WO2004058732A1

WO2004058732A1 - Oxazolidine derivative, methods of preparation and uses

Info

Publication number: WO2004058732A1
Application number: PCT/CN2002/000928
Authority: WO
Inventors: Yushe Yang; Yingjie Cui; Ruyun Ji; Kaixian Chen
Original assignee: Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences; Nanjing Chang'ao Pharmaceutical Science And Technology Limited Company
Priority date: 2002-12-30
Filing date: 2002-12-30
Publication date: 2004-07-15
Also published as: AU2002357561A1; AU2002357561A8

Abstract

The present invention provide oxazoldines derivative of formula (I) or salts of thereof wherein R is F (I) Or NR2R3, R1 is optionally substituted alkylsulfortyl, arylsulfonyl, heteroarylsulfonyl, alkylcarbonyl derived from amino acid, arylcarbonyl, arylaminocarbonyl, arylaminothiocarbonyl; R2 is optionally substituted alkylsulfonyl, arylsulfonyl, arylcarbonyl, heteroarylsunlfonyl; R3 is H or alkyl. The present invention also relates to the method of preparation of these compounds and the use of production of medicines, which are useful in treating and preventing an infection disorder especially, induced by drug-fast bacteria.

Description

Oxazolone compounds, preparation method and application thereof

The invention relates to the fields of medicinal chemistry and chemotherapeutics, in particular to the synthesis of oxazolidinone compounds and its use in the preparation of a medicament for the treatment of infectious diseases, especially infectious diseases caused by multidrug-resistant bacteria. Background technique

With the widespread use of antibiotics in the world for many years, the abuse of antibiotics is becoming increasingly common. Therefore, the emergence of superbugs resistant to multiple antibiotics has posed a new threat to human health. At present, both Gram-positive and negative bacteria have a tendency to become resistant, and the problem of resistance to Gram-positive bacteria is more serious. Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), multi-drug resistant Mycobacterium tuberculosis, and vancomycin-resistant enterococci (VRE) appear worldwide It is the main problem in the current clinical situation (Swartz, MN Proc. Natl. Acad. Sci. USA 1994, 91, 2420.) ₀ Especially the emergence of vancomycin-resistant enterococci (VRE) has broken through the treatment of patients with severe infections. "Last resort".

Oxazolidone represents a very promising class of new synthetic antibacterial agents. Its mechanism of inhibiting early bacterial protein synthesis is different from all currently known antibiotics, meaning that the possibility of cross-resistance is less likely. The focus of the new generation of oxazolidone drugs is to increase antibacterial activity and expand the antibacterial spectrum, including activity against Gram-negative bacteria.

It is an object of the present invention to provide a novel oxazolidinone compound having antibacterial activity, particularly anti-multidrug resistant bacteria activity, and a pharmaceutically acceptable salt thereof.

Another object of the present invention is to provide a method for preparing a novel oxazolidinone compound having antibacterial activity, particularly anti-multidrug resistance, and a pharmaceutically acceptable salt thereof.

Yet another object of the present invention is to provide the use of such compounds and pharmaceutically acceptable salts thereof in the preparation of a medicament for treating infectious diseases, especially infectious diseases caused by multidrug-resistant bacteria. Summary of invention

The present invention provides an oxazolidinone compound having the structure of the following formula (I) and a pharmaceutically acceptable salt thereof:

Substituted amidylsulfonyl, Substituted arylsulfonyl, Substituted aromatic heterocyclic sulfonyl, Substituted amino acid formyl, Substituted arylformyl, Substituted aryl Carbamoyl, arylaminothioformyl which may be substituted;

= Substituted sulfenyl, substituted arylsulfonyl, substituted arylformyl, substituted heteroaromatic formyl; and

R ₃ = H or alkyl.

The present invention also provides two methods for preparing the oxazolidinone compound and the salt thereof having the structure of the formula (I). The first preparation method includes the following steps −

(1) (S) -N- [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethyl] acetamide and sulfonylation 1-48 小时， A compound in a non-polar solvent at -10 ~ 80 ° C to obtain a reaction of 1-9;

(2) Compounds 6-8 are subjected to catalytic hydrogenation in a polar solvent in the presence of a metal catalyst to obtain compounds 10-12;

(3) Compound 10-12 is subjected to an acetylation reaction at -10 ~ 80 ° C in a non-polar solvent for 0.1-12 hours to obtain compound 13-15;

(4) arylcarboxylic acid chloride and (S) -N_ [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethyl] acetamide Reaction in a non-polar solvent at -10 ~ 80 ° C for 0.1-48 hours to obtain compounds 16, 17, 18; or aryl formic acid or amino acid with N-hydroxysuccinimide (H0SU) or monohydroxybenzo Triazole (HOBt) or dicyclohexylcarbodiimide (DCC) and then react with (S) -N- [3- [3-fluoro- 4- (1-piperazinyl) phenyl] -2- 1-48 hours to obtain compounds 16, 17, 18; oxo-5-oxazolidinylmethyl] acetamide is reacted in a non-polar solvent at -10 ~ 80 ° C;

(5) According to need, prepare corresponding pharmaceutically acceptable salts.

The second preparation method includes the following steps:

(1) (S) -N- [3- (3-fluoro- 4-aminophenyl) -2-oxo- 5-oxazolylmethyl] acetamide and sulfonylating agent in a non-polar solvent In the reaction at -10 ~ 80 ° C for 0. 1-48 hours, to obtain compounds 21-27;

(2) Compounds 26-27 are subjected to a catalytic hydrogenation reaction in a polar solvent in the presence of a metal catalyst to room temperature for 8-24 hours to obtain compounds 28-29;

(3) Compound 28-29 is subjected to an acetylation reaction at -10 ~ 80 ° C in a non-polar solvent for 0.1-12 hours to obtain Compound 30-31;

(4) arylcarboxylic acid chloride and (S) -N- [3- [3- [fluoro] 4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethyl] ethyl The amide is reacted in a non-polar solvent at -10 ~ 80 ° C for 0.1-48 hours to obtain compound 32-33;

(5) According to need, prepare corresponding pharmaceutically acceptable salts.

The present invention further provides an application of the oxazolone compound and its salt represented by formula ((I)) in the preparation of a medicament for treating an infectious disease, especially an infectious disease caused by a multidrug-resistant bacteria. Detailed description of the invention

Unless otherwise specified, the terms used herein have the following definitions:

"Alkyl" means a saturated or unsaturated, substituted or unsubstituted straight-chain, branched alkane chain, and specific examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary Butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 1-methylbutyl, 2-methylpropyl, hexyl, isohexyl, 1-methylpentyl, 2- Methylpentyl, 3-methylpentyl, 2-methylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2 , 3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2 -Trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl and the like. Among these groups, fluorenyl groups having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, and butyl are preferred, and methyl, ethyl, and propyl are more preferred. Methyl and ethyl are the best.

"Aryl" means an aromatic hydrocarbon group, preferably an aryl group of 6 to 14 carbon atoms, specifically phenyl, tolyl, xylyl, biphenyl, naphthyl, indenyl, anthracenyl, phenanthryl , More preferably phenyl or naphthyl, and most preferably phenyl.

"Aromatic heterocyclyl" means a five- or six-membered heteroaryl group containing 1-4 heteroatoms selected from oxygen, nitrogen or sulfur atoms, furyl, thienyl, pyrrolyl, imidazolyl, thiazolyl , Pyrazolyl, isothiazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazolyl, tetrazolyl, and the like. Of these groups, thienyl, furyl, oxazolyl, isoxazolyl and thiazolyl are preferred, and thienyl, oxazolyl and isoxazolyl are more preferred.

"Substitutable fluorenyl", "substitutable aryl", and "substitutable aromatic heterocyclic group" respectively represent the above-mentioned "alkyl", "aryl" and "aromatic heterocyclic group" are optional They are selected from atoms, alkyl, alkoxy, _{acyloxy, - 0H, _NH 2, N0} 2, - NHAc substituent group.

The "sulfonylating agent" is selected from the group consisting of a sulfonyl chloride which may be substituted with an alkyl group or an aryl group, a sulfonyl bromide which may be substituted with an alkyl group or an aryl group, and a sulfonic anhydride which may be substituted with a carbaryl group or an aryl group.

Specific examples of the "pharmaceutically acceptable salt" include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, and phosphoric acid, and formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, and succinic acid. , Fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, ethanesulfonic acid and other organic acids and acid such as aspartic acid and glutamic acid Addition salts, or salts with bases, such as salts of inorganic bases such as sodium, potassium, calcium, aluminum, ammonium salts, methylamine salts, ethylamine salts, ethanolamine salts, etc., or with lysine, arginine, Salt formed from basic amino acids such as ornithine.

