WO2003093247A2

WO2003093247A2 - Antibacterial agents

Info

Publication number: WO2003093247A2
Application number: PCT/IB2003/001571
Authority: WO
Inventors: Shiv Kumar Agarwal; Surendrakumar Satyanarayan Pandey
Original assignee: Orchid Chemicals & Pharmaceuticals Ltd
Priority date: 2002-04-30
Filing date: 2003-04-25
Publication date: 2003-11-13
Also published as: AU2003224345A1; AU2003224345A8; WO2003093247A3

Abstract

The present invention provides novel oxazolidinone derivatives of the formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their hydrates, their solvates, their pharmaceutically acceptable salts and pharmaceutically acceptable compositions containing them. The present invention more particularly provides novel oxazolidinone derivatives of the general formula (I).

Description

NEW ANTIBACTERIAL AGENTS

Field of the Invention

The present invention also provides a process for the preparation of the above said novel oxazolidinone derivatives of the formula (I) their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their hydrates, their solvates, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them.

The novel oxazolidinone derivatives of the present invention are useful as antibacterial agents and hence useful in the treatment of conditions such as nosocomial pneumoniae, community acquired pneumoniae, vancomycin resistance enterococci (VRE) caused by methicillin resistance staphylococcus aureus (MRSA) and penicillin resistant streptococcus pneumoniae. The compounds of the present invention are effective against a number of human or animal pathogens, clinical isolates, including Vancomycin resistant organisms, methicillin resistant organisms. Background of Invention

Several oxazolidinone derivatives have been reported in the literature some of which are given here: i) US patent number 5,688,792 discloses and claims compounds of formula (II)

in which X is O, S, SO, S0₂, SNR¹⁰ or S(0)NR¹⁰; R is a hydrogen, (C_rC₈)alkyl optionally substituted with one or more F, Cl, hydroxy, (C C₈)alkoxy, (C C₈)acyloxy, or -0-CH₂-Ph; (C₃-C₆)cycloalkyl, amino, (Cι-C₈)alkylamino, (C C₈)dialkylamino or (Cι-C₈)alkoxy; R¹ is hydrogen except when X is O then R¹ can be hydrogen, CH₃, CN, C0₂H, C0₂R, or (CH₂)_mR^π (m is 1 or 2); R² is independently hydrogen, fluoro or chloro; R is hydrogen except when X is O and R¹ is CH₃, then R³ can be hydrogen or CH₃; R¹⁰ is independently hydrogen, (C C )alkyl optionally substituted with chloro, fluoro, hydroxy, (Cι-C₈)alkoxy, amino, (CrC₈)alkylamino, or (CrC₈)dialkylamino or p-toluenesulfonyl; R¹¹ is hydrogen, hydroxy, OR, OCOR, amino, NHCOR or N(R¹⁰)₂ and n is 0, 1 or 2. ii) US patent number 5,547,950 discloses and claims compounds of formula (III)

or pharmaceutically acceptable salts there of wherein each n is independently 1 to 3; Y is selected from a-n as defined in the patent; wherein each occurrence of (C C₆)alkyl may be substituted with one or more of fluoro, chloro, bromo, iodo, OR¹, CO₂R¹, CN, SR¹ or R¹ (where R¹ is a hydrogen or (C_rC₄)alkyl); U, V and W are independently (Cι-C₆)alkyl, fluoro, chloro, bromo, hydrogen or a (Cι-C₆)alkyl substituted with one or more of fluoro, chloro, bromo or iodo, preferably U and V are fluoro and W is hydrogen; R is hydrogen, (C Cι₂)alkyl, (C₃-Cι₂)cycloalkyl, (C C₆)alkoxy, (Cι-C₆)alkyl substituted with one or more of fluoro, chloro, bromo, iodo or hydroxy and q is 0 to 4 inclusive.

Objective of the Invention We have focused our research to identify novel oxazolidinone derivatives, which are effective against resistant organisms. Our sustained efforts have resulted in novel oxazolidinone derivatives of the formula (I). The novel oxazolidinone derivatives of the present invention are useful as antibacterial agents and hence useful in the treatment of conditions such as nosocomial pneumoniae, community acquired pneumoniae, vancomycin resistance enterococci (VRE) caused by methicillin resistance staphylococcus aureus (MRSA) and penicillin resistant streptococcus pneumoniae. The compounds of the present invention are effective against a number of human or animal pathogens, clinical isolates, including Vancomycin resistant organisms, methicillin resistant organisms

Summary of the Invention

The present invention relates to novel oxazolidinone derivatives of the formula (I)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, wherein Y is O or S; X is O, NR⁷, S, SO, S0₂, wherein R⁷ represents hydrogen or -(C=0)_rn-(CH₂)_rZ where m is an integer 0 or 1 , 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (Cι-C₆)alkyl, aryl, heteroaryl, (C C₈)alkoxy, aryloxy, aralkoxy, acyl, (Cι-C₈)alkylthio, (C C₈)alkylsulfonyl, arylsulfonyl, sulfamyl, (Cι-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, (Cι-C )monoalkylamino, or (CrC₈)dialkylamino; R¹ represents hydrogen, (C_\- C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R represents aminoacid residue which is attached through acid moiety; R³ and R may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C_rC₆)alkyl, (C C₆)alkoxy, (C_rC₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

Detailed Description of the Invention

Suitable groups represented by R¹ may be selected from hydrogen, (C_rC ) alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n- pentyl, isopentyl, hexyl and the like; (C₃-C₆)cycloa_kyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; aryl group such as phenyl or naphthyl.

Suitable aminoacid residue represented by R may be selected from glycine, alanine, lysine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, iso-leucine, leucine, methionine, phenyl alanine, proline, serine, threonine, tryptophan, tyrosine or valine. Suitable groups represented by R and R may be selected from hydrogen or halogen atom such as fluorine or chlorine. Suitable groups represented by R⁵ and R may be selected from hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (Cι-C₆)alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, hexyl and the like; (C C₆)alkoxy group, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like; (C C₆)alkylthio group such as methylthio, ethylthio, n-propylthio, iso- propylthio and the like; (C₃-C₆)cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like.

Suitable groups represented by Z may be selected from hydrogen, hydroxyl, halogen such as chlorine, fluorine, bromine or iodine; substituted or unsubstituted, linear or branched (Cι-C₆)alkyl group such as methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, t-butyl, n-pentyl, isopentyl, hexyl and the like; aryl group such as phenyl or naphthyl, the aryl group may be substituted; heteroaryl group may be mono or bicyclic system such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, pyridazine, pyrazine, benzopyranyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyrolyl, benzoxadiazolyl, benzothiadiazolyl and the like, the heteroaryl group may be substituted; (C C₈)alkoxy group, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like, which may be substituted; aryloxy group such as phenoxy, napthoxy, the aryloxy group may be substituted; aralkoxy group such as phenylmethyl, phenylethyl, phenylpropyl, and the like, which may be substituted; acyl group such as -C(=0)CH₃, -C(=0)C₂H₅, -C(=0)C₃H₇₎ -C(=0)C₆H,₃, - C(=S)CH₃, -C(=S)C₂H₅, -C(=S)C₃H₇, -C(=S)C₆H_13. benzoyl and the like, which may be substituted; (d-C₈)alkylthio group such as methylthio, ethylthio, n- propylthio, iso-propylthio and the like, the alkylthio group may be substituted; (C C₈)alkylsulfonyl group such as methyl sulfonyl, ethylsulfonyl, n-propylsulfonyl, iso- propylsulfonyl and the like, the alkylsulfonyl group may be substituted; arylsulfonyl group such as phenylsulfonyl or naphthylsulfonyl, the arylsulfonyl group may be substituted; sulfamyl, (C]-C₈)alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and the like, the alkoxycarbonyl group may be substituted; aryloxycarbonyl group such as phenoxycarbonyl, napthoxycarbonyl, the aryloxycarbonyl group may be substituted; (Cι-C₆)monoalkylamino group such as NHCH₃, NHC₂H₅, NHC₃H_7; NHC₆H₁₃, and the like, which may be substituted;, or (C]-C₈)dialkylamino group such as N(CH₃)₂, NCH₃(C₂H₅), N(C₂H₅)₂ and the like, which may be substituted.

