CN1328464A - Use of phosphonoformic acid derivatives for treating infections - Google Patents
Use of phosphonoformic acid derivatives for treating infections Download PDFInfo
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- CN1328464A CN1328464A CN99813747A CN99813747A CN1328464A CN 1328464 A CN1328464 A CN 1328464A CN 99813747 A CN99813747 A CN 99813747A CN 99813747 A CN99813747 A CN 99813747A CN 1328464 A CN1328464 A CN 1328464A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P33/00—Antiparasitic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/04—Amoebicides
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- A61P33/00—Antiparasitic agents
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- A61P33/06—Antimalarials
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Abstract
The invention relates to the use of a compound of formula (I) for the prophylaxis and therapy of infectious processes in humans and animals, which processes are induced by bacteria, fungi or parasites. The inventive compound is also used as fungicidal, bactericidal or herbicidal agent in plants.
Description
The present invention relates to phosphonoformic acid derivatives in prevention and treatment since the infection of the humans and animals that antibacterial, fungus or parasite cause and in plant as antifungal, antibacterial and the herbicide applications of plant.According to the present invention, described phosphonoformic acid derivatives comprises that its physiology goes up compatible salt, ester and amide.
Known phosphonoformic acid derivatives has antivirus action.4215113rd, 4339,4665062 and No. 4771041 United States Patent (USP)s have been described treatment medicine for treating viral infections preparation.
Specifically, WO98/16537 and WO 98/25938 have described the antivirus action of phosphonoformic acid derivatives and its preparation.
Disease and the alternative scope of protective plant for the broadening treatment humans and animals; the pharmaceutical preparation that is provided is provided not only wants active high; and it is littler than the side effect of other medicines preparation or plant quarantine agent; and the influence to environment is less, and is therefore littler to the danger of human beings'health.
Thereby an object of the present invention is to provide a kind of material that can satisfy above demand, it can be widely used in treatment because the humans and animals that antibacterial, fungus and parasite cause infects, and also can be used for antifungal, antibacterial and the herbicide of plant as plant.
Very surprisingly, the defined chemical compound of claim 1 can reach this purpose.This class material has anti-infectious function to antibacterial, fungus and unicellular and many cells parasite, also can be used for antifungal, antibacterial and the herbicide of plant as plant.
According to the present invention, employed organic phosphorus compound has following general formula I:
Wherein: R
11Be selected from one group that forms by following radicals: C
1-26Alkyl contains the C of the two keys of 1-6
2-26Alkenyl contains 1-6 triple-linked C
2-26Alkynyl group, C
1-6Acyl group, aryl-C
0-26Alkyl, C
3-8Cycloalkyl-C
0-26Alkyl contains the C of or two nitrogen, oxygen or sulfur
3-8Heterocyclylalkyl-C
0-26Alkyl, halogen and OX
11, wherein above-mentioned all groups can be by C
1-9Alkyl, C
1-9Alkoxyl, hydroxyl, amino, halogen or oxo group replace, wherein X
11Be selected from one group that forms by following radicals: hydrogen, C
1-26Alkyl contains the C of the two keys of 1-6
2-26Alkenyl contains 1-6 triple-linked C
2-26Alkynyl group, aryl-C
0-26Alkyl, C
3-8Cycloalkyl, C
1-26Acyl group contains the C of or two nitrogen, oxygen or sulfur
3-8Heterocyclylalkyl-C
0-26Alkyl, C
1-26Silicyl, wherein above-mentioned all groups can be by C
1-9Alkyl, C
1-9Alkoxyl, hydroxyl, amino, halogen or oxo group replace, and X
11The metal that comprises I, II and III main group in organic and cation, the especially periodic table of elements inorganic base, ammonium replaces ammonium and by ethylenediamine or amino acid derived ammonium compounds, R
1And R
2Be independently selected from one group that forms by following radicals respectively: C
1-24Alkyl, C
3-8Cycloalkyl, C
3-8Cycloalkyl-C
1-24Alkyl, C
1-24Alkoxyl, C
1-24Alkylthio group, C
1-24Alkoxy-C
1-24Alkyl and C
1-24Alkylthio group-C
1-24Alkyl, acyl group, aryl-C
1-24Alkyl, C
3-8Heterocyclylalkyl-C
0-24Alkyl, halogen and hydrogen, and each C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contains the undersaturated group of the two keys of 2-6, can be selectively by hydroxyl, amino, sulfydryl, halogen, oxo or C
1-24Alkoxyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkoxy-carbonyl oxy, C
1-24Alkylthio group, C
1-24Alkyl-carbonyl sulfenyl, C
1-24Alkyl amino, two (C
1-24Alkoxyl) amino, C
1-24Alkyl-carbonyl-amino, C
1-24Alkyl-(C
1-24Alkyl-carbonyl) amino, C
1-24Alkoxycarbonyl amino or C
1-24Alkyl-(C
1-24Alkoxy carbonyl) the amino replacement; Wherein each aralkyl, heterocyclic radical, C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contain two keys of 2-6 or triple-linked unsaturated group, or R
1-CH-CH-R
2Constitute C
4-8An isocyclic part, it is optionally by hydroxyl, sulfydryl, amino, halogen, oxo or C
1-24Alkyl, C
1-24Alkoxyl, C
1-24Alkylthio group, C
1-24Alkylamino, two (C
1-24Alkyl) amino, C
1-24Alkyl-carbonyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkoxy carbonyl, C
1-24Alkyl-carbonyl sulfenyl or C
1-24Alkyl-carbonyl-amino, C
1-24Alkyl-(C
1-24Alkyl-carbonyl) the amino replacement, wherein each C
1-24Alkyl can be side chain or non-side chain, can be saturated or contain the unsaturated group of the two keys of 1-6, or R wherein
10Be the C of side chain or non-side chain
1-4Alkyl, perhaps R
1-CH-CH-R
2Constitute the part of furanose and pyranose ring in the middle of the sugar, D-ribose for example, D-arabinose, the D-xylose, D-lyxose, D-glucose, the D-galactose, the D-mannose, D-talose, D-allose, the D-altrose, the D-gulose, D-idose or corresponding L isomer, wherein each hydroxyl is optionally by hydrogen, amino, azido, oxo, sulfydryl or C
1-24Alkoxyl, C
1-24Alkylthio group, C
1-24Alkylamino, two (C
1-24Alkyl) amino, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkyl-carbonyl sulfenyl, C
1-24Alkyl-carbonyl-amino, C
1-24Alkyl-(C
1-24Alkyl-carbonyl) the amino replacement, wherein each C
1-24Alkyl can be side chain or non-side chain, can be saturated or contain the unsaturated group of the two keys of 1-6, with and the pharmacology go up acceptable salt, ester, amide, and ester salt and optical isomer.
