Title of Invention	OXAZOLIDINONE DERIVATIVES
Abstract	The present invention relates to novel compounds of the general formula (I), their stereoisomers, their derivatives, their pharmaceutically acceptable, salts and compositions. The present invention more particularly provides novel Oxazolidinone derivatives of the general formula (I).

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Field of the Invention The present invention relates to novel compounds of the general formula (I), their stereoisomers, their derivatives, and their pharmaceutically acceptable, salts and compositions. The present invention more particularly provides novel Oxazolidinone derivatives of the general formula (I). The present invention also provides a process for the preparation of the above said novel Oxazolidinone derivatives of the formula (I), their stereoisomers, their derivatives, their pharmaceutically acceptable, salts and compositions. The novel Oxazolidinone derivatives of the present invention are expected to be more soluble and can be easily formulated in a appropriate vehicle for the purpose of intravenous delivery. Also the present invention provides methods and exemplary compounds with enhanced solubility, which might be useful for the design of better compounds with improved therapeutic index towards second-generation Oxazolidinone antibacterials. The novel Oxazolidinone derivatives of the present invention may be useful as antibacterial agents, particularly for intravenous injections, and are also useful in the treatment of conditions such as nosocomial pneumoniae, community acquired pneumoniae, Vancomycin resistant enterococci (VRE) caused by Methicillin resistant 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, and Methicillin resistant organisms. Background of Invention The Oxazolidinone class of compounds represents totally synthetic antibacterials endowed with a mechanism different from the mode of action of known antibacterial compounds. The Oxazolidinones interact with 50S ribosomal subunit to form an initiation complex and thus prevent the bacterial translation necessary for the replication of the bacteria. These compounds had shown antibacterial activity against gram +ve organisms and a host of opportunistic pathogens such as Methicillin resistant Staphylococcus Aureus (MRSA), penicillin resistant Streptococcus Pneumoniae (PRSP), and Vancomycin resistant Enterococci (VRE), The best-represented compounds are Linezolid and Eperezolid, Linezolid being approved by the US FDA for treatment of severe bacterial infections. A lot of work had been done however; there is still a need for research to extend the activity of Oxazolidinones to act against gram -ve pathogens. Some literature and patents are available where efforts have been made to modify the Oxazolidinone moiety to impart the gram -ve activity. In the literature there are many inventions in this class of compounds but there are problems regarding bioavailability, metabolic stability and in particular solubility. It is also mentioned in the literature that the Oxazolidinone antibacterials developed had severe problems of rapid metabolism or have poor permeability. The present compounds represented by this patent have largely alleviated solubility and represent a novel class of Oxazolidinone compounds with very good water solubility. Several Oxazolidinone derivatives have been reported in the literature. Few prior art reference which disclose the closest Oxazolidinone derivatives are given here: 1. US 5,547,950 discloses and claims compounds of formula (I), 1 2 wherein, Z and Z may be same or different and represent O or S; Suitable groups represented by R1 may be selected from halogen atom such as