The substituents on the group Z may be selected from halogen, hydroxy, nitro, cyano, azido, amino, formyl, alkyl, aryl, cycloalkyl, alkoxy, aryloxy, aralkoxy and these substituents are as defined above.

Suitable n is an integer in the range of 0, 1, or 2, preferably n represents 1 or 2.

Pharmaceutically acceptable salts of the present invention include alkali metal salts like Li, Na, and K salts, alkaline earth metal salts like Ca and Mg salts, salts of organic bases such as diethanolamine, α-phenylethylamine, benzylamine, piperidine, morpholine, pyridine, hydroxyethylpyrrolidine, hydroxyethylpiperidine, choline and the like, ammonium or substituted ammonium salts, aluminum salts. Salts also include amino acid salts such as glycine, alanine, cystine, cysteine, lysine, arginine, phenylalanine, guanidine etc. Salts may include acid addition salts where appropriate which are, sulphates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates, tartrates, maleates, citrates, succinates, palmoates, methanesulphonates, tosylates, benzoates, salicylates, hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates, ketoglutarates and the like. Pharmaceutically acceptable solvates may be hydrates or comprising other solvents of crystallization such as alcohols.

Representative compounds according to the present invention include: (S) N-[(3-(3-F_uoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ; (S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ;

(S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ; (S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-phenyl propionamide dihydrochloride or its salts ;

(S) N- [(3 -(3 -Fluoro-4-((N-4-hydroxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-amino propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ; (S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide or its salts ; (S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide or its salts ; (xS) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin- 5-yl)methyl]-2-amino acetamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino-4-methylthio butyramide or its salts ;

5-yl)methyl]-2-amino-3-phenyl propionamide or its salts ; (5) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino-3-(indol-3-yl)propionamide or its salts ;

5-yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin- 5-yl)methyl]-2-amino-4-methyl pentanamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ;

(R) N- [(3 -(3 -Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin- 5 -yl)methyl] -2- amino acetamide or its salts ; (R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ; (R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide or its salts ; (R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide dihydrochloride or its salts ;

(R) N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-amino propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ; (R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ;

(R) N- [(3 -(3 -Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin- 5 -yl)methyl] -2- amino-3 -phenyl propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide or its salts ; (R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino acetamide or its salts ;

5-yl)methyl]-2-amino-4-methylthio butyramide or its salts ;

5-yl)methyl]-2-amino-3-phenyl propionamide or its salts ;

5-yl)methyl]-2-amino-3-(indol-3-yl)propionamide or its salts ;

5-yl)methyl](pyrrolidin-2-yl)formamide or its salts and

(R) N- [(3 -(3 -Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino-4-methyl pentanamide or its salts.

According to another embodiment of the present invention, there is provided a process for the preparation of novel oxazolidinone derivatives of the formula (I) where all symbols are as defined earlier, which comprises reacting a compound of the formula (la)

wherein R¹ represents hydrogen and all other symbols are as defined earlier, with protected amino acid and deprotecting to yield the compound of formula (I) as defined earlier. The protecting groups used in this reaction are conventional protecting groups such as t-butoxy carbonyl (t-Boc), acetyl, trityl, trifluoroacetyl, benzyloxy, 9-fluorenyl methylcarbonate (Fmoc), vinyl carbamate, benzyloxy carbonyl (Cbz), 2,2,2-trichloroethyl carbamate (Troc), allyl carbamate. The reaction of compound of formula (la) with protected amino acid residue may be carried out using carbodiimides such as dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), l-[3-dimethylarninopropyl]-3- ethylcarbodiimide hydrochloride (EDCI), l-[3-dimethylaminopropyl]-3- ethylcarbodiimide and the like, in the presence of a solvent selected from acetonitrile, dichloromethane, dimethylsulfoxide, N,N-dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N-dimethyl acetamide. The reaction may be carried out at a temperature in the range of -10 to 60 °C. The duration of the reaction may range from 6 to 10 h.

The deprotection is carried out using conventional deprotecting agents selected from 4-(aminornethyl)piperidine, moφholine, piperidine, tris(2- aminoethyl)amine, hydrazine hydrate, tris(2-arninoethyl)amine polymer supported 5 % Pd/C, 10 % Pd/C or the deprotection may be carried out by passing HC1 gas in the presence of solvent selected from acetonitrile, dichloromethane, dimethylsulfoxide, N,N-dimethylformamide, tetrahydrofuran, 1 -methyl -2- pyrrolidinone, N,N-dimethylacetamide. The reaction may be carried out at a temperature in the range of -10 to 20 °C.

In yet another embodiment of the present invention, there is provided a process for the preparation of novel oxazolidinone derivatives of the formula (I)

7 7 wherein X represents NR , wherein R represents -(C=0)_m-(CH₂)ι-Z is as defined earlier and all other symbols are as defined earlier, which comprises i) reacting the compound of the formula (Ia-1)

wherein R¹ representd hydrogen, P is protecting group and all other symbols are as defined earlier with protected amino acid to yield compound of formula (lb)

wherein R ' is protected amino acid residue and all other symbols are as defined earlier, ii) deprotecting the compound of formula (lb) to produce compound of formula

(Ic)

wherein all symbols are as defined earlier, iii) reacting the compound of formula (Ic) with R⁷'-H, wherein R⁷' is protected R⁷ to produce compound of formula (Id)

wherein all symbols are as defined earlier and iv) deprotecting the compound of formula (Id) to produce compound of formula (I) as defined earlier.

The protecting groups used in this reaction are conventional protecting groups such as t-butoxy carbonyl (t-Boc), acetyl, trityl, trifluoroacetyl, benzyloxy, 9-fluorenyl methylcarbonate (Fmoc), vinyl carbamate, benzyloxy carbonyl (Cbz), 2,2,2-trichloroethyl carbamate (Troc), allyl carbamate.

The reaction of compound of formula (la) with protected amino acid residue may be carried out using carbodiimides such as dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), l-[3-dimethylaminopropyl]-3- ethylcarbodiimide hydrochloride (EDCI), l-[3-dimethylaminopropyl]-3- ethylcarbodiimide and the like, in the presence of a solvent selected from acetonitrile, dichloromethane, dimethylsulfoxide, N,N-dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N-dimethylacetamide. The reaction may be carried out at a temperature in the range of -10 to 60 °C. The duration of the reaction may range from 6 to 10 h.

The deprotection of compound of formula (lb) is carried out using conventional deprotecting agents selected from ammonium formate, 4- (aminomethyl)piperidine, moφholine, piperidine, tris(2-aminoethyl)amine, hydrazine hydrate, tris(2-aminoethyl)amine polymer supported 5 % Pd/C, 10 % Pd/C or the deprotection may be carried out by passing HC1 gas in the presence of solvent selected from acetonitrile, dichloromethane, methanol, dimethylsulfoxide, dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N- dimethylacetamide and the like or mixtures thereof. The reaction may be carried out at a temperature in the range of -10 to 20 °C.

The reaction in step (iii) is carried out in the presence of solvent selected from acetonitrile, dichloromethane, methanol, dimethylsulfoxide, N,N- dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N- dimethylacetamide and the like or mixtures thereof and a base such as triethylamine, pyridine and the like. The reaction may be carried out at a temperature in the range of -10 to 20 °C. The deprotection of compound of formula (Id) is carried out using conventional deprotecting agents selected from ammonium formate, 4- (aminomethyl)piperidine, moφholine, piperidine, tris(2-aminoethyl)amine, hydrazine hydrate, tris(2-aminoethyl)amine polymer supported 5 % Pd/C, 10 % Pd/C or the deprotection may be carried out by passing HCl gas in the presence of solvent selected from acetonitrile, dichloromethane, methanol, dimethylsulfoxide, N,N-dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N- dimethylacetamide and the like or mixtures thereof. The reaction may be carried out at a temperature in the range of -10 to 20 °C. In yet another embodiment of the present invention, there is provided a process for the preparation of novel oxazolidinone derivatives of the formula (I) wherein X represents NR⁷, wherein R⁷ represents-(C=0)_rn-(CH₂)|-Z is as defined earlier and all other symbols are as defined earlier, which comprises i) deprotecting the compound of the formula (Ie)

wherein P is a protecting group and all other symbols are as defined earlier to yield compound of formula (If)

wherein all symbols are as defined earlier, ii) reacting the compound of formula (If) with R⁷'-H, wherein R⁷' is protected

R to produce compound of formula (Ig)

wherein all symbols are as defined earlier, iii) reducing the compound of formula (Ig) to produce compound of formula (Ih)

wherein all symbols are as defined earlier and iv) reacting the compound of formula (Ih) with protected amino acid to produce compound of formula (Ii)

v) deprotecting the compound of formula (Ii) to produce compound of formula (I) as defined earlier.