Especially, R
1And R
2Can independently be selected from one group that forms by following radicals respectively: carboxyl, carboxamide groups (carboxamido), aryl, aryloxy carbonyl, aryl-C
1-24Alkyl, C
1-24Alkoxy-carbonyl oxy, C
1-24Alkyl amino-carbonyl, two (C
1-24Alkyl) amino carbonyl, aryl-C
1-24Alkoxy carbonyl, aryl-C
1-24Alkyl amino-carbonyl, C
1-24Alkyl-carbonyl oxygen base-(C
1-24) the alkyl methoxycarbonyl group, C
1-24The alkoxy-carbonyl oxy methoxycarbonyl group, C
1-24Alkoxy-carbonyl oxy-(C
1-24Alkyl) methoxycarbonyl group, wherein each C
1-24Alkyl can be side chain or non-side chain, can be saturated or contain the unsaturated group of the two keys of 2-6, and each C
1-4Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or unsaturated group, and each aryl has following general formula I I
R wherein
3And R
4Can be identical or different, be selected from one group that forms by following radicals respectively: hydrogen, halogen, C
1-4Alkyl, C
1-4Alkoxyl, formoxyl, acetyl group, propiono, bytyry, formyloxy, acetoxyl group, propionyloxy, butyryl acyloxy, C
1-4Alkoxy carbonyl group, more than all groups can be side chain or non-side chain, perhaps R
3And R
4Form the saturated alkylidene of the non-side chain of 3-4 carbon atom together, it is positioned at the ortho position of phenyl ring, perhaps R
3And R
4Form methylene-dioxy together, 1,1-ethylenedioxy (ethylidenedioxy), 1, the inferior ethylene dioxy base of 1-, 1,1-ethylene two oxy (ethylenedioxy) or 1, the 2-ethylene two oxy, it is positioned at the ortho position of phenyl ring.Preferred such chemical compound, the wherein R of using
1And R
2Be selected from one group that is made up of following radicals respectively: hydrogen, hydroxyl, formoxyl, acetyl group and methyl, wherein methyl can be optionally by hydroxyl, sulfydryl, C
1-24Alkoxyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkylthio group or C
1-24The alkyl-carbonyl sulfenyl replaces, wherein C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contains the undersaturated group of the two keys of 1-6.
Particularly preferably be R
1Be methyl, it can be optionally by hydroxyl, sulfydryl, C
1-24Alkoxyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkylthio group or C
1-24The alkyl-carbonyl sulfenyl replaces, wherein C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contain the undersaturated group of the two keys of 1-6, and R
2Be hydrogen.
Following chemical compound can obtain good especially effect, wherein, and R
1And R
2Be selected from one group that forms by following radicals respectively: hydrogen and n-octadecane base-methyl, wherein R
1N-octadecane base-methyl preferably, and R
2Be hydrogen.If being configured as of chemical compound (R), then advantage is obvious especially.
R
11Be preferably hydroxyl.
Below provide characteristics described above and suitable example:
" acyl group " refers to come from the substituent group of carboxylic acid; Tathagata is from organic carboxylic acid; carbonic acid; carbamic acid; perhaps corresponding to above each sour thio-acid or imino acid; or from organic sulfonic acid, wherein the molecule of every kind of acid all comprises fatty, armaticity and/or heterocyclic group and carbamoyl or imino group formoxyl.
Below provide the suitable example of acyl group:
Aliphatic acyl radical is defined as the acyl residue from fatty acid, comprises following group: alkanoyl (for example formoxyl, acetyl group, propiono, bytyry, isobutyryl, valeryl, isovaleryl, valeryl etc.); Alkenoyl (for example acryloyl group, methacryl, crotonyl etc.); Alkylthio alkanoyl (for example methyl ethanethioyl, ethylenebis dithiocarbamate acetyl group etc.); Alkanesulfonyl (for example mesyl, ethylsulfonyl, third sulfonyl etc.); Alkoxy carbonyl group (for example methoxycarbonyl group, carbethoxyl group, the third oxygen carbonyl, the different third oxygen carbonyl, butoxy carbonyl, isobutyl boc etc.); Alkyl-carbamoyl (for example methylamino formoxyl etc.); (N-alkyl) thiocarbamoyl (for example (N-methyl) thiocarbamoyl etc.); Alkyl carbamimidoyl (for example methyl carbamimidoyl etc.); Oxalo; Alkane oxalyl group (for example methoxalyl, ethoxalyl-, third oxalyl group etc.).
In the example of above-mentioned aliphatic acyl radical, the aliphatic hydrocarbon part, particularly alkyl or alkane residue can randomly have one or more suitable substituent groups, as amino, halogen (for example fluorine, chlorine, bromine etc.), hydroxyl, oximido, carboxyl, alkoxyl (for example methoxyl group, ethyoxyl, propoxyl group etc.), alkoxy carbonyl group, acylamino-(for example benzyloxycarbonyl amino etc.), acyloxy (for example acetoxyl group, benzoyloxy etc.) etc.; Contain these substituent aliphatic acyl radicals and be preferably, for example, by amino, carboxyl, the alkanoyl that amino and carboxyl, halogen, acylamino-etc. replace.
Aromatic acyl is defined as those acyl groups that comes the acid of self-contained replacement or unsubstituting aromatic yl, and wherein aryl can comprise phenyl, toluyl groups, xylyl and naphthyl etc.; Its suitable example is as follows: aroyl (for example benzoyl, toluyl groups, dimethylbenzene acyl group, naphthoyl and phthalyl etc.); Aralkanoyl (for example phenylacetyl group etc.); Virtue alkenoyl (for example cinnamoyl etc.); Virtue oxygen alkanoyl (for example benzene oxygen acetyl group etc.); Aryl sulfo-alkanoyl (for example phenyl ethanethioyl etc.); Arylamino alkanoyl (for example N-phenyl glycyl etc.); Aromatic hydrocarbons sulfonyl (for example benzenesulfonyl, tosyl, dimethylbenzene sulfonyl, naphthalene sulfonyl base etc.); Aryloxy carbonyl (for example carbobenzoxy, naphthalene oxygen carbonyl etc.); Aralkoxycarbonyl (for example benzyloxycarbonyl group etc.); Aryl-amino-carbonyl (for example phenyl amino formoxyl, naphthyl carbamoyl etc.); Aryl glyoxyl-based (for example phenyl glyoxyl-based etc.).
In the example of above-mentioned aromatic acyl; aromatic hydrocarbons part (especially aryl) and/or aliphatic hydrocarbon part (particularly alkane residue) can randomly have one or more suitable substituent groups, as those suitable substituent substituent groups of having described as alkyl or alkane residue.The aralkanoyl that aroyl, hydroxyl, oximido, the saturated dihalide acyloxy imino group that the example that preferably contains the aromatic acyl of specified substituent is the aroyl that replaces of halogen and hydroxyl, halogen replaces replaces, and aryl thiocarbamoyl (for example phenyl thiocarbamoyl etc.); With aryl carbmimidoyl (for example phenyl carbmimidoyl etc.).