The oxazolone compounds or salts thereof of the present invention can be made into various preparations containing 0.01 to 99.9% by weight of the active ingredient and an appropriate amount of a pharmaceutically acceptable carrier, such as suitable for oral, injection or intestinal Formulations used for oral administration.

The medicine containing a therapeutically effective amount of the compound of the present invention can be administered to a subject according to the subject's age (months or weeks), general health, disease severity and duration, route of administration, individual sensitivity to the drug, etc. preparation.

The oxazolidinone compound represented by the formula (I) of the present invention and a salt thereof are prepared according to the following scheme.

Process I

Examples: a. Fluorenyl or arylsulfonyl chloride, pyridine, 0 ~ 20 ° C; b. H ₂ / Pd / C; c. Acetic anhydride, pyridine, 0 ~ 20

° C; d. Aryl formic acid or amino acid, H0SU or H0Bt, DCCc

The implementation of process I is listed as follows:

1. Using 3, 4-difluoronitrobenzene as a raw material, according to a known method (Brickner, SJ et al J. Med. Chem. 1996, 39, 673-679) through several steps to synthesize the intermediate (S)- N-3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethylacetamide.

2. (S)-N- 3- [3-Fluoro 4- (1-piperazinyl) phenyl] -2-oxo-5 -oxazolylmethylacetamide with sulfonyl chloride in benzene and toluene , Pyridine, dichloromethane, chloroform, tetrahydrofuran and other non-polar solvents at -10 ~ 80 ° C for 0.1 to 48 hours, the best condition is to use pyridine as a solvent at 0 ~ 20 ° C for 8-24 hours To obtain compound 1-9.

3. Compounds 6-8 use methanol, ethanol, acetic acid, etc. as solvents, and use palladium / carbon or other metal catalysts containing palladium or nickel as catalysts. Compounds 10-12 are obtained by catalytic hydrogenation at normal temperature and pressure. The best conditions for the reaction are methanol as the solvent, 5% or 10% palladium / carbon as the catalyst, and catalytic hydrogenation at normal temperature and pressure. 4. Compound 10-12 and acetic anhydride are reacted in a non-polar solvent such as benzene, toluene, pyridine, dichloromethane, chloroform, tetrahydrofuran at -10 ~ 80 ° C for 0.1-12 hours, and the optimal condition is to Pyridine was used as a solvent at 0-20 ° C for 8-10 hours to obtain compound 13-15.

5. Aryl formic acid chloride and (S) -N-3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethylacetamide in benzene , Toluene, pyridine, dichloromethane, chloroform, tetrahydrofuran and other non-polar solvents at -10 ~ 80 ° C for 0.1-48 hours, the best condition is to use pyridine as a solvent at 0 ~ 20 ° C for 8- 24 hours to obtain compounds 16, 17, 18; or aryl formic acid or amino acid reacted with N-hydroxysuccinimide (HOSU) or monohydroxybenzotriazole (HOBt) or dicyclohexylcarbodiimide (DCC), And then (_! ^-3- [3-fluoro-4- (1-piperazinyl) phenyl.]-2-oxo-5 -oxazolidinylmethylacetamide in dry tetrahydrofuran, dichloro Formamidine, chloroform, and other non-polar solvents are reacted at -10 ~ 80 ° C for 0.1-48 hours, and the best condition is to use pyridine as a solvent at 0 ~ 20 ° C for 8-24 hours to obtain compound 16, 17, 18.

6. Prepare the corresponding salt as required.

Process II

Examples: a. Alkyl or arylsulfonyl chloride, pyridine, 0 ~ 20 ° C; bH ₂ / Pd / C _; c. Acetic anhydride, pyridine, 0 ~ 20 ° C; d. Arylacyl chloride, pyridine, 0 ~ 20 ° C.

The implementation of process II is listed as follows:

1. Using 3, 4-difluoronitrobenzene as a raw material, according to a known method (Genin, MJ et al J. Med. Chem. 2000, 43, 953-970) through several steps to synthesize the intermediate (S)- N-3- (3-Fluoro-4-aminophenyl) -2-oxo-5-oxazolidinylmethylacetamide.

2. (S) -N-3- (3-Fluoro-4-aminophenyl) -2-oxo-5-oxazolidinylmethylacetamide and sulfonyl chloride in benzene, toluene, pyridine, and dichloromethane 1-48 小时， Non-polar solvents such as chloroform, tetrahydrofuran and the like in -Γ0 ~ 80Ό The optimal conditions are to react pyridine as a solvent at 0-20 ° C for 8-24 hours to obtain compounds 21-27.

'3. Compounds 26-27 use methanol, ethanol, acetic acid, etc. as solvents, and use palladium / carbon or other palladium-containing catalysts to react in the range of 0 ° to room temperature for 8-24 hours. 10% palladium / carbon was used as a catalyst to catalyze hydrogenation under normal temperature and pressure to obtain compounds 28-29. ·

4. Compounds 28-29 and acetic anhydride are dissolved in non-polar solvents such as benzene, toluene, pyridine, dichloromethane, chloroform, tetrahydrofuran, etc. at a temperature of -10 ~ 80 ° C for 0.1-12 hours. The optimal condition is to Pyridine was used as a solvent for 8-10 hours at 0-20 ° C to obtain compounds 30-31.

5. Aryl formic acid chloride and (S) -N- [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethyl] acetamide Benzene, toluene, pyridine, dichloromethane, chloroform, tetrahydrofuran and other non-polar solvents at -10 ~ 80 ° C for 0.1-48 hours, the best condition is to use pyridine as a solvent at 0 ~ 20 ° C Reaction for 8-24 hours gives compound 32-33.

6. Prepare the corresponding pharmaceutically acceptable salts as required. Among the oxazolone compounds represented by formula (I) of the present invention, the representative compounds are as follows:

1. (S> -N-3_ [3-fluoro-4- (4-methanesulfonyl-piperidinyl) phenyl] -2 -oxo-5 -oxazolidinylmethylacetamide; 2. (S) -N-3- [3-fluoro-4 (4-phenylsulfonyl-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethylacetamide;

3. (S) -N-3- [3-Fluoro-4- 4- [4- (4-methylbenzenesulfonyl) -1-piperazinyl] phenyl]-2-oxo-5-oxazolidinyl Methylacetamide

4. (S) -N-3- [3-Fluoro-4- (4-methoxybenzenesulfonyl-1-piperazinyl) phenyl] -2-oxo-5-oxazolylalkylmethyl Acetamide

5. (S) -N-3- [3-fluoro- 4- [4- (4-bromobenzenesulfonyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolylalkyl Methylacetamide

6. (S) -N-3- [3-fluoro- 4- [4- (4-nitrobenzenesulfonyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolyl Methylmethylacetamide

7. (S) -N-3- [3-fluoro- 4- [4- (3-nitrobenzenesulfonyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolyl Methylmethylacetamide

8. (S) -N-3- [3-fluoro- 4- [4- (2-nitrobenzenesulfonyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolyl Methylmethylacetamide

9. (S) -N-3- [3-fluoro-4- [4- (2-thiophenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazolidinylmethyl Acetylacetamide

10. (S)-N- 3- [3-fluoro- 4- [4- (4-aminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5 -oxazolyl Methylacetamide

11. (S) -N-3- [3-fluoro-4- [4- (3-aminobenzenesulfonyl) -1dipiperazinyl] phenyl] -2-oxo-5-oxazolidinyl Methylacetamide

12. (S) -N-3- [3-fluoro-4- [4- (2-aminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazolidinyl Methylacetamide

13. (S) -N- 3- [3-fluoro-4- [4- (4-acetylaminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo- 5-oxazolidine Methylmethylacetamide

14. (S) -N-3- [3-Fluoro- 4- [4- (3-acetylaminobenzenesulfonyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolidine Methylmethylacetamide

15. (S) -N-3- [3-fluoro- 4- [4- (2-acetylaminobenzenesulfonyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolidine Methylmethylacetamide

16. (S)-N-3- [3-fluoro-4- [4- [3- (2-fluoro-6-chlorophenyl) _5_methyl- 4-isooxazoleformyl]-1- Piperazinyl] phenyl] -2-oxo-5-oxazolylmethylacetamide;

17. (S) -N-3- [3-fluoro-4- [4- (2-hydroxybenzoyl)-1-piperazinyl] phenyl] -2-oxo-5 -oxazolyl Methylacetamide

18. (S)-N- 3- [3-fluoro-4- [4- (L-phenylalanyl) -1-piperidinyl] phenyl] -2-oxo-5-oxazolidinyl Methylacetamide