fluorine, chlorine, bromine or iodine; azido, nitro, cyano, XR6, N7aR7b), -NHC(=Y)R8; -NHS(O)p(CrC4)alkyl, -NHS(O)p(CrC4)aryl or -NHS(O)p(CrC4)heteroaryl; R6 represents hydrogen, formyl, (CpC6)alkyl, cycloalkyl, aryl, etc; R7a and R7b represent hydrogen, formyl, (C1-C6)alkyl, aryl, aralkyl, etc; R8 is hydrogen, (C1 C6)alkyl, (C1-C6)alkoxy, aryl, (C3-C6)cycloalkyl, amino, etc; R2 and R3 represent hydrogen, halogen, hydroxy, alkyl, alkoxy; R4 and R5 represent hydrogen, cyano, nitro, amino, halogen, hydroxyl, substituted or unsubstituted groups selected from (C1-C6)alkyl, haloalkyl, (C1-C6)alkoxy, (C1-C6)alkylthio, etc; n is 0, 1 or 2; A represents a NHR9, cycloalkyl, aryl, five to seven membered heteroaryl, heterocyclyl etc. 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 novel Oxazolidinone derivatives of the formula (I) wherein functionalities such as oxoimino, hydroxy, amido, fluoro, oxo and more particularly the oxoimino could be introduced either individually or in combination with aromatic and heterocyclic moieties containing one or more nitrogen atoms, sulphur and oxygen either singly or in combination, through reaction schemes as described herein. These novel Oxazolidinone derivatives may be useful as antibacterial agents and hence are useful in the treatment of conditions such as nosocomial pneumoniae, community acquired pneumoniae, Vancomycin resistant enterococci (VRE) caused by Methicillin resistant Staphylococcus aureus (MRSA) and penicillin resistant Streptococcus pneumoniae. The compounds of the present invention are effectiv* against a number of human or animal pathogens, clinical isolates, including Vancomycin, and Methicillin resistant organisms. Summary of the invention The present invention relates to novel Oxazolidinone derivatives of the formula (I), their stereoisomers, their derivatives, and their pharmaceutically acceptable, salts and compositions, wherein X represents O or S; R1 is selected from hydrogen, alkyl, haloalkyl, O-alkyl, S- alkyl, NH2, NH-alkyl or N(alkyl)2, O-het, S-het or -NH-het; R2 and R3 may be same or different and independently represent hydrogen, halogen, hydroxy, haloakyl, alkyl or alkoxy; R4 and R5 may be same or different and independently represent hydrogen, cyano, nitro, amino, halogen, hydroxy, haloalkyl, alkylthio, alkyl or alkoxy; Z represents S, O and NR6; R6 represents hydrogen, hydroxy, alkyl or alkoxy; R represents a five to seven membered heterocyclic ring, aryl, alkyl, aryalkyl, arylalkylamino, arylalkylthio, and is further substituted by a group selected from halogen, cyano, nitro, alkoxy, acyl, phenyl, aralkyl, heteroaryl, heterocyclyl, amino groups or substituted or unsubstituted groups selected from alkyl, alkoxy, acyl, aralkyl, cycloalkyl groups, -OCH2R7; R7 represents hydrogen, halogen, hydroxy, alkyl, cycloalkyl, aryl, aralkyl, amino, arylakylamino, heteroaryl, heterocyclyl. n is an integer of 0-1, with the condition that when n is 1 then Z is not S, and when n is 0 then Z is S, X represents O, R represents -OCH2R7 and R1represents substituted or unsubstituted haloalkyl. Detailed Description of the Invention Suitable groups represented by X may be selected from O or S; Suitable groups represented by R] may be selected from hydrogen, (C1-C4) alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl and the like; haloalkyl such as dichloromethyl, difluoromethyl, chloro, trifluormethyl and the like; methyl, O-alkyl, S- alkyl, NH2, NHalkyl or N(alkyl)2, O-het, S-het or -NH-het, het is a C-linked five or six membered saturated or unsaturated heterocyclic ring having 1, 2 or 3 hetero atoms selected from the group consisting of oxygen , sulfur and nitrogen , which is optionally fused to a benzene ring such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isooxazolyl, oxadiazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzopyranyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyrrolyl, benzoxadiazolyl, benzothiadiazolyl, benzodioxolyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl and the like, which may be substituted; Suitable groups represented by R2 and R3 are selected from hydrogen, halogen atom such as fluorine, chlorine, bromine or iodine; hydroxy, (C1-C6)alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl and the like; (C1-C6)alkoxy groups, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like; haloalkyl groups such as chloromethyl, chloroethyl, trifluoromethyl, trifluoroethyl, dichloromethyl, dichloroethyl and the like. Suitable groups represented by R4 and R5 are selected from hydrogen, cyano, nitro, amino, hydroxy; halogen atom such as fluorine, chlorine, bromine or iodine; (C1-C4) alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, and the like; haloalkyl groups such as chloromethyl, chloroethyl, trifluoromethyl, trifluoroethyl, dichloromethyl, dichloroethyl and the like; (C1-C4)alkoxy group, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like; (C1-C6)alkylthio groups such as methylthio, ethylthio, n-propylthio, iso-propylthio and the like. Suitable groups represented by R6 are selected from hydrogen, hydroxy; (C1-C4) alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, and the like, (C1-C4) alkoxy group, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like. Suitable groups represented by R7 are selected from hydrogen, halogen, hydroxy, substituted or unsubstituted linear or branched (C1-C4) alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, and the like; (C4-C8) cycloalkyl groups such as cyclobutyl, cyclopentyl, cyclohexyl and the like; aryl groups such as phenyl, naphthyl and the like, which may be substituted; aralkyl groups such as phenylmethyl, phenylethyl, naphthylmethyl, naphthylethyl and the like, the aralkyl group may be substituted; amino group, which may be substituted; arylalkylamino groups such as benzylamino and the like, the arylalkylamino group may be substituted; heteroaryl groups such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isooxazolyl, oxadiazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzopyranyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyrrolyl, benzoxadiazolyl, benzothiadiazolyl, benzodioxolyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl and the like, which may be substituted; heterocyclyl group such as pyrrolidinyl, thiazolidinyl, oxazolidinyl, morpholinyl, thiomorpholinyl, piperidinyl, piperazinyl, and the like, which may be substituted. Suitable groups represented by R is selected from hydrogen, halogen, cyano, nitro, amino, halogen, hydroxy substituted or unsubstituted linear or branched (C1-C4) alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, and the like; acyl groups such as -C(=O)CH3, -C(=O)C2H5) benzoyl and the like, which may be substituted; alkylcarboxy; alkylcarboxyalkyl; (C1-C1o)alkoxy groups, such as methoxy, ethoxy, n-propoxy, isopropoxy, butoxy and the like, which may be substituted; aryl groups such as phenyl, naphthyl and the like, which may be substituted; aralkyl groups such as phenylmethyl, phenylethyl, naphthylmethyl, naphthylethyl and the like, the aralkyl group may be substituted; amino group, which may be substituted; arylalkylamino groups such as benzylamino and the like, the arylalkylamino group may be substituted ; heteroaryl groups such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isooxazolyl, oxadiazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzopyranyl, indolyl, indolinyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzopyrrolyl, benzoxadiazolyl, benzothiadiazolyl, benzodioxolyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl and the like, which may be substituted; heterocyclyl groups such as pyrrolidinyl, thiazolidinyl, oxazolidinyl, morpholinyl, thiomorpholinyl, piperidinyl, piperazinyl, and the like, which may be substituted. Suitable groups represented by Z are selected from O, S and NR6; n is an integer of 0-1, with the condition that when n is 1 then Z is not S, and when n is 0 then Z is S, X represents O, R represents -OCH2R7 and R1 represents substituted or unsubstituted haloalkyl. L represents a suitable leaving group selected from fluoro, chloro, bromo, and similar leaving groups. The substituents on any of the groups represented by R, R1, R2, R3, R4, R5, R6 and R7 are selected from halogen, hydroxy, formyl, nitro, cyano, azido, amino, alkyl, aryl, alkylamino, alkylaminocarbonyl, haloalkyl, acylamino, alkoxy, acyl and these substituents are as defined above. The compounds of this invention may be useful in their natural form or as their salts. The salt when required for infusion may be formulated in its stable non-toxic and non-allergic acceptable form. Typically the acceptable salts are those formed with acids which form under physiological conditions as anion or conjugate base, for example tosylate, mesylate, acetate, tartarate, succinate, malonate, base of phosphate, citrate and lactate. Also suitable inorganic salts such as hydrochloride, hydroiodide, methyl iodide, sulfate, nitrate, carbonate, bicarbonate and bisulphate. The pharmacologically acceptable salts of the present invention include alkali metals like Li, Na, and K, alkaline earth metals like Ca and Mg, salts of organic bases such as diethanolamine, a-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; 3- {4-[4-(l -Methylethanon-2yl)piperazinyl]3-fluorophenyl} -2-oxo-1,3-oxazolidin-5-methyl acetamide; 3 - {4- [4-( 1 -(1 -Methyl)ethanoneoxime-2-yl)piperazinyl]3 -fluorophenyl} -2-oxo-1,3-oxazolidin-5-methyl acetamide; 3-{4-[4-(l-(4-Fluorophenyl)ethanon-2-yl)piperazinyl]3-fluorophenyl}-2-oxo-l,3-oxazolidin-5-methyl acetamide; 3-{4-[4-(l-(4-Fluorophenyl)ethanoneoxime-2-yl)piperazinyl]3-fluorophenyl}-2-oxo-1,3-oxazolidin-5-methyl acetamide; 3-{4-[4-(l-(3-Methoxyphenacyl)ethanon-2-yl)piperazinyl]3-fluorophenyl}-2-oxo- 1,3-oxazolidin-5-methyl acetamide; 3-{4-[4-(l-(3-Methoxyphenyl)ethanoneoxime-2-yl)piperazinyl]3-fluorophenyl}-2- oxo-1,3-oxazolidin-5-methyl acetamide; 3-{4-[4-(l-(4«Methylphenyl)ethanon-2-yl)piperazinyl]3-fluorophenyl}-2-oxo-l,3- oxazolidin-5-methyl acetamide; 3- {4-[4-( 1 -(4-Methylphenyl)-ethanoneoxime-2-yl)piperazinyl]3-fluorophenyl} -2- oxo-1,3-oxazolidin-5-methyl acetamide; 3- {4-[4-(4-Methoxyphenacyl)piperazinyl]3-fluorophenyl} -2-oxo-l ,3-oxazolidin-5- methyl acetamide; 3- {4-[4-( 1 -(4-Methoxyphenyl)ethanoneoxime-2-yl)piperazinyl]3-fluorophenyl} -2- oxo-153-oxazolidin-5-methyl acetamide; 3- {4-[4-( 1 -(4-Methoxyphenacyl))piperazinyl]3-fluorophenyl} -2-oxo-1,3- oxazolidin-5-methylthio acetamide; O-Methyl4-[4-(5- {[(dichloroacetyl)amino]methyl} -2-oxo-1,3-oxazolidin-3-yl)-2- fluorophenyljpiperazine-1 -carbothioate and O-Methyl4-[4-(5-{[(difluoroacetyl)amino]methyl}-2-oxo-l,3-oxazolidin-3-yl)-2- fluorophenyl]piperazine-1 -carbothioate. The compounds of general formula (I) may be prepared by one or more schemes or combinations of reactions given below and are outlined in detail. The method comprises: i) Scheme I: a) Deprotecting the compound of formula (la), wherein P is the protecting group and all the other groups are as defined earlier, to produce the compound of formula (1b). The compound of formula (la) is prepared according to the procedure described in our WO 2004/018439. iii) Scheme III: Optionally converting the compound of formula (3c) wherein Z represents S, R represents imidazolyl and n represents 0 to the compound of formula (3d) wherein R represents -OCH2R7, R1 represents substituted or unsubstituted haloalkyl and all the other symbols are as defined earlier. The reactions described in the process outlined above may be performed by using the methods described herein: Scheme I: Compounds of the general formula (I) may be obtained from the compound of general formula (la) by deprotecting the compound of formula (la) where P is the protecting group and all other groups are as defined earlier to produce the compound of formula (lb) with suitable reagents such as TFA and the like in the presence of solvents such as DCM and the like. Reacting the compound of formula (lb) with the compound of the formula (2a) (wherein L is a leaving group and all other symbols are as defined earlier) is carried out in the presence of an organic base such as triethylamine, pyridine, dimethylamine and the like or in the presence of an inorganic base such as potassium carbonate, sodium carbonate and the like and in solvents selected from toluene, trifluoroacetic acid, DMF, tetrahydrofuran, chloroform, dichloromethane, dichloroethane, ethyl acetate, or a mixture thereof. The reaction may be carried out at a temperature in the range of 0 °C to 50 °C. The duration of the reaction may range from 4 to 24 hours, to produce the compound of the general formula (3 a). Optionally the compound of formula (3a) is converted to the respective oxime and to obtain the compound of formula (3b) by treatment with hydroxylamine hydrochloride in the presence of a base such as sodium acetate and the like and in the presence of solvents such as mefhanol, ethanol and the like or the mixture thereof. The reaction may be carried out at a temperature in the range of 10 °C to 100 °C. The reaction time ranges from 1 to 12 hours. Scheme II: Compounds of general formula (I) may be obtained by converting the compound of formula (la) to the thioamides by using Lawesson's reagent in the presence of a base such as triethylamine, pyridine and the like and solvents such as toluene, benzene, tetrahydrofuran, chloroform, dichloromethane, dichloroethane, ethyl acetate, o-dichlorobenzene or a mixture thereof. The reaction may be carried out at a temperature in the range of 80 ° to 120 °C. The duration of the reaction may range from 4 to 8 hours to produce the compound of formula (lc). The reaction of the compound of formula (lc) with suitable reagents such as TFA and the like in the presence of solvents such as DCM and the like leads to the compound of formula (Id). The reaction of the compound of formula (Id) with the compound of the formula (2a) (wherein L is a leaving group and all the other symbols are as defined earlier) is carried out in the presence of an organic base such as triethylamine, pyridine, dimethylamine and the like or in the presence of an inorganic base such as potassium carbonate, sodium carbonate and the like and in solvents selected from toluene, trifluoroacetic acid, DMF, tetrahydrofuran, chloroform, dichloromethane, dichloroethane, ethyl acetate, or a mixture thereof. The reaction may be carried out at a temperature in the range of 0 °C to 50 °C. The duration of the reaction may range from 4 to 24 hours to produce the compound of the general formula (3 a). Optionally the compound of formula (3 a) is converted to the oxime to obtain the compound of formula (3b) by treatment with hydroxylamine hydrochloride in the presence of a base such as sodium acetate and the like in the presence of solvents such as methanol, ethanol and the like or the mixture thereof The reaction may be carried out at a temperature in the range of 10 to 100 °C. The reaction time ranges from 1 to 12 hours. Scheme III: Compounds of the general formula (3d) may be obtained by converting the compound of formula (3c) to the carbothioate ester by treatment with R7CH2OH in the presence of base such as sodium acetate, potassium carbonate, cesium carbonate and the like, and in the presence or absence of a suitable solvent such as dimethylformamide, dichloromethane, toluene, acetonitrile, dioxane, methyl ethyl ketone and the like or the mixture thereof. The reaction may be carried out at a temperature in the range of 10 to 100 °C. The reaction time ranges from 1 to 36 hours. The protecting groups P used in the invention are conventional protecting groups such as t-butoxy carbonyl (t-Boc), trityl, trifluoroacetyl, benzyloxy, benzyloxy carbonyl (Cbz) and the like. It is appreciated that in any of the above-mentioned reactions, any reactive group in the substrate molecule may be protected according to the 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 pharmaceutical composition may be in the forms normally employed, such as tablets, capsules, powders, syrups, solutions, aerosols, 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 the active compound, the remainder of the composition being the pharmaceutically acceptable carriers, diluents or solvents. The present invention is provided by the examples shown below, which are provided by way of illustration only and should not be considered to limit the scope of the invention. Example 1 Synthesis of 3-{4-[4-(l-(4-methoxyphenyl)ethanoneoxime-2-yl)piperazinyl]3-fluorophenyl}-2-oxo-l,3-oxazolidin-5-methylacetamide. Step-I Preparation of 3-{4-[4-(4-methoxy phenacyl)piperazinyl]3-fluorophenyl}-2- oxo-l,3-oxazoIidin-5-methylacetamide. To a cold solution of 0.77g (2.29 m.mol) 3-{4-[l-piperazinyl]-3-fluorophenyl}-2-oxo-l,3-oxazolidin-5-methylacetamide in 30ml of DMF, was added 0.66g (2.88 m.mol) of 4-methoxyphenacyl bromide, 0.93g (6.9 m.mol) of potassium carbonate and the resulting mixture was stirred for 5 hours at ambient temperature. The reaction mixture was extracted with ethyl acetate and water, the organic phase was separated, dried over Na2SO4 and evaporated under reduced pressure to afford the crude product, which was purified by column chromatography using silicagel 60-120 mesh to afford the pure product (250mg). H'-NMR (DMSO-ck) 8: 1.82(s, 3H), 2.6 (t, 4H), 2.98 (t, 4H), 3.38 (t, 2H), 3.67(t, 1H), 3.82 (s, 2H), 3.84 (s, 3H), 4.05(t, 1H), 4.67 (m, 1H), and 7.03 - 7.99 (m, 7H). MS m/z: 485 (M++l). (DMSO-d6) 8: 1.41 (s, 9H), 2.43 (t, 3H), 2.9 (t, 4H)3 3.62 (t, 4H), 3.46 (t, 4H), 3.76 (t, 1H), 3.87 (m, 2H), 4.1(t, 1H), 4.93 (m, 1H), and 7.06 -7.71(m, 3H). MS m/z: 453 (M++l). Step II Synthesis of 3-{4-[4-(l-(4-methoxyphenacyl))piperazinyl]3-fluorophenyl}-2- oxo-l,3-oxazolidin-5-methylthioacetamide. To solution of 3-{4-[4(tert-butoxycarbonyl)piperazinyl]-3-fluorophenyl}-2-oxooxazolidin-5-methylthioacetamide (3.0432g 6.73 m.mol, obtained according to the procedure described in step-I) in dichloromethane (50 ml) was added 8 % trifluoroacetic acid at 4 °C under stirring and continued the stirring for 4 hours. After which triethylamine (12 ml, 86 m.mol) was added and stirring was continued for another 10 minutes and then it was evaporated under vacuum to afford the crude product, which was dissolved in DMF and cooled (0-4 °C). To the resulting solution was added potassium carbonate (2.72 g, 20 m.mol) and 4-methoxyphenacyl bromide (1.96 g, 8.56 mmol) under stirring. The stirring was continued for 8 hours at ambient temperature, after which the reaction mixture was extracted with ethyl acetate and water, the organic phase was separated and evaporated under reduced pressure to afford the crude product. The crude product thus obtained was purified by column chromatography using silica gel 60-120A° mesh to afford the pure product (2.77g). H^NMR (DMSO-c^) 5: 2.4 (s, 3H), 2.6 (t, 4H), 2.98 (t, 4H), 3.38 (t, 2H), 3.67 (t, 1H), 3.82 (s, 2H), 3.84 (s, 3H), 4.05 (t, 1H), 4.67 (m, 1H), and 7.03 - 7.99 (m, 7H). MS m/z: 502 (M++l). Step HI Synthesis of 3-{4-[4-(l-(4-methoxyphenyl)ethanoneoxime-2-yI)piperazinyl]3-fluorophenyl}-2-oxo-l,3-oxazolidin-5-methylthio acetamide. the procedure described in our PCT IB03/03459 ) in dimethylformamide (70ml), was first added potassium carbonate (1.24g, 9 mmol) and then dichloroacetyl chloride (2.2g, 14.8 mmol) under stirring at 0°C. After stirring for 1 hour at 0°C the reaction mass was further stirred at 37°C for 24 hours. On completion of the reaction, as confirmed by TLC using ethyl acetate as the solvent system, the reaction mixture was poured on to ice-water mixture. The resulted solid was extracted with ethyl acetate (250 ml) and finally the organic layer was washed with water (100ml). The resultant organic layer was collected and dried over anhydrous sodium sulphate, then distilled under vacuum to yield the crude product (1.8g, 66% yield), which was used in the step-II without further purification. Step II: Synthesis of2,2-Dichloro-A^{[3-(3-fluoro-4-piperazin-l-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl} acetamide To the solution of tert butyl 4-[4-(5-{[(dichloroacetyl)amino]methyl}-2-oxo-l,3-oxazolidin-3-yl)-2-fluorophenyl]piperazine-l-carboxylate (1.8g, 3 mmol, obtained in the step-I) in dichloromethane (35 ml) was added thioanisole (2.2g, 17.5 mmol), trifluoroacetic acid (3.4g, 30 mmol) at 0°C under stirring. After 1 hour of stirring at this condition the reaction mixture was allowed to further stir at 37°C. On completion of the reaction, as confirmed by TLC using ethylacetate:hexane (8:2) as solvent system, the reaction mixture was neutralized by using triethylamine at 0°C. The reaction mixture was concentrated to dryness under vacuum to yield the crude product (0.8gm, 57%). Step III: Synthesis of A'-[(3-{4-[4-(lJflr-Imidazol-l-yIcarbonothioyl)piperazin-l-yl]-3-fluorophenyl}-2-oxo-l,3-oxazolidin-5-yl)methyl]-2,2-dichloroacetamide. To a solution of 2,2-dichloro-N-{[3-(3-fluorO"4-piperazin-l-ylphenyl)-2-oxo-l,3-oxazolidin-5-yl]methyl}acetamide (0.8g, 1.9 mmol, obtained in the step-II) in dimethylformamide (25ml) was added triethylamine (0.57g, 5.9 mmol), 1,1-thiocarbonyldiimidazole (l.Og, 5.7 mmol) under stirring at 0°C. After lhour of stirring, the reaction mixture was allowed to stir for another 24 hours at 37°C. On completion of the reaction, the reaction mixture was poured on to ice-water mixture. The solid obtained was extracted with ethyl acetate (100ml) and the organic layer was washed with cold water (50 ml), and dried over anhydrous sodium sulphate. The solvent was distilled off under vacuum to yield the crude product, which was purified by column chromatography using silica gel and ethyl acetate:hexane mixture as eluent, to yield the title compound (0.2g, 19.8 % yield). 'H-NMR (DMSO-C^) 5: 3.19 (s, 4H), 3.73 - 3.54 (m, 3H), 4.05 - 4.1 (m, 5H), 4.83 (s, 1H)5 5.94 (s, 1H), 6.91 - 6.95 (m, 2H), 7.08 - 7.13 (m, 2H), 7.24 (s, 1H), 7.3 - 7.49 (m, 1H), 7.91 (s, 1H). MS m/z (M++l): 516.9. Step IV; Synthesis of 0-Methyl4-[4-(5-{[(dichloroacetyl)amino]methyl}-2-oxo-l,3-oxazolidin-3-yl)-2-fluorophenyl]piperazine-l-carbothioate Potassium carbonate (0.06g5 4.6 mmol) was added to the solution of N-[(3-{4-[4-(l//-imidazol-1 -ylcarbonothioyl)piperazin-1 -yl]-3-fluorophenyl} -2-oxo-1,3-oxazolidin-5-yl)methyl]-2,2-dichloroacetamide (0.2 g, 0.38 mmol, obtained in the step III) in methanol (20 ml) under stirring. The resulted reaction mixture was refluxed until completion of the reaction as confirmed by TLC using (ehtylacetate:hexane, 8:2) as the solvent system. The resultant reaction mass was allowed to cool to room temperature and filtered the solid thus obtained at suction. This solid was washed with ethyl acetate:hexane (1:1 mixture, 10 ml) to yield the pure compound (0.08g, 43% yield, purity 99.59 % by HPLC). JH-NMR (DMSO-d6) 5: 2.98 - 3.03 (m, 4H), 3.52 - 3.54 (t, 2H), 3.69 - 3.72 (m, 1H)5 3.83 - 3.86 (m, 2H), 3.96 (s, 3H), 4.09 - 4.14 (m, 3H), 4.76 - 4.8 (m, 1H), 6.48 (s, 1H), 7.06 -7.11 (m, 1H), 7.16 - 7.18 (m, 1H), 7.47 - 7.51 (d, 1H), and 8.97 (s, 1H, D2O exchangeable). MS m/z (M++l): 480.9 The following compound was prepared according to the procedure given in the Example 11 Antimicrobial Activity The compounds of the present invention showed in vitro antibacterial activity when tested by the Agar Dilution Method as specified in documents published by the National Committee for Clinical Laboratory Standards (NCCLS), USA (now CLSI). Briefly, the compounds of the invention were weighed, dissolved in dimethyl sulfoxide, serially two fold diluted in the same solvent and then incorporated into molten Mueller Hinton Agar in a petridish before solidification, with each petridish containing a different concentration of a compound. The bacterial inoculum was prepared by picking 3 to 5 well isolated bacterial colonies with the same morphological appearance from an 18-24 hours old culture with an inoculating loop, then transferring the growth to a tube containing 3 ml of normal saline and adjusting the turbidity of the saline suspension to 0.5 Me Farland Turbidity Standard equivalent to a bacterial Q population of 1.5 x 10 colony forming units (CFU) per ml of the suspension. The suspension was diluted 1:10 in saline (i.e. 0.5 ml suspension + 4.5 ml saline) to get a bacterial population of 1.5 x 107 cfu/ml as inoculum. The bacterial inoculum prepared in the above manner was inoculated onto petri dishes containing Mueller Hinton Agar which had earlier been incorporated with different dilutions of the compounds of invention by a Multipoint Inoculator with each inoculum spot containing approximately,1 x 104 colony forming units (CFU) of bacteria. The inoculated petridishes were incubated at 35°C in an ambient atmosphere for 16-20 hours. Petridishes containing different concentrations of Vancomycin and Oxacillin and inoculated with Staphylococcus aureus, Coagulase Negative Staphylococci and Enterococci were incubated for 24 hours. The petridishes after incubation were placed on a dark non-reflecting surface and the Minimum Inhibitory Concentration (MIC) was recorded as the concentration, which showed no growth of the inoculated culture. 1) S.aureus - Staphylococus aureus 2) S.epidermidis - Staphylococcus epidermidis 3) E.faecium - Enterococcus faecium 4) E.faecalis - Enterococcus faecalis 5) M.catarrhalis - Moraxella catarrhalis

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1253-CHE-2006 AMENDED CLAIMS 18-11-2011.pdf

1253-CHE-2006 AMENDED PAGES OF SPECIFICATION 18-11-2011.pdf

1253-CHE-2006 CORRESPONDENCE OTHERS 11-06-2012.pdf

1253-CHE-2006 EXAMINATION REPORT REPLY RECEIVED 18-11-2011.pdf

1253-CHE-2006 AMENDED PAGES OF SPECIFICATION 28-06-2012.pdf

1253-CHE-2006 AMENDED CLAIMS 19-10-2012.pdf

1253-CHE-2006 AMENDED CLAIMS 28-06-2012.pdf

1253-CHE-2006 CORRESPONDENCE OTHERS 28-06-2012.pdf

1253-CHE-2006 EXAMINATION REPORT REPLY RECEIVED 19-10-2012.pdf

1253-che-2006-abstract.pdf

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1253-che-2006-claims.pdf

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