Heterocyclic acyl represents to come the acyl group of the acid of self-contained heterocyclic group, comprising:
The heterocycle carbonyl, wherein heterocyclic radical is to contain at least one heteroatomic aromatic series that is selected from nitrogen, oxygen and sulfur or five of aliphatic or six element heterocycles (for example thiophenyl, furanylcarbonyl, pyrrolylcarbonyl, nicotinoyl (nicotinyl) etc.);
Heterocycle-alkanoyl, wherein heterocyclic radical is to contain at least one to be selected from heteroatomic five Yuans or six element heterocycles (for example benzene sulfur acetyl group, furan acetyl group, imidazoles propiono, tetrazolium acetyl group, 2-(2-amino-4-thiazolyl)-2-methoxyimino acetyl group etc.) of nitrogen, oxygen and sulfur etc.
In the example of above-mentioned heterocyclic acyl, heterocycle and/or aliphatic hydrocarbon part can randomly comprise one or more suitable substituent groups, and for example the substituent group with abovementioned alkyl and alkane group is identical.
Aryl is the aromatic hydrocarbons residue, and as phenyl, naphthyl etc., it can randomly comprise one or more suitable substituent groups, as alkyl, alkenyl, alkynyl, alkoxyl (for example methoxyl group, ethyoxyl etc.), halogen (for example fluorine, chlorine, bromine etc.), nitro etc.
" aralkyl " comprises one, two, the triphenyl alkyl, as benzyl, phenethyl, benzhydryl, trityl etc., wherein the aromatic series part can randomly comprise one or more suitable substituent groups, as alkoxyl (for example methoxyl group, ethyoxyl etc.), halogen (for example fluorine, chlorine, bromine etc.), nitro etc.
R
1And R
2Outside five and the hexa-member heterocycle de-carbon of expression, contain one or two nitrogen, oxygen or sulfur on the ring skeleton, it can be saturated or unsaturated.
WO98/25938 provides the detailed description of synthetic these chemical compounds.
These organic phosphorus compounds are particularly suitable for treating and prevent infection by antibacterial, unicellular and many cells parasite and fungus-caused humans and animals.
These chemical compounds are to unicellular parasite (protozoacide), especially to bring out malaria and sleeping sickness, bring out chagas disease, the organism of toxoplasmosis, amebic dysentery, leishmaniasis, trichomonacide, interstitial plasma cell pneumonia, balantidiosis, cryptosporidiosis, sarcosporidiasis, acanthamoebosis, naegleriasis, coccidiosis, giardiasis and Lambliasis has activity.
Therefore these chemical compounds are particularly suited for prevention of malaria and sleeping sickness, and chagas disease, toxoplasmosis, amebic dysentery, leishmaniasis, trichomonacide, interstitial plasma cell pneumonia, balantidiosis, cryptosporidiosis, sarcosporidiasis, acanthamoebosis, naegleriasis, coccidiosis, giardiasis and Lambliasis.
Active substance of the present invention is particularly suitable for resisting following antibacterial:
The Propionibacteriaceae antibacterial, especially propionibacterium, especially Propionibacterium, the Actinomy cetaceae antibacterial, especially actinomyces, corynebacterium genus bacteria, especially corynebacterium diphtheriae and pseudoconcretion the rod bacillus, the Mycobacteriaceae antibacterial, the mycobacterium antibacterial, especially Mycobacterium leprae, Mycobacterium tuberculosis, cow mycobacteria and bird mycobacterium, the Chlamydiaceae antibacterial, especially sand holes chlamydia and chlamydia psittaci, Listera belongs to antibacterial, especially Listeria monocytogenes, the erysipelothrix rhusiopathiae antibacterial, the fusobacterium antibacterial, the Yersinia antibacterial, Yersinia pestis, artificial tuberculosis yersinia genus, yersinia enterocolitica and Lu Shi yersinia, the Mycoplasmataceae antibacterial, mycoplasma and urea mycoplasma antibacterial, especially Mycoplasma pneumoniae, the Brucella antibacterial, the Bordetella antibacterial, the eisseriaceae antibacterial, especially eisseria and moraxella antibacterial, especially Neisseria meningitidis, Diplococcus gonorrhoeae and cattle catarrhalis, the vibrionaceae antibacterial, especially vibrio, Aeromonas, Plesiomonas and Photobacterium antibacterial, especially vibrio cholera, Listonella anguillarum and aeromonas salmonicida, campylobacter, especially campylobacter jejuni jejunum subspecies, large intestine Campylobacter and embryo's Campylobacter, the Helicobacterium antibacterial, especially helicobacter pylori, Spirochaetaceae and Leptospiraceae antibacterial, especially treponema, Borrelia and Leptospira antibacterial, especially B. burgdorferi bacterium, the Actinobacillus antibacterial, legion Cordycepps antibacterial, the Legionnella antibacterial, Rickettsiaceae and Bartonellaceae antibacterial, Nocardia and Rhod antibacterial, the Dermatophilus antibacterial, the pseudomonadaceae antibacterial, especially Rhodopseudomonas and xanthomonas antibacterial, enterobacteriaceae lactobacteriaceae, especially Escherichia, Klebsiella, proteus, Providencia, Salmonella, Serratia and Shigella antibacterial, the Pasteurellaceae antibacterial, especially Haemophilus spp, micrococcaceae antibacterial, especially Micrococcus and staphylococcus bacteria, the Streptococcaceae antibacterial, especially Streptococcus and Enterococcus antibacterial, Bacillaceae antibacterial, especially bacillus and fusobacterium antibacterial.
Therefore organic phosphorus compound and derivant thereof are suitable for treating diphtheria, acne vulgaris, listeriosis, the pig erysipelas of animal, the gas gangrene of humans and animals, the malignant edema of humans and animals, the tuberculosis of humans and animals, the leprosy of humans and animals and further mycobacterial disease, the paratuberculosis of animal, the plague, the adenomesenteritis of humans and animals and pseudotuberculosis, cholera, legionnaires disease, the borreliosis of humans and animals, the leptospirosis of humans and animals, syphilis, the campylobacter enteritis of humans and animals infects, Moraxella keratoconjunctivitis and the oromeningitis of animal, the brucellosis of humans and animals, the anthrax of humans and animals, the actinomycosis of humans and animals, streptotrichosis, psittacosis/ornithosis of animal, Q heat and Paul Ehrlich bacterium disease.
These chemical compounds are also effective to the Helicobacter pylori of eradicating in the gastrointestinal ulceration.
These chemical compounds also can be used in combination the above-mentioned disease of treatment with other antibiotic.Isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, prothionamide and dapsone are particularly suitable for being used for the treatment of tuberculosis with other anti-infective combination preparations.