The protecting groups used in this reaction are conventional protecting groups such as t-butoxy carbonyl (t-Boc), acetyl, trityl, trifluoroacetyl, benzyloxy, 9-fluorenyl methylcarbonate (Fmoc), vinyl carbamate, benzyloxy carbonyl (Cbz), 2,2,2-trichloroethyl carbamate (Troc), allyl carbamate. The deprotection of compound of formula (Ie) is carried out using conventional deprotecting agents selected from ammonium formate, 4- (aminomethyl)piperidine, moφholine, piperidine, tris(2-aminoethyl)amine, hydrazine hydrate, tris(2-aminoethyl)amine polymer supported 5 % Pd/C, 10 % Pd/C or the deprotection may be carried out by passing HCl gas in the presence of solvent selected from acetonitrile, dichloromethane, methanol, dimethylsulfoxide, N,N-dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N- dimethylacetamide and the like or mixtures thereof. The reaction may be carried out at a temperature in the range of -10 to 20 °C.

The reaction in step (ii) is carried out in the presence of solvent selected from acetonitrile, dichloromethane, methanol, dimethylsulfoxide, N,N- dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N- dimethylacetamide and the like or mixtures thereof and a base such as triethylamine, pyridine and the like. The reaction may be carried out at a temperature in the range of-10 to 20 °C. The reduction of compound of formula (Ig) may be carried out in the presence of gaseous hydrogen and a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal, alumina, asbestos and the like. The reduction may be conducted in the presence of a solvent such as dioxane, acetic acid, ethyl acetate, THF, alcohol such as methanol, ethanol and the like or mixtures thereof. A pressure between atmospheric pressure to 60 psi may be used. The reaction may be carried out at a temperature in the range of 25 to 60 °C, preferably at room temperature. The reaction time ranges from 2 to 48 h. The reduction may also be carried out by employing PPh₃ in water.

The reaction of compound of formula (Ih) with protected amino acid residue may be carried out using carbodiimides such as dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), 1 -[3-dimethylaminopropyl]-3- ethylcarbodiimide hydrochloride (EDCI), l-[3-dimethylaminopropyl]-3- ethylcarbodiimide and the like, in the presence of a solvent selected from acetonitrile, dichloromethane, dimethylsulfoxide, N.N-dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N-dimethylacetamide. The reaction may be carried out at a temperature in the range of -10 to 60 °C. The duration of the reaction may range from 6 to 10 h. The deprotection of compound of formula (Ii) is carried out using conventional deprotecting agents selected from ammonium formate, 4- (aminomethyl)piperidine, moφholine, piperidine, tris(2-aminoethyl)amine, hydrazine hydrate, tris(2-aminoethyl)amine polymer supported 5 % Pd/C, 10 % Pd/C or the deprotection may be carried out by passing HCl gas in the presence of solvent selected from acetonitrile, dichloromethane, methanol, dimethylsulfoxide, N,N-dimethylformamide, tetrahydrofuran, l-methyl-2-pyrrolidinone, N,N- dimethyl acetamide and the like or mixtures thereof. The reaction may be carried out at a temperature in the range of -10 to 20 °C. The compounds of formula (I) where X represents S is oxidized to a compound of formula (I) where X represents SO using sodium metaperiodate in a mixture of water and methanol.

The compounds of formula (I) where X represents S or SO is oxidized to a compound of formula (I) where X represents S0₂ using oxone or 4-methyl moφholine-N-oxide and catalytic amount of osmium tetroxide in aqueous acetone.

In yet another embodiment of the present invention, there is provided a novel intermediate of formula (lb)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein in which P is a protecting group; R ' is protected amino acid residue; Y is O or S; R represents hydrogen, (Cj-C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C C₆)alkyl, (C C₆)alkoxy, (C C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

In yet another embodiment of the present invention, there is provided a novel intermediate of formula (Ic)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein in which R ' is protected amino acid residue; Y is O or S; R¹ represents hydrogen, (C C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R and R⁴ may be same or different and independently represent hydrogen or halogen; R and R may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C_\- C₆)alkyl, (C_rC₆)alkoxy, (C C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

In yet another embodiment of the present invention, there is provided a novel intermediate of formula (Id)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein in which R⁷' is

7 7 protected R , wherein R represents hydrogen or -(C=0)_m-(CH₂)ι-Z where m is an integer 0 or 1, 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (C C )alkyl, aryl, heteroaryl, (Q- C₈)alkoxy, aryloxy, aralkoxy, acyl, (C C₈)alkylthio, (C C₈)alkylsulfonyl, arylsulfonyl, sulfamyl, (C]-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, (C C₆)monoalkylamino, or (C C₈)dialkylamino; R ' is protected amino acid residue; Y is O or S; R¹ represents hydrogen, (C]-C₆)alkyl, aryl or (C₃- C₆)cycloalkyl; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C_t-C₆)alkyl, (C C₆)alkoxy, (C C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

It is appreciated that in any of the above-mentioned reactions, any reactive group in the substrate molecule may be protected according to conventional chemical practice. Suitable protecting groups in any of the above-mentioned reactions are those used conventionally in the art. The methods of formation and removal of such protecting groups are those conventional methods appropriate to the molecule being protected.

The pharmaceutically acceptable salts are prepared by reacting the compound of formula (I) with 1 to 4 equivalents of a base such as sodium hydroxide, sodium methoxide, sodium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, tetrahydrofuran, methanol, t-butanol, dioxane, isopropanol, ethanol etc. Mixture of solvents may be used. Organic bases such as diethanolamine, α-phenylethylamine, benzylamine, piperidine, moφholine, pyridine, hydroxyethylpyrrolidine, hydroxyethylpiperidine, choline and the like, ammonium or substituted ammonium salts, aluminum salts. Amino acid such as glycine, alanine, cystine, cysteine, lysine, arginine, phenylalanine, guanidine etc may be used for the preparation of amino acid salts. Alternatively, acid addition salts wherever applicable are prepared by the treatment with acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, p-toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid, salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, tetrahydrofuran, dioxane etc. Mixture of solvents may also be used.

The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as brucine, cinchona alkaloids and their derivatives and the like. Commonly used methods are compiled by Jaques et al in "Enantiomers, Racemates and Resolution" (Wiley Interscience, 1981). More specifically the compound of formula (I) may be converted to a 1 : 1 mixture of diastereomeric amides by treating with chiral amines, aminoacids, aminoalcohols derived from aminoacids; conventional reaction conditions may be employed to convert acid into an amide; the diastereomers may be separated either by fractional crystallization or chromatography and the stereoisomers of compound of formula (I) may be prepared by hydrolysing the pure diastereomeric amide.

Various polymoφhs of compound of general formula (I) forming part of this invention may be prepared by crystallization of compound of formula (I) under different conditions. For example, using different solvents commonly used or their mixtures for recrystallization; crystallizations at different temperatures; various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymoφhs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of polymoφhs may be determined by solid probe nmr spectroscopy, ir spectroscopy, differential scanning calorimetry, powder X-ray diffraction or such other techniques.

