabolism inhibitors. They may be used as inhibitors that regulate fat intake, the same inhibitors that regulate fat synthesis. Such inhibitors include the anion exchanger, preferably cholestyramine and colestipol, βsitosterine, nicotinic acids and derivatives thereof such as nicotinyl alcohol, clofibrates and derivatives thereof such as clofibrinic acid ethyl ester, as well as analogues such as bezofibrate, 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, pyrophosphonic acid derivatives, phosphin phosphonic acid derivatives, phosphinyl diphosphonic acid derivatives, phosphinyl phosphonic acid derivatives, phosphinyl diphosphonic acid derivatives phosphinylmethylphosphonic acid, squalene monooxygenase inhibitors, and other cholesterol synthesis inhibitors.

• · ·········· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ···················

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

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

Infectious compounds and their esters, as well as their salts, exhibit potent cytotoxic activity against monocellular and multicellular parasites, fungi, bacteria, and virus-infected cells when used separately or in timed 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 application in the prevention of these diseases.

The combined preparations are effective against unicellular parasites (protozoa), in particular against malaria and sleeping sickness agents as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, acarcospherbiosis, sarcocystesbiosis, sarcocystesbiosis, sarcocystesbiosis, sarcocystesbiosis, sarcocystesbiosis, sarcocystebiosis.

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, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcocystosis, acantamebosis, naegleriosis, coccidiosis, coccidiosis.

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 the genus Actinomyces, bacteria of the genus Corynebacterium, in particular species Corynebacterium diphteriae and Corynebacterium pseudotubiaculea, Mycobacterium Mycobacterium avium; Chlamydiaceae bacteria, especially species • B B e B B B B B B

BBB B B · ·

BB B B B B ·· ·· · ·

Chlamydia trachomatis and Chlamydia psittaci, bacteria of the genus Listeria, especially Listeria monocytogenes \ bacteria of the genus Erysipelthrix rhusiopathiae, bacteria of the genus Clostridiunr, bacteria of the genus Yersinia, species Yersinia pesiis, Yersinia pseudotubiniacopiae in particular Mycoplasma pneumoniae, Brucella, Bordetella, Neiseriaceae, in particular Neisseria and Moraxela, in particular Neisseria meningitides, Neisseria gonorrhoeae and Mor axela bovis', Vibrioniume, Vibrionlese, and Pibrobioaceae, in particular, Pibrobioaceae, and Pibrobioaceae; in particular Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas species, Campylobacter species, in particular Campylobacter jejuni species, Campylobacter coli and Campylobacter fetus species, in particular Helicobacter pylori species, b Spirochaetaceae and Leptospiraceae, in particular Treponema, Borrelia and Leptospira, in particular Borrelia burgdorferi ', Actinobacillus, Legionellaceae, Legionella, Rickettsiaceae and Noccactia', and Bartuselia spp. Pseudomonadaceae, in particular Pseudomonas and Xanthomonas, enterobacteriaceae, in particular Escherichia, Klebsiella, Proteus, Providencia, Salmonella, Serratia and Shigella, bacteria of the Pasteurellaceae family, in particular Micrococcus spp. 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, listeriosis, animal robin, human and animal gas gangrene, human and animal paragonimosis, human and animal tuberculosis, leprosy and other human and animal mycobacteria, paratuberculosis of animals , plague, mesenteric lymphadenitis and pseudotuberculosis in humans and animals, cholera, legionnaires disease, human and animal borreliosis, human and animal leptospirosis, syphilis, Campylobacter enteritis in human and animals, Moraxella keratoconjunctivitis and animal brucosities • spleen in humans and animals, actinomycosis in humans and animals, streptotrichosis, psittacosis / ornithosis in animals and Q-fever and Ehrlichiosis.

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

Other combinations with another antibiotic may be used to treat the above-mentioned diseases. Particularly suitable lipid metabolism inhibitors with other antiinfective agents are isoniazid, rifampicin, etambutol, pyrazinamide, streptomycin, protionamide and dapson for the treatment of tuberculosis.

The combination preparations according to the invention can be further used, in particular, in infections with the following viruses: Parvoviridae: parvoviruses, dependoviruses, denzoviruses; · Adenoviridae. adenoviruses, mastadenoviruses, aviadenoviruses; Papovaviridae. papovaviruses, especially papillomaviruses (so-called wart viruses), polyomaviruses, in particular JC-virus, BK-virus and miopapovaviruses; Herpesviridae. all herpesviruses, in particular Herpessimplex viruses, varicela / zoster viruses, human cytomegalovirus, Epstein Barrier viruses, all human herpesviruses, human herpesvirus 6, human herpesvirus 7, human herpesvirus 8; Poxviridae \ poxviruses, orthopox-, parapox-, molluscum-contagiosum-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; Hepadna viruses: all hepatitis viruses. Hepatitis B viruses, hepatitis D viruses; Picornaviridae '. picornaviruses, all enteroviruses, all polioviruses, all coxsack viruses, all echoviruses, all rhinoviruses, hepatitis-A-virus, aftoviruses; · Calciviridae. hepatitis E virus; 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 stomatitis virus; · Coronaviridae. coronaviruses; Bunyaviridae: bunyaviruses, nairovirus, flebovirus, uucvirus, hantavirus; Árenaviridae \ arenaviruses, lymphocytic choriome70 · t · t t t t t t t t t t t t t t t t t t 9

9999 99 99 ·· ··· ningitis virus; Retroviridae. retroviruses, all HTL-viruses, human Tcell leukemia virus, oncornaviruses, spumaviruses, lentiviruses, all HI-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, especially genital tumors caused by papillomaviruses in humans. Eradication of JC-and BK-viruses, eradication of herpesviruses, eradication of human herpesviruses 8 for treatment of Kaposi's sarcoma, eradication of cytomegalitic viruses prior to transplantation, eradication of Epstein-Barr viruses prior to transplantation for hepatitis virus-associated viral prophylaxis with episodes of hepatitis B for the prophylaxis of liver tumors and liver cirrhoses, 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, respiratory tract infection , pharyngitis, bronchitis, pneumonia), sensory organs (keratoconjunctivitis), nervous system (poliomyelitis, meningoencephalitis, encepha lithitis, subacute sclerosing panencephalitis, SSPE, progressive multifocal leukoencephalopathy, lymphocytic choriomeningitis, stomach and intestinal tract (stomatitis, gingivostomatitis, esophagitis, gastritis, hepatitis, gastroenteritis gastroenteritis) (mononucleosis, lymphadenitis), hematopoietic system, genital organs (mumpsorchitis), skin (warts, dermatitis, Herpes labialis, fever blisters, Herpes zoster, shingles), mucous membranes (papillomas, conjunctivaplasty, hyperplasia, dysplasia) (arthritis, myocarditis, endocarditis, pericarditis), kidney and urinary tract, genital organs (anogenital lesions, warts, genital warts, congested condylomas, dysplasias, papillomas, cervical dysplasias, condyloma a········· · * ·· • 4 · cuminate, epidermodysplasia verruciformis), locomotive organs (myositis, myalgia), treatment infections of papule and hoofed animals, 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, including, generally, pharmaceutically acceptable salts, esters, salts of such esters, or even compounds which upon administration provide compounds of the invention as metabolism or degradation products, also called prodrugs, can 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.

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

Tablets, dragees, capsules, pills, and granules may optionally be provided with opaque compositions comprising coatings and packagings and formulated in such a way that they deliver the active substances only or preferentially in a certain part of the intestinal tract, optionally elongated, substances and waxes.

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

The suppositories may contain, in addition to the active ingredients, conventional, water-soluble or water-insoluble carriers, e.g. polyethylene glycols, fats, e.g. cocoa butter and higher esters (e.g., Cu-alcohol with C 18 -fatty acid) or mixtures thereof.

Ointments, pastes, creams and gels may contain, in addition to the active ingredients, conventional carriers, e.g. 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, e.g. milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures thereof. The sprays may additionally contain conventional expellers e.g. chlorofluorocarbons.

Solutions and emulsions may contain conventional carriers such as solvents, solubilizers and emulsifiers, e.g. water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glyceral, , tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan fatty acid esters or mixtures thereof.

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, customary carriers such as liquid diluents, e.g. water, ethyl alcohol, propylene glycol, suspending agents e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitan esters and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agaragar and tragacanth, or mixtures thereof.

The active compound (s) of the formulas (I) to (XIV) should preferably be present in the above pharmaceutical preparations 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 which are administered as a rule are 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 (pamidronate).

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

Thus, the combination preparations according to the invention may further comprise sulfonamide, sulfadoxin, artemizinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesine, tetracycline, doxycycline, proguanil, metronidazole, praziquantil, nicazanebendine, tazacycline, nicazamidine, tendacycline, niclozamide, piperazine, pyrivine, metrifonate, oxamnichine, bitionol or suramine or more.

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 substance (s).

In particular in amounts of from about 0.5 to about 200, in particular from 1 to 60 mg / kg body weight. Of course, it may be desirable to deviate from the aforementioned dosage, depending on the type and body weight of the patient to be treated, the type and severity of the disease, the type of formulation and the drug being administered, as well as the time period and time. the interval at which administration takes place.

In order to obtain the desired effects, fat metabolism inhibitors have been shown to be administered in dosage ranges known to treat 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 in 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 of body weight. Of course, it may be desirable to deviate from the aforementioned dosage, depending on the type and body weight of the patient to be treated, the type and severity of the disease, the type of formulation and the drug being administered, as well as the time period and time. the interval at which administration takes place. Thus, the aminobisphosphonates have to be taken into account that their resorbability is very low. This property is an advantage in the intestinal involvement (for example in the case of amoebic dysentery). Here oral doses of pamidronate up to 10 mg / kg body weight are administered. Injection rates of up to 2 mg / kg body weight are generally sufficient.