Described chemical compound, promptly unicellular the and many cells parasite of the organic phosphorus compound of formula I and ester thereof, amide and salt pair has and shows strong cytotoxic activity, especially to bringing out the microorganism of malaria and sleeping sickness.Therefore used chemical compound helps to treat catching by antibacterial, parasite and fungus-caused humans and animals according to the present invention.These chemical compounds also are suitable for prevention by antibacterial, parasite and fungus-caused disease.
The used organic phosphorus compound according to the present invention, generally include the chemical compound (being also referred to as " prodrug ") that provides chemical compound of the present invention after the salt of for this purpose the acceptable salt of pharmacy, amide, ester and ester or the administration with metabolite or catabolite, they can be to have the similar mode of reagent (with nontoxic, the acceptable mixed with excipients of the pharmacy) prescription of anti-infectious function with administration with known.
The acceptable salt of the pharmacy of these chemical compounds comprises the formed organic acid of protonated form or the ammonium salt of mineral acid, for example ammonium salt of hydrochloric acid, sulphuric acid, citric acid, maleic acid, fumaric acid, tartaric acid, p-methyl benzenesulfonic acid of formula I chemical compound of the present invention.
The particularly suitable salt of pharmacy also comprises, as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylamine salt, hexanamine salt and amino acid whose salt, for example arginine salt, aspartate, glutamate, Glu.
The use test system determines the activity of material.This system is based on the inhibition of external test to antibacterial, parasite, fungus or plant growing.Method known to those skilled in the art partly is used for this purpose.
For example, by measuring the malaria activity is determined in the inhibition of malarial parasite growth in the blood cultivation thing.
Antibacterial activity is according to the inhibition of the growth of antibacterial on Nutrient medium and fluid medium is determined.
Antifungal activity is determined according to the inhibition that fungus is grown on Nutrient medium and fluid medium.
Some microorganisms that will study can only be studied in animal model, in this case, will use proper model.
The active material of demonstration is further studied in the model then in vivo in the in-vitro measurements system.
In suitable animal model, further estimate parasiticide, antifungal, antibacterial activity.
The screening of activity of weeding by the Sargassum system and under standard conditions the isoprene of plant discharge and to determine.
Has the pharmaceutical preparation that the reagent of pharmaceutical active can be made unit dose.This means that preparation can be the form of independent component, for example tablet, coated tablet, capsule, pill, suppository and ampulla, its content of active substance equals an individually dosed part or several times.Dosage unit can contain individually dosed 1,2,3 or 4 times, and perhaps individually dosed 1/2,1/3 or 1/4.The individually dosed active substance that preferably contains the amount of single administration, be generally dosage every day whole, half, 1/3rd or 1/4th.
The excipient that nontoxic, inert pharmacy is fit to refers to solid, semisolid or liquid diluent, filler and various formulation adjuvant.
Preferred drug substances is tablet, coated tablet, capsule, pill, granule, suppository, solution, suspensoid and Emulsion, paste, ointment, gel, emulsifiable paste, lotion, powder and spray.Tablet, coated tablet, capsule, pill and granule can contain active substance and conventional excipients, for example (a) filler and extender, starch for example, lactose, sucrose, glucose, mannitol and silicon dioxide, (b) binding agent, carboxymethyl cellulose for example, alginate, gelatin, polyvinyl pyrrolidone, (c) wetting agent, for example glycerol, (d) suspending agent, agar for example, calcium carbonate and sodium carbonate, (e) dissolving retardant is as paraffin and (f) absorption enhancer, as quaternary ammonium compound, (g) wetting agent is as spermol, glyceryl monostearate, (h) adsorbent, as Kaolin and bentonite, (i) lubricant is as Pulvis Talci, calcium stearate and magnesium stearate and solid polyethylene glycol, the perhaps mixture of the material described in above (a) to (i).
Tablet, coated tablet, capsule, pill and granule can have conventional coating and shell, described coating and shell randomly contain opacifier, also can constitute like this so that it postpone to discharge or preferentially at the specific part release of active agent of intestinal, for example wherein can use polymer or wax as substrate.
Active substance randomly with one or more above-mentioned excipient, also can exist with the form of microcapsule.
Suppository can also contain conventional water solublity or water-insoluble excipient except that active substance, Polyethylene Glycol for example, fat, for example cocoa butter and senior ester (C for example
14Pure and mild C
16Or the mixture of these materials the ester of fatty acid).
Ointment, paste, emulsifiable paste and gel can also contain conventional excipients except that active substance, for example the mixture of animal and plant fat, wax, paraffin, starch, tragacanth, cellulose derivative, Polyethylene Glycol, polysiloxanes, bentonite, silicon dioxide, Pulvis Talci and zinc oxide or these materials.
Powder and spray can also contain conventional excipients except that active substance, as the mixture of lactose, Pulvis Talci, silicon dioxide, aluminium hydroxide, calcium silicates and polyamide powder or these materials.Spray can also contain conventional propellant in addition, as chlorofluorocarbon.
Solution and Emulsion can also contain conventional excipients except that active substance, as solvent, solubilizing agent and emulsifying agent, for example water, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzylalcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, dimethyl formamide, oil, especially Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, Semen Maydis oil, olive oil, castor bean oil and Oleum sesami, glycerol, glycerol formal, tetrahydrofurfuryl alcohol, Polyethylene Glycol and dehydration sorbitol fatty acid ester, or the mixture of these materials.
For solutions for parenteral administration agent or Emulsion also can with aseptic, etc. the form of oozing exist.
Suspensoid can contain conventional excipients except that active substance, as liquid diluent, for example water, ethanol, propylene glycol, suspending agent, for example ethoxylation isooctadecane alcohol, polyoxyethylene sorbitol and dehydration Pyrusussuriensis sugar ester, microcrystalline Cellulose, aluminium hydroxide, bentonite, agar and tragacanth partially, or the mixture of these materials.
Above-mentioned prescription can also contain coloring agent, antiseptic and improve taste and the additive of abnormal smells from the patient, for example Oleum menthae and Eucalyptus oil, and sweeting agent, for example glucide.
In the said medicine preparation, the concentration of the active substance of general formula I is preferably the 0.1-99.5wt.% of whole approximately mixture, preferably accounts for the 0.5-95wt.% of whole mixture.
Remove outside the active substance of general formula I, pharmaceutical preparation can also contain other pharmaceutically active substances.