19. (S) -N-3- [3-fluoro-4- [4- (phenylaminocarbonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazolylalkylmethyl Acetamide

20. (S) -N-3- [3-fluoro- 4- [4- (phenylaminothiocarbonyl) -1-piperazinyl] phenyl] -2-oxo-5-5-oxazolidinyl Methylacetamide

21. (S) -N-3- (3-fluoro-4 -methanesulfonylaminophenyl) -2-oxo-5-oxazolylmethylacetamide;

22. (S) -N-3- (3-Fluoro-4-benzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

23. (S) -N-3- (3-fluoro-4-p-toluenesulfonylaminophenyl)-2-oxo-5-oxazolidinylmethylacetamide; 24. (S)- N-3- (3-fluoro-4-p-bromobenzenesulfonylaminophenyl) -2-oxo-5-oxazolylmethylacetamide;

25. (S) -N_3 (3-fluoro-4 -p-methoxybenzenesulfonylaminophenyl) -2_oxo-5-oxazolidinylmethylethiazole;

26. (S) -N-3- (3-fluoro-4-p-nitrobenzenesulfonylaminophenyl)-2 -oxo-5 -oxazolidinylmethylacetamide;

27. (S) -N-3- (3-fluoro-4-m-bromobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

28. (S) -N-3- (3-fluoro-4-p-aminobenzenesulfonylaminophenyl) -2_oxo-5 -oxazolylmethylacetamide; 29. (S)-N -3- (3-Fluoro-4-m-aminobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide; 0. (S)-N- 3- (3-fluoro- 4-p-acetaminobenzenesulfonylaminophenyl) -2-oxo-5 -oxazolylmethylacetamide; 1. (S)- N-3- (3 -fluoro-4 -m-acetylaminobenzenesulfonylaminophenyl) -2-oxo-5 -oxazolidinylmethylacetamide; 2. (S) -N-3- (3 -Fluoro- 4-o-acetoxybenzenesulfonylaminophenyl)-2-oxo-5-oxazolidinylmethylacetamide; and 3. (S)-N-3- [3-fluoro-4 -[3- (2-Fluoro-6-chlorophenyl) -5-methyl-4-isoxazolylamido] phenyl] -2-oxo-oxazolylmethylacetamide.

The structural formulas of the above compounds are shown in Tables 1 and 2.

Table 1

Reference Ri

1 CH ₃ S0 ₂

2 PhS0 ₂

3 4-CH _3- PhS0 ₂

4 4-C¾0_PhS0 ₂

5 4-Br-PhS0 ₂

6 4-N0 ₂ -PhS0 ₂

7 3-N0 ₂ -PhS0 ₂

8 2-N0 ₂ -PhS0 ₂

10 4-NH -PhS0 ₂

11 3- H ₂ -PhS0 ₂

12 2- H ₂ -PhS0 ₂

13 4- HAc-PhS0 ₂

14 3- NHAc-PhS0 ₂

15 2-NHAc-PhS0 ₂

17 2-OH-PhCO- 18 L-PhCH ₂ CH ₂ (NH ₂ ) CO- 19 PhNHCO- 20 Ph HCS-

Table 2

Reference Ri R ₃

21 CH ₃ S0 ₂ H

22 PhS0 ₂ H

z,

'' 23 4-CH _3- PhS0 ₂ H

24 4-Br-PhS0 ₂ H

25 4-CH ₃ 0-PhS0 ₂ H

26 4-N0 ₂ -PhS0 ₂ H

27 3-N0 ₂ -PhS0 ₂ H

28 4-NH ₂ -PhS0 ₂ H

29 3-Li 2-PhS0 ₂ H

30 4- HAc-PhS0 ₂ H

31 3-NHAc-PhS0 ₂ H

32 H

33 H in vitro antibacterial activity determination:

1. Test method: 测定 Determine the minimum inhibitory concentration (MIC) of the compound against the test strain by agar dilution method. That is, 1 ml of the test compound is pipetted into a sterilized plate, and then 19 ml of M-H agar medium (thaw to 50 ° C) is added to the plate, so that the final concentration of the compound in each plate is 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0. 254 _g / ml, and then inoculated the bacteria on the surface of each dish with a multi-point inoculation device (Denley A400), the final concentration of the bacterial solution was 10 FU / ml. Incubate at 37 ° C for 20 hours. Observe the results. The lowest concentration of the drug in the bacteria-free growth plate is the minimum inhibitory concentration (MIC) of the bacteria.

2. Test strains: All the test strains used were clinically isolated pathogenic bacteria collected in Sichuan in 2001 and used after re-identification by conventional methods. After the test compound was solubilized with CH ₃ 0H or DMS0, a mother liquor of 256 g / ml was prepared with sterilized distilled water for use.

3. The positive control group was Linezolid.

4. MIC _{5 of} each compound. , MIC ₉ . Values are shown in Table 3. From Table 3, we can see that 1, 2, 4, 7, among 33 test compounds. 10, 11, 13, 17, 19, 20, 32 had good antibacterial activity against the 20 Gram-positive bacteria tested, and the activity of 11 was stronger than the positive control Linezolid.

The oxazolidone derivatives and pharmaceutically acceptable salts thereof used in the present invention can be used to treat infectious diseases, especially infectious diseases caused by multidrug-resistant bacteria.

In vitro antibacterial activity of 33 compounds against Gram-positive bacteria

1 2 3 4 5 6 7 10 11 13 14 16 17 18 19 Streptococcus pneumoniae 01181 2 2> 128 8> 128 128 1 16 1 32〉 128> 128 8 64 16 Non-ABD Streptococcus 01121 2 2 64 4〉 128 64 0.5 2 1 32> 128> 128 8 64 16

A streptococcus 991 2 2 128 2> 128 64 1 16 1 8> 128〉 128 4 64 16

D Streptococcus 992 4 4 128 16〉 128〉 128 4 16 1 32>128> 128 4 64 16 Hemolytic Staphylococcus 011925 2 1 64 2> 128 32 0.5 0. 25 0. 25 4>128> 128 8 32 8 Hemolytic Staphylococcus 011926 2 0.5 4 0.5〉 128 16 0.25 0. 25 0. 25 1>128> 128 4 32 8 Staphylococcus aureus ATCC25923 4 4 128 2> 128 128 2 16 0.5.32>128> 128 4 64 16 Staphylococcus aureus 01193 4 4 128 16〉 128〉 128 4 16 0. 5 32>128> 128 4 64 16 Staphylococcus aureus 01194 2 1 8 2〉 128 64 0.25 0. 25 0. 25 2> 128〉 128 4 16 4 Staphylococcus aureus 011910 4 4 128 4〉 128 128 1 1 0. 5 32>128> 128 4 64 8 Staphylococcus aureus 011911 4 4 128 4> 128 128 1 8 0. 5 32〉 128〉 128 4 64 8 Staphylococcus aureus 011912 4 4 128 4〉 128 128 1 8 0. 5 16>128> 128 4 64 4 Staphylococcus aureus 011915 1 0.5 8 0.5> 128 4 0.25 0. 25 0. 25 1〉 128> 128 2 16 1 Staphylococcus aureus 011916 4 4 128 8〉 128 128 1 1 0. 5 16〉 128〉 128 4 64 16 Staphylococcus 01206 0.5 0.25 2 0.5 128 4 0.25 0. 25 0.25 1> 128〉 128 2 8 1 Staphylococcus 01207 0.5 0.25 2 0.25 128 8 0.25 0. 25 0.25 0. 5>128> 128 4 8 0.5 Staphylococcus 01208 0.5 0.25 2 0.25 128 8 0.25 0. 25 0.25 1> 128〉 128 4 8 2 E.staphylococcus 012010 0.5 0.25 4 0.5 128 8 0.25 0. 25 0.25 0.5>128> 128 2 16 1 E.staphylococcus 012011〉 128> 128〉 128〉 128〉 128 〉 128> 128〉 128〉 128>128> 128〉 128> 128〉 128> 128 Staphylococcus 012013>128>128>128>128>128>128>128>128>128>128>128>128>128> 128 >128> 128

Comparison of in vitro antibacterial activity of 33 compounds against Gram-positive bacteria m 囷

20 21 22 23 24 25 26 27 28 29 30 31 32 33 LZ Streptococcus pneumoniae 01181 8> 128> 128> 128> 128> 128> 128> 128> 128> 128> 128 128 8> 128 2 Non-ABD Streptococcus 01121 2 128> 128> 128> 128> 128> 128> 128> 128> 128 16> 128 64 0. 5> 128 2

Streptococcus A. 991 8〉 128> 128〉 128〉 128> 128> 128> 128> 128 128> 128 64 0.5.128 1

