CN1342078A - Use of 3-isoxazolidinones and hydroxylamine acids for treatment of infections - Google Patents
Use of 3-isoxazolidinones and hydroxylamine acids for treatment of infections Download PDFInfo
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- CN1342078A CN1342078A CN00802779A CN00802779A CN1342078A CN 1342078 A CN1342078 A CN 1342078A CN 00802779 A CN00802779 A CN 00802779A CN 00802779 A CN00802779 A CN 00802779A CN 1342078 A CN1342078 A CN 1342078A
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- methyl
- dimethyl
- chlorophenyl
- chloro
- isoxazolidinone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
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- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention relates to medicaments containing at least one compound of the formula (I) and to their use for the therapeutic and prophylactic treatment of bacterial, fungal and parasitic infections in humans and animals.
Description
The present invention relates to the purposes that salt as the 3-isoxazole alkyl ketone (isoxazolidinone) of reactive compound and hydroxyamino (hydroxylamic acid) and their salt, ester and ester is used for the treatment of and prevents the infection that is caused by antibacterial, fungus and parasite of humans and animals.
Still very need provide and effectively to treat the medicine that humans and animals infects.
Therefore, the purpose of this invention is to provide and can be used for the infection that causes by antibacterial, fungus and parasite of humans and animals and the material that satisfies above-mentioned condition.
US Patent specification 4405357 discloses 3-isoxazole alkyl ketone and the hydroxyamino as herbicide.
Be surprisingly found out that 3-isoxazole alkyl ketone and hydroxyamino realization above-mentioned purpose now.This group material demonstrates anti-infectious function to antibacterial, fungus and unicellular and many cells parasite.According to the present invention, unicellular parasite is interpreted as protozoon.
According to the present invention, contain chemical compound in the medicine corresponding to general formula (I):
R
3Be selected from hydrogen, alkyl, alkoxyl-(C
0-26) alkyl, C
3-14Cycloalkyl-(C
0-26) alkyl, cycloalkyloxy-(C
0-26) alkyl, amino-(C
0-26) alkyl, silicyl-(C
0-26) alkyl and sulfo--(C
0-26) alkyl, wherein each alkyl and each alkoxyl can be side chain or non-side chain, and each alkyl, each alkoxyl and each cycloalkyl can or have one or more pairs of keys or triple-linked unsaturated group by replace saturated of hydroxyl, amino, halogen, oxo group and alkoxyl, and one or two carbon atom of cycloalkyl can be substituted R by nitrogen, oxygen or sulphur atom
4Be selected from hydrogen, alkyl, acyl group and cycloalkyl-(C
0-26) alkyl, wherein each alkyl and each acyl group can be side chain or non-side chain, and each alkyl, each acyl group and each cycloalkyl can or have one or more pairs of keys or triple-linked unsaturated group by replace saturated of hydroxyl, amino, halogen, oxo group and alkoxyl, and one or two carbon atom of cycloalkyl can be substituted by nitrogen, oxygen or sulphur atom; R
1And R
2Identical or different, be selected from hydrogen, hydroxyl, halogen, amino, alkyl, alkoxyl and cycloalkyl-(C
0-26) alkyl, wherein each alkyl and each alkoxyl can be side chain or non-side chain, each amino, alkyl, each alkoxyl and each cycloalkyl can or have one or more pairs of keys or triple-linked unsaturated group by replace saturated of hydroxyl, amino, halogen, oxo group and alkoxyl, and one or two carbon atom of cycloalkyl can be substituted R by nitrogen, oxygen or sulphur atom
5, R
6And R
7Identical or different, be selected from hydrogen, hydroxyl, halogen, C
1-C
26Alkyl, cycloalkyl-(C
0-26) alkyl, cycloalkyloxy-(C
0-26) alkyl, alkoxyl-(C
0-26) alkyl, amino and sulfo--(C
0-26) alkyl and acyl group; wherein each alkyl, each alkoxyl and each acyl group can be side chain or non-side chain; and each alkyl, each alkoxyl and each cycloalkyl can or have one or more pairs of keys or triple-linked unsaturated group by replace saturated of hydroxyl, amino, halogen, oxo group and alkoxyl; and one or two carbon atom of cycloalkyl can be substituted by nitrogen, oxygen or sulphur atom, wherein R
5Also can with R
1Form ring, and R
3And R
7Can comprise carbon-oxygen singly-bound, have ring structure like this.
The present invention also provides the salt of the acceptable salt of pharmacy, ester and ester.
R
1And R
2Preferably identical or different, be selected from replacement and unsubstituted alkyl, be preferably C
1-C
4Alkyl.
R
3Be preferably selected from hydrogen, replacement and unsubstituted alkyl, be preferably C
1-C
4Alkyl, replacement and unsubstituted aromatics C
7-C
14Cycloalkyl, pyranose, t-butyldimethylsilyl and
R wherein
8Be selected from replacement and unsubstituted alkyl, be preferably alkyl, replacement and unsubstituted cycloalkyl (C that halogen replaces
0-26) alkyl, replacement and unsubstituted amino, replacement and unsubstituted alkoxyl, replacement and unsubstituted phenoxy, replacement and unsubstituted alkylthio group, replacement and unsubstituted aromatic ring alkylthio group, be preferably unsubstituted or by halogen, methyl, methoxyl group, nitro, amino or CF
3The aromatic ring alkylthio group that replaces.
R
4Being preferably selected from hydrogen, replacement and unsubstituted alkyl, replacement and unsubstituted phenyl reaches
Wherein X is selected from hydrogen, halogen, C
1-4Alkyl and phenyl and Y are selected from hydrogen, halogen, C
1-4Alkyl, nitro, methoxyl group, methylene-dioxy, wherein n is 0 or 1.
R
7Be preferably selected from hydrogen and halogen, perhaps R
3And R
7Comprise carbon-oxygen singly-bound, have ring structure like this.
Particularly preferred chemical compound is R wherein
1And R
2Be independently from each other the chemical compound of methyl and ethyl, R
4Be
And R
5And R
6Be independently selected from hydrogen, chlorine, bromine and methoxyl group.
Particularly preferred chemical compound is R wherein
4It is the chemical compound of following general formula
Wherein X is selected from 2-chlorine, 2-bromine, 2-fluorine, and Y is selected from 4-chlorine, 4-bromine, 4-fluorine, 5-fluorine and 4, the 5-methylene-dioxy, and wherein n is 0 or 1.
Particularly preferred chemical compound is R wherein
1And R
2Be methyl, R
3And R
7Be hydrogen or the chemical compound that comprises the carbon-oxygen bond that forms ring structure.
Preferred examples for compounds is 3-chloro-N-(2-chlorphenyl) methyl-N-hydroxyl-2,2-dimethyl propylene amide, N-(2-chlorphenyl) methyl-N-hydroxyl-2,2-dimethyl propylene amide, 3-chloro-N-hydroxy-n-phenyl-2,2-dimethyl propylene amide, N-(2-bromophenyl) methyl-3-chloro-N-hydroxyl-2,2-dimethyl propylene amide, 3-chloro-N-hydroxyl-2,2-dimethyl-N-(2-aminomethyl phenyl) methyl propanamide, 3-chloro-N-hydroxyl-2,2-N-trimethyl propionic acid amide., 3-chloro-N-hydroxyl-2,2-dimethyl-N-(benzyl) propionic acid amide., 3-chloro-N-(2,4-dichloro-benzenes methyl)-N-hydroxyl-2,2-dimethyl propylene amide, 3-chloro-N-(2-chlorphenyl) methyl-N-methoxyl group-2,2-dimethyl propylene amide, 3,3-two chloro-N-(2-chlorphenyl) methyl-N-hydroxyl-2,2-dimethyl propylene amide, 3-chloro-N-(2-fluorophenyl) methyl-N-hydroxyl-2,2-dimethyl propylene amide, 3-bromo-N-(2-chlorophenylmethyl) methyl-N-hydroxyl-2,2-dimethyl propylene amide, N-benzoyloxy-3-chloro-N-(2-chlorphenyl) methyl-2,2-dimethyl propylene amide, N-acetoxy-3-chloro-N-(2-chlorphenyl) methyl-2,2-dimethyl propylene amide, N-(chloroethene acyloxy)-3-chloro-N-(2-chlorphenyl) methyl-2,2-dimethyl propylene amide, 2-(2-chlorphenyl) methyl-4,4-dimethyl-3-isoxazole alkyl ketone, 4,4-dimethyl-2-phenyl-3-isoxazole alkyl ketone, 2-(2-bromophenyl) methyl-4,4-dimethyl-3-isoxazole alkyl ketone, 4,4-dimethyl-2-(2-aminomethyl phenyl) methyl-3-isoxazole alkyl ketone, 2,4,-trimethyl-3-isoxazole alkyl ketone, 4,4-dimethyl-2-benzyl-3-isoxazole alkyl ketone, 2-(2, the 4-Dichlorobenzene base) methyl-4,4-dimethyl-3-isoxazole alkyl ketone, 5-chloro-2-(2-chlorphenyl) methyl-4,4-dimethyl-3-isoxazole alkyl ketone, 2-(2-chlorphenyl) methyl-5-methoxyl group-4,4-dimethyl-3-isoxazole alkyl ketone, 2-(2-fluorophenyl) methyl-4,4-dimethyl-3-isoxazole alkyl ketone, the N-[(2-chlorphenyl) methyl]-N, 3-dihydroxy-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-(methylamino-carbonyl oxygen base) propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-the N-[(2-THP trtrahydropyranyl) oxygen-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[dimethyl (1, the 1-dimethyl ethyl) siloxy propionic acid amide., 3-acetoxyl group-N-[(2-chlorophenoxy)-methyl]-N-hydroxyl-2,2-dimethyl propylene amide, 2-[(2-chloro-4-fluorophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2-chloro-5-fluorophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2,4, the 5-trichlorophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2-chloro-6-fluorophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-ethyoxyl-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-phenyl amino-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-hydroxyl-4,4-dimethyl-3-isoxazole alkyl ketone, 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[(phenyl amino) carbonyl oxygen base] propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-([(2-chlorphenyl) methyl]-2,2-dimethyl-N-carbonyl phenoxy oxygen base) propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-N-ethoxy carbonyl oxygen base-2,2-dimethyl propylene amide, N-benzoyloxy-3,3-two chloro-N-[(2-chlorphenyls) methyl]-2,2-dimethyl propylene amide, N-(2-bromophenyl) methyl-3,3-two chloro-N-hydroxyls-2, the 2-dimethyl) propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-N-(4-nitrobenzoyl acyloxy)-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) ethyl]-2,2-dimethyl-N-[(2-aminomethyl phenyl) carbonyl oxygen base] propionic acid amide., 3-chloro-N-dichloro-acetoxy-N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[(4-tolyl) sulfonyloxy] propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[(1, the 1-dimethyl ethyl) carbonyl oxygen base] propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[(ethylmercapto group) carbonyl oxygen base] propionic acid amide., 3-chloro-N-[(2,2,2-three chloroethoxies) carbonyl oxygen base]-the N-[(2-chlorphenyl) methyl]-2,3-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) amino carbonyl oxygen base]-the N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-chloro-N-[(4-chlorphenyl) amino carbonyl oxygen base]-the N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-(phenyl methoxyl group) propionic acid amide., 3-chloro-N-[(2, the 4-dichlorophenoxy) acetoxyl group]-the N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[(3-trifluoromethyl) benzoyloxy] propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-2,2-dimethyl-N-[(4-tolyl) amino carbonyl oxygen base] propionic acid amide., 3-chloro-N-[(2-chlorphenyl) methyl]-N-[(3, the 4-chlorphenyl) amino carbonyl oxygen base]-2,2-dimethyl propylene amide, 3-chloro-N-(3-chloro-2,2-dimethyl-1-oxygen-propoxyl group)-N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-bromo-N-[(2-bromophenyl) methyl]-N-hydroxyl-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-the N-[(2-fluorophenyl) amino carbonyl oxygen base]-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-the N-[(4-methoxyphenyl) amino carbonyl oxygen base]-2,2-dimethyl propylene amide, 3-chloro-N-[(2-chlorphenyl) methyl]-the N-[(3-trifluoromethyl) amino carbonyl oxygen base]-2,2-dimethyl propylene amide, 3-bromo-N-[(2-chlorphenyl) methyl]-N-[methylamino carbonyl oxygen base]-2,2-dimethyl propylene amide, 3-bromo-N-(2-chloroethene acyloxy)-N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-chloro-N-[2,5-dichloro (formamido group)-benzoyl] oxygen-N-[(2-chlorphenyl) methyl]-2,2-dimethyl propylene amide, 3-bromo-N-[(2-bromophenyl) methyl]-N-chloroethene acyloxy-2,2-dimethyl propylene amide, 3-bromo-N-[(2-bromophenyl) methyl]-N-first carbonyl oxygen base-2,2-dimethyl propylene amide, 3-bromo-N-[(2-bromophenyl) methyl]-the N-[(2-chlorphenyl) amino carbonyl oxygen base]-2,2-dimethyl propylene amide, the 2-[(2-chlorphenyl) methyl]-N-hydroxyl-2,2-dimethyl-3-methyl mercapto propionic acid amide., 3-phenyl carbonyl oxygen base-N-[(2-chlorphenyl) methyl]-N-hydroxyl-2,2-dimethyl propylene amide, the 2-[(4-chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(3, the 4-Dichlorobenzene base) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone-5-yl acetate, the 2-[(chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone-5-yl benzoic acid ester, the 2-[(chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone-5-base dichloroacetic acid ester, the 2-[(chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone-5-base phenyl urethan, the 2-[(chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone-5-base methylamino formic acid esters, 2-[(2-chloro-4-cyano-phenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2-chloro-5-methoxyphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2-chloro-4-methoxyphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2, the 4-difluorophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(4-bromo-2-chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2-bromo-4-fluorophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(6-chloro-1,3-benzo dioxolanes-5-yl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-phenoxy group-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-(1-methyl ethoxy)-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-(phenyl methoxyl group)-3-isoxazole alkyl ketone, the 2-[(2-bromophenyl) methyl]-5-chloro-4,4-dimethyl-3-isoxazole alkyl ketone, 2-[(2, the 5-Dichlorobenzene base) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-propoxyl group-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-(2-propenyloxy group)-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-(2-third alkynyloxy group)-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-(methoxy ethoxy)-3-isoxazole alkyl ketone, 2-[(4-fluoro-2-iodophenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-cyclopentyloxy-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-5-(4-nitrophenoxy)-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-cyclopropyl-methoxyl group-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-bromophenyl) methyl]-4,4-dimethyl-5-(2-third alkynyloxy group)-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-(3-fourth alkynyloxy group)-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-(2-butyne oxygen base)-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-(3-butenyloxy)-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-amoxy-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-hexyloxy-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-(1-methyl propoxyl group)-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-(3-methyl-3-butenyloxy)-4,4-dimethyl-3-isoxazole alkyl ketone, the 2-[(2-chlorphenyl) methyl]-5-butoxy-4,4-dimethyl-3-isoxazole alkyl ketone and 2-[(2-chlorphenyl) methyl]-4,4-dimethyl-3-isoxazole alkyl ketone.
Provide the specific meanings and the example of above-mentioned definition below:
" acyl group " is the substituent group from acid, and Tathagata perhaps from organic sulfonic acid, in each situation, comprises aliphatic series, aromatics and/or heterocyclic group from organic carboxylic acid, carbonic acid, carbamic acid or corresponding to above each sour thio-acid or imidic acid in these acid molecules; And carbamoyl or imino group formoxyl (carbamimidoyl).
Provide the suitable example of acyl group below.
Acyl group from aliphatic acid is called as aliphatic acyl, and this comprises: 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 imino formoxyl (for example methyl-imino formoxyl etc.); Oxalo; Alkane oxalyl group (for example methoxalyl, ethoxalyl-, third oxalyl group etc.).
In the example of above-mentioned aliphatic acyl, 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 benzyloxy carbon acylamino etc.), acyloxy (for example acetoxyl group, benzoyloxy etc.) etc.; Contain this substituent aliphatic acyl and be preferably, for example, by amino, carboxyl, the alkanoyl that amino and carboxyl, halogen, acylamino-etc. replace.
The acyl group that carries the acid of replacement or unsubstituted aryl is called as aromatic acyl group, and 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 group; 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 mentioned as alkyl or alkane residue.Especially; the example that preferably contains the aromatic acyl group of specified substituent is halogen and the aroyl of hydroxyl replacement or the aroyl that is replaced by halogen; and the acyloxy and the aralkanoyl that are replaced by hydroxyl, oximido, saturated dihalide acyloxy imino group, and aryl thiocarbamoyl (for example phenyl thiocarbamoyl etc.): aryl imino group formoxyl (for example phenylimino formoxyl 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 aromatics that is selected from nitrogen, oxygen and sulfur or aliphatic series five Yuans or six element heterocycles (for example sulfur phenenyl, furanylcarbonyl, pyrrolylcarbonyl, nicotinoyl (nicotinyl) etc.);
The heterocycle alkanoyl, wherein heterocyclic radical is to contain at least one to be selected from heteroatomic five Yuans or six element heterocycles (for example sulfur phenylacetyl 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.
Except as otherwise noted, " alkyl " is to have the nearly straight or branched alkyl of 26 carbon atoms, as methyl, ethyl, propyl group, isopropyl, butyl, isobutyl group, the tert-butyl group, amyl group, hexyl etc.It can be by for example hydroxyl, amino, halogen (as fluorine, bromine, chlorine), oxo group and alkoxyl, and for example methoxyl group, ethyoxyl replace.
Except as otherwise noted, " alkoxyl " is to have nearly the straight or branched alkoxyl of 26 carbon atoms, for example methoxyl group, ethyoxyl etc.It can be replaced as methoxyl group, ethyoxyl by for example hydroxyl, amino, halogen, oxo group and alkoxyl.
" alkoxyl-(C
0-26) alkyl " be alkoxyl, this group also can link to each other with basic structure by alkyl.The definition of alkyl and alkoxyl as above.
Except as otherwise noted, " cycloalkyl-(C
0-26) alkyl " be cyclic compound with 3-8 carbon atom, this group directly or by alkylidene links to each other with basic structure.Alkylidene can be unsaturated group side chain or straight chain, saturated or that have two keys.The possible substituent group of cycloalkyl is, especially alkoxyl, alkyl, hydroxyl, halogen, amino, oxo group.Cycloalkyl can also be the aromatic group with two keys of respective number, i.e. aryl-(C
0-26) alkyl (as phenyl, pyridine radicals, naphthyl etc.).The aromatics cyclic compound especially can further have substituent group, for example nitro and CF
3And phenyl.
" cycloalkyloxy-(C
0-26) alkyl " be cyclic compound with 3-8 carbon atom, this group can directly link to each other with basic structure by oxygen or by alkylidene.Alkylidene can be unsaturated group side chain or non-side chain, saturated or that have two keys.Possible substituent group on the cycloalkyl is, especially alkoxyl (comprising alkylene dioxo base, as methylene-dioxy), alkyl, hydroxyl, halogen, amino, oxo group.Cycloalkyl can also be multi-ring base and the aromatic group (as phenoxy group, pyridyloxy, naphthoxy etc.) with two keys of respective number.The aromatics cyclic compound especially can further have substituent group, for example nitro and CF
3And phenyl.
" amino " can be substituted, for example by alkyl or cycloalkyl-(C as defined above
0-26) the alkyl replacement.
" amino-(C
0-26) alkyl " be amino, it also can link to each other with basic structure by alkyl.The definition of alkyl and amino as above.
" silicyl " can be substituted, for example by alkyl or cycloalkyl-(C as defined above
0-26) the alkyl replacement.
" silicyl-(C
0-26) alkyl " be silicyl, it also can link to each other with basic structure by alkyl.The definition of alkyl and silicyl as above.
" sulfo--(C
0-26) alkyl " can be substituted, for example by alkyl or cycloalkyl-(C as defined above
0-26) the alkyl replacement.(C
0-26) alkyl is the alkylidene of straight or branched, for example methylene, ethylidene, propylidene, isopropylidene, butylidene, isobutylidene, the inferior tert-butyl group, pentylidene, hexylidene etc.They can comprise two keys or triple bond and can be substituted, for example by hydroxyl, amino, halogen (as fluorine, bromine, chlorine), oxo group and alkoxyl.Replace as methoxyl group, ethyoxyl.
The chemical compound of molecular formula of the present invention (I) allows to exist stereoisomer, for example radicals R
1-R
7Comprise two keys or chirality.The purposes of The compounds of this invention comprises the pure product that use all stereoisomers or their mixture.
This chemical compound is particularly suitable for treating and prevents infection by antibacterial, unicellular and many cells parasite and fungus-caused humans and animals.
These chemical compounds are to unicellular parasite (protozoon), especially antagonism bring out malaria and sleeping sickness, bring out chagas disease, the pathogen of toxoplasmosis, amebic dysentery, leishmaniasis, trichomonacide, interstitial plasma cell pneumonia, balantidiosis, cryptosporidiosis, sarcosporidiasis, acanthamoebosis, naegleriasis, coccidiosis, giardiasis and Lambliasis.
Therefore they 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 this chemical 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 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.
The purposes that is used for the elimination Helicobacter pylori treatment of gastrointestinal ulceration also is useful.
These chemical compounds also are 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.
According to chemical compound of the present invention, generally include the salt of the acceptable salt of pharmacy, ester and this ester, or after giving, provide the chemical compound of chemical compound of the present invention with metabolite or catabolite, be also referred to as " prodrug ", they can be to have the similar mode of reagent (mixing with nontoxic, the pharmaceutically acceptable carrier material) prescription of anti-infectious function to give 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 the chemical compound of molecular formula of the present invention (I).
Also be that the particularly suitable salt of pharmacy is, 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.
In test macro, determine 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, the inhibition of measuring malarial parasite growth in the blood cultivation thing is used for determining the malaria activity.
Antibacterial activity is according to the inhibition of the growth of antibacterial on Nutrient medium and fluid medium is determined.
Fungicidally active 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, use proper model here.
The active material of demonstration is further studied in the model in vivo in the in-vitro measurements system.In corresponding suitable animal model, further estimate parasiticide, antifungal or antibacterial activity.
Pharmaceutically active agent can be filled a prescription into the pharmaceutical preparation of unit dose.This means that preparation can be a form separately partly, 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 that once gives, be generally dosage every day whole, half, 1/3rd or 1/4th.
The carrier mass that nontoxic, inert pharmacy is fit to refers to solid, semisolid or liquid diluent, filler and various formulation adjuvant.
Preferred pharmaceutical formulation 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 carrier mass, 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 listed material 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, it also can be such compositions, they only or preferentially in a part of intestinal randomly with the delayed mode release of active compounds, for example may use polymer and wax as embedding composition.
Reactive compound or chemical compound can randomly exist with the form of one or more above-mentioned carrier mass with microcapsule.
Suppository can also contain conventional water solublity or water insoluble carrier material except that active substance, Polyethylene Glycol for example, fat, for example cocoa butter and senior ester (for example pure and mild C16 fatty acid of C14), or the mixture of these materials.
Ointment, paste, emulsifiable paste and gel can also contain conventional carrier mass 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 carrier mass 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 carrier mass 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.
Solution that gives for parenteral or Emulsion also can be aseptic, with the isoosmotic form of blood.
Suspensoid can contain conventional carrier mass 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 prescription, the concentration of the reactive compound 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.
Except that the active substance of general formula (I), pharmaceutical formulation can also contain other pharmaceutically active substances.
These chemical compounds can be antibiotic with having of having described before this, the material of antiviral, 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 in Klinik 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), phenoxy group penicillin 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, Bay Y3118, 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, WR 238,605, 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.
Chemical compound of the present invention can be present in the pharmaceutical composition 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 several these combinations of substances.
Use known method to prepare the said medicine prescription, for example carrier mass or material and reactive compound or compound 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) give the human or animal, and be used for the treatment of chamber, endoceliac infection.Solution that admissible suitable prescription is injection, oral medication and suspensoid, gel, preserved material prescription, Emulsion, ointment or drop.Topical therapeutic can use ophthalmology and department of dermatologry prescription, silver and other salt, ear drop, ophthalmic ointment, powder or solution.Can also give animal with proper formula by feedstuff or drinking water.Can use gel, powder, powder, tablet, slow releasing tablet, premix mixture, concentrate, granule, pill, tablet, boli, capsule, aerosol, spray, inhalant to humans and animals.Can also introduce in other carrier mass according to chemical compound of the present invention, for example plastics (plastic links that is used for topical therapeutic), collagen or bone cement.
Usually, under the situation of human and veterinary medicine, according to per 24 hours about 0.05-600 of proof, the reactive compound or the chemical compound of the molecular formula (I) of preferred 0.5-200 mg/kg body weight optionally give with several discrete dosages form, can realize the result who expects.Discrete dosages preferably contains about 1-200, especially the reactive compound of 1-60 mg/kg body weight or chemical compound.But, may need to depart from described dosage, particularly can giving and administration time or at interval according to the character of the character of treatment patient's symptom and body weight, disease and the order of severity, prescription and medicine.Therefore, in some cases, the reactive compound that is less than above-mentioned amount may be just enough, but in other cases, must surpass the chemical compound of above-mentioned amount.The professional can determine the optimal dose and the administering mode of the reactive compound of concrete needs according to its Professional knowledge.
The compounds of this invention can conventional concentration and prescription give animal with feedstuff or feed formula or drinking-water.
The preparation method of material of the present invention is known in the art, for example is recorded in No. the 4405357th, the United States Patent (USP).
The activity of some The compounds of this invention is described by embodiment below:
Following material is studied: material 1:
Material 2:
Material 3:
Material 4:
The effect that test shows chemical compound is based on the inhibition to 1-deoxy-D-xylulose 5-phosphate ester (DOXP) metabolic pathway, and it can measure in antibacterial, parasite and fungus, but does not detect in human body.The following example demonstrates the effect of chemical compound of the present invention to DOXP reduction isomerase.
Embodiment 1
Colibacillary DOXP reduction isomerase is a kind of recombinant protein at expression in escherichia coli.In the mixture that contains 100 mMs/rise Tns-HCl (pH=7.5), 1 mM/rise manganous chloride, 0.3 mM/rise NADPH and 1 mM/rise DOXP, measure the activity of DOXP reduction isomerase.In spectrophotometer, measure the oxidation of NADPH in 365 nanometers.For suppressing research, in the presence of the chemical compound 1-4 of the variable concentrations of 0.1-100 micromoles per liter, measure DOXP and reduce the activity of isomerase.Determine that by the value of measuring enzyme is suppressed to the concentration (IC of half at utmost the time
50).As a result, i.e. IC
50Value is listed in the table.
Embodiment 2
On the In vitro culture thing of malaria disease substance Plasmodium falciparum, measure the antimalarial active of material 1-4.Adding 200 microlitre parasitemias in each hole of 96 hole microdroplet plates is 0.4%, and hematocrit is nonsynchronous Plasmodium falciparum culture of 2%.With the step of three times of dilutions, preparation concentration is the series of compounds diluent of 100-0.14 micromoles per liter.Plate was cultivated 48 hours in 37 ℃, 3% carbon dioxide and 5% oxygen.Then, 27 μ Ci/ml[have been added toward each hole adding
3H] hypoxanthic 3 microlitre culture medium.Cultivate after 24 hours, on glass fibre filter, filter the results parasite and measure the radioactivity of mixing.The percentage that mixes with tritium suppresses to measure the inhibition that parasite grows.The inhibition of parasite growth suppresses expression with the percentage that mixes with the tritium of comparing that does not contain test substances.Maximum half-inhibition concentration (the IC of test substances
50) measure by extrapolation.As a result, i.e. IC
50In being listed in the table below:
Table
| Material number | IC50/ (micromoles per liter) (reduction isomerase) | IC50/ (micromoles per liter) (parasite) |
| ?????1 | ????????20 | ?????????28 |
| ?????2 | ????????37 | ?????????32 |
| ?????3 | ????????24 | ?????????33 |
| ?????4 | ????????40 | ?????????48 |
Claims (12)
1, the salt of the chemical compound of at least a molecular formula (I) or the acceptable salt of their pharmacy, ester and ester is used to prevent or treats purposes by antibacterial, parasite or fungus-caused infection:
R
3Be selected from hydrogen, alkyl, alkoxyl-(C
0-26) alkyl, C
3-14Cycloalkyl-(C
0-26) alkyl, cycloalkyloxy-(C
0-26) alkyl, amino-(C
0-26) alkyl, silicyl-(C
0-26) alkyl and sulfo--(C
0-26) alkyl, wherein each alkyl and each alkoxyl can be side chain or non-side chain, and each alkyl, each alkoxyl and each cycloalkyl can or have one or more pairs of keys or triple-linked unsaturated group by replace saturated of hydroxyl, amino, halogen, oxo group and alkoxyl, and one or two carbon atom of cycloalkyl can be substituted R by nitrogen, oxygen or sulphur atom
4Be selected from hydrogen, alkyl, acyl group and cycloalkyl-(C
0-26) alkyl; wherein each alkyl and each acyl group can be side chain or non-side chain; and each alkyl, each acyl group and each cycloalkyl can or have one or more pairs of keys or triple-linked unsaturated group by replace saturated of hydroxyl, amino, halogen, oxo group and alkoxyl; and one or two carbon atom of cycloalkyl can be substituted R by nitrogen, oxygen or sulphur atom
1And R
2Identical or different, be selected from hydrogen, hydroxyl, halogen, replacement and unsubstituted amino, replacement and unsubstituted alkyl, replacement and unsubstituted alkoxyl and replacement and unsubstituted cycloalkyl-(C
0-26) alkyl, wherein each alkyl and each alkoxyl can be side chain or non-side chain, each alkyl, each alkoxyl and each cycloalkyl can be saturated or have one or more pairs of keys or triple-linked unsaturated group, and one or two carbon atom of cycloalkyl can be substituted R by nitrogen, oxygen or sulphur atom
5, R
6And R
7Identical or different, be selected from hydrogen, hydroxyl, halogen, replacement and unsubstituted C
1-C
26Alkyl, replacement and unsubstituted cycloalkyl-(C
0-26) alkyl, replacement and unsubstituted cycloalkyloxy-(C
0-26) alkyl, replacement and unsubstituted alkoxyl-(C
0-26) alkyl, replacement and unsubstituted amino and unsubstituted sulfo--(C
0-26) alkyl and replacement or unsubstituted acyl; wherein each alkyl, each alkoxyl and each acyl group can be side chain or non-side chain; and each alkyl, each alkoxyl and each cycloalkyl can be saturated or have one or more pairs of keys or triple-linked unsaturated group; and one or two carbon atom of cycloalkyl can be substituted by nitrogen, oxygen or sulphur atom, wherein R
5Also can with R
1Form ring, and R
3And R
7Can comprise carbon-oxygen singly-bound, have ring structure like this.
2, according to the purposes of claim 1, be characterised in that R
1And R
2Identical or different, be selected from replacement and unsubstituted alkyl, be preferably C
1-C
4Alkyl.
3, according to the purposes of one of aforementioned claim, be characterised in that R
3Be selected from hydrogen, replacement and unsubstituted alkyl, be preferably C
1-C
4Alkyl replaces and unsubstituted aromatics C
7-C
14Cycloalkyl, pyranose, t-butyldimethylsilyl and
R wherein
8Be selected from replacement and unsubstituted alkyl, be preferably the alkyl that halogen replaces, replace and unsubstituted cycloalkyl (C
0-26) alkyl, replacement and unsubstituted amino, replacement and unsubstituted alkoxyl, replacement and unsubstituted phenoxy, replacement and unsubstituted alkylthio group, replacement and unsubstituted aromatic ring alkylthio group, be preferably aromatic ring alkylthio group unsubstituted or that replaced by halogen, methyl, methoxyl group, nitro, amino or CF3.
4, according to the purposes of one of aforementioned claim, be characterised in that R
4Being preferably selected from hydrogen, replacement and unsubstituted alkyl, replacement and unsubstituted phenyl reaches
Wherein X is selected from hydrogen, halogen, C
1-4Alkyl, phenyl, and Y is selected from hydrogen, halogen, C
1-4Alkyl, nitro, methoxyl group, methylene-dioxy, wherein n is 0 or 1.
5, according to the purposes of claim 4, be characterised in that X is selected from chlorine, bromine, fluorine, and Y is selected from 4-chlorine, 4-bromine, 4-fluorine, 5-fluorine and 4, the 5-methylene-dioxy, wherein n is 0 or 1.
6, according to the purposes of one of aforementioned claim, be characterised in that R
7Be selected from hydrogen and halogen, perhaps R
3And R
7Comprise carbon-oxygen singly-bound, have ring structure like this.
7, according to the purposes of one of aforementioned claim, be characterised in that R
1And R
2Be independently from each other methyl and ethyl, R
4Be
R
5And R
6Be independently selected from hydrogen, chlorine, bromine and methoxyl group.
8, according to the purposes of one of aforementioned claim, be characterised in that R
1And R
2Be methyl, R
3And R
7Be hydrogen or comprise the carbon-oxygen bond that forms ring structure.
9, the use according to claim 8, characterized in that it comprises as active compound
At least one substance selected from the following: 3 - Chloro-N-(2 - chlorophenyl) methyl-N-hydroxy-2 ,2 - dimethyl-
Propanamide, N-(2 - chlorophenyl) methyl-N-hydroxy-2 ,2 - dimethyl-propionamide 3 - chloro-N-hydroxy -
N-phenyl-2, 2 - dimethyl-propionamide, N-(2 - bromophenyl) methyl-3 - chloro-N-hydroxy-2 ,2 - dimethyl-
Propionamide 3 - chloro-N-hydroxy-2 ,2 - dimethyl-N-(2 - methylphenyl) methyl propionamide 3 - chloro -
N-hydroxy -2,2-N-trimethyl-propionamide 3 - chloro-N-hydroxy-2 ,2 - dimethyl-N-(phenylmethyl) propyl
Amide 3 - chloro-N-(2,4 - dichlorobenzyl)-N-hydroxy-2 ,2 - dimethyl-propionamide 3 - chloro-N-(2
- Chlorophenyl) methyl-N-methoxy-2 ,2 - dimethyl-propionamide, 3,3 - dichloro-N-(2 - chlorophenyl) methyl
Yl-N-hydroxy-2 ,2 - dimethyl-propionamide 3 - chloro-N-(2 - fluorophenyl) methyl-N-hydroxy -2,2 -
Methyl-propionamide 3 - bromo-N-(2 - chlorophenyl) methyl-N-hydroxy-2 ,2 - dimethyl-propionamide, N
- Benzoyloxy-3 - chloro-N-(2 - chlorophenyl) methyl -2,2 - dimethyl-propionamide, N-acetyl group -
3 - chloro-N-(2 - chlorophenyl) methyl -2,2 - dimethyl-propionamide, N-(chloroacetyl)-3 - chloro-N-(2
- Chlorophenyl) methyl -2,2 - dimethyl-propionamide, 2 - (2 - chlorophenyl) methyl -4,4 - dimethyl-3 - Clomazone
Oxazolidinone, 4,4 - dimethyl-2 - phenyl-3 - isoxazolidinone, 2 - (2 - bromophenyl) methyl -4,4 -
Dimethyl-3 - isoxazolidinone, 4,4 - dimethyl-2 - (2 - methylphenyl) methyl-3 - isoxazolidine
Ketones, 2,4 - trimethyl-3 - isoxazolidinone, 4,4 - dimethyl-2 - phenyl-3 - isoxazolidinone,
2 - (2,4 - dichlorophenyl) methyl -4,4 - dimethyl-3 - isoxazolidinone, 5 - chloro -2 - (2 - chlorophenyl) methyl
-4,4 - Dimethyl-3 - isoxazolidinone, 2 - (2 - chlorophenyl) methyl-5 - methoxy-4 ,4 - dimethyl -
3 - isoxazolidinone, 2 - (2 - fluorophenyl) methyl -4,4 - dimethyl-3 - isoxazolidinone, N-[(2 -
Chlorophenyl) methyl]-N, 3 - dihydroxy-2, 2 - dimethyl-propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]
-2,2 - Dimethyl-N-(methylamino - carbonyloxy) propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-
[(2 - tetrahydropyranyl) oxy -2,2 - dimethyl-propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl] -2,2 -
Dimethyl-N-[dimethyl (1,1 - dimethylethyl) siloxy propionamide 3 - acetoxy-N
- [(2 - chlorophenoxy) - methyl]-N-hydroxy-2 ,2 - dimethylpropanamide, 2 - [(2 - chloro-4 - fluorophenyl)
Methyl] -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chloro-5 - fluorophenyl) methyl] -4,4 - dimethyl -
3 - isoxazolidinone, 2 - [(2,4,5 - trichloro-phenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone, 2
- [(2 - chloro-6 - fluorophenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl]
-5 - Ethoxy-4 ,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl -
5 - phenyl-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
Yl] propanamide 3 - chloro-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-N-([(2 - chlorophenyl) methyl] -
2,2 - dimethyl-N-phenoxycarbonyl) propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-ethoxycarbonyl-
Oxy -2,2 - dimethyl-propionamide, N-benzoyloxy-3 ,3 - dichloro-N-[(2 - chlorophenyl) methyl] -
2,2 - dimethyl-propionamide, N-(2 - bromophenyl) methyl-3 ,3 - dichloro-N-hydroxy-2 ,2 - dimethyl) propyl
Amide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-(4 - nitro-benzoyloxy) -2,2 - dimethyl-propionyl
Amine 3 - chloro-N-[(2 - chlorophenyl) ethyl] -2,2 - dimethyl-N-[(2 - methylphenyl) carbonyloxy] propionyl
Amine 3 - chloro-N-dichloro-acetoxy-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-propionamide 3 -
Chloro-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-N-[(4 - methylphenyl) sulfonyloxy] propionamide 3 -
Chloro-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-N-[(1,1 - dimethylethyl) carbonyloxy] propionyl
Amine 3 - chloro-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-N-[(ethylthio) carbonyloxy] propionamide
3 - chloro-N-[(2,2,2 - trichloro-ethoxy) carbonyloxy]-N-[(2 - chlorophenyl) methyl] -2,3 - dimethyl-C
Amide 3 - chloro-N-[(2 - chlorophenyl) amino carbonyloxy]-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-
Propionamide 3 - chloro-N-[(4 - chlorophenyl) amino carbonyloxy]-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl
Propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl] -2,2 - Dimethyl-N-(phenylmethoxy) propionic acid
Amine 3 - chloro-N-[(2,4 - dichlorophenoxy) acetoxy]-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl
Propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-N-[(3 - trifluoromethyl) benzoic
Acyloxy] propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl] -2,2 - dimethyl-N-[(4 - methylphenyl) amino
Ylcarbonyloxy] propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-[(3,4 - chlorophenyl) amino carbonyloxy
Yl] -2,2 - dimethyl-propionamide 3 - chloro-N-(3 - chloro -2,2 - dimethyl-1 - O - propoxy)-N-[(2 -
Chlorophenyl) methyl] -2,2 - dimethyl-propionamide 3 - bromo-N-[(2 - bromophenyl) methyl]-N-hydroxy-2,
2 - 2-methyl-propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-[(2 - fluorophenyl) amino carbonyloxy]
-2,2 - Dimethyl-propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-[(4 - methoxyphenyl) amino
Carbonyloxy] -2,2 - dimethyl-propionamide 3 - chloro-N-[(2 - chlorophenyl) methyl]-N-[(3 - (trifluoromethyl)
Phenyl) amino carbonyloxy] -2,2 - dimethyl-propionamide 3 - bromo-N-[(2 - chlorophenyl) methyl]-N-[methyl
Carbonyloxy amino] -2,2 - dimethyl-propionamide 3 - bromo-N-(2 - chloro-acetyloxy)-N-[(2 - chlorophenyl)
Methyl] -2,2 - dimethyl-propionamide 3 - chloro-N-[2,5 - dichloro-(formylamino) - benzoyl] oxy-N-
[(2 - chlorophenyl) methyl] -2,2 - dimethyl-propionamide 3 - bromo-N-[(2 - bromophenyl) methyl]-N-chloroacetyl
Acyloxy -2,2 - dimethyl-propionamide 3 - bromo-N-[(2 - bromophenyl) methyl]-N-methyl-carbonyloxy-2 ,2 -
Dimethyl-propionamide 3 - bromo-N-[(2 - bromophenyl) methyl]-N-[(2 - chlorophenyl) aminocarbonyl] -2,
2 - 2-methyl-propionamide, 2 - [(2 - chlorophenyl) methyl]-N-hydroxy-2 ,2 - dimethyl-3 - (methylthio) propionate
Amide 3 - phenyl carbonyloxy-N-[(2 - chlorophenyl) methyl]-N-hydroxy-2 ,2 - dimethyl-propionamide, 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 - isoxazolidine
-5 - yl acetate, 2 - [(chlorophenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone -5 - yl benzoic
Ester, 2 - [(chlorophenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone -5 - yl ester of dichloroacetic acid, 2
- [(P-chlorophenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone -5 - phenyl carbamate, 2 - [(chloro-
Phenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone -5 - yl methyl carbamate, 2 - [(2 - chloro -4 -
Cyano-phenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chloro-5 - methoxy-phenyl) methyl
Yl] -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 - isoxazolidine
One, 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 - benzodioxol -
5 - yl) methyl] -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl -
5 - phenoxy-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl-5 - (1 - methyl-ethyl
Oxy) -3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl-5 - (phenylmethoxy) -
3 - isoxazolidinone, 2 - [(2 - bromophenyl) methyl] -5 - chloro -4,4 - dimethyl-3 - isoxazolidinone, 2
- [(2,5 - dichlorophenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -
4,4 - dimethyl-5 - propoxy-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl-5
- (2 - propenyl)-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl-5 - (2 - C
Alkynyloxy) -3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -4,4 - dimethyl-5 - (methoxy-ethoxy-
Yl) -3 - isoxazolidinone, 2 - [(4 - fluoro-2 - iodo-phenyl) methyl] -4,4 - dimethyl-3 - isoxazolidine
One, 2 - [(2 - chlorophenyl) methyl] -5 - cyclopentyloxy-4 ,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 -
Chlorophenyl) methyl] -4,4 - dimethyl-5 - (4 - nitrophenyl) -3 - isoxazolidinone, 2 - [(2 - chlorophenyl
Yl) methyl] -5 - cyclopropyl - methoxy-4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - bromophenyl)
Methyl] -4,4 - dimethyl-5 - (2 - propynyl) -3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -
5 - (3 - butynyloxy) -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -5 - (2 -
Butynyloxy) -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -5 - (3 - butylene oxide
Yl) -4,4 - dimethyl-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -5 - pentyloxy-4 ,4 - dimethyl
-3 - isoxazolidinone, 2 - [(2 - chlorophenyl) methyl] -5 - hexyl-4 ,4 - dimethyl-3 - isoxazolyl
Oxazolidinone, 2 - [(2 - chlorophenyl) methyl] -5 - (1 - methyl-propoxy) -4,4 - dimethyl-3 - isoxazolidine
One, 2 - [(2 - chlorophenyl) methyl] -5 - (3 - methyl - 3 - butenyl oxy) -4,4 - dimethyl-3 - isoxazolidine
One, 2 - [(2 - chlorophenyl) methyl] -5 - butoxy-4 ,4 - dimethyl-3 - isoxazolidinone and 2 - [(2 - chloro-
Phenyl) methyl] -4,4 - dimethyl-3 - isoxazolidinone.
...
10, according to the purposes of one of claim 1-9, be used for prevention and treatment by unicellular parasite (protozoon), promptly cause the infection that the pathogen of following disease 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, purposes according to one of claim 1-9, be used to prevent and treat be selected from following bacterial infection: 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, the Bacillaceae antibacterial, especially bacillus and fusobacterium antibacterial, and the radical treatment of Helicobacter pylori that is used for gastrointestinal ulceration.
12, the method for the infection that caused by antibacterial, fungus or parasite of treatment wherein suffers from the patient of the infection that is caused by antibacterial, fungus or parasite with the therapeutic activity amount as the described chemical compound of one of claim 1-11.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19900907 | 1999-01-13 | ||
| DE19903666.7 | 1999-01-30 | ||
| DE19900907.4 | 1999-01-30 | ||
| DE19903666A DE19903666A1 (en) | 1999-01-13 | 1999-01-30 | Medicines containing 3-isoxazolidinones and hydroxylamic acids as an active ingredient and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1342078A true CN1342078A (en) | 2002-03-27 |
Family
ID=26051290
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00802779A Pending CN1342078A (en) | 1999-01-13 | 2000-01-12 | Use of 3-isoxazolidinones and hydroxylamine acids for treatment of infections |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP1143941A3 (en) |
| JP (1) | JP2002534440A (en) |
| CN (1) | CN1342078A (en) |
| AU (1) | AU2436600A (en) |
| BR (1) | BR0007491A (en) |
| CA (1) | CA2360366A1 (en) |
| CZ (1) | CZ20012380A3 (en) |
| HU (1) | HUP0105412A2 (en) |
| IL (1) | IL143795A0 (en) |
| NO (1) | NO20013464L (en) |
| PL (1) | PL350128A1 (en) |
| SK (1) | SK9502001A3 (en) |
| TR (1) | TR200102019T2 (en) |
| WO (1) | WO2000041473A2 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003035073A1 (en) | 2001-10-25 | 2003-05-01 | Astrazeneca Ab | Isoxazoline derivatives useful as antimicrobials |
| GB202209172D0 (en) * | 2022-06-22 | 2022-08-10 | Syngenta Crop Protection Ag | Improvements in or relating to organic compounds |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL45174A (en) * | 1973-08-10 | 1976-12-31 | Merck & Co Inc | Antibacterial compositions containing 3-fluoro-d-alanine type compound and n-substituted cycloserine compound |
| US3911007A (en) * | 1974-08-08 | 1975-10-07 | Searle & Co | N-substituted N-benzyloxy-2-methyl-2-(4-halophenoxy)propionamides |
| FR2290442A1 (en) * | 1974-11-06 | 1976-06-04 | Aries Robert | Cycloserine-(hexahydro)rifamycin SV condensates - antibiotics, prepd from 3-formyl rifamycins and opt N-alkylated cycloserine |
| DE3686632T2 (en) * | 1985-04-30 | 1993-01-21 | Takeda Chemical Industries Ltd | ANTIBIOTIC DERIVATIVES, THEIR PRODUCTION AND USE. |
| GB8531838D0 (en) * | 1985-12-30 | 1986-02-05 | Wellcome Found | Aryl derivatives |
| JPS63119462A (en) * | 1986-11-05 | 1988-05-24 | Takeda Chem Ind Ltd | 5-membered-ring n-sulfo compound |
| JPS63119476A (en) * | 1986-11-05 | 1988-05-24 | Takeda Chem Ind Ltd | Isoxazolidone derivative |
| US5288896A (en) * | 1992-01-15 | 1994-02-22 | Warner-Lambert Company | 3,5-di-t-butyl-4-hydroxylphenylmethylhydroxylamines and their derivatives, pharmaceutical compositions, and methods of use therefor |
| CA2158352A1 (en) * | 1993-03-16 | 1994-09-29 | Michael John Crimmin | Hydroxamic acid derivatives as metalloproteinase inhibitors |
| CA2170158A1 (en) * | 1993-08-23 | 1995-03-02 | Roy A. Black | Inhibitors of tnf-alpha secretion |
| GB9401129D0 (en) * | 1994-01-21 | 1994-03-16 | British Bio Technology | Hydroxamic acid derivatives as metalloproteinase inhibitors |
| WO1996013263A2 (en) * | 1994-11-01 | 1996-05-09 | Research Corporation Technologies, Inc. | Methods of treatment of viral disease with inhibitors of sphingolipid biosynthesis |
| US5919790A (en) * | 1996-10-11 | 1999-07-06 | Warner-Lambert Company | Hydroxamate inhibitors of interleukin-1β converting enzyme |
| US6251913B1 (en) * | 1997-03-28 | 2001-06-26 | Zeneca Limited | Hydroxamic acids substituted by heterocycles useful for inhibition of tumor necrosis factor |
| AUPO721997A0 (en) * | 1997-06-06 | 1997-07-03 | Queensland Institute Of Medical Research, The | Anticancer compounds |
-
2000
- 2000-01-12 BR BR0007491-8A patent/BR0007491A/en not_active Application Discontinuation
- 2000-01-12 WO PCT/EP2000/000165 patent/WO2000041473A2/en not_active Application Discontinuation
- 2000-01-12 CA CA002360366A patent/CA2360366A1/en not_active Abandoned
- 2000-01-12 CZ CZ20012380A patent/CZ20012380A3/en unknown
- 2000-01-12 SK SK950-2001A patent/SK9502001A3/en unknown
- 2000-01-12 HU HU0105412A patent/HUP0105412A2/en unknown
- 2000-01-12 TR TR2001/02019T patent/TR200102019T2/en unknown
- 2000-01-12 EP EP00902582A patent/EP1143941A3/en not_active Withdrawn
- 2000-01-12 PL PL00350128A patent/PL350128A1/en not_active Application Discontinuation
- 2000-01-12 IL IL14379500A patent/IL143795A0/en unknown
- 2000-01-12 CN CN00802779A patent/CN1342078A/en active Pending
- 2000-01-12 AU AU24366/00A patent/AU2436600A/en not_active Abandoned
- 2000-01-12 JP JP2000593097A patent/JP2002534440A/en active Pending
-
2001
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| Publication number | Publication date |
|---|---|
| BR0007491A (en) | 2001-11-20 |
| CZ20012380A3 (en) | 2002-01-16 |
| WO2000041473A3 (en) | 2001-11-29 |
| TR200102019T2 (en) | 2002-04-22 |
| NO20013464D0 (en) | 2001-07-12 |
| SK9502001A3 (en) | 2002-05-09 |
| HUP0105412A2 (en) | 2002-05-29 |
| WO2000041473A2 (en) | 2000-07-20 |
| AU2436600A (en) | 2000-08-01 |
| EP1143941A3 (en) | 2002-02-06 |
| CA2360366A1 (en) | 2000-07-20 |
| EP1143941A2 (en) | 2001-10-17 |
| JP2002534440A (en) | 2002-10-15 |
| IL143795A0 (en) | 2002-04-21 |
| PL350128A1 (en) | 2002-11-04 |
| NO20013464L (en) | 2001-09-12 |
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