These chemical compounds can be antibiotic with having of having described before this, the material of antifungal and parasiticide character uses.These materials are particularly including the chemical compound of having used or still being used to some extent in treatment.List in Red List or Simon/Stille, Antibiokia-Therapie inKlinik und Praxis, the 9th edition, 1998, Schatauer Verlag, perhaps the material of http:/www.customs.treas.gov/imp-exp/rulings/harmoniz/hrm 129.html is particularly suitable for this purpose on internet.Specifically, described derivant can exist with following medicine especially: penicillins, benzylpenicillin (benzylpenicillin), the phenoxy group penicillin, the isoxazolyl penicillin, Aminopenicillin, ampicillin, the amoxicillin, bacampicillin, penicillin carboxy, ticarcillin, its Moses woods, Acylaminopenicillin, the azlocillin, the mezlocillin, piperacillin, the apalcillin, mecillinam, cephalosporins, the cefazolin sodium class, cefuroxime, the cefoxitin class, cefoxitin, cefotetan, cefmetazole, latamoxef, flomoxef, the cefotaxime class, cefazidime, the ceftazidime class, ceftazidime, Cefpirome, cefepime, conventional cephalosporins, the yellow pyridine of cephalo, cefoperazone, the oral cephalosporin class of cefalexin class, Lorabid, cefprozil, new wide spectrum oral cephalosporin class, cefixime, Cefpodoxime Proxetil, cefuroxime, cefetamet, Cefotiam Hexetil, the cephalo Horizon, ceftibuten, other beta-Lactam antibiotic class, carbapenem, imipenum/cilastatin, Metro is south doubly, biapenem, aztreonam, beta-lactamase inhibitor, clavulanic acid/amoxicillin, clavulanic acid/ticarcillin, sulbactam/amoxicillin, TZB/piperacillin, Tetracyclines, tetracycline, rolitetracycline nitrate, doxycycline, minocycline, chloromycetin, aminoglycosides, gentamycin, tobramycin, netilmicin, amikacin, spectinomycin, Macrolide, erythromycin, clarithromycin, Roxithromycin, Azinomycin B, dirithromycin, spiramycin, josamycin, the lincosamide class, clindamycin, fusidic acid, the glycopeptide antibiotic class, vancomycin, tecoplanin, the pyostacin derivatives class, fosfomycin, antibiotic antifol, sulfonamides, co-trimoxazole, trimethoprim, other di-amino-pyrimidine sulfanilamide combination, nitrofuran, nitrofurantoin, furacilin, gyrase inhibitors (quinolones), norfloxacin, ciprofloxacin, ofloxacin, Sparfloxacin, enoxacin, fleroxacin, pefloxacin, lomefloxacin, BayY3118, nitro glyoxaline, mycobacteria reagent, isoniazid, rifampicin, Mycobutin, pyrazinamide, streptomycin, capreomycin, prothionamide, Urovalidin, dapsone, clofazimine, topical antibiotics, bacitracin, Tyrothricin, polymyxin, neomycin, kanamycin, paromomycin, Mupirocin Ointment, Anti-virus agent, acyclovir, ganciclovir, azidothymidine AZT, Didanosine, zalcitabine, the thiophene cytidine, stavudine, ribavirin, idoxuridine, trifluridine, phosphine card naphthalene replaces, amantadine, interferons, the tibol derivant, protease inhibitor, antimycoin, polyalkenes, amphotericin B, nysfungin, natamycin, azoles system, the azoles system of sepsis treatment, miconazole, ketoconazole, Itraconazole, fluconazol, UK-109496, the azoles system of topical application, clotrimazole, econazole, isoconazole, oxiconazole, bifonazole, flucytosine, griseofulvin, ciclopirox olamine, tolnaftate, Na Fu is for fragrant, terbinafine, amorolfine, the anthraquinone class, belulinic acid Betulinic acid, half anthraquinone class, xanthone, the naphthoquinone class, the virtue alkamine, quinine, quine class D, mefloquine, Halofantrine, chloroquine, amodiaquine, acridine, the benzo naphthyridines, mepacrine, the pyridine of naphthalene Lip river, sulphadione, sulfonamides, sulfadoxine, sulfalene, trimethoprim, proguanil, chlorproguanil, diaminopyrimidine, pyrimethamine, primaquine, the quinolin-2-ylamine class, WR238,605, tetracycline, doxycycline, clindamycin, norfloxacin, ciprofloxacin, ofloxacin, arteannuin, dihydroartemisinine, the 10b Artemether, Artemether, atresunate, Atovaquone, suramin, melarsoprol, nifurtimox, sodium stibogluconate, pentylenetetrazol, amphotericin B, metronidazole, nioform, mebendazole, niclosamide, praziquantel, pyrantel, Tiabendazole, DEC, ivermectin, Bithionol, oxamniquine, metrifonate, piperazine citrate, embonate.
In addition, organic phosphorus compound can be present in the pharmaceutical preparation with sulfanilamide, sulfadoxine, arteannuin, Atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, Halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, praziquantel, niclosamide, mebendazole, pyrantel, Tiabendazole, diethylcarbamazine, piperazine, povan, metrifonate, oxamniquine, bithionol or suramin or two or more these combinations of substances.
Use known method to prepare the said medicine preparation, for example excipient and active substance are mixed with usual manner.
Above-mentioned preparation can oral administration, in the rectum, parenteral (intravenous, intramuscular, subcutaneous), brain pond, intravaginal, intraperitoneal, local use (powder, ointment, drop) deliver medicine to the human or animal, and be used for the treatment of chamber, endoceliac infection.Admissible appropriate formulation is solution and suspensoid, gel, preserved material prescription, Emulsion ointment or the drop of injection, oral medication.Topical therapeutic can use ophthalmology and department of dermatologry prescription, silver and other salt, ear drop, ophthalmic ointment, powder or solution.Can also proper formula be delivered medicine to animal by feedstuff or drinking water.Can use gel, powdered formula, powder, tablet, controlled release tablet, premix mixture, concentrate, granule, pill, tablet, boli, capsule, aerosol, spray, suction prescription to humans and animals.Used chemical compound can also add other carrier wherein according to the present invention, plastics (plastic links that is used for topical therapeutic) for example, collagen or bone cement.
Confirmed that the total amount to the active substance of humans and animals administration general formula I is per 24 hours 0.05-2000 mg/kg body weight, it is favourable being preferably 5-1000 mg/kg body weight, for reaching desirable result, randomly at twice or multiple dosing.Each dosage that uses separately preferably contains the about 0.25-2000 milligram of active substance, divides 1-4 administration every day.But according to the patient's who treats characteristics and body weight, the characteristic of disease and the order of severity, may need to depart from above-mentioned dosage at the characteristics of preparation and the route of administration of pharmaceutical preparation and administration cycle.
The liquid preparation of the oral administration that exists with solution, syrup, Emulsion or suspensoid form contains for example active substance of 0.1-50wt.%.And contained active substances such as the solution of topical, gel, suspensoid preferably account for the 0.05-20wt.% of preparation.