Pharmaceutically acceptable solvates of the compounds of formula (I) forming part of this invention may be prepared by conventional methods such as dissolving the compounds of formula (I) in solvents such as water, methanol, ethanol, mixture of solvents such as acetone:water, dioxane:water, N.N- dimethylformamide:water and the like, preferably water and recrystallizing by using different crystallization techniques. The compounds of the present invention are useful for the treatment of microbial infections in humans and other warm blooded animals, under both parenteral and oral administration. In addition to the compounds of formula (I) the pharmaceutical compositions of the present invention may also contain or be co- administered with one or more known drugs selected from other clinically useful antibacterial agents such as β-lactams or aminoglycosides. These may include penicillins such as oxacillin or flucloxacillin and carbapenems such as meropenem or imipenem to broaden the therapeutic effectiveness against, for example, methicillin-resistant staphylococci. Compounds of the formula (I) of the present invention may also contain or be co-administered with bactericidal/permeability- increasing-g protein product (BPI) or efflux pump inhibitors to improve activity against gram negative bacteria and bacteria resistant to antimicrobial agents.

The pharmaceutical composition may be in the forms normally employed, such as tablets, capsules, powders, syrups, solutions, suspensions and the like, may contain flavoring agents, sweeteners etc. in suitable solid or liquid carriers or diluents, or in suitable sterile media to form injectable solutions or suspensions. Such compositions typically contain from 1 to 20 %, preferably 1 to 10 % by weight of active compound, the remainder of the composition being pharmaceutically acceptable carriers, diluents or solvents.

The present invention is provided by the examples given below, which are provided by way of illustration only and should not be considered to limit the scope of the invention.

Example 1

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)pheny_)-2-oxo-oxazolidin-5-yl)methyl]-2- a ino propionamide hydrochloride

Step (i)

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-y_)phenyl)-2-oxo-oxazolidin-5-y_)methyl]-2- t-butoxycarbonylamino propionamide

A solution of (<S)-5-(aminomethyl)-3-(3-fluoro-4-(moφholin-4-yl)-phenyl)-l ,3- oxazolidin-2-one (200mg, 67mmol) (prepared according to the procedure described in Journal of Medicinal Chemistry 1996, vol. 39, No. 3, 673-679) and N-t- butoxycarbonylamino propionic acid (160mg, 84mmol) in dichloromethane (7ml) was stirred for 15 minutes at 0-5 °C. N,N'-dicyclohexylcarbodiimide (192mg, 94mmol) was added to the reaction mass and stirred for 6 hr at ambient temperature. Water (5ml) was added to the reaction mixture and stirred for 10 minutes. The organic layer was separated and washed with water (10ml), dried (sodium sulfate) and concentrated to give the crude title compound, which was purified by column chromatography to furnish the title compound (218mg, 69%), mp: 113 -5 °C. IR (KBr): 3344, 1733, 1667; 1HNMR (CDC1₃, 400 MHz): δ 7.5 (d, IH), 7.0 (d, IH), 6.8 (t, IH), 4.3 (m, IH), 4.1 (t, IH), 3.8 (t, 4H), 3.7 (t, IH), 3.6 (t, 2H), 3.06 (q, 4H), 2.1 (s, 5H), 1.4 (s, 9H); m/z^M+1467.

Step (ii)

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)_τιethyl]-2- amino propionamide hydrochloride

To a solution of (_S)-N-[(3-(3-fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl]-2-t-butoxycarbonylamino propionamide (lOOmg, 21mmol) obtained in step (i) in dichloromethane (3ml), HCl gas was bubbled at 0-5 °C for 15 minutes. The excess HCl gas was removed by bubbling nitrogen gas. The reaction mixture was concentrated to dryness to afford the title compound (60mg, 76%). 1HNMR (D₂0, 400 MHz): δ 7.4 (d, IH), 7.2 (t, IH), 7.1 (d, IH), 4.1 (t, IH), 3.9 (d, IH), 3.8 (t, 4H), 3.7 (d, 2H), 3.6 (d, IH), 3.5 (d, IH), 3.1 (t, 4H), 2.0 (s, IH), 1.4 (d, IH), 1.2 (d, 2H); m/z^M+1367.

Example 2

(_S -N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide hydrochloride

Step (i)

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-y_)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- t-butoxycarbonylamino acetamide The title compound was prepared from (_S -5-(aminomethyl)-3-(3-fluoro-4- (moφholin-4-yl)-phenyl)-l,3-oxazolidin-2-one (200mg, 67mmol) and N-t- butoxycarbonylamino acetic acid (144mg, 82mmol) by following the procedure as described in step (i) of example 1 (203mg, 66%). IR (KBr): 3361, 1729, 1682; 1HNMR (CDC1₃, 400 MHz): δ 7.4 (d, IH), 7.1 (m, IH), 6.9 (t, IH), 6.6 (s, IH), 5.0 (s, IH), 4.8 (d, IH), 4.1 (m,lH), 4.0 (d, IH), 3.86 (d, 4H), 3.79 (d, 2H), 3.0 (t, 4H), 1.2 (s, 9H); m/z^M+,453.

Step (ii) (S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide hydrochloride

The title compound was prepared from (_S -N-[(3-(3-fluoro-4-(moφholin-4- yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino acetamide

(lOOmg, 22mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (68mg, 75%).

IR (KBr): 3422, 1743, 1682; 1HNMR (D₂0, 400 MHz): δ 7.3 (d, IH), 7.1 (d, 2H), 5.2 (s, IH), 4.1 (t, IH), 3.8 (s, 2H), 3.7 (t, 2H), 3.59 (s, IH), 3.58 (s, IH), 3.56 (s, IH), 3.18 (s, IH), 3.08 (s, 2H), 2.0 (s, IH); m/z^M+1353.

Example 3

(S)-N-[(3-(3-Fluoro-4-(morpholin-4-y_)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide hydrochloride

Step (i) (iS -N-[(3-(3-Fiuoro-4-(morpholin-4-yl)-phenyl)-2-oxo-oxazolidin-5-yl)methyI]- 2-t-butoxycarbonylamino-4-methylthio butyramide

The title compound was prepared from (_S)-5-(aminomethyl)-3-(3-fluoro-4- (moφholin-4-yl)-phenyl)-l,3-oxazolidin-2-one (200mg, 67mmol) and N-t- butoxycarbonylamino-4-rnethylthiobutyric acid (202mg, δlmmol) by following the procedure as described in step (i) of example 1 (185mg, 51%). IR (KBr): 3431, 1750, 1707; 1HNMR (CDC1₃, 400 MHz): δ 7.4 (d, IH), 7.2 (s, IH), 7.1 (d, IH), 6.9 (s, IH), 6.9 (s, IH), 6.8 (s, IH), 5.1 (s, IH), 4.7 (d, IH), 4.0 (s, IH), 3.8 (t, 4H), 3.6 (s, 2H), 3.0 (m, 4H), 2.5 (d, 2H), 1.2 (s, 9H); m/z^M+1527.

Step (ii)

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide hydrochloride

The title compound was prepared from (5 -N-[(3-(3-fluoro-4-(moφholin-4-yl)- phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino-4-methylthio butyramide (150mg, 28mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (lOOmg, 82%).

'HNMR (D₂0, 400 MHz) : δ 7.5 (d, IH), 7.35 (d, IH), 7.29 (s, IH), 5.1 (m, IH),

4.8 (s, IH), 4.2 (t, IH), 4.0 (t, IH), 3.9 (t, 4H), 3.8 (t, IH), 3.4 (d, IH), 3.3 (t, 4H), 2.4 (m, IH), 2.0 (m, 2H), 1.9 (s, 2H), m/z^M+1427.

Example 4

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-phenyl propionamide hydrochloride

Step (i)

(iS)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- t-butoxycarbonylamino-3-phenyl propionamide

The title compound was prepared from ( )-5-(aminomethyl)-3-(3-fluoro-4-

(moφholin-4-yl)-phenyl)-l,3-oxazolidin-2-one (200mg, 67mmol) and N-t- butoxycarbonylamino-3-phenyl propionic acid (216 mg, 81mmol) by following the procedure as described in step (i) of example 1 (182mg, 50%).