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 skill of the artisan

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

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

·· ·· ····

DETAILED DESCRIPTION OF THE INVENTION

Production of anti-infective agent

(1) The required amount of sterile, anti-infectious agent, 500 mg of 3- (N-acetyl-N-hydroxylamino) propylphosphonic acid monosodium salt and 90 mg of 3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid disodium salt were divided into vials or ampoules. The vials were hermetically sealed to eliminate bacteria. It is injected in 500 ml of saline.

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

(2) 250 mg of 3- (N-formyl-N-hydroxylamino) propylphosphonic acid monosodium salt and 1 mg of 3-methylpentylamino-1-hydroxypropylidene-1,1-bisphosphonic acid disodium salt are used 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 acid disodium salt are used as the active substance for injection

Production of tablets

A suitable tablet formulation was made with the following mixtures:

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

Lovastatin 10 mg

mannitol

400 mg · e · e e · e e e e e mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg mg ·· ·· ·· ·· ··· ·· ·· ····

starch

Magnesium stearate mg mg

Manufacture of capsules

3- (N-formyl-N-hydroxylamino) propylphosphonic acid monopotassium salt

300 mg

Simvastatin mg

Magnesium stearate mg

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

Claims (22)

PATENT CLAIMS Combination preparation, characterized in that it contains, as active substances, at least one anti-infectious compound which inhibits the metabolic pathway of 2-C-methylerythrose-4 and at least one fat metabolism inhibitor, wherein the fat metabolism inhibitor and the anti-infective compound are not identical. Combined preparation according to claim 1, characterized in that the fat metabolism inhibitors are selected from the group consisting of cholestyramine, β-sitosterol, colestipol, probucol, nicotinic acid, nicotinyl alcohol, clofibrinic acid derivatives and analogues of clofibrinic acid derivatives, HMG- inhibitors CoA synthetases, HMG-CoA reductase inhibitors, squalene synthetase inhibitors and squalene monooxygenase inhibitors. Combination preparation according to claim 2, characterized in that the fat metabolism inhibitors are inhibitors of squalene synthetase, in particular pyrophosphates, pyrophosphate derivatives, bisphosphonic acid derivatives, phosphinylmethylphosphonic acid derivatives, phosphinylformyl derivatives, phosphonocarboxy derivatives, phosphonosulfonic acid derivatives, acid derivatives fosfinylmetylfosfónovej. Combined preparation according to claim 2, characterized in that the inhibitors of fat metabolism 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 derivatives of clofibrinic acid and analogues thereof, in particular gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate and clinofibrate. Combined 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 ibandronate, alendronic acid derivatives, in particular alendronate , zoledronic acid derivatives, in particular zoledronate, rizedronic acid derivatives, tiludronic acid derivatives and cimadronic acid derivatives. Combination preparation according to one of Claims 1 to 6, characterized in that it contains as an active substance at least one aminohydrocarbylphosphonic acid derivative of the formula I: while R 11 and R 12 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, 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 alkyl of 1 to 26 carbon atoms; And unsubstituted hydroxyalkyl of 1 to 26 carbon atoms, from substituted and unsubstituted aryl, substituted and unsubstituted hydroxyalkyl of 1 to 26 carbon atoms. unsubstituted acyl, 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 and X 14, X 14, halogen, X 14, X 14, X 13 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 alkyl. 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 or inorganic base, a third major group 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: wherein one or more of the carbon atoms selected from C 13, C 14, C 15, together with their substituents may be absent and at least one of the existing substituents B 1 to B ₁₀ is C ₃ . ₈ -cycloalkyl- (C 0 - 9) alkyl, wherein as C 3-8 -cycloalkyl as well (C 0-9) 80, the alkyl group may have one or more double groups. bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms, and wherein both cycloalkyl and alkyl may be substituted by hydroxy-, halo-, oxo, branched or unbranched C 1-9 -alkyl and C 2-9 -alkenyl, wherein C 1-9 -alkyl and C 2-9 alkenyl groups may be substituted with hydrogen, hydroxy, amino, halogen and oxo and the remaining existing substituents Bn to Bno are selected from the group consisting of hydrogen, hydroxy, halogen, amino, C 1-6 -alkyl radicals, C 1-6 -alkoxy radicals, C 1-6 -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; alcoholic the xyl 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. Combination preparation according to one of Claims 1 to 6, characterized in that it contains, as the active substance, at least one bisphosphonic acid of the general formula II wherein: X111, X112, X113, X114, which may be the same or different and 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 of the first 1., 2. and 3. main group · · φ · φ · · · · · · · φ · · · ® · φφ φφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφφ Pins 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 absent, 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 radical; and SR, II3, C1 and -NR113R114, wherein R113, R114 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 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. 9th Combination preparation according to one of Claims 1 to 6, characterized in that it contains as active substance at least one compound of the general formula III: where ·· ·· ···· Rome 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 aryl and unsubstituted aralkyl, substituted and unsubstituted heterocyclic, halogen, OXnn, wherein Xiiii is selected from the group consisting of hydrogen, substituted and unsubstituted acyl, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted, unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, silyl, substituted a substituted and unsubstituted 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 , substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic, halogen and OXm4 and OXnn, wherein Χ1Π4 and X1 113 are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted alkyl, substituted and unsubstituted substituted and unsubstituted aralkyl, substituted and unsubstituted cycloalkyl, silyl, substituted and unsubstituted heterocyclic radicals, cations of organic and inorganic bases, in particular metal of the first, second but bo third main trial83 99 9999 ·· · · · · · ··· 99 99 99 9 of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids, and A 1 and A 2, of which one or both may be absent, are the same or different and represent an alkylene radical, an alkenylene radical, an oxo group, a hydroxy group or an oxo-hydroxyalkylene radical. Combination preparation according to one of Claims 1 to 6, characterized in that it contains as an active substance at least one compound of the general formula IV: rivi Riv3 Riv 4 wherein Riv 1 and Riv 2 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, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen, OXiv 1 and O xiv 2, wherein Xiv 1 and Xiv 2 may be the same or different and are selected from the group consisting of substituted hydrogen, unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, ·· • · ·· • · ·· • · ···· • ·· · • • · · • · • i · · • e • • • · • • · • · • • · · ···· · · · · t · · · Biv is selected from the group consisting of ether group IVA --- A | _V 1 --- 0 --- A | v2 --- I --- (I VA) Wherein wherein Äivi and iviv2, in which ivivi may be absent, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, keto IVB ABOUT --- A | V3 ------ A | y4 --- (iVB) wherein Aiv3 and Aiv4, one or both of which may be absent, are the same or different and are selected from the group consisting of an alkylene moiety , an alkenylene radical and a hydroxyalkylene radical, and a 5- and 6-membered cyclic, in particular heterocyclic compound, containing, in addition to carbon, at least one heteroatom as part of the ring, the heteroatom being 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 up to 26 carbon atoms, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OXiv3 and OXiv4, Where Xiv3 and Xiv4 may be the same or different, and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl of up to 26%; 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 unsubstituted heterocyclic radical, silyl, cation of an organic and inorganic base, in particular a metal of the first, second or third main group 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 salts esters. Combination preparation according to one of Claims 1 to 6, characterized in that it contains as an active substance at least one phosphonic acid derivative of the general formula V: OH OXv4 taking Av 1 and Av 2, of which one or both may be absent, are the same or different and are selected from the group consisting of alkylene, alkenylene and hydroxyalkylene, and in particular a -Avi-CHOH-Av2-carbon chain composed of 2 to 5 carbon atoms, preferably preferably of 3-4 carbon atoms, Bv is selected from the group consisting of the remainder of the formula VA wherein Rvi 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 cycloalkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted halogen, from the rest of formula VB Ry ² Rv3 Wherein Rv2, Rv3 and Rv4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted alkyl; unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted C, C, and C, heterocyclic, ) ·· ·· ··········································································· Wherein R vs, R v6 and R v7 are the same or different and are selected from the group consisting of hydrogen, OH, substituted and unsubstituted alkyl, substituted and unsubstituted a 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 radical, and halogen, and wherein X _{in the} 3 or XV4 may the same or different and 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 heterocyclic radicals, silyl, cations of organic and inorganic bases, in particular of metal of the first, second or third a major 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. Combination preparation according to one of Claims 1 to 6, characterized in that it contains as active substance at least one compound of the general formula VI: Bvi --- I --- Rv | 3 (VI) RVI4 with 9 9 9 9 9 9 9 9 9 9 9 99 99 99 99 Rvb and Rvu 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 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, halogen, OXvi3 and OXvi4, and OXvi4 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 aryl. 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 and inorganic base, in particular a metal a third major group of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids; and Bvi is selected from the group consisting of VIA Rvik yJ --- Avi --- (VIA) Rvi2 ^Z and VIB RVU - N = Avi-- (VIB) in which Avi is selected from the group consisting of an alkylene amine residue, an alkenylene amine residue, a hydroxyalkylene amine residue, an alkyleneimine residue, an alkenyleneimine residue and a hydroxyalkyleneimine residue, the nitrogen atom being in the chain linking the phosphorous atom to the nitrogen atom of the group or group A line in which Rvn and Rvi2 in group VIA are the same or different and Rvn and Rvi2 for group VIA and Rvn 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 heterocyclyl, OX, halogen, Xvii and Xvi2 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 , substituted and unsubstituted 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: RVIP (villas) RviH in which Avn is selected from the group consisting of a (C 1-9) -alkyl radical, which may have one or more double bonds and may be substituted with hydroxy, halogen, amino, branched or unbranched C 1-9 -alkyl and C 2-9 alkenyl groups wherein the C 1-9 -alkyl and the C 2-9 -alkenyl groups may be substituted by hydrogen, hydroxy-, amino-, halogen- and oxo, -COC- and -CNC-, wherein the -COC- and -CNC- carbon atoms may be substituted with alkyl of up to 7 carbon atoms or hydroxy, or wherein Avn is of the following formula VIIA: (VIIA) wherein one or more carbon atoms selected from Cvib, Cvii4, Cvii5, together with their substituents may also be absent and at least one of the existing substituents Bvm to Bvmo is C 3-8 cycloalkyl- (C 0 -C 9) -alkyl, wherein both C 3-8 -cycloalkyl and C 0-9 -alkyl 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 and alkyl groups may be substituted hydroxy groups91, halogen, amino, branched or unbranched C1-C9-hydroxy groups; -alkyl and C 2-9 -alkenyl groups, wherein the C 1-9 -alkyl and C 2-9 -alkenyl groups may be substituted with hydrogen, hydroxy, halogen, amino and oxosines and the remaining exi the substituents Bvm to Bvnio are selected from the group consisting of 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 taken together form an oxo group, wherein each C 1-6 -alkyl radical and each C 1-6 -alkoxy radical may be branched or unbranched, saturated or unsaturated with one or more double bonds and may be substituted with hydroxy, amino, halo and oxo groups, in which Rv 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 by hydroxy, halogen , amino, branched or unbranched C 1-8 -alkyl and C 2-9 -alkenyl, wherein the C 1-9 -alkyl and the 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, amino, halogen and oxo groups in which: Rvii3 and Rvii4 are the same or different and are selected from the group consisting of hydrogen, 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 C 1-6 -alkenyl, substituted and unsubstituted C 1-6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OXvIII and OXvIII, wherein: Xvii3 and Xvii4 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C1-C4. ₂ 6 alkyl, substituted and unsubstituted hydroxy-C. ₂ 6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C. ₂ 6 alkenyl, substituted and unsubstituted C]. ₂ 6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine 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 VIII as active substance: RviiH (vili) wherein wherein the wavy line indicates a bond having either a or β configuration, n is 0 or 1, · · · · · · ··· ···· · · · · ··· · · ··· R vnm 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 and unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyl substituted and unsubstituted C 1-6 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, halogen and OXvnm, wherein: Xvimi 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 C 1-6 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, cations of 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 Rvmi is selected from the group consisting of C 24-alkyl radicals, C2.24alkenylové radicals, C2-24-alkapolyénové radicals containing 2 to 6 double bonds, C ₂ .24-alkynyl radicals, C _{3. 8} -cycloalkyl radicals, C3. _8- cycloalkyl-C1-24-alkyl radicals and C1-12-alkoxy-C1-12-alkyl radicals, Rvni2, Rvih3 and Rviii4 are each independently selected from the group consisting of hydrogen, halogen, amino, acetylamino, azido, and XRviii, wherein X is O or S and Rvuie is selected from the group consisting of hydrogen, branched or C1-4 alkyl radicals and C2-4 alkenyl radicals, wherein both C1-4 alkyl radicals and C2-4 alkenyl radicals may be optionally substituted by hydrogen, amino-, halogen- or 0x0-, or · · · · · · · · · · · · · · · · · · 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99 99 99 99 99 99 999 Rviii2, Rviii3 and Rvni4 together with the respective geminal hydrogen group give an oxo group, R VIII is selected from the group consisting of hydrogen, Ci-24-alkyl, _C3 8-cycloalkyl, Ar (C 24 alkyl) groups, aryl groups, acyl groups, heterocyclic radicals, halogen, wherein all radicals may be branched or unbranched and may be optionally substituted by hydroxy-, amino-, halogen- or oxo- and may contain 2-6 double and triple bonds, or Rviiis is a phenyl radical of formula VIIIA or VIIIB, (VIIIA) wherein: VIII8 Rviii7 and Rviiis are the same or different and are attached at two arbitrary positions of the phenyl ring and are each independently selected from the group consisting of hydrogen, halogens, C 1-4 -alkyl radicals, C 1-4 -alkoxy radicals, formyl, acetyl, propionyl or butyryl, formyloxy-, acetoxy-, propionyloxy-, butyryloxy-, C2-5alkoxycarbonyl radicals, all of which may be branched or unbranched or Rvnn and Rviiis together may form an alkylene chain of 3 to 4 carbon atoms which is bonded to adjacent positions, e.g. The 2,3-position or 3,4-position of the phenyl ring, or Rv17 and Rviiis together form a methylenedioxy radical, 1,1-ethylidenedioxy radical or 1,2-ethylenedioxy radical, which are bonded to the 2,3- or 3-radical. , 4-positions of the phenyl ring, or Rviiis is selected from the group consisting of Rviii9COOCHRviiiio- and Rviii90COOCHRvii-> wherein Rviii9 is selected from the group consisting of Ci.e-alkylamino, C2-6-alkenyl radicals, C ₂ -6-alkynyl radicals, C 3-8 · · · · · · · · · 4 ···· 9 9 9 9 9 9 9 9 9 99 9999 · 9 · cycloalkyl radicals, C 3-8 -cycloalkyl-C 1-6 -alkyl radicals and C 1-6 -alkyl radicals; 6-alkoxy-C 1-6 -alkyl residues, all of which may be branched or unbranched and optionally substituted by hydroxy, amino-, halogen- or oxo-; R vmio is a branched or unbranched C 1-4 alkyl moiety, and wherein the configuration of the substituents R vni2, Rvni3. Rvni4 and RvnisOOCPO (OH) OCH2- in (VIII), when n is 1, are independently D-gluco, L-gluco, Dgalacto, L-galacto, D-mano, L-mano, D-talo, L-talo, D-alo, L-alo, Daltro, L-altro, D-gulo, L-gulo, D-ido or L-ido, or Rviii2, Rviii3, and Rviii5OOCPO (OH) OCH2- in (VIII) substituent configurations 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: W / V '(ix) where 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: Xixn is selected from the group consisting of hydrogen, substituted and unsubstituted C 1. ₂ 6 -alkyl, substituted and unsubstituted hydroxy-C 26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 26-alkenyl, substituted and unsubstituted C 26alkinylu, substituted and unsubstituted cycloalkyl, substituted and unsubstituted a heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids, wherein: Rix 1 and Rix 2 are now independently selected from the group consisting of C 1-4 alkyl, C 3-8 -cycloalkyl, C 3-8 -cycloalkyl-C 1. C 1 -C 24 -alkyl radicals, C 1 -C 24 -alkoxy radicals, C 1 -C 24 -alkylthio radicals, C 1 -C 24 -alkylthio radicals; ₂ 4-alkoxy-C 1-24 alkyl radicals, C 1-24 alkylthio-C 1-2 alkyl radicals, acyl radicals, aryl radicals, aralkyl radicals, heterocyclic radicals, halogen and hydrogen, and each C 1-4 alkyl and C 1-4 -alkoxy radicals the 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 C1-24-alkoxy radicals, C1-24-alkylcarbonyloxy radicals, C1-2 -24-alkoxycarbonyloxy radicals, C124 alkylthio radicals, C1-4alkyloxycarbonyloxy radicals, C1-4alkylthio radicals; _{2-4-alkylcarbonylthio} radicals, C1.24alkylamínovými radicals, di (C 24 alkyl) amino radicals, C1.24alkylkarbonylaminovými radicals, C 24 -alkyl- (C. ₂ 4-alkylcarbonyl) amino radicals, C 24 alkoxycarbonyl, amino radicals or C1-24-alkyl- (C1-24-alkoxycarbonyl) amino radicals, wherein each aralkyl radical, a heterocyclic radical, a C1 -C4 -alkynyl radical or a C1 -C4 -alkyloxycarbonyl radical, a C1 -C4 -alkyloxycarbonyl radical; _The 2-4-alkyl radical and the C1-24-alkoxy radical may be branched or unbranched, saturated or unsaturated with from 2 to 6 double or triple bonds, or Wherein Rix 1 -CH-CH-Rix 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. 24-alkyl radicals, C1-24-alkoxy radicals, C1-24-alkylthio-radicals, C1-24-alkylamino-radicals, di (C1-24alkyl) amino-radicals, C1-24-alkylcarbonyl radicals, C1-24-alkylcarbonyloxy radicals , Ci. ₂ 4-alkoxycarbonyloxy radicals, C1-24 alkylcarbonylthio radicals or C1-24-alkylcarbonylamino radicals, wherein each C1-24-alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 double bonds, or wherein Rixio is branched or an unbranched C 1-4 alkyl radical, and wherein Rix 1 -CH-CH-Rix 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-alose, D-altrose, D-gulose, D-idose, or the corresponding L- isomers, wherein the hydroxyl groups may be optionally appropriately substituted by hydrogen, amino-, azido-, 0x0-, mercapto-, or C 1-24 -alkoxy radicals, C 1-6 -alkyl, C 1-8 -alkoxy, or C 1-8 -alkoxy; ₂₄ -alkyltiozbyškami, C ₂ 4-alkylamino radicals, di (C | .24-alkyl) amino radicals, C1.24alkylkar-carbonyloxy radicals, C-24-alkylcarbonylthio radicals, C1.24alkylkarbonyl-amino radicals, 2 C ₄ alkyl- (C 2 ₄ alkylcarbonyl) amino radicals, wherein each C] .24 alkyl radical may be branched or unbranched, saturated or unsaturated with 1 to 6 double bonds, and pharmaceutically acceptable salts, esters, and amides and ester salts as well as their optical isomers. Rix 1 and Rix 2 can each independently be independently selected from the group consisting of carboxyl residues, carboxamide residues, aryl residues, aryloxycarbonyl residues, aryl-C 1. ₂ 4-alkyl radicals, C ₂ 4-alkoxycarbonyloxy radicals, C. ₂₄ -alkylaminokarbonylové radicals, di (Ci. ₂₄ alkyl) aminocarbonyl radicals, aryl radicals 2alkyl ₄ -alkoxycarbonyl, aryl-2alkyl -alkylaminokarbonylové ₄ radicals, C. _24- alkylcarbonyloxy- (Ci. ₄ ) alkylmethoxycarbonyl radicals, C 1-6 alkyl; _{24--alkoxykarbonyloxy} The methoxycarbonyl radicals, C] .2 ₄ -alkoxycarbonyloxy- (Ci. ₄ alkyl) methoxy-xykar ·· ·· ·· ·· ···· ···· · · · · · · · · • Bonyl radicals, wherein each C 1-4 -alkyl radical may be branched or unbranched, saturated or unsaturated with 2 to 6 carbon atoms; 6 double bonds and each C 1-4 -alkyl radical and C 1-4 -alkoxy radical may be branched or unbranched and saturated or unsaturated and each aryl radical of formula IXA 1X4 (IXA) where Rix 3 and Rix 4 are the same or different and are each independently selected from the group consisting of hydrogen, halogens, C 1-4 alkyl, C 1-4 alkoxy, formyl, acetyl, propionyl or butyryl, formyloxy-, acetoxy-, propionyloxy -, butyryloxy-, C 1-4 -alkoxycarbonyl radicals, all of which may be branched or unbranched, or Rix 3 and Rix 4 may together form an unbranched, saturated C 3 -C 4 alkylene chain which is bonded to adjacent positions of the phenyl ring or R 1 _{X 3,} and Rix ₄ together form a methylenedioxy radical, a 1,1-ethylidenedioxy radical or a 1,2-ethylenedioxy radical which are attached to adjacent positions of the phenyl ring. Combination preparation according to one of Claims 1 to 6, characterized in that it contains as an active substance at least one compound of the general formula X: in which · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · R xi is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1-8 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl , substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen and ΟΧχι, wherein: Xxi is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -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 radicals, wherein R 2 2 is selected from the group consisting of C 1-6. _2-6 alkylamino, Ci-26-alkoxy radicals, C ₂ -C 6 -alkoxy-Ci.26-alkyl radicals, C3. 8-cycloalkyl- (Co-26) -alkyl residue, wherein one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur, each C3.26-alkyl residue and each C 3 _'2 6-alkoxy radical can be branched, and straight and each a C 3-8 -cycloalkyl radical, each C2-26-alkyl radical and each C2-26-alkoxy radical may be saturated or unsaturated with one or more double bonds and each _C3-.8 cycloalkyl group, each C _The 2-6-alkyl radical and each C 1-6 -alkoxy radical may be substituted by hydroxy-, amino-, halogen and oxo- or carbyl COCR 3 groups, wherein R 3C 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 and unsubstituted aralkyl, substituted and unsubstituted C 1-6 -alkenyls lu, substituted and unsubstituted C1.26BB * Β · Β ·· BB BB B BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB BB ···· B · BB BB · 100 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen and O3χ3, wherein Χχ3 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 C 1-6 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radicals, silyl, anorganic barium, cationic barium metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium, and ammonium compounds which 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: wherein Ζχι is a phosphorus or sulfur atom in which the Axium is an unbranched C2-9-alkylene chain with substituents which may be the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, amino and oxo, a C ₂ 6 alkyl radicals, Ci.26 alkoxy radicals, C. ₂ 6-alkoxy-C 1. _2-6 alkyl, or C 3-8 cycloalkyl- (9) -alkyl, wherein each Cl-26-alkyl residue and each C 26-alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double bonds and may be substituted by hydroxy, amino, and h 101 logén- and oxo groups, such as C3-8-cycloalkyl, and Co-9-alkyl, _C3-.8 cycloalkyl (Co-9) alkyl groups can have one or more double bonds and one or two carbon atoms of the cycloalkyl groups may be be replaced by nitrogen, oxygen or sulfur atoms and wherein both cycloalkyl and alkyl can be substituted by hydroxy, halogen, amino and oxo groups with branched or unbranched C 1-9 -alkyl and C 2-9 -alkenyl, wherein the C 1-9 -alkyl and the C 1-9 -alkyl; ₂ .9-alkenyl may be substituted by hydrogen, hydroxy, amino, halo, and oxo groups, wherein RXII and Rxi2 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C1.9alkylu, substituted and unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen, OXxn and ΟΧχι ₂ , wherein Xxu and Χχπ are the same or different and are selected from the group consisting of hydrogen, and unsubstituted C 1-9 alkyl, substituted and unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals wherein 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. ₂ 6 -alkyl, hydroxy-C 26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted Ci-26-alkenyl, substituted and unsubstituted C. ₂ 6 -alkynyl, substituted and 102 9 9 99 unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, ΟΧχπ and ΟΧχι ₄ , where Χχπ and Χχι ₄ may be 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 aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26-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 their pharmaceuticals prij salts, esters and amides, and ester salts. Combination preparation according to one of Claims 1 to 6, characterized in that it contains as active substance at least one compound of the general formula (XII): ΪΙ ^ ΧΙΗ --- N --- O --- Rxi | 3 (XII) where Αχπ is selected from the group consisting of hydrogen, substituted and unsubstituted C 1-28 -alkyl residues, substituted and unsubstituted alkoxy- (C 0-28) -alkyl groups, substituted and unsubstituted cycloalkyl- (C 0-28) -alkyl groups, 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) groups. ) -alkyl radicals and halogen, each alkyl radical; 103 ·· 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 radical may be saturated or unsaturated with one or more double or triple bonds and one or more radicals; two carbon atoms of cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, Rxii3 is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted alkoxy- (C 0-6) -alkyl, substituted and unsubstituted C 3-14 cycloalkyl- (C 0-6) -alkyl, substituted and unsubstituted cycloalkoxy - (Co-26) -alkyl groups, substituted and unsubstituted amino- (Co-26) -alkyl groups, substituted and unsubstituted silyl (Co-26) -alkyl groups, and substituted and unsubstituted thio- (Co-2e) alkyl groups, each 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 group may be replaced by a nitrogen, oxygen atom or sulfur, or a carbon chain of two C-atoms in Αχπ with Rxm forms a ring 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- (C0-26) -alkyl groups, wherein each alkyl radical and each acyl radical may be branched or unbranched, and each alkyl moiety, each acyl moiety 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. ·························· 104 ·· ···· ··· Combination preparation according to one of Claims 1 to 6, characterized in that it contains as active substance at least one compound of the general formula (XIII): wherein n is an integer from 0 to 4 and wherein Rxime, Rxiii2, Rxih3, Rxiii4, Rxiii5 and Rxnie are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted and unsubstituted cycloalkyl radicals, substituted and unsubstituted cycloalkyl radicals, - (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. 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: φ • · φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ · · • φ φ φ (xiv) where Υχιν is Ci. _{A 3-} alkenylene group which is substituted with substituents Rxivi and Rxiv2 and optionally substituents Rxiv3 to Rxiv4, wherein: RxIVi to RxIVs are the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, substituted and unsubstituted alkyl, substituted and unsubstituted cycloalkyl (C 0-2) -alkyl, substituted and unsubstituted cycloalkoxy (C 0-) (26) -alkyl, substituted and unsubstituted alkoxy- (Co-26) -alkyl, substituted and unsubstituted amino, and substituted and unsubstituted thio- (Co-26) -alkyl, substituted and unsubstituted sulfonyl- (Co-26) -alkyl, substituted- 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 radical 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, t oxygen or sulfur atoms and Rxivi3 and Rxívu are defined as Rxívi to Rxívs, or together form an oxo group, where Ζχιν is a phosphororganic group Rxívio ·············································· ···· ·· ·· ·· · 106 wherein R xiv 9 and R xivio are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted (C 1-2) alkyl, substituted and unsubstituted hydroxy (C 1-26) alkyl, substituted and unsubstituted cycloalkyl- (Co) -26) alkyl groups, substituted and unsubstituted acyl, halogen, OXxIV 9 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 and each cycloalkyl radical may be saturated or 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, wherein Χχιν9 or Χχινιο may be the same or different and selected from the group consisting of hydrogen, substituted and I carry substituted and unsubstituted cycloalkyl- (Co26) -alkyl groups, substituted and unsubstituted acyl, silyl, cations of organic and inorganic bases, in particular of the first, second and second metal, substituted or unsubstituted hydroxy (C1-26) -alkyl groups or a third major group of the periodic system, ammonium, substituted ammonium, and ammonium compounds 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 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, or wherein Ζχιν is an amino group N ---- ---- Rxívii RXIV11 ·· MM • · 107 44 ·· · 4 · 4 · 4 4 4 4 44 ·· · 4 ··· 444 444444 44 ··· ···· · 'and the Rxívii Rxivi2 are the same or different and are selected from the group consisting of H, substituted and unsubstituted alkyl groups, substituted and unsubstituted cycloalkyl- (C ₀ 26) -alkyl, substituted and unsubstituted cycloalkoxy- (C 0-6) -alkyl groups, substituted and unsubstituted alkoxy- (C 0-6) -alkyl groups, 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 the 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, wherein Βχιν is selected from the group consisting of substituted and unsubstituted C 1-6 -alkenylene groups wherein one C-atom may be replaced by an oxygen atom and one C-atom of a sulfur atom, or two C-atoms may be replaced by an S-heterocycle and wherein each alkenylene radical may be branched or unbranched and saturated or unsaturated with one or more double or triple bonds and substituted with one or more hydroxy, halo 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 man, animal and plant and as a herbicide in plants. Use according to claim 21, characterized in that the infectious processes are caused by unicellular or multicellular parasites, fungi, bacteria or viruses.