In some cases, it is just enough that the consumption of active substance is less than above-mentioned dosage, the then essential active substance that uses more than above-mentioned amount in the other situation.Those skilled in the art will determine optimum dosage and route of administration according to the technical ability of oneself for specific situation.
Used chemical compound can be with conventional concentration and dosage form with feedstuff, feed formulations or drinking water administration animal according to the present invention.
Used chemical compound also can perform well in bactericide, antifungal and the herbicide of plant according to the present invention.
The antiprotozoal effect of embodiment
Following material is used to measure its antiprotozoal effect: material 1:2-(2-ethoxycarbonyl phenoxy) carbonyl]-1,3,2-dioxy phosphorus six ring-2-oxide material 2:2-[(2-ethoxycarbonyl phenoxies) carbonyl]-4-dodecane acyl-oxygen ylmethyl-1,3,2-dioxy phosphorus six ring-2-oxide material 3:2-[(2-ethoxycarbonyl phenoxies) carbonyl]-4-decoyl sulfenyl methyl isophthalic acid, 3,2-dioxy phosphorus six ring-2-oxide material 4:2-[(2-ethoxycarbonyl phenoxies) carbonyl]-4-dodecanoyl sulfenyl methyl isophthalic acid, 3,2-dioxy phosphorus six ring-2-oxide material 5:2-methylol-2-[(2-ethoxycarbonyl phenoxies) carbonyl] Alendronate material 6:2-dodecane acyl-oxygen base-2-hydroxypropyl-[(2-ethoxycarbonyl phenoxy) carbonyl] Alendronate material 7:2-decoyl sulfenyl-2-hydroxypropyl-[(2-carbethoxyl group material 8:2-dodecanoyl sulfenyl-2-hydroxypropyl-[(2-ethoxycarbonyl phenoxy) carbonyl] Alendronate material 9:2-hydroxyl-1,4,2-dioxy phosphorus glycosides (phosphorinane) 2,3-dioxide sodium material 10:2-hydroxyl-5-dodecane acyl-oxygen ylmethyl-1,4,2-dioxy phosphorus glycosides 2,3-dioxide sodium material 11:2-hydroxyl-5-decoyl sulfenyl methyl isophthalic acid, 4,2-dioxy phosphorus glycosides 2,3-dioxide sodium material 12:2-hydroxyl-5-dodecanoyl sulfenyl methyl isophthalic acid, 4,2-dioxy phosphorus glycosides 2,3-dioxide sodium
The biological In vitro culture that the microorganism Plasmodium falciparum of malaria is brought out in use is measured the malaria activity of material 1-12.200 microlitres contain the asynchronous Plasmodiumfalciparum culture of 0.4% haematozoon and each hole that 2% haematocrit puts into 96 hole microdroplet plates.With the solution of a series of these chemical compounds of three steps preparation, concentration is between 100-0.14 μ mol/l.Plate is placed on 37 ℃, cultivates 48 hours in 3% carbon dioxide and 5% the oxygen atmosphere.Replenish 27 μ Ci/ml[
3H]-hypoxanthic 30 microlitre culture medium are added in each hole.Parasite was collected parasite with glass fiber filter after cultivating 24 hours, measured the radioactivity that mixes.Inhibition percentage after the inhibition of parasite growth is mixed with tritium is recently measured.Inhibition percentage ratio after tritium mixed is compared when not having these materials, obtains the inhibition to the parasite growth.The numerical value extrapolation is obtained the middle inhibition concentration (IC of these materials
50),
Following table provides the result, i.e. IC
50Value:
Table
| The material numbering | ????IC 50/(nM) |
| ?????1 | ?????415 |
| ?????2 | ?????357 |
| ?????3 | ?????518 |
| ?????4 | ?????653 |
| ?????5 | ?????215 |
| ?????6 | ?????640 |
| ?????7 | ?????517 |
| ?????8 | ?????387 |
| ?????9 | ?????946 |
| ?????10 | ?????384 |
| ?????11 | ?????862 |
| ?????12 | ?????751 |
Claims (11)
1, have the chemical compound of general formula I or its pharmacology go up acceptable salt, ester, amide, ester salt with and optical isomer in prevention and treatment since the infection of the humans and animals that antibacterial, fungus or parasite cause and in plant as antifungal, antibacterial and the herbicide applications of plant
Wherein: R
11Be selected from one group that forms by following radicals: C
1-26Alkyl contains the C of the two keys of 1-6
2-26Alkenyl contains 1-6 triple-linked C
2-26Alkynyl group, C
1-26Acyl group, aryl-C
0-26Alkyl, C
3-8Cycloalkyl-C
0-26Alkyl contains the C of or two nitrogen, oxygen or sulfur
3-8Heterocyclylalkyl-C
0-26Alkyl, halogen and OX
11, wherein above-mentioned all groups can be by C
1-9Alkyl, C
1-9Alkoxyl, hydroxyl, amino, halogen or oxo group replace, wherein X
11Be selected from one group that forms by following radicals: hydrogen, C
1-26Alkyl contains the C of the two keys of 1-6
2-26Alkenyl contains 1-6 triple-linked C
2-26Alkynyl group, aryl-C
0-26Alkyl, C
3-8Cycloalkyl, C
1-26Acyl group contains the C of or two nitrogen, oxygen or sulfur
3-8Heterocyclylalkyl-C
0-26Alkyl, C
1-26Silicyl, wherein above-mentioned all groups can be by C
1-9Alkyl, C
1-9Alkoxyl, hydroxyl, amino, halogen or oxo group replace, and X
11The metal that comprises I, II and III main group in organic and cation, the especially periodic table of elements inorganic base, ammonium replaces ammonium and by ethylenediamine or amino acid derived ammonium compounds, R
1And R
2Be independently selected from one group that forms by following radicals respectively: C
1-24Alkyl, C
3-8Cycloalkyl, C
3-8Cycloalkyl-C
1-24Alkyl, C
1-24Alkoxyl, C
1-24Alkylthio group, C
1-24Alkoxy-C
1-24Alkyl and C
1-24Alkylthio group-C
1-24Alkyl, acyl group, aryl-C
1-24Alkyl, C
3-8Heterocyclylalkyl-C
0-24Alkyl, halogen and hydrogen, and each C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contains the undersaturated group of the two keys of 2-6, can be selectively by hydroxyl, amino, sulfydryl, halogen, oxo or C
1-24Alkoxyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkoxy-carbonyl oxy, C
1-24Alkylthio group, C
1-24Alkyl-carbonyl sulfenyl, C
1-24Alkyl amino, two (C
1-24Alkoxyl) amino, C
1-24Alkyl-carbonyl-amino, C
1-24Alkyl-(C
1-24Alkyl-carbonyl) amino, C
1-24Alkoxycarbonyl amino or C
1-24Alkyl-(C
1-24Alkoxy carbonyl) the amino replacement; Wherein each aralkyl, heterocyclic radical, C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contain two keys of 2-6 or triple-linked unsaturated group, or R
1-CH-CH-R
2Constitute C
4-8An isocyclic part, it is optionally by hydroxyl, sulfydryl, amino, halogen, oxo or C
1-24Alkyl, C
1-24Alkoxyl, C
1-24Alkylthio group, C
1-24Alkylamino, two (C
1-24Alkyl) amino, C
1-24Alkyl-carbonyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkoxy carbonyl, C
1-24Alkyl-carbonyl sulfenyl or C
1-24Alkyl-carbonyl-amino, C
1-24Alkyl-(C
1-24Alkyl-carbonyl) the amino replacement, wherein each C
1-24Alkyl can be side chain or non-side chain, can be saturated or contain the unsaturated group of the two keys of 1-6, or R wherein
10Be the C of side chain or non-side chain
1-4Alkyl, and R
1-CH-CH-R
2Constitute the part of furanose and pyranose ring in the middle of the sugar, D-ribose for example, D-arabinose, the D-xylose, D-lyxose, D-glucose, the D-galactose, the D-mannose, D-talose, but D-Lip river sugar, the D-altrose, the D-gulose, D-idose or corresponding L isomer, wherein each hydroxyl is optionally by hydrogen, amino, azido, oxo, sulfydryl or C
1-24Alkoxyl, C
1-24Alkylthio group, C
1-24Alkylamino, two (C
1-24Alkyl) amino, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkyl-carbonyl sulfenyl, C
1-24Alkyl-carbonyl-amino, C
1-24Alkyl-(C
1-24Alkyl-carbonyl) the amino replacement, wherein each C
1-24Alkyl can be side chain or non-side chain, can be saturated or contains the unsaturated group of the two keys of 1-6.