IR (KBr): 3313 , 2923 , 1707 ; 1HNMR (CDC1₃ 400 MHz) : δ 7.4 (d, IH), 7.2 (m,

7H), 4.6 (m, IH), 4.25 (t, IH), 3.9 (s, IH), 3.8 (s, 5H), 3.61 (d ,1H), 3.0 (m, 6H),

1.3 (s, 9H), m/z^M+1543.

Step (ii)

(_S)-N-[(3-(3-FIuoro-4-(morpholin-4-yI)phenyI)-2-oxo-oxazoIidin-5-yl)methyl]-2- amino-3-phenyl propionamide hydrochloride

The title compound was prepared from (_S)-N-[(3-(3-fluoro-4-(moφholin-4- yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino-3-phenyl propionamide (lOOmg, 18mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (68mg, 83%). 'HNMR (D₂0, 400 MHz): δ 8.8 (d, IH), 8.2 (s, 2H), 7.49 (s, IH), 7.48 (s, 5H), 7.2 (s, IH), 7.0 (d, IH), 4.5 (m, IH), 4.0 (d, 2H), 3.7 (t, 4H), 3.5 (d, IH), 2.9 (t, 6H), 1.2 (s, IH); m/z^M+1443. Example 5

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide hydrochloride

Step (i)

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)pheny_)-2-oxo-oxazolidin-5-yl)methyl]-2- t-butoxycarbonylamino-3-(indol-3-yl)propionamide

The title compound was prepared from (_S)-5-(aminomethyl)-3-(3-fluoro-4- (moφho_in-4-yl)-phenyl)-l,3-oxazolidin-2-one (200mg, 67mmol) and N-t- butoxycarbonylamino-3-indole propionic acid (192 mg, 63mmol) by following the procedure as described in step (i) of example 1 (172mg, 43%). IR (KBr): 3321, 2926, 1747, 1665; HNMR (CDC1_3> 400 MHz): δ 7.6 (d, IH), 7.32 (m, 2H), 7.2 (t, IH), 7.1 (t, IH), 7.0 (d, 2H), 4.1 (q, IH), 3.88 (t, 4H), 3.81 (t, IH), 3.5 (m, 2H), 3.4 (m, IH), 3.0 (t, 4H), 2.9 (s, IH), 2.8 (s, 4H), 2.0 (s, IH), 1.4 (s, 9H); m/z^M+1582.

Step (ii)

(5)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide hydrochloride The title compound was prepared from (5)-N-[(3-(3-Fluoro-4-(moφholin-4- yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino-3-(indol-3- yl)propionamide (80mg, 13mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (60mg, 90%). 'HNMR (CD₃OD, 400 MHz): δ 7.7 (t, IH), 7.6 (d, IH), 7.5 (d, IH), 7.38 (d, 2H), 7.30 (d, IH), 7.0 (t, IH), 4.5 (m, IH), 4.1 (t, IH), 4.0 (t, IH), 3.8 (t, 4H), 3.6 (d, 2H), 3.1 (s, 4H), 2.8 (s, IH), 2.0 (d, IH), m/z^M+1482.

Example 6

(5 -N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide hydrochloride

Step (i) (S)-N-[(3-(3-FIuoro-4-(morphoIin-4-yI)phenyl)-2-oxo-oxazoIidin-5- yl)methyl](N-t-butoxycarbonylpyrrolidin-2-yl)formamide

The title compound was prepared from (ιS)-5-(aminomethyl)-3-(3-fluoro-4- (moφholin-4-yl)phenyl)-l,3-oxazolidin-2-one (200mg, 67mmol) and N-t- butoxycarbonyl pyrrolidine carboxylic acid (175mg, 81mmol) by following the procedure as described in step (i) of example 1 (172mg, 51%).

'HNMR (DMSO-d₆, 400 MHz): δ 8.4 (t, IH), 8.0 (s, IH), 7.9 (t, IH), 7.8 (t, IH), 7.0 (q, IH), 4.7 (q, IH), 4.1 (d, 2H), 3.7 (d, 4H), 2.9 (s, 4H), 2.8 (s, IH), 2.7 (s, IH), 1.33 (s, 9H) ; m/z^M+1493.

Step (ii)

(S)-N-[(3-(3-Fluoro-4-(morpholin-4-yι)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-y_)formamide hydrochloride The title compound was prepared from (5)-N-[(3-(3-fluoro-4-(moφholin-4- yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl](N-t-butoxycarbonylpyrrolidin-2- yl)formamide (80mg, 16mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (60mg, 95.2%). 1HNMR (CD₃OD, 400 MHz): δ 8.8 (t, IH), 7.6 (d, IH), 7.3 (d, 2H), 4.2 (t, IH), 4.1 (t, 4H), 3.9 (t, 4H), 3.8 (d, 2H), 3.6 (s, IH), 3.3 (d, IH), 3.2 (t, 4H), 2.9 (s, IH), 2.8 (s, IH), m/z^M+l393.

Example 7 (_S)-N-[(3-(3-Fluoro-4-(morpholin-4-y_)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide hydrochloride

Step (i)

(_S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- t-butoxycarbonylamino-4-methyl pentanamide

The title compound was prepared from (<S)-5-(aminomethyl)-3-(3-fhιoro-4- (moφholin-4-yl)-phenyl)-l,3-oxazolidin-2-one (200mg, 67mmol) and N-t- butoxycarbonylamino pentanoic acid (187mg, 80mmol) by following the procedure as described in step (i) of example 1 (137mg, 39%). 'HNMR (CD₃OD, 400 MHz): δ 8.8 (q, IH), 7.5 (d, IH), 7.2 (d, IH), 7.1 (t, IH), 4.9 (s, 2H), 4.1 (t, IH), 3.8 (t, 3H), 3.7 (t, 2H), 3.6 (t, IH), 3.0 (t, 4H), 2.9 (s, IH), 1.6 (t, 9H), 1.4 (s, 2H), 1.3 (s, 6H), 1.2 (s, 2H); m/z^M+1509.

Step (ii) (S)-N-[(3-(3-Fluoro-4-(morpholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide hydrochloride

The title compound was prepared from (S)-N-[(3-(3-fluoro-4-(moφholin-4- yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino-4-methyl pentanamide (70mg, 13mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (50mg, 89%).

'HNMR (CDC1₃, 400 MHz): δ 8.0 (s, IH), 7.5 (d, IH), 7.2 (s, IH), 7.0 (d, IH), 6.9

(d, IH), 4.7 (t, IH), 3.9 (s, IH), 3.8 (m, 7H), 3.5 (m, IH), 3.0 (t, 4H), 0.8 (t, 6H); m/z^M+1409.

Example 8

(5)-N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-phenyl propionamide dihydrochloride

Step (i)

(__ -N-[(3-(3-Fluoro-4-(4-N-t.butoxycarbonylpiperazin-l-yl)phenyI)-2-oxo- oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino-3-phenyl propionamide

The title compound was prepared from (S)-5-(aminomethyl)-3-(3-fluoro-4-(N-4-t- butoxycarbonylpiperazin-l-yl-phenyl)-l,3-oxazolidin-2-one (250mg, 0.634mmol) and N-t-butoxycarbonylamino-3-phenyl propionic acid (168mg, 0.634mmol) by following the procedure as described in step (i) of example 1 (240mg, 59 %). 'HNMR (CDCI₃, 400 MHz): δ 7.44 (dd, IH), 7.26 (m, 5H), 7.07 (dd, IH), 6.92 (t, IH), 6.4 (bs, IH), 4.9 (bs, IH), 4.76 (m, IH), 4.30 (d, IH), 3.94 (t, IH), 3.70 (t, IH), 3.58 (m, 6H), 3.05 (m, 6H), 1.4 (s, 9H) 1.33 (s, 9H); m/z^M+1642. Step (ii)

(S)-N-[(3-(3-FIuoro-4-(piperazin-l-yl)phenyI)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-phenyl propionamide dihydrochloride The title compound was prepared from (_S -N-[(3-(3-fluoro-4-(4-N- t.butoxycarbonylpiperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t- butoxycarbonylamino-3 -phenyl propionamide (70mg, 0.109mmol) obtained in step (i) by following the procedure as described in step (ii) of example 1 (56mg, 100%). 'HNMR (D₂0, 400 MHz): δ 7.55 (dd, IH), 7.34 (m, 6H), 7.12 (t, IH), 4.78 (m, IH), 4.10 (m, 2H), 3.72 (m, 2H), 3.50 (m, IH), 3.37 (m, 4H), 3.30 (m, 4H), 3.20 (m, IH), 3.09 (m, IH); m/z^M+1442.

Example 9

(_S)-N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-amino propionamide hydrochloride

Method 1 Step (i)

(5)-N-[(3-(3-Fluoro-4-((N-4-benzyloxycarbonyl)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino propionamide

A solution of (5)-N-(3-(3-fluoro-4-((N-4-carbobenzoxy)piperaz_n-l-yl)phenyl)-2- oxo-oxazolidin-5-yl)methylamine (580mg, 1.35mmol) and N-t- butoxycarbonylamino propionic acid (256mg, 1.35mmol) in dichloromethane (20ml) was stirred for 30 minutes at 0-5 °C and N,N'-dicyclohexylcarbodiimide was added. The reaction mixture was stirred for 4 hr at ambient temperature. Water (10ml) was added and stirred for 10 minutes. The organic layer was separated, washed with water (10ml), dried over sodium sulfate and concentrated to give the crude product, which was purified over silica gel column chromatography to yield the title compound (390mg, 40%), mp: > 250 °C.

'HNMR (CDC1₃, 400 MHz): δ 7.46 (dd, IH), 7.35 (m, 5H), 7.06 (dd, IH), 6.92 (t, IH), 6.75 (bs, IH), 5.16 (s, 2H), 4.89 (d, IH), 4.76 (m, IH), 4.2 (m, IH), 4.0 (m, IH), 3.67 (t, 6H), 3.36 (m, IH), 3.0 (m, 4H), 1.40 (s, 9H), 1.25 (d, 3H); m/z^M+1600.

Step (ii)

(5)-N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- t-butoxycarbonylamino propionamide

A mixture of (_S)-N-[(3-(3-fluoro-4-((N-4-benzyloxycarbonyl)piperazin-l- yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino propionamide (180mg. 0.3mmol) obtained in step (i) in methanol (15ml), dichloromethane (5ml) and ammonium formate (276mg, 4.38mmol) was stirred at ambient temperature for 15 minutes. 10% Pd/C (180mg) was added and stirred for 1 hr at 40 - 45 °C. The catalyst was filtered off and the filtrate was concentrated to give the title compound (139mg, 100%). 'HNMR (CDCI₃, 400 MHz): δ 7.43 (dd, IH), 7.06 (dd, IH), 6.92 (t, IH), 6.72 (bs, IH), 4.82 (bs, IH), 4.76 (m, IH), 4.21 (m, IH), 3.99 (t, IH), 3.75 (t, IH), 3.67 (t, 2H), 3.03 (m, 8H), 1.40 (s, 9H), 1.31 (d, 3H); m/z^M+1465.

Step (iii) (5 -N-[(3-(3-Fluoro-4-((N-4-benzyloxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino propionamide A solution of (5)-N-[(3-(3-fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl]-2-t-butoxycarbonylam_no propionamide (135mg. 0.29mmol) obtained in step (ii) and triethylamine (87mg, 0.87mmol) in dichloromethane (15ml) was stirred for 15 minutes at 0 °C. Benzyloxy acetyl chloride (64mg, 0.34mmol) was added and stirring was continued for 30 minutes at 0 °C and for 30 minutes at ambient temperature. Aqueous NaHCθ₃ solution (5%, 15ml) was added and stirred for 10 minutes. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under vacuum to afford the title compound (160mg, 90%). 'HNMR (CDC1₃, 400 MHz): δ 7.46 (dd, IH), 7.35 (m, 5H), 7.2 (dd, IH), 6.9 (t, IH), 6.78 (bs, IH), 5.01 (bs, IH), 4.76 (m, IH), 4.61 (s, 2H), 4.22 (s, 2H), 4.12 (m, 2H), 3.98 (t, IH), 3.78 (m, 3H), 3.64 (m, 3H), 3.01 (m, 4H), 1.4 (s, 9H), 1.32 (d, 3H); m/z^M+1614.

Step (iv) (5)-N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-amino propionamide hydrochloride

A mixture of (_S)-N-[(3-(3-fluoro-4-((N-4-benzyloxyacetyl)piperazin-l-yl)phenyl)- 2-oxo-oxazolidin-5-yl)methyl]-2-t-butoxycarbonylamino propionamide (120mg, 0.195mmol) obtained in step (iii), methanol (15ml), water (5ml), dichloromethane (5ml), ammonium formate (184mg, 2.92mmol) and 10% Pd/C (120mg) was refluxed for 7 hr. The catalyst was filtered off and filtrate was concentrated to give viscous oil. The viscous oil thus obtained was dissolved in dichloromethane and concentrated to dryness to afford the title compound (77mg, 75%). IR (KBr): 3445, 3348, 2929, 2853, 1735, 1685, 1664, 1641, 1520, 1447, 1387; 'HNMR (CDCI₃, 400 MHz), δ ppm: 7.49 (dd, IH), 7.09 (dd, IH), 6.90 (t, IH), 6.61 (bs, IH), 4.80 (bs, IH), 4.76 (m, IH), 4.21 (s, 2H), 4.10 (t, IH), 4.01 (t, IH), 3.84 (t, 2H), 3.77 (t, IH), 3.68 (m, 3H), 3.44 (t, 2H), 3.06 (bs, 4H), 1.40 (s, 9H), 1.33 (d, 3H); m/z^M+1524.

Step (v) (_S)-N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyI)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-amino propionamide hydrochloride

The title compound was prepared from (S)-N-[(3-(3-fluoro-4-((N-4- hydroxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t- butoxycarbonylamino propionamide (60mg, 0.114mmol) obtained in step (iv) by following the procedure as described in step (ii) of example 1 (48mg, 99%).

'HNMR (D₂0, 400 MHz): δ 7.57 (dd, IH), 7.24 (m, 2H), 4.83 (m, IH), 4.36 (s, 2H), 4.21 (t, IH), 4.02 (q, IH), 3.77 (m, 4H), 3.59 (6s, 2H), 3.55 (d, IH), 3.15 (m, 4H), 1.37 (s, 3H); m/z^M+1424.

Method 2 Example 10

Step (i)

(_S)-N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl] azide

HCl gas was bubbled to the stirred solution of (_S)-N-[3-((3-fluoro-4-[N-4-t- butoxycarbonyl]piperazin-l-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl azide (1.0g, 2.38mmol) in dichloromethane (25ml) for 2 hr at 0-5 °C. The excess of HCl gas was removed by N₂ bubbling. Dichloromethane was concentrated to dryness to furnish the title compound (800mg, 94.5%).

'HNMR (CD₃OD, 400 MHz): δ 7.5 (dd, IH), 7.15 (dd, IH), 7.06 (t, IH), 4.75 (m, IH), 4.04 (t, IH), 3.76 (m, IH), 3.65 (d, IH), 3.55 (dd, IH), 3.31 (t, 4H), 3.23 (m, 5H), m/z^M+1321.

Step (ii)

(_S)-N-[(3-(3-Fluoro-4-((N-4-benzyloxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazo!idin-5-yl)methyl] azide

A solution of (_S)-N-[(3-(3-fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl] azide (760mg, 2.37mmol) obtained in step (i) in dichloromethane (25ml) was stirred for 30 minutes at 0-5 °C. To this triethylamine (2ml) was added and stirring was continued for 15 minutes at 0-5 °C. Benzyloxy acetyl chloride (518mg, 2.85mmol) was added and stirred for further 30 minutes at 0-5 °C and for 1 hr and then at ambient temperature. Water (20ml) was added and stirred for 10 minutes. The organic layer was separated, washed with 5% NaHCθ₃ (25ml), dried over anhydrous sodium sulfate and concentrated to give the title compound (1.lg, 99%). 'HNMR (CDCI₃, 400 MHz): δ 7.47 (dd, IH), 7.35 (m, 5H), 7.10 (d, IH), 6.90 (t, IH), 4.75 (m, IH), 4.61 (s, 2H), 4.22 (s, 2H), 4.04 (t, IH), 3.69 (m, 7H), 3.03 (m, 4H); m/z^M+1469.

Step (iii)

(_S)-N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]amine

A solution of (5)-N-[(3-(3-fluoro-4-((N-4-benzyloxyacetyl)piperazin-l-yl)phenyl)- 2-oxo-oxazolidin-5-yl)methyl]azide (900mg, 1.92mmol) obtained in step (ii), ammonium formate (2.1g, 33.3mmol), methanol (40ml), dichloromethane(lθml) and water (10ml ) was stirred for 15 minutes at ambient temperature. 10% Pd/C (1.2g) was added and stirred for 7 hr at 60 °C. The catalyst was filtered off and concentrated. The residue thus obtained was dissolved in water (40ml), basified with aqueous ammonia solution (2ml) and extracted with dichloromethane. The organic layer was washed with water, dried (sodium sulfate) and concentrated to yield the title compound (390mg, 57.6%).

'HNMR (CDC-₃, 400 MHz): δ 7.51 (d, IH), 6.92 (t, IH), 4.76 (m, IH), 4.21 (s, 2H), 4.01 (t, IH), 3.83 (m, 3H), 3.44 (t, 2H), 3.13 (t, IH), 3.05 (m, 6H); m/z^M+1353.

Step (iv)

(_S)-N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl] 2-t-butoxycarbonylamino propionamide

A solution of (S)-N-[(3-(3-fluoro-4-((N-4-hydroxyacetyl)piperazin-l-yl)phenyl)-2- oxo-oxazolidin-5-yl)methyl]amine (200mg, 0.56mmol) obtained in step (iii) and N- t-butoxycarbonylamino propionic acid (107mg, 0.56mmol) in dichloromethane (15ml) was stirred for 30 minutes at 0-5 °C. N,N'-Dicyclohexylcarbodiimide (140mg, 0.68mmol) was added and stirred for 30 minutes at 0-5 °C and for 2 hr at ambient temperature. Water (0.5ml) was added and stirred for 15 minutes. The organic layer was separated, washed with water, dried (sodium sulfate) and concentrated to give the crude product, which was purified by column chromatography to yield the title compound (190mg, 63%).

'HNMR (CDC1₃, 400 MHz): δ 7.49 (dd, IH), 7.09 (dd, IH), 6.90 (t, IH), 6.61 (bs, IH), 4.80 (bs, IH), 4.76 (m, IH), 4.21 (s, 2H), 4.10 (t, IH), 4.01 (t, IH), 3.84 (t, 2H), 3.77 (t, IH), 3.68 (m, 3H), 3.44 (t, 2H), 3.06 (bs, 4H), 1.4 (s, 9H), 1.33 (d, 3H), m/z^M+1524. Step (v)

(5)-N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin-l-yl)phenyl)-2-oxo- oxazoIidin-5-yI)methyI]-2-amino propionamide hydrochloride

The title compound was prepared from (5)-N-[(3-(3-fluoro-4-((N-4- hydroxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2-t- butoxycarbonylamino propionamide (60mg, 0.114mmol) obtained in step (iv) by following the procedure as described in step (ii) of example 1 (48mg, 99%). 'HNMR (D₂0, 400 MHz): δ 7.57 (dd, IH), 7.24 (m, 2H), 4.83 (m, IH), 4.36 (s, 2H), 4.21 (t, IH), 4.02 (q, IH), 3.77 (m, 4H), 3.59 (6s, 2H), 3.55 (d, IH), 3.15 (m, 4H), 1.37 (s, 3H); m/z^M+1424.

Pharmacological Testing

The compounds of the invention displayed antibacterial activity when tested by the agar incoφoration method. The in vitro antibacterial activity of the compounds were demonstrated by the agar incoφoration method (NCCLS). Briefly, the compounds were dissolved in DMSO and doubling dilution of the compounds were incoφorated into Meuller Hilton agar before solidification. Inoculum was prepared by suspending 4 to 5 colonies into 5 ml of normal saline solution and adjusting the turbidity to 0.5 Macfarland turbidity standard tables ( 1.5. times.10⁸ CFU/ml), after appropriate dilutions, 10⁴ CFU/spot was transferred into the surface of dried plate and incubated for 18 hours. The concentration showing no growth of the inoculated culture was recorded as the MIC. Appropriate ATCC standard strains were simultaneously tested and result recorded.

The following minimum inhibitory concentrations (μg/ml) were obtained for representative compounds of the invention which are given in the following table : Antimicrobial Screening (MIC) (μg/ml)

1) S.aureus ATCC 29213—Staphylococus aureus ATCC 29213

2) S.aureus ATCC 43300-Staphylococus aureus ATCC 43300

3) Ent. faecalis ATCC 29212-Enterococcus faecalis ATCC 29212

The in vitro antibacterial activity of the compounds were demonstrated by the agar incoφoration method (NCCLS). Briefly, the compounds were dissolved in DMSO and doubling dilution of the compounds were incoφorated into Meuller Hilton agar before solidification. Inoculum was prepared by suspending 4 to 5 colonies into 5 ml of normal saline solution and adjusting the turbidity to 0.5 Macfarland turbidity standard tables (1.5. times.10 CFU/ml), after appropriate dilutions, 10⁴ CFU/spot was transferred into the surface of dried plate and incubated for 18 hours. The concentration showing no growth of the inoculated culture was recorded as the MIC. Appropriate ATCC standard strains were simultaneously tested and result recorded.

Claims

Claims :

1. A compound of the formula (I)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein Y is O or S; X is O, S,

NR⁷, SO, S0₂, wherein R⁷ represents hydrogen or -(C=0)_m-(CH₂)_rZ where m is an integer 0 or 1, 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (C C₆)alkyl, aryl, heteroaryl, ( -

C₈)alkoxy, aryloxy, aralkoxy, acyl, (Cι-C₈)alkylthio, (Cι-C₈)alkylsulfonyl, arylsulfonyl, sulfamyl, (C|-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, (Cι-C₆)monoalkylamino, or (Cι-C₈)dialkylamino; R¹ represents hydrogen, ( - C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R represents aminoacid residue which is attached through acid moiety; R and R may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C,-C₆)alkyl, (C_rC₆)alkoxy, (C,-C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

2. The compound as calimed in claim 1, wherein aminoacid residue is selected from glycine, alanine, lysine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, histidine, iso-leucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine.

3. A compound of formula (I) as claimed in claim 1, which is selected from : (xS) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ; (xS) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ; (S) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ;

(xS) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide dihydrochloride or its salts ; (S) N-[(3-(3-Fluoro-4-((N-4-hydroxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo- oxazolidin-5-yl)methyl]-2-amino propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ;

(xS) N- [(3 -(3 -Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin- 5-yl)methyl] -2- amino-3 -phenyl propionamide or its salts ; (S) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide or its salts ; (S) N- [(3 -(3 -Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin- 5 - yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ; (S) N- [(3 -(3 -Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino propionamide or its salts ;

5-yl)methyl]-2-amino acetamide or its salts ;

(S) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin- 5-yl)methyl]-2-amino-4-methylthio butyramide or its salts ;

(S) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino-3-phenyl propionamide or its salts ;

5-yl)methyl]-2-amino-3-(indol-3-yl)propionamide or its salts ; (S) N- [(3 -(3 -Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(iS) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin-l-yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino-4-methyl pentanamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ; (R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide or its salts ; (R) N- [(3 -(3 -Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin- 5 -yl)methyl] -2- amino-3-(indol-3-yl)propionamide or its salts ;

(R) N- [(3 -(3 -Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin- 5 - yl)methyl](pyrrolidin-2-yl)formamide or its salts ; (R) N-[(3-(3-Fluoro-4-(moφholin-4-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methyl pentanamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3 -phenyl propionamide dihydrochloride or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)ρhenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino acetamide or its salts ; (R) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-4-methylthio butyramide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin-l-yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino- 3 -phenyl propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5-yl)methyl]-2- amino-3-(indol-3-yl)propionamide or its salts ;

(R) N-[(3-(3-Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-5- yl)methyl](pyrrolidin-2-yl)formamide or its salts ;

(R) N- [(3 -(3 -Fluoro-4-(piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin- 5-yl)methyl] -2- amino-4-methyl pentanamide or its salts ; (R) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino propionamide or its salts ; (R) N-[(3-(3-Fluoro-4-(4-(methoxyacetyl)piperazin- 1 -yl)phenyl)-2-oxo-oxazolidin-

5-yl)methyl]-2-amino acetamide or its salts ;

5-yl)methyl]-2-amino-4-methylthio butyramide or its salts ;

5-yl)methyl]-2-amino-3-phenyl propionamide or its salts ;

5-yl)methyl]-2-amino-3-(indol-3-yl)propionamide or its salts ;

5-yl)methyl](pyrrolidin-2-yl)formamide or its salts and

5-yl)methyl]-2-amino-4-methyl pentanamide or its salts.

4. The compound as claimed in claim 3, wherein the salt is selected from hydrochloride or hydrobromide.

5. A process for the preparation of compound of the formula (I)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein Y is O or S; X is O, S, NR , SO, S0₂, wherein R represents hydrogen or -~(C=0)_m-(CH₂)rZ where m is an integer 0 or 1, 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (C C₆)alkyl, aryl, heteroaryl, (C C₈)alkoxy, aryloxy, aralkoxy, acyl, (Cι-C₈)alkylthio, (Cι-C₈)alkylsulfonyl, arylsulfonyl, sulfamyl, (C]-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,

(Cι-C₆)monoalkylamino, or (Cι-C₈)dialkylamino; R¹ represents hydrogen, (C

C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R² represents aminoacid residue which is attached through acid moiety; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl,

(C,-C₆)alkyl, (C,-C₆)alkoxy, (C,-C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2, which comprises reacting a compound of the formula (la)

wherein R¹ represent hydrogen and all other symbols are as defined above, with protected amino acid and deprotecting to yield the compound of formula (I).

6. A process for the preparation of compound of the formula (I)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein Y is O or S; X is NR⁷, wherein R⁷ represents -(C=0)_m-(CH₂)ι-Z where m is an integer 0 or 1, 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (Cι-C₆)alkyl, aryl, heteroaryl, (C]-C₈)alkoxy, aryloxy, aralkoxy, acyl, (Cι-Cg)alkylthio, (Cι-Cg)alkylsulfonyl, arylsulfonyl, sulfamyl, (C]-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, (Q- C )monoalkylamino, or (Cι-C₈)dialkylamino; R¹ represents hydrogen, (Cι-C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R represents aminoacid residue which is attached through acid moiety; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C C₆)alkyl, (C_rC₆)alkoxy, (C_rC₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2, which comprises i) reacting the compound of the formula (Ia-1)

wherein R¹ represent hydrogen, P is protecting group and all other symbols are as defined above with protected amino acid to yield compound of formula (lb)

wherein R ' is protected amino acid residue and all other symbols are as defined above, ii) deprotecting the compound of formula (lb) to produce compound of formula

(Ic)

wherein all symbols are as defined above, iii) reacting the compound of formula (Ic) with R '-H, wherein R ' is protected

R⁷ to produce compound of formula (Id)

wherein all symbols are as defined above and iv) deprotecting the compound of formula (Id) to produce compound of formula (I) as defined above.

7. A process for the preparation of compound of the formula (I)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein Y is O or S; X is NR , wherein R⁷ represents -(C=0)_m-(CH₂)ι-Z where m is an integer 0 or 1, 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (Cj-C₆)alkyl, aryl, heteroaryl, (C C₈)alkoxy, aryloxy, aralkoxy, acyl, (Cj-C₈)alkylthio, (Cι-C₈)alkylsulfonyl, arylsulfonyl, sulfamyl, (C]-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, ( - C₆)monoalkylamino, or (Cι-C₈)dialkylamino; R¹ represents hydrogen, (Cι-C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R represents aminoacid residue which is attached through acid moiety; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C C₆)alkyl, (C_rC₆)alkoxy, (C_rC₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2, which comprises i) deprotecting the compound of the formula (Ie)

wherein P is a protecting group and all other symbols are as defined above to yield compound of formula (If)

wherein all symbols are as defined above, ii) reacting the compound of formula (If) with R^7,-H, wherein R⁷' is protected

R⁷ to produce compound of formula (Ig)

wherein all symbols are as defined above, iii) reducing the compound of formula (Ig) to produce compound of formula (Ih)

wherein all symbols are as defined above, iv) reacting the compound of formula (Ih) with protected amino acid to produce compound of formula (Ii)

wherein all symbols are as defined above and v) deprotecting the compound of formula (Id) to produce compound of formula

(I) as defined above.

8. A process for the preparation of compound of the formula (I)

wherein X represents SO and all other symbols are as defined in claim 1, comprising oxidizing the compound of formula (1) where X represents S using sodium metaperiodate in a mixture of water and methanol.

9. A process for the preparation of compound of the formula (I)

wherein represents SO₂ and all other symbols are as defined in claim 1 , comprising oxidizing the compound of formula (1) where X represents S or SO using oxone or

4-methyl, moφholine-N-oxide and catalytic amount of osmium tetroxide in aqueous acetone.

10. A pharmaceutical composition, which comprises a compound of formula (I)

as defined in claim 1 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

11. A pharmaceutical composition as claimed in claim 10, in the form of a tablet, capsule, powder, syrup, solution, aerosol or suspension.

12. Use of a compound of formula (I) as claimed in claim 1, for treating or preventing an infectious disorder in a human or animal.

13. Use of a compound as claimed in claim 12, wherein the infectious disorder is caused by bacteria.

14. Use of a compound as claimed in claim 3, for treating or preventing an infectious disorder in a human or animal.

15. Use of a compound as claimed in claim 14, wherein the infectious disorder is caused by bacteria.

16. Use of a composition as claimed in claim 10, for treating or preventing an infectious disorder in a human or animal.

17. A method as claimed in claim 16, wherein the infectious disorder is caused by bacteria.

18. A compound of formula (lb)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein in which P is a

7 1 protecting group; R ' is protected amino acid residue; Y is O or S; R represents hydrogen, (Cι-C₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, ( -C^alkyl, (Cι-C₆)alkoxy, (C C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

19. A compound of formula (Ic)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymoφhs, their pharmaceutically acceptable salts, wherein in which R ' is protected amino acid residue; Y is O or S; R¹ represents hydrogen, (C_rC₆)alkyl, aryl or (C₃-C₆)cycloalkyl; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C_\- C₆)alkyl, (C_rC₆)alkoxy, (C_rC₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.

20. A compound of formula (Id)

their derivatives, their analogs, their tautomeric forms, their stereoisomers, their

• • 7 polymoφhs, their pharmaceutically acceptable salts, wherein in which R ' is protected R⁷, wherein R⁷ represents hydrogen or -(C=0)_m-(CH₂)ι-Z where m is an integer 0 or 1, 1 is an integer 0 to 3, Z represents hydrogen, hydroxyl, halogen, substituted or unsubstituted groups selected from (Cι-C₆)alkyl, aryl, heteroaryl, (C C₈)alkoxy, aryloxy, aralkoxy, acyl, (Cι-C₈)alkylthio, (C C₈)alkylsulfonyl, arylsulfonyl, sulfamyl, (Cj-C₈)alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, (Cι-C₆)monoalkylamino, or (Cι-Cg)dialkylamino; R²' is protected amino acid residue; Y is O or S; R¹ represents hydrogen, (Cι-C₆)alkyl, aryl or (C₃- C₆)cycloalkyl; R³ and R⁴ may be same or different and independently represent hydrogen or halogen; R⁵ and R⁶ may be same or different and independently represent hydrogen, cyano, nitro, amino, oxo, thioxo, hydroxyl, (C C₆)alkyl, ( C₆)alkoxy, (C C₆)alkylthio, (C₃-C₆)cycloalkyl and n is 0, 1 or 2.