D Streptococcus 992 8> 128> 128> 128> 128〉 128〉 128> 128> 128 128> 128 128 1> 128 2 Hemolytic Staphylococcus 0Π925 2 128> 128> 128> 128> 128> 128> 128> 128 > 128> 128 64 0. 25> 128 1 Hemolytic Staphylococcus 011926 0. 5 128> 128> 128> 128> 128> 128> 128> 128> 128> 128> 128 16 0. 25> 128 0. 25 Staphylococcus aureus ATCC25923 2 128> 128> 128> 128> 128> 128> 128> 128> 128 16> 128 64 1> 128 2 Staphylococcus aureus 01193 2 128> 128> 128> 128> 128> 128> 128> 128> 128> 128 128 4> 128 2 Staphylococcus aureus 01194 2 64> 128> 128> 128 128> 128> 128> 128> 128> 128 64 0. 5> 128 0. 5 Staphylococcus aureus 011910 8 128> 128> 128> 128 128> 128> 128> 128 128> 128 64 1> 128 0.5 0.5 Staphylococcus aureus 011911 8> 128> 128> 128> 128> 128> 128> 128> 128 64> 128 2> 128 0.5 0.5 Staphylococcus aureus 011912 2 〉 128〉 128〉 128> 128〉 128> 128> 128> 128 64> 128 128 8> 128 1 Staphylococcus aureus 011915 2 128> 128> 128> 128> 128> 128> 128> 128> 128> 128> 128 64〉 0. 25〉 128 0. 5 Staphylococcus aureus 011916 2 128〉 128〉 128〉 128> 128> 128> 128> 128 > 128〉 128 64 0. 5〉 128 1 Table staphylococcus 01206 1 64> 128〉 128> 128 128〉 128> 128> 128> 128> 128 32 0.25> 128 0. 25 Table staphylococcus 01207 0.5 64〉 128〉 128〉 128〉 128> 128〉 128 128 32〉 128 16 0. 25〉 128 0. 25 Staphylococcus 01208 0. 5 64 64> 128> 128 128> 128> 128〉 128 2> 128 32 4> 128 0. 25 E.staphylococcus 012010 0. 5 64 64> 128> 128 128> 128> 128> 128 0. 25> 128 32 0. 5> 128 0. 5 E.staphylococcus 012011> 128> 128> 128 〉 128〉 128> 128> 128〉 128〉 128> 128〉 128〉 128> 128> 128 128 Staphylococcus 012013> 128> 128〉 128> 128> 128〉 128> 128> 128〉 128〉 128> 128〉 128〉 128〉 128 32

LZ = linezolid

detailed description

The present invention is further described below with reference to the examples, but these examples are by no means intended to limit the present invention in any way. In all examples, the melting point is measured with a MEL-TEMP melting point meter, and the thermometer is not calibrated; ¾- should be recorded with a Varian Mercury 400 nuclear magnetic resonance instrument, and the chemical shift is expressed in δ (ppm); the silica gel used for the separation is not specified as 200-300 Head. Example 1: (S) -N-3_ [3-Fluoro 4- (4-methanesulfonyl-1-piperazinyl) phenyl]-2-oxo-5 -oxazolidinylmethylacetamide (1)

(S)-N- 3- [3-Fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-5-oxazolylmethylacetamide (177.0 mg, 0.53 ol) Suspend in 5 ml of pyridine, add methanesulfonyl chloride (1.0 ml, 1.28 mmol) under stirring and cooling with ice water. The reaction temperature is slowly raised to room temperature and reacted overnight. After the reaction mixture was diluted with dichloromethane (20.0 mL), it was washed with 1N hydrochloric acid, water, saturated sodium bicarbonate solution, and saturated brine in this order, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was separated by column chromatography ( Eluent: dichloromethane: methanol = 20: 1) to give the title compound as a white solid, 53.0 mg, with a yield of 24.2%. Melting point: 209.5-211 ° C. ¾-wake-up R (CDC1 ₃ ): δ 8.40 (t, IH), 7.89 (dd, IH), 7.35 (dd, IH), 7.18 (dd, IH), 7.12 (dd, IH), 6.00 (m, IH ), 4.80 (m, IH), 3.94-4.10 (m, 13H), 3.58-3.84 (m, 6H), 3.28-3.40 (m, 3H), 3.25 (brs, 3H), 2.0 3 (s, 3H ). Example 2: (S) -N- 3- [3-Fluoro- 4- (4-benzenesulfonyl-1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethylethyl Amide (2)

The procedure was similar to the synthesis of compound 1 to give the title compound as a white solid, 189.0 mg, yield 82.9%. Melting point: 191-193 ° C o ¾-NMR (CDC1 ₃ ): δ 7.75 (d, 2H), 7.63 (m, IH), 7.58 (dd, IH), 7.42 (dd, IH), 7.02 (dd, IH ), 6.95 (t, IH), 6.08 (m, IH), 4.74 (m, 1H), 3.98 (t, IH), 3.55--3. 75 (m, 3H), 3.20 (brs, 4H), 3.10 ( brs, 4H), 1.98 (s, 3H). Example 3: (S) -N-3_ [3-Fluoro- 4- [4- (4-methylbenzenesulfonyl) -1-piperazinyl] phenyl]-2-oxo-5-oxazole Fluorenylmethylacetamide (3)

The procedure was similar to the synthesis of compound 1 to give the title compound as a white solid, 169.0 mg, yield 69.0%. Melting point: 224-227 ° C o ¾-NMR (CDC1 ₃ ): δ 7.65 (d, 2H), 7.45 (dd, IH), 7.35 d, 2H), 6.95-7.05 (m, 2H), 6.15 (ra, IH), 4.75 (m, IH), (4.00 (t, IH), 3.56- 3.76 (m, 3H), 3.12-3.22 (m, 8H), 2.18 (s, 3H), 2.00 (s, 3H). Example 4: (S) -N-3- [3-Fluoro 4- [4- (4-methoxybenzenesulfonyl) -1 -piperazinyl ] Phenyl] -2-oxo-5-oxazolidinylmethylacetamide (4)

Omg, Yield 83.0%. Melting point:> 230 ° C. ¾-NMR (CDC1 ₃ ): S 8, 37 (t, IH), 7.86 (dd, IH), 7.70-7.75 (m, 2H), 7.30 (dd, IH), 7.01-7.10 (m, 3H), 6.15 (m, IH), 4.80 (m, IH), 3.86— 4.10 (m, 3H), 3.56- 3.84 (m, 8H), 3.20 (brs, 3H), 2.00 (s, 3H). Example 5: (S) -N-3- [3-fluoro-4- [4- (4-bromobenzenesulfonyl) -1-piperazinyl] phenyl] _2-oxo-5-oxazolidine Methyl Acetamide (5)

The procedure was similar to the synthesis of compound 1 to obtain 210.0 mg of the title compound as a white solid in a yield of 75.7%. Melting point: 203-205 ° Cc-wake R (CDC1 ₃ ): δ 7.60-7.73 (m, 7H), 7.06 (dd, 1H), 6.16 (t, IH), 4.80 (m, IH), 4.00 (ra, 3H), 3.40-3.50 (ra, 7H), 3.30 (brs, IH), 2.00 (s, 3H). Example 6: (S) -N-3- [3-fluoro-4- [4- (4-nitrobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5_oxazole Alkyl methylacetamide (6)

The procedure was similar to the synthesis of compound 1 to give the title compound as a yellow solid, 590.0 mg, yield 56.6%. Point: 188-190. C. ¾- N set (DMS0): δ 8.20 (d, 2H), 7.95 (d, 2H), 7.45 (dd, 2H),

6.94-7.05 (m, 2H), 6.03 (t, IH), 4.74 (m, IH), 3.56-3.84 (m, 3H), 3.26 (brs, 4H), 3.15 (br rs, 4H), 2.00 (s , 3H). Example 7: (S) -N- 3- [3-fluoro-4- [4- (3-nitrobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5 -oxa Azolidinylmethylacetamide (7)

The procedure was similar to the synthesis of compound 1 to give the title compound as a yellow solid, 511.0 mg, yield 63.0%. Melting point: 175-178 ° Co-Li R (CDC1 ₃ ): δ 8.63 (t, 1H), 8.50 (m, 21H), 8.15 (m, IH),

7.80 (t, IH), 7.45 (dd, IH), 7.98-8 · 04 (m, 2H), 6.10 (t, IH), 4.76 (m, IH), 4.00 (t, IH), 3.60-3.85 ( m, 3H), 3.30 (brs, 4H), 3.18 (brs, 4H), 2.00 (s, 3 H). Example 8: (S) -N-3- [3-fluoro-4- [4- (2-nitrobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5 -oxalic Amidazolylmethylacetamide (8)

The procedure was similar to the synthesis of compound 1 to give the title compound 355.0 mg as a yellow solid, yield 52.4%. Melting point: 158-162 ° C. ¾-NMR (DMSO): δ 7, 99-8, 04 (m, 2H), 7.85-7, 95 (m, 2H), 7.47 (dd, IH), 7.15 (dd, IH), 7.06 (t, IH), 4.69 (m, IH), 4.05 (t, IH), 3.68 (q, IH), 3.39 (m, 2H), 3.04 (brs, 4H), 1.80 (s, 3H). Example 9: (S) -N-3- [3-Fluoro-4- [4- (2-thiophenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5 -oxazolidine Methyl Acetamide (9)

The operation was similar to the synthesis of compound 1 to give the title compound 156.0 Omg as a white solid, yield 85.0%. Melting point: 202-205 V. -Bandit R (CDC1 ₃ ): δ 7.63 (dd, IH), 7.55 (dd, IH), 43 (dd, IH), 7.15 (q, IH), 7.03 (dd, IH), 6.93 (t, 1H) , 6.10 (t, IH), 4.74 (m, IH), 3.98 (t, IH), 3.54-3.7 4 (m, 3H), 3.23 (m, 4H), 3.14 (m, 4H), 2.00 (s, 3H). Example 10: (S) -N-3- [3-fluoro-4- [4- (4-aminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Alkyl methylacetamide (10)

Compound 6 (490. Orag 0.94 mmol) was dissolved in a mixture of methanol (30.0 mL) and methylene chloride (30 mL), 5% palladium on carbon (65.0 mg) was added, and catalytic hydrogenation was performed at room temperature and pressure overnight. The catalyst was filtered off, the solvent was concentrated under reduced pressure, and the residue was separated by column chromatography (eluent: dichloromethane: methanol = 20: 1) to obtain the title compound as a white solid, 420.0 Omg, with a yield of 91.0%.

Melting point:> 230 ° C ¾-NMR (DMS0): δ 8.20 (t, IH), 7.40- 7.45 (m, 3H), 7.00- 7.15 (m, 2H), 6.65 (d, 2H), 4.70 (m, IH), 4.04 (m, IH), 3.66 (q, IH), 3.30 (brs, 5H), 2.93— 3.00 (m, 8H), 1.80 (s, 3H). Example 11: (S) -N-3- [3-fluoro-4- [4- (3-aminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Fluorenylmethylacetamide (11)

The procedure was similar to the synthesis of compound 10 to give the title compound as a white solid, 312.0 mg, in a yield of 80.7%. Melting point: 206-210. C. ¾-NMR (DMSO): δ 8.20 (t, IH), 7.45 (dd, IH), 7.25 (t, IH), 7.14 (dd, IH), 7.04 (t, IH), 6.92 (t, IH), 6.79-6.85 (m, 2H), 4.68 (m, IH), 4.04 (t, IH) , 3.65 (m, 1H), 3.00 (m, 10H), 1.80 (s, 3H). Example 12: (S) -N-3- [3-Fluoro-4- [4- (2-aminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Alkyl methylacetamide (12)

The procedure was similar to the synthesis of compound 10, and the title compound was obtained as a white solid (110 mg, 43.5%). Melting point:> 230 ° C. ¾-Rigid R (CDC1 ₃ ): δ 7.58 (d, IH), 7.46 (dd, 1H), 7.32 (t, IH), 6.95-7.06 (m, 2H), 6.75-6.80 (m, 2H), 6.05 (brs, IH), 4.75 (brs, 1H), 4.00 (t, IH), 3.58-3.76 (m, 3H), 3.30 (brs, 4H), 3.12 (brs, 4H), 2.00 (s, 3H ). Example 13: (S) -N-3- [3-fluoro-4_ [4- (4-acetylaminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Alkyl methylacetamide (13)

Compound 10 (2720. mgO.56 mol) was dissolved in pyridine (10.0 mL). Under ice-water cooling and stirring, acetic anhydride (1.0 mL) was added dropwise and stirred overnight. The reaction mixture was diluted with dichloromethane, washed successively with 1N hydrochloric acid, water, a saturated sodium bicarbonate solution, a saturated saline solution, and dried over anhydrous sodium sulfate. Filtration, the filtrate was concentrated, and the residue was separated by column chromatography (eluent: dichloromethane: methanol = 12: 1) to obtain the title compound as a beige solid, 196.0 mg, in a yield of 66%. Melting point: 228-230 ° C. ¾- NMR (DMSO): S8.20 (t, 1H), 7.84 (d, 2H), 7.70 (d, 2H), 7.45 (dd, IH), 7.15 (dd, lH), 7.04 (t, IH) , 4.68 (m, IH), 4.04 (t, IH), 3.00 (m, 8H),

2.08 (s, 3H), 1.80 (s, 3H). Example 14: (S) -N-3- [3-Fluoro-4- [4- (3-acetylaminobenzenesulfonyl) -1-piperazinyl] phenyl]-2-oxo-5-ox Oxazolidinylmethylacetamide (14)

The procedure was similar to the synthesis of compound 13 to obtain the title compound as a colorless solid, 31.0 mg, in a yield of 27.7%. Melting point: 222-225 ° C ¾-NMR (DMS0): δ 10.35 (s, IH), 8.09 (s, IH), 7.85 (d, IH), 7.58 (t, IH), 7.00-7.15 (m, 2H ), 7.14 (dd, IH), 7.04 (t, IH), 4.70 (m, IH), 4.04 (t, IH),

3.65 (q, 3H), 3.00 (m, 10H), 2.06 (s, 3H), 1.80 (s, 3H). Example 15: (S) -N-3- [3-Fluoro-4- [4- (2-acetylaminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxo Oxazolidinylmethylacetamide (15)

The procedure was similar to the synthesis of compound 13 to obtain 15.5 mg of the title compound as a yellow solid. Yield 30.0.7%. Melting point: 156-158 ° C. ¾-R (DMSO): δ 9.57 (s, 1Η), 8.07 (dd, 1H), 7.71-7.77 (m, 1H), 7.58-7.64 (m, 1H), 7.21-7.31 (m, 1H), 7.06—7.09 (m, 1H), 6.88-6.98 (m, 1H), 4.82 (m, 1H), 4.18 (dXt, 1H), 4.08 (m, 1H), 3.86 (m, 1H), 3.70 (m, 1H), 3.36 (m, 2H), (3.25 (m, 2H), 3.10 (m, 4H), 2.35 (s, 3H), 2.20 (s, 3H). Example 16: (S)-N- 3 -[3-fluoro- 4- [4- [3- (2-fluoro-6-chlorophenyl)-5-methyl-4-isoxazolyl] -1-piperazinyl] phenyl]- 2-oxo-5-oxazolylmethylacetamide (16)

5-Methyl-4- (2-fluoro-6-chlorophenyl) 4-isoxazole acid (422.0 mg, 1.65 drawing 1) was dissolved in dry tetrahydrofuran (10 mL), and thionyl chloride was added dropwise while stirring at room temperature. (0.5 mL) and the reaction mixture was heated at reflux overnight. The solvent was concentrated under reduced pressure to obtain a red liquid (stand-by). Compound (S) -N- [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethyl] acetamide (52.0 mg, 0.17raraol) was suspended in pyridine (8 mL), and the red liquid was added dropwise under cooling and stirring in ice water, and the raw material point disappeared after four hours. The reaction mixture was diluted with ethyl acetate, washed with 1N hydrochloric acid, water, saturated sodium bicarbonate solution and saturated brine in this order, and dried over anhydrous sodium sulfate. 0mg ，二 After filtration, the filtrate was concentrated, and the residue was separated by column chromatography (eluent: methylene chloride: methanol = 20: 1) to give a light yellow solid 47.0 mg, and the ethyl acetate was recrystallized to give the title compound 17.0 mg, two Total step yield is 20%. Melting point: 218- 220 ° C. -NMR (DMSO): δ 7.59-7.65 (m, 1H), 7.41-7.54 (m, 3H), 7.18 (dd, 1H), 7.00 (t, lH), 4.70 (m, lH), 4.07 (t, 1H), 3.70 (q, 1H), 3.44—3.62 (brs, 3H), 3.40 (ra, 3H), 2.74-2.90 (brs, 2H), 3.10 (m, 4H), 2.58 (s, 3H), 1.83 (s, 3H). Example 17: (S) -N-3- [3-fluoro-4- [4- (2-hydroxybenzoyl) -1-piperazinyl] phenyl]-2-oxo

-5 -oxazolidinylmethylacetamide (17)

2-Hydroxybenzoic acid (46.0mg, 0.36 leg ol) was dissolved in dry tetrahydrofuran (10 mL), and under cooling with ice water and stirring, H0SU (37.0mg) and DCC (60.0mg) were added. After the reaction overnight, compound (¾ -1 ^-[3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethyl] acetamide (65.0mg, 0.19mmol), continue The reaction was allowed to proceed overnight. The reaction mixture was filtered, the filtrate was concentrated, and the residue was separated by column chromatography (eluent: methylene chloride: methanol = 10: 1) to obtain the title compound as a white solid, 20.0 mg, yield: 23.0%. 162 ° C. ¾-Band R (DMSO): 68.23 (t, 1H), 7.47 (dd, 1H), 7.02-7.25 (m, 4H), 6.85 (m, 2H), 4.68 (m, 1H), 4.06 (t, 1H), 3.70 (m, 2H), 3.40 (m, 3H), 2.95 (brs, 4H), 1.83 (s, 3H). Example 18 (S) -N-3- [3-Fluoro-4- [4- (L-phenylalanyl) -1-piperazinyl] phenyl] -2-oxo-5-5-oxazolidine Methyl Acetamide (18)

B0C-protected L-phenylalanine (126. Omg 0.46 ol) was dissolved in dry tetrahydrofuran (10 mL). Under ice-water cooling and stirring, HOBt (90.0 mg) was added, and DCC (130.0 mg) was added after one hour. And compound (S) -N- [3- [3-Fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethyl] acetamide (167.0 mg, 0.50 mmol), reaction overnight. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. Filtration, the filtrate was concentrated, and the residue was separated by column chromatography (eluent: dichloromethane: methanol = 20: 1) to obtain 285 mg of a yellow oil. The above yellow oil was dissolved in dichloromethane (6.0 mL), and trifluoroacetic acid (3.8 mL) was added under stirring at room temperature. After half an hour, the starting point of TLC detection basically disappeared. The solvent was concentrated. It was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the residue was separated by column chromatography (methanol) to obtain the title compound as a white solid (133.0 mg) in a two-step total yield of 55.0%. Melting point: 152-154 ° C. -¾ R (DMS0): δ 8.22 (t, 1H), 7.48 (dd, 1H), 7.14-7.28 (m, 6H), 6.94 (t, 1H), 4.68 (m, 1H), 4.05 (t, lH), 3.95 (t, 1H), 3.60-3,70 (ra, 2H), 3.40-3.55 (m, 2H), 2.60-3.00 (m, 6H), 1.83 (s, 3H). Example 19: (S) -N-3- [3-fluoro-4- [4- (phenylaminocarbonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazolyl Methylacetamide (19)

Compound (S) -N- [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethyl] acetamide (62.0 mg, 0.18 The ol) was dissolved in methanol (5.0 mL), and phenyl isocyanate (0.12 mL, 1.1 mol) and triethylamine (0.1 mL) were added dropwise with stirring at room temperature, and the reaction was allowed to proceed overnight. Omg, Yield 26%. TLC detection of the starting point disappeared, the resulting solid was filtered, the solid was dried in air to give the title compound as a white solid 20. Omg, yield 26%. Melting point:> 230 ° Cc ^! H-NMR (DMS0): δ 8.40 (s, 1H), 8.23 (t, 1Η), 7.50 (d, 1H), 7.43-7.48 (m, 1H), 7.15-7.24 (m , 2H), 7.09 (t, 1H), 6.92 (t, 1H), 4.70 (m, 1H), 4.07 (t, 1H), 3.69 (q, 1H), 3.60 (m, 3H), 3.40 (t, 2H), 2.97 (m, 4H), 1.80 (s, 3H). Example 20: (S) -N-3- [3-fluoro-4- [4- (phenylaminothiocarbonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Fluorenylmethylacetamide (20)

The procedure was similar to the synthesis of compound 19 to obtain 22.0 mg of the title compound as an off-white solid with a yield of 22%. Melting point: 218—220 ° C. ¾-wake R (DMSO): δ 7.50 (dd, IH), 7.27-7.7.30 (m, 4H), 7.18 (dd, IH), 7.08-7.12 (m, 2H), 4.70 (m, IH), 4.05 (m, 5H), 3.70 (in, IH), 3.40 (m, 2H), 3.02 (m, 4H), 1.80 (s, 3H). Example 21: (S) -N-3- (3-fluoro-4-methanesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (21)

Using (S) -N-3- (3-fluoro-4aminophenyl) -2-oxo-5-oxazolidinylmethylacetamide as a raw material, the other operation steps are similar to the synthesis of compound 1. 54.0 mg of the title compound was obtained as a white solid in a yield of 41.8%. Melting point: 223-224 ° C. ¾-wake-up R (CDC1 ₃ ): δ 7.70 (dd, IH), 7.35 (t, IH), 6.03 (m, IH), 4.80 (m, IH), 4.05 (t, IH), 3.80 (q, IH ), 3.68 (in, 2H), 3.43 (s, 3H), 2.04 (s, 3H). Example 22: (S) -N-3- (3-fluoro-4-benzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (22)

The procedure was similar to the synthesis of compound 21 to give the title compound as a white solid, 91.0 mg, yield 55.0%. Melting point:> 230. C. ¾-NMR (CDCls): δ 7.95 (dd, 2H), 7.68 (t, IH), 7.51-7.58 (m, 3H), 7.20 (m, IH), 7.09 (t, IH), 7.20 (d, 2H ), 6.00 (brs, IH), 4.79 (m, IH), 4.05 (t, 1H), 3.60-3.80 (ra, 3H), 2.04 (s, 3H). Example 23: (S) -N-3- (3-Fluoro-4-p-toluenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (23)

The procedure was similar to the synthesis of compound 21 to give the title compound 54.0 Omg as a white solid, yield 64.0%. Melting point: 202-204 ° Co-NMR (CDC1 ₃ ): δ 7.60 (d, 2H), 7.55 (t, IH), 7.47 (dd, IH), 7.20 (d, 2H), 6.99 (m, IH), 6.65 (brs, IH), 6.00 (t, IH), 4.74 (m, IH), 3.98 (t, IH), 3.54-3.74 (m, 3H), 2.37 (s, 3H), 2.00 (s, 3H) . Example 24: (S) -N-3- (3-Fluoro-4-p-bromobenzenesulfonylaminophenyl) -2-oxo-5-oxazolylmethylacetamide (24)

The procedure is similar to the synthesis of compound 21. 170.0 mg of the title compound was obtained as a yellow-red solid in a yield of 85.0%. Melting point:> 230 ° Co ¾-NMR (CDC1 ₃ ): δ 7.78 (dd, 2H), 7.68 (dd, 2H), 7.56 (dd, 1H), 7.20 (m, IH), 7.05 (t, IH), 6.00 (t, IH), 4.79 (brs, IH), 4, 05 (t, 1H), 3.79 (t, IH), 3.60-3.70 (ra, 2H), 2.03 (s, 3H). Example 25: (S) -N-3- (3-Fluoro-4-p-methoxybenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (25)

The procedure was similar to the synthesis of compound 21 to give the title compound as a white solid, 224.0 mg, yield 77.0%. Melting point:> 230 ° Co ¾-NMR (CDCla): δ 7.83-7.88 (m, 2H), 7.54 (dd, IH), 7.18 (d, IH),

7.07 (t, IH), 6.96-7.00 (m, 2H), 6.03 (brs, IH), 4.79 (brs, IH), 4.04 (t, IH), 3.88 (s, 3H), 3.78 (t, IH) , 3.60-3.68 (m, 2H), 2.03 (s, 3H). Example 26: (S) -N-3- (3-Fluoro-4-p-nitrobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (26)

The procedure was similar to the synthesis of compound 21 to give the title compound as a yellow solid, 303.0 mg, yield 30.0%. Melting point: 218-222 ° C ¾-R (COC): δ 8.29 (d, 2H), 7.92 (d, 2H), 7.59 (t, IH), 7.50 (dd, IH), 7.10 (d, IH) , 6.77 (brslH), 5.96 (brs, IH), 4.79 (m, 1H), 4.00 (t, IH), 3.65-3, 80 (m, 2H), 3.60 (m, IH), 2.00 (s, 3H ). Example 27: (S) -N-3- (3-Fluoro-4-m-bromobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (27)

The procedure was similar to the synthesis of compound 21, and 683.0 mg of the title compound was obtained as a pale yellow solid.

72.0%. Melting point: 210-214 ° C. ¾-wake-up R (CDC1 ₃ ): δ 8.56 (I, IH), 8.38-8.42 (m, IH),

8.03-8.06 (m, IH), 7.67 (q, IH), 7.58 (t, IH), 7.49 (dd, IH), 7.08 (m, IH), 6.92 (brs, IH), 6.00 (brs, IH) , 4.79 (m, IH), 4.00 (t, IH), 3.60-3.80 (m, 3H), 2.00 (s, 3H). Example 28: (S) -N-3- (3-fluoro-4-p-aminobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (28)

Compound 26 (200. mg, 0.44 mol) was dissolved in methanol (50.0 mL), 5% palladium on carbon (50.0 mg) was added, and catalytic hydrogenation was performed at room temperature overnight. The catalyst was filtered off, the solvent was concentrated under reduced pressure, and the residue was separated by column chromatography (eluent: methylene chloride: methanol = 20: 1) to obtain the title compound as a white solid 106.0 mg, yield 60%. Melting point: 189-194 V. ¾-Wake R (CDC1 ₃ ) 7.50-8.20 (m, 3H), 7.20-7.40 (m, 2H), 7.00 (brs, IH), 4.65 (brs, 2H), 3.94 (m, 1H), 3.69 (brs, IH), 1.80 (s, 3H). Example 29: (S) -N-3- (3-Fluoro-4-m-aminophenylsulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (29)

The procedure was similar to the synthesis of compound 21 to obtain 100.0 mg of the title compound as a white solid with a yield of 20.0%. Melting point: 218-222 ° C. ¾-R (DMS0): δ 8.22 (d, 1H), 7.44 (d, IH), 7.10-7.20 (ra, 3H), 6.88 (brs, IH), 6.69-6.78 (m, 2H), 5.74 (s, IH), 4.68 (brs, IH), 3.04 (t, IH), 3.69 (m, IH), 1.80 (s, 3H). Example 30: (S) -N-3- (3-Fluoro-4-p-acetylaminobenzenesulfonylaminophenyl) -2-oxo-5-oxazole alkylmethylacetamide (30)

Compound 28 (70.0 mg, 0.18 mmol) was dissolved in pyridine (5.0 mL), and acetic anhydride (1.0 mL) was added dropwise under cooling with stirring in ice water, and the reaction was performed overnight. The reaction mixture was diluted with dichloromethane, and washed successively with IN hydrochloric acid, water, a saturated sodium bicarbonate solution and a saturated saline solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the residue was separated by column chromatography (eluent: methylene chloride: methanol = 12: 1) to obtain the title compound (78.0 mg) as a white solid in a yield of 90.0%. Melting point> 230. C. ¾-NMR (DMS0): δ 10.45 (s, 1H), 8.25 (t, lH), 7.85 (dXt, 4H), 7.70 (dd, lH), 7.56 (t, IH), 7.45 (dd, IH), 4.68 (ra, IH), 4.19 (t, lH), 3.80 (m, lH),

3.42 (m, 2H), 2.09 (s, 3H), 1.83 (s, 3H). Example 31: (S) -N-3- (3-fluoro-4-m-acetylaminobenzenesulfonylaminophenyl) -2-oxo-5-oxazole alkylmethylacetamide (31)

The procedure was similar to the synthesis of compound 30 to obtain the title compound 24.0 mg as a white solid, yield 42.0%. Melting point> 230 ° C. — NMR (DMS0): δ 10.37 (s, IH), 8.29 (brs, 1H), 8.25 (t, lH), 7.90 (dd, 1H), 7.75 (dd, IH), 7.59 (m, 3H), 7.45 (dd, IH), 4.76 (m, IH), 4.19 (t, IH),

4.05 (q, IH), 3.79 (q, IH), 3.42 (m, 2H), 2.07 (s, 3H), 1.83 (s, 3H). Example 32: (S) -N-3- (3-fluoro-4-o-acetoxybenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (32) Compound (S)-N-3- (3-fluoro-4-aminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (59.0 mg, 0.221 mmol) was dissolved in dry tetrahydrofuran (8.0 mL), under ice-water cooling and stirring, 2-acetoxybenzoyl chloride (0.70 mL) and 3 drops of triethylamine were added dropwise and reacted overnight. The reaction mixture was diluted with ethyl acetate, washed with 1N hydrochloric acid, water, a saturated sodium bicarbonate solution, a saturated saline solution, and dried over anhydrous sodium sulfate in this order. 0%。 Filtration, the filtrate was concentrated, the residue was separated by column chromatography (eluent: dichloromethane: methanol = 25: 1) to give the title compound as a white solid 23.0 mg, yield 24.0%. Melting point: 220-222 V. ¾-Earn (DMS0): δ 10. 03 (s, 1H) '7. 70 (d, 1H), 7. 60 (m, 3H), 7. 38 (t, 1H), 7. 25 (m, 2H), 4. 73 (m, 1H), 4. 10 (t, 1H), 3. 73 (m, 1H),

3. 40 (m, 2H), 2. 20 (s, 3H), 1. 82 (s, 3H). Example 33: (S) -N-3- [3-Fluoro-4- [3- (2-fluoro-6-chlorophenyl) -5-methyl-4-isoxazolylamido] phenyl] -2-oxo-5-oxazolidinylmethylacetamide (33)

Compound (S) -N-3- (3-fluoro-4aminophenyl) -2-oxo-5-oxazolidinylmethylacetamide (53. Omg 0. 20mmol) was dissolved in pyridine (8. 0mL), and under ice-water cooling and stirring, 5-methyl-4- (2-fluoro-6-chlorophenyl) 4-isoxazolecarboxyl chloride (453. 4mg, 1.665 phr. 1) was added dropwise. After two hours, the starting point of TLG detection basically disappeared. The reaction mixture was diluted with ethyl acetate, washed with 1N hydrochloric acid, water, saturated sodium bicarbonate solution and saturated brine in this order, and dried over anhydrous sodium sulfate. 0%。 Filtration, the filtrate was concentrated, the residue was separated by column chromatography (eluent: dichloromethane: methanol = 25: 1) to give the title compound as a white solid 97. Omg, yield 97.0%. Melting point: 181- 184 ° C. ¾-Band R (DMS0): δ 8. 23 (t, 1H), 7. 50-7. 7. 60 (m, 3Η), 7. 48 (d, 1H), 7. 38 (m, 1H) , 7. 25 (d, 1H),

4. 70 (m, 1H), 4. 08 (t, 1H), 3. 70 (q, 1H), 2. 72 (s, 3H), 1. 83 (s, 3H).

Claims

Claim

1. An oxazolidinone compound or a pharmaceutically acceptable salt thereof represented by the following formula (I):

R produces alkylsulfonyl which can be substituted, arylsulfonyl which can be substituted, aromatic heterocyclic sulfonyl which can be substituted, amino acid formyl which can be substituted, arylformyl which can be substituted, which can be substituted Arylcarbamoyl, arylaminothioformyl which can be substituted;

R ₂ = fluorenylsulfonyl which may be substituted, arylsulfonyl which may be substituted, arylformyl which may be substituted, aromatic heterocyclic formyl which may be substituted;

R ₃ = H or alkyl.

The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein the compound is-

(1) (S) -N-3- [3-fluoro-4- (4-methanesulfonyl-1 -piperazinyl) phenyl] -2-oxo-5-oxazolidinylmethylacetamide ;

(2) (S)-N-3- [3-Fluoro-4- (4-benzenesulfonyl-1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethylacetamide ;

(3) (S) -N-3- [3-fluoro-4- [4- (4-methylbenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Alkyl methylacetamide

(4) (S) -N-3- [3-Fluoro-4- (4-methoxybenzenesulfonyl-1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethyl Acetylacetamide

(5) (S) -N-3- [3-fluoro-4- [4- (4-bromobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-5-oxazolidine Methylmethylacetamide

(6) (S) -1 ^ -3- [3-fluoro-4- [4- (4-nitrobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-5-oxo Azole Alkyl methylacetamide

(7) (S) -N-3- [3-fluoro-4- [4- (3-nitrobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-5-oxazole Fluorenylmethylacetamide;

(8) (S) -N-3- [3-Fluoro-4- [4- (2-nitrobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazole Fluorenylmethylacetamide;

(9) (S) -N-3- [3-fluoro-4- [4- (2-thiophenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-5-oxazolidinyl Methylacetamide

(10) (S) -N-3- [3-Fluoro-4- [4- (4-aminobenzenesulfonylpiperazinyl) phenyl] -2-oxo-5-oxazolidinylmethylacetamide ;

(11) (S) -N-3- [3-Fluoro-4- [4- (3-aminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazolidine Methylmethylacetamide

(12) (S) -N-3- [3-fluoro- 4- [4- (2-aminobenzenesulfonyl) -1-piperazinyl] phenyl] _2-oxo- 5-oxazolidinyl Methylacetamide

(13) (S) -N-3- [3-fluoro-4- [4- (4-acetylaminobenzenesulfonyl)-1-piperazinyl] phenyl]-2-oxo- 5-oxazole Alkylformamidineacetamide;

(14) (S) -N- 3- [3-fluoro- 4- [4- (3-acetylaminobenzenesulfonyl) -1-piperazinyl] phenyl] -2-oxo- 5-oxazole Alkyl methylacetamide

(15) (S) -N-3- [3-Fluoro-4- [4- (2-acetylaminobenzenesulfonyl) -1-piperazinyl] phenyl]-2-oxo- 5-oxazole Alkyl methylacetamide

(16) (S)-N- 3- [3-Fluoro- 4- [4- [3- (2-fluoro-6-chlorophenyl)-5-methyl- 4-isoxazolyl formyl]- 1-piperazinyl] phenyl] -2-oxo-5-oxazolidinylmethylacetamide;

(17) (S) -N-3- [3-Fluoro-4- [4- (2-hydroxybenzoyl) 1-piperazinyl] phenyl] -2-oxo-5-oxazolidinyl Methylacetamide

(18) (S) -N- 3- [3-fluoro- 4- [4- (L-phenylalanyl) -1-piperazinyl] phenyl] -2-oxo-5-oxazolyl Methylmethylacetamide

(19) (S) -N-3- [3-Fluoro 4- [4- (phenylaminocarbonyl)-1-piperazinyl] phenyl] -2-oxo-5-oxazolylmethyl Acetylacetamide

(20) (S) -N-3- [3-fluoro-4- [4- (phenylaminothiocarbonyl) -1-piperazinyl] phenyl] -2-oxo-5 -oxazolidine Methylmethylacetamide

(21) (S) -N-3- (3-fluoro-4-methanesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(22) (S) -N-3- (3-fluoro-4-benzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(23) (S) -N-3- (3-fluoro-4-p-methylbenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(24) (S) -N-3- (3-fluoro-4-p-bromobenzenesulfonylaminophenyl)-2-oxo-5-oxazolylmethylacetamide;

(25) (S) -N-3- (3-fluoro-4-p-methoxybenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(26) (S) -N-3- (3-fluoro-4-p-nitrobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(27) (S) -N-3- (3-fluoro-4-m-bromobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(28) (S) -N- 3- (3-fluoro-4-p-aminobenzenesulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(29) (S) -N-3- (3-fluoro-4 -m-aminoaminosulfonylaminophenyl) -2-oxo-5-oxazolidinylmethylacetamide;

(30) (S) -N- 3- (3-fluoro-4-p-acetaminobenzenesulfonylaminophenyl) -2-oxo-5-oxazolylmethylacetamide;

(31) (S) _N-3- (3-fluoro-4-m-acetylaminobenzenesulfonylaminophenyl) -2-oxo-5-oxazolylmethylacetamide;

(32) (S) -N-3- (3-fluoro-4-o-acetoxybenzenesulfonylaminophenyl) -2-oxo-5-oxazolylmethylacetoacetamide; or

(33) (S) _N-3- [3-Fluoro-4- [3- (2-fluoro-6-chlorophenyl) -5-methyl-4-isoxazolamide] phenyl] -2 -Oxo- 5-oxazolidinylmethylacetamide.

3. Preparation method of oxazolidinone compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof Where R represents \ / or -NR ₂ R ₃ , where

Substituted amidylsulfonyl, Substituted arylsulfonyl, Substituted aromatic heterocyclic sulfonyl 'group, Substituted amino acid formyl, Substituted arylformyl, Substituted Arylcarbamoyl, arylaminothioformyl which can be substituted;

5 alkylsulfonyl which may be substituted, arylsulfonyl which may be substituted, arylformyl which may be substituted, aromatic heterocyclic formyl which may be substituted;

R ₃ = H or alkyl,

The method is characterized by comprising the following steps:

(1) (S) -N- [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-oxazolylmethyl] acetamide 10 and sulfonyl 1-48 小时， Chemical agent in a non-polar solvent at -10 ~ 80 ° C to obtain a compound 1-9;

(2) Compounds 6-8 are subjected to catalytic hydrogenation in a polar solvent in the presence of a metal catalyst to obtain compounds

10-12;

15 (4) Arylcarboxylic acid chloride and (S) -N- [3- [3-fluoro- 4- (1-piperazinyl) phenyl] -2-oxo-5-5-oxazolylmethyl] Acetamide in a non-polar solvent at -10 ~ 8 (TC reaction 0.1-48 hours to obtain compounds 16, 17, 18; or aryl formic acid or amino acid with N-hydroxysuccinimide (H0SU) or monohydroxy Benzotriazole (HOBt) or dicyclohexylcarbodiimide (DCC), and then with (S)-N- [3- [3-fluoro-4- (1-piperazinyl) phenyl]- 1-48 小时得化 2- 2-oxo-5-oxazolidinylmethyl] acetamide is reacted in a non-polar solvent at -10 ~ 80 ° C for 0.1-48 hours

20 compounds 16, 17, 18;

(5) Prepare the corresponding salt as required.

4. The method according to claim 3, wherein the sulfonylating agent in (1) is selected from the group consisting of a sulfonyl chloride which may be substituted by a radical or an aryl group, a sulfonyl bromide which may be substituted by an alkyl group or an aryl group, Sulfonic anhydride which may be substituted by fluorenyl or aryl; non-polar solvent selected from benzene, toluene, methylene chloride, chloroform, and tetrahydrofuran.

25. The method according to claim 4, wherein the sulfonylating agent is an alkyl or arylsulfonyl chloride, the non-polar solvent is benzene, and the reaction is performed at 0 to 20 ° C for 8 to 24 hours.

The method according to claim 3, wherein the polar solvent described in (2) is selected from the group consisting of methanol, ethanol, and acetic acid, and the metal catalyst is palladium / carbon or another catalyst containing palladium or nickel.

7. The method according to claim 6, wherein the polar solvent is methanol, and the metal catalyst is 5% or 10% Palladium / carbon, catalytic hydrogenation is carried out at normal temperature and pressure.

8. Preparation method of oxazolidinone compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof

Fluorenylsulfonyl which may be substituted, arylsulfonyl which may be substituted, arylformyl which may be substituted, aromatic heterocyclic formyl which may be substituted;

R ₃ = H or fluorenyl,

The method is characterized by comprising the following steps −

(1) (S)-N- [3- (3-Fluoro-4-aminophenyl) _2_oxo- 5-oxazolidinylmethyl] acetamide and sulfonylating agent in a non-polar solvent 1-48 hours at -10 ~ 80 ° C, to obtain compounds 21-27;

(2) Compounds 26-27 are subjected to a catalytic hydrogenation reaction in a polar solvent in the presence of a metal catalyst in the range of (TC to room temperature) for 8-24 hours to obtain compounds 28-29;

(3) Compounds 28-29 are subjected to an acetylation reaction at -10 ~ 80 ° C in a non-polar solvent for 0.1-12 hours to obtain compounds 30-31;

(4) arylcarboxylic acid chloride and (S) -N_ [3- [3-fluoro-4- (1-piperazinyl) phenyl] -2-oxo-5-5-oxazolylmethyl] acetamide 1-48hrs at -10 ~ 80 ° C in a non-polar solvent to obtain compounds 32-33;

(5) Prepare the corresponding salt as required.

9. The method according to claim 8, wherein the sulfonylating agent described in (1) is selected from the group consisting of a sulfonyl chloride which may be substituted by an alkyl group or an aryl group, a sulfonyl bromide which may be substituted by an alkyl group or an aryl group, Sulfonic anhydride which can be substituted by alkyl or aryl; non-polar solvent is pyridine, and the reaction is performed at 0 ~ 20 ° C for 8-24 hours.

10. The method according to claim 8, wherein the polar solvent described in (2) is selected from the group consisting of methanol, ethanol, and acetic acid, and the metal catalyst is rake / carbon or other catalysts containing palladium or nickel.

The method according to claim 10, wherein the polar solvent is methanol, the metal catalyst is 5% or 10% palladium / carbon, and the catalytic hydrogenation is performed at normal temperature and pressure.

12. Use of an oxazolidinone compound represented by formula (I) or a salt thereof in the preparation of a medicament for treating an infectious disease.

13. The use according to claim 12, wherein the infectious disease is an infection caused by a multidrug-resistant bacteria.