2, according to the application of claim 1, it is characterized in that R
1And R
2Can independently be selected from one group that forms by following radicals respectively: carboxyl, carboxamide groups, aryl, aryloxy carbonyl, aryl-C
1-24Alkyl, C
1-24Alkoxy-carbonyl oxy, C
1-24Alkyl amino-carbonyl, two (C
1-24Alkyl) amino carbonyl, aryl-C
1-24Alkoxy carbonyl, aryl-C
1-24Alkyl amino-carbonyl, C
1-24Alkyl-carbonyl oxygen base-(C
1-24) the alkyl methoxycarbonyl group, C
1-24The alkoxy-carbonyl oxy methoxycarbonyl group, C
1-24Alkoxy-carbonyl oxy-(C
1-4Alkyl) methoxycarbonyl group, wherein each C
1-24Alkyl can be side chain or non-side chain, can be saturated or contain the unsaturated group of the two keys of 2-6, and each C
1-4Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or unsaturated group, and each aryl has following general formula I I
R wherein
3And R
4Can be identical or different, be selected from one group that forms by following radicals respectively: hydrogen, halogen, C
1-4Alkyl, C
1-4Alkoxyl, formoxyl, acetyl group, propiono, bytyry, formyloxy, acetoxyl group, propionyloxy, butyryl acyloxy, C
1-4Alkoxy carbonyl group, more than all groups can be side chain or non-side chain, perhaps R
3And R
4Form the saturated alkylidene of the non-side chain of 3-4 carbon atom together, it is positioned at the ortho position of phenyl ring, perhaps R
3And R
4Form methylene-dioxy together, 1,1-ethylenedioxy, 1, the inferior ethylene dioxy base of 1-, 1,1-ethylene two oxy or 1, the 2-ethylene two oxy, it is positioned at the ortho position of phenyl ring.
3, according to the application of claim 1, R wherein
1And R
2Be selected from one group that is made up of following radicals respectively: hydrogen, hydroxyl, formoxyl, acetyl group and methyl, wherein methyl can be optionally by hydroxyl, sulfydryl, C
1-24Alkoxyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkylthio group or C
1-24The alkyl-carbonyl sulfenyl replaces, wherein C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contains the undersaturated group of the two keys of 1-6.
4, according to the application of claim 3, R wherein
1Be methyl, it can be optionally by hydroxyl, sulfydryl, C
1-24Alkoxyl, C
1-24Alkyl-carbonyl oxygen base, C
1-24Alkylthio group or C
1-24The alkyl-carbonyl sulfenyl replaces, wherein C
1-24Alkyl and C
1-24Alkoxyl can be side chain or non-side chain, can be saturated or contain the undersaturated group of the two keys of 1-6, and R
2Be hydrogen.
5, according to the application of claim 1, R wherein
1And R
2Be not selected from hydrogen and n-octadecane ylmethyl.
6, according to the application of claim 5, R wherein
1Be the n-octadecane ylmethyl, and R
2Be hydrogen.
7, according to the application of claim 6, wherein chemical compound is the R configuration.
8, according to the application of above arbitrary claim, it is used for the treatment of by antibacterial, fungus or infection unicellular or that the many cells parasite causes.
9, application according to Claim 8, it is to be used for the treatment of the infection that is caused by the antibacterial that is selected from following group: the Propionibacteriaceae antibacterial, especially propionibacterium, especially Propionibacterium, the Actinomy cetaceae antibacterial, especially actinomyces, corynebacterium genus bacteria, especially corynebacterium diphtheriae and pseudoconcretion the rod bacillus, the Mycobacteriaceae antibacterial, the mycobacterium antibacterial, especially Mycobacterium leprae, Mycobacterium tuberculosis, cow mycobacteria and bird mycobacterium, the Chlamydiaceae antibacterial, especially sand holes chlamydia and chlamydia psittaci, Listera belongs to antibacterial, especially Listeria monocytogenes, the erysipelothrix rhusiopathiae antibacterial, the fusobacterium antibacterial, the Yersinia antibacterial, Yersinia pestis, artificial tuberculosis yersinia genus, yersinia enterocolitica and Lu Shi yersinia, the Mycoplasmataceae antibacterial, mycoplasma and urea mycoplasma antibacterial, especially Mycoplasma pneumoniae, the Brucella antibacterial, the Bordetella antibacterial, the eisseriaceae antibacterial, especially eisseria and moraxella antibacterial, especially Neisseria meningitidis, Diplococcus gonorrhoeae and cattle catarrhalis, the vibrionaceae antibacterial, especially vibrio, Aeromonas, Plesiomonas and Photobacterium antibacterial, especially vibrio cholera, Listonella anguillarum and aeromonas salmonicida, campylobacter, especially campylobacter jejuni jejunum subspecies, large intestine Campylobacter and embryo's Campylobacter, the Helicobacterium antibacterial, especially helicobacter pylori, Spirochaetaceae and Leptospiraceae antibacterial, especially treponema, Borrelia and Leptospira antibacterial, especially B. burgdorferi bacterium, the Actinobacillus antibacterial, legion Cordycepps antibacterial, the Legionnella antibacterial, Rickettsiaceae and Bartonellaceae antibacterial, Nocardia and Rhod antibacterial, the Dermatophilus antibacterial, the pseudomonadaceae antibacterial, especially Rhodopseudomonas and xanthomonas antibacterial, enterobacteriaceae lactobacteriaceae, especially Escherichia, Klebsiella, proteus, Providencia, Salmonella, Serratia and Shigella antibacterial, the Pasteurellaceae antibacterial, especially Haemophilus spp, the micrococcaceae antibacterial, especially Micrococcus and staphylococcus bacteria, the Streptococcaceae antibacterial, especially Streptococcus and Enterococcus antibacterial, Bacillaceae antibacterial, especially bacillus and fusobacterium antibacterial; And the Helicobacterium of eradicating intestines and stomach ulcer.
10, application according to Claim 8, it is used to prevent and treat the infection that is caused by unicellular parasite, and described unicellular parasite is selected from the organism that causes malaria, sleeping sickness, chagas disease, toxoplasmosis, amebic dysentery, leishmaniasis, trichomonacide, interstitial plasma cell pneumonia, balantidiosis, cryptosporidiosis, sarcosporidiasis, acanthamoebosis, naegleriasis, coccidiosis, giardiasis and Lambliasis.
11, the method that catches that causes by antibacterial, fungus or parasite of treatment, wherein will treat effective dose according to the described compound administration of one of claim 1-7 in the patient who suffers from the infection that causes by antibacterial, fungus or parasite.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19854310.7 | 1998-11-25 | ||
| DE19854310A DE19854310A1 (en) | 1998-11-25 | 1998-11-25 | Use of phosphonoformic acid derivatives for the therapeutic and prophylactic treatment of infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1328464A true CN1328464A (en) | 2001-12-26 |
Family
ID=7888924
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99813747A Pending CN1328464A (en) | 1998-11-25 | 1999-11-20 | Use of phosphonoformic acid derivatives for treating infections |
Country Status (16)
| Country | Link |
|---|---|
| EP (1) | EP1133302A2 (en) |
| JP (1) | JP2002530343A (en) |
| CN (1) | CN1328464A (en) |
| AP (1) | AP2001002164A0 (en) |
| AU (1) | AU1859100A (en) |
| BR (1) | BR9915605A (en) |
| CA (1) | CA2352511A1 (en) |
| CZ (1) | CZ20011819A3 (en) |
| DE (1) | DE19854310A1 (en) |
| EA (1) | EA200100585A1 (en) |
| IL (1) | IL142775A0 (en) |
| NO (1) | NO20012540L (en) |
| OA (1) | OA11718A (en) |
| PL (1) | PL348354A1 (en) |
| TR (1) | TR200101431T2 (en) |
| WO (1) | WO2000030653A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104940211A (en) * | 2015-06-08 | 2015-09-30 | 曹晓宏 | Application of betulinic acid in preparation of drugs for resisting fungus biofilms |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1408984E (en) | 2001-07-20 | 2008-12-26 | Bioagency Ag | Organo-phosphorous compounds for activating gamma/delta t cells |
| CA2518763A1 (en) * | 2003-03-14 | 2004-09-23 | Epistem Limited | Treatment and/or prevention of non-viral epithelial damage |
| US20050171063A1 (en) * | 2003-10-20 | 2005-08-04 | Pawan Malhotra | Use of phosphono derivatives as anti-malarials |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995012604A1 (en) * | 1993-11-05 | 1995-05-11 | Aktiebolaget Astra | Novel amino acid derivatives |
| SE9604582D0 (en) * | 1996-12-13 | 1996-12-13 | Astra Ab | Novel compounds |
| RU2116790C1 (en) * | 1997-07-02 | 1998-08-10 | Закрытое акционерное общество "Рефарм" | Antiinfectious agent "repharm" for external using |
| DE19859668A1 (en) * | 1998-06-24 | 1999-12-30 | Hassan Jomaa | Treating or preventing viral, bacterial, fungal or parasitic infections using bis-phosphonic acid compounds, also having herbicidal activity |
-
1998
- 1998-11-25 DE DE19854310A patent/DE19854310A1/en not_active Withdrawn
-
1999
- 1999-11-20 CA CA002352511A patent/CA2352511A1/en not_active Abandoned
- 1999-11-20 EP EP99962147A patent/EP1133302A2/en not_active Withdrawn
- 1999-11-20 CN CN99813747A patent/CN1328464A/en active Pending
- 1999-11-20 OA OA1200100130A patent/OA11718A/en unknown
- 1999-11-20 AU AU18591/00A patent/AU1859100A/en not_active Abandoned
- 1999-11-20 CZ CZ20011819A patent/CZ20011819A3/en unknown
- 1999-11-20 WO PCT/EP1999/008964 patent/WO2000030653A2/en not_active Application Discontinuation
- 1999-11-20 PL PL99348354A patent/PL348354A1/en unknown
- 1999-11-20 BR BR9915605-9A patent/BR9915605A/en not_active IP Right Cessation
- 1999-11-20 AP APAP/P/2001/002164A patent/AP2001002164A0/en unknown
- 1999-11-20 IL IL14277599A patent/IL142775A0/en unknown
- 1999-11-20 JP JP2000583536A patent/JP2002530343A/en active Pending
- 1999-11-20 EA EA200100585A patent/EA200100585A1/en unknown
- 1999-11-20 TR TR2001/01431T patent/TR200101431T2/en unknown
-
2001
- 2001-05-23 NO NO20012540A patent/NO20012540L/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104940211A (en) * | 2015-06-08 | 2015-09-30 | 曹晓宏 | Application of betulinic acid in preparation of drugs for resisting fungus biofilms |
Also Published As
| Publication number | Publication date |
|---|---|
| CZ20011819A3 (en) | 2001-12-12 |
| EA200100585A1 (en) | 2002-04-25 |
| IL142775A0 (en) | 2002-03-10 |
| AP2001002164A0 (en) | 2001-06-30 |
| JP2002530343A (en) | 2002-09-17 |
| WO2000030653A2 (en) | 2000-06-02 |
| EP1133302A2 (en) | 2001-09-19 |
| AU1859100A (en) | 2000-06-13 |
| OA11718A (en) | 2005-01-26 |
| NO20012540D0 (en) | 2001-05-23 |
| CA2352511A1 (en) | 2000-06-02 |
| BR9915605A (en) | 2001-08-14 |
| PL348354A1 (en) | 2002-05-20 |
| WO2000030653A3 (en) | 2000-11-16 |
| NO20012540L (en) | 2001-07-24 |
| TR200101431T2 (en) | 2001-10-22 |
| DE19854310A1 (en) | 2000-06-29 |
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| C06 | Publication | ||
| C10 | Entry into substantive examination | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |