COMPLETE AFTER PROVISIONAL

FORM 2THE PATENT ACT 1970 (39 of 1970) &The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rule 13)
1. TITLE OF THE INVENTION:SUBSTITUTED THIO-PIPERIDINO PHENYLOXAZOLIDINONES HAVINGANTIMICROBIAL ACTIVITY
2. APPLICANT (S)(a) NAME(b) NATIONALITY(c) ADDRESS : Wockhardt Limited: Indian: Wockhardt TowersBandra-Kurla Complex, Bandra (E)Mumbai - 400 051, India
3. PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the invention and the which it is to be performed. manner in

sBr

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14 SEP 2006
SUBSTITUTED THIO-PIPERIDINO PHENYLOXAZOLIDINONES HAVING ANTIMICROBIAL ACTIVITY
FIELD OF INVENTION
The present invention relates generally to substituted thio-piperidino phenyloxazolidinones having antimicrobial activity. The invention also relates to the processes for preparation of the compounds, to pharmaceutical compositions containing the compounds and to methods for treating or preventing microbial infections using the compounds.
BACKGROUND OF INVENTION
Oxazolidinones represent a novel chemical class of synthetic antimicrobial agents, with a first representative, Linezolid, of this class. This advance enabled the profiling of the unique properties of the members of this class, which is that they display activity against important Gram-positive human and veterinary pathogens including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE) and (3-lactam resistant Streptococcus pneumoniae (PRSP). The deficiencies of this class of oxazolidinones have also surfaced. They are inactive against Enterobacteriaceae.
Other limitations that have appeared through the clinical development studies and use of Linezolid and its potential successors in development are that the class has a propensity to induce myelosuppression with consequent thrombocytopenia. Inhibition of monoamine oxidase by oxazolidinones has prompted a recommendation made to clinicians that clinical use of members of this class be done with caution during concomitant usage of adrenergic or serotonergic agents and selective serotonin re-uptake inhibitors.
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INFORMATION DISCLOSURE
There are several patents cited in the literature, which refer to oxazolidinones having antibacterial activity. Piperidinylphenyl moiety bearing oxazolidinones are described in following patents: WO95/25106 discloses substituted piperidino phenyloxazolidinones. WO96/13502 discloses phenyloxazolidinones having a multisubstituted azetidinyl or pyrrolidinyl moiety. PCT application Nos PCT/IN03/00237, PCT/IN03/00238 and PCT/IN04/00276 discloses piperidinyl phenyl oxazolidinones of antimicrobial use. However in all above cited patents, substituted thio-alkyls and substituted or unsubstituted thio-heteroaryl bearing piperidinophenyl oxazolidinone compounds are not disclosed.
SUMMARY OF INVENTION
The present invention relates to novel substituted thiopiperidinophenyl oxazolidinone compounds of Formula -1.

wherein
X and Y represent a group each and independently selected from CH, CF, CCI, N;
Ri is selected from the group comprising of C1-C6 alkylsulfonyloxy, C1-C6 alkylamido,
substituted C1-C6 alkylamido, C1-C6 thioalkylamido, substituted C1-C6 thioalkylamido,
heteroaryl, substituted heteroaryl, NHR4;
wherein R4 is selected from the group comprising cyano, COORa, CSORa,
CONRbRc, CSNRbRc;
wherein Ra is selected from C1-C6 alkyl, substituted C1-C6 alkyl, cycloalkyl,
heterocyclyl;
Rb, Rc are selected from C1-C6 alkyl, substituted C1-C6 alkyl, 3-6 membered
cycloalkyl or Rb and Rc together form a 5-6 membered cycloalkyl or heterocyclyl
ring;
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R2 represents group selected from H, CH3, OH, halogen or OCOR5."
wherein R5 is selected from d-C6 alkyl, substituted C1-C6 alky I, 5-6 membered
cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl,
aralkyl:
W is either absent or -CH2-, pyridyl;
"a" is optional double bond;
Q is represents S, SO, S02;
R3 is selected from the group consisting of
hydrogen, cyano, C1-C6 alkylcarbonyl, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6
alkenyl, substituted C2-C6 alkenyl, C1-C6 alkylcarbonyl, aryl, heteroaryl, substituted
aryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl,
substituted heterocyclyl.
DESCRIPTION OF TERMS:
In above definitions
C1-C6 alkyl" refers to saturated, straight or branched chain hydrocarbon having
C1-C6 number of carbon atoms such as methyl, ethyl, propyl, isopropyl and so on;
"C2-C6 alkenyl' means straight or branched chain hydrocarbon comprising C1-C6
carbon atom containing one or more carbon-carbon double bonds for examples
ethenyl, propenyl, butenyl, pentenyl, hexenyl;
"substituted C1-C6 alkyl" refers to one or more hydrogen atom of the alkyl group
substituted with halogen, amino, hydroxy, carboaxldehyde, mercapto, nitro, C1-C6
alkoxy, carboxy, alkoxycarbonyl, carboxamide, aryl, heteroaryl, substituted aryl,
substituted heteroaryl;
"substituted C2-C6 alkenyl" refers to one or more hydrogen atom of the alkyl group
substituted with halogen, amino, hydroxy, carboaxldehyde, mercapto, nitro, C1-C6
alkoxy, carboxy, C1-C6-alkoxycarbonyl, carboxamide, aryl, heteroaryl, substituted
aryl, substituted heteroaryl;
C1-C6 alkylsulfonyloxy" means groups such as methanesulfonyloxy,
ethanesulfonyloxy, propylsulfonyloxy and so on;
C1-C6-alkyloxycarbonyr' means group such as methyloxycarbonyl, ethyloxycabonyl,
propyloxycarbonyl and so on;
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"halogen" or "halo" means atom selected from atom such as fluorine, chlorine,
bromine;
C1-C6 alkylcarbonyl" means groups such as acetyl, ethylcarbonyl, propylcarbonyl;
C1-C6 alkylthio" means groups such as methylthio, ethylthio, propylthio;
"aryl" refers to a mono, fused bicyclic or fused tricyclic carbocyclic ring system
having one or more aromatic rings including but not limited to phenyl, napthyl,
indanyl, indenyl and so on;
"substituted aryl" refers to an aryl group as defined herein substituted by
independent replacement of one or more hydrogen atoms thereon with CI, Br, F, I,
OH, CN, C1-C6 alkyl, cycloalkyl, heterocyclyl, C1-C6 alkoxy, haloalkyl, amino,
alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl,
carboxamide, aryl, heteroaryl, thioalkyi, thioaryl, thioheteroaryl for example p-tolyl, 3-
fluorophenyl, 3,4-difluorophenyl, 4-morpholino-3-fluorophenyl;
"heteroaryl" refers to mono, fused bicyclic or tricyclic aromatic radical having 5-10
ring atoms of which one or more carbon atom of the ring is replaced by an atom
selected from N, 0, S, for example pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl,
oxadiazolyl, furanyl, thiadiazolyl, thiazolyl, oxazolyl, isooxazolyl, pyridyl, pyrimidinyl,
benzotriazolyl, quinolinyl, isoquinolinyl, benzimidazole, benzthiazole, benzoxazolyl,
indazolyl, indolyl and the like;
"substituted heteroaryl" refers to a heteroaryl group as defined herein substituted by
independent replacement of one or more hydrogen atoms thereon with CI, Br, F, I,
OH, CN, C1-C6 alkyl, C1-C6 alkoxy, haloalkyl, amino, alkylamino, dialkylamino,
mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl, carboxamide, aryl,
heteroaryl, thioalkyi, thioaryl, thioheteroaryl for example, 1-methyl imidazolyl, 5-
pyridin-4-yl-[1,3,4]oxadiazolyl, 5-methyl-[1,3,4]thiadiazolyl, 5-amino-
[1,3,4]thiadiazolyl, 5-furan-2-yl-[1,3,4]oxadiazolyl, 5-pyridin-4-yl-[1,3,4]thiadiazolyl, 6-
bromo-3H-imidazole-[4,5-b] pyridine, 1-methyl-5-(1-methyl-1 H-imidazol-2-ylsulfanyl)-
1 H-imidazole, 1-methyl-tetrazole, 1 H-imidazo-[4,5-c]pyridine, 5-acetylamino-1,3,4-
thiadiazole, 6-aminobenzimidazole, 3-amino-1,2,4-triazole, 5-amino-1,3,4-thiadiazol,
5-aminopropionyl-1,3,4-thiadiazole, 5-aminobenzimidazole, 4-amino-2,3,5-triazole
and the like;
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"cycloalkyl" means mono-, bi- or tri- cyclic ring systems which may be partially or fully
saturated having 3-10 ring atoms. The individual rings may be 3-8 membered.
Examples include cyclopropyl, cyclobutyl, cyclohexane and so on.
"heterocyclyl" means mono-, bi- or tri- cyclic ring systems which may be partially or
fully saturated having 3-10 ring atoms. The individual rings may be 3-8 membered
bearing one or more heteroatom selected from N, 0, S. This includes aryl and
heteroaryl ring stems fused to non-aromatic ring. For example, aziridinyl, oxiranyl,
piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxadiazolonyl, oxazolidinonyl,
thiadiazolonyl and so on;
"substituted heterocyclyl" or "substituted cycloalkyl" refers to a heterocyclic or
cycloalkyl group as defined above substituted by independent replacement of one or
more hydrogen atoms thereon with CI, Br, F, I, OH, CN, C1-C6 alkyl, C1-C6 alkoxy,
haloalkyl, amino, alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde,
carboxy, alkoxycarbonyl, carboxamide;
"aralkyl" means groups like benzyl, benzhydryl, trityl and so on;
"haloalkyl" refers to C1-C6 alkyl group substituted with a halogen for example
chloromethyl, bromoethyl and the like;
" C1-C6 alkoxy" refers for the C1-C6 alkyl group linked via ether linkage for example
methoxy, ethoxy and so on.
C1-C6 alkylamido" means an alkylamide where a hydrogen atom has been removed
from the amine group. Examples of alkyamido groups include HCO-NH-, CH3C(0)-
NH-, C2H5C(0)-NH-, C3H7C(0)-NH- and so on;
" C1-C6 thioalkylamido" refers to (C1-C6 alkyl)-C(S)-NH-, examples of thioalkyamido
groups include HCS-NH-, CH3C(S)-NH-, C2H5C(S)-NH-, C3H7C(S)-NH- and so on.
"substituted C1-C6 alkylamido" means an alkylamido wherein the at least one
hydrogen of the alkyl group is replaced by halogen, cyano, hydroxyl;
"substituted C1-C6 thioalkylamido" means thioalkylamido wherein the at least one
hydrogen of the alkyl group is replaced by halogen, cyano, hydroxyl;
"carboxy", as used herein refers to a group of the formula -COOH;
"cyano", as used herein refers to a group of the formula -CN.
Preferred salts are those of hydrochloride, hydrobromide, hydroiodlde, sulphate, phosphate and salts of organic acids such as acetate, lactate, succinate, oxalate,
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maleate, fumarate, malate, tartrate, citrate, ascorbate, cinnamate, gluconate, benzoate, methane sulfonate and p-toluene sulfonate; lithium, sodium, magnesium, calcium and potassium salts, and amino acids salts such as alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan tyrosine or valine.
Some examples of oxazolidinone derivatives represented by the general Formula-1
are as follows:
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfanylmethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfanyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl]-acetamide;
(S)-N-{3-[4-(phenylsulfinyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfinylmethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfanyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfanylmethyl-piperidin-1-yl)-3,5-difluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfinylmethyl-piperidin-1-yl)-3,5-difluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzimidazole-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzothiazole-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfonyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfinyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
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(S)-N-{3-f4-(4-(1H-benzothiazol-2-yisuIfinyl)-ptperidin-1-yl)-3I5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-
oxo-oxazolidin-5-ylm8thyl}-ac8tamide;
(R)-2-{3-[4-(4-ph8nylsulfanyl-piperidin-1-yl)-3,5-difluoroph8nyl]-2-oxo-oxazolidin-5-
ylmethyl}-2H-1,2,3-triazole;
(R)-1 -{3-[4-(4-phenylsulfanyl-pip8ridin-1 -yl)-3,5-difluorophenyl]-2-oxo- oxazolidin-5-
ylmethyl}-1 H-1,2,3-triazole;
(S)-N-{3-[4-(4-(1H-benzimidazole-2-sulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzimidazole-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-ac8tamide;
(S)-N-{3-[4-(4-(2-hydroxyethylsulfanyl)-piperidin-1-yl)-3,5-difluoroph8nyl]-2-oxo-
oxazolidin-5-ylmethyl}-ac8tamide;
(S)-N-{3-[4-(4-toluenesulfanyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-(3-fluoro-4-morpholin-4-yl-phenylsulfanylmethyl)-4-hydroxy-piperidin-
1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3,4-difluoro-phenylsulfanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-toluenesulfanylm8thyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzoxazolyl-2-sulfanyl)-pip9ridin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzoxazolyl-2-sulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(3-hydroxy-propylsulfanylmethyl)-pip8ridin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(2-hydroxyethylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
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(S)-N-{3-[4-(4-thioacetyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-yl
methyl}-acetamide;
(S)-N-{3-[4-(4-thiocynato-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl]-acetamide; (S)-N-{3-[4-(4-thiocynato-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-
acetamide;
(S)-N-{3-[4-(4-toluenesulfanyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl]-acetamide;
(S)-N-{3-[4-(4-toluene-sulfinyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3,4-difluorophenylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3,4-difluorobenzenesulfinyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-thioacetyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-mercapto-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(pyridin-2-ylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl]-acetamide;
(S)-N-{3-[4-(4-(pyridin-2-ylsulfinyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(pyridin-2-ylsulfanylmethyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(pyridin-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-yl methyl]-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3,5-difluoro-
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3-fluoro-
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamlde;
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(S)-N-{3-[4-(4-hydroxy-4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)-piperidin-1 -yl)-
3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(pyridin-2-ylsulfanylmethyl)-pip9ridin-1-yl)-3,5-clifluoro-
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(thiophen-2-ylsulfanylm9thyl)-piperidin-1-yl)-3-fluoroph9nyl]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-pyridin-4-yl-[1,3,4]oxaadiazole-2-ylsulfanyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylm9thyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(5-methyl-[1,3,4]thiadiazole-2-ylsulfanylm9thyl)-piperidin-1-
yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-ac9tamide;
(S)-N-{3-[4-(4-(5-amino-[1,3,4]thiadiazole-2-ylsulfanyl)-pip9ridin-1-yl)-3-fluorophenyl]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-[1,3,4]thiadiazol-2-ylsulfanylm9thyl)-4-hydroxy-piperidin-1-
yl)-3-fluoroph9nyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylm9thyl) piperidin-1 -
yl)-3-fluoroph9nyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-m9thyl-[1,3,4]thiadiazol9-2-ylsulfanyl)-piperidin-1-yl)-3-fluoroph9ny]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4,5-dihydro-thiazol-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-[1,3,4]thiadiazol9-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluoro
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-[3-{3-fluoro-4-[4-(pyridine-2-ylsulfanylmethyl)-pip9ridin-1-yl]-ph9nyl}-2-oxo-
oxazolidin-5-ylmethyl]-acetamide;
(S)-N-{3-[4-(4-(5-furan-2-yl-[1,3,4]oxadiazol-2-ylsulfanylmethyl)-4-hydroxy piperidin-
1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-(1 -m9thyl-1 H-[1,3,4]triazol-2-ylsufanylm9thyl)-piperidin-1 -yl)-
3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-m9thyl-[1,3,4]thiadiazole-2-ylsulfanyl)-piperidin-1-yl)-3,5-
difluoroph9nyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-pyridin-4-yl-[1,3,4]thiadiazole-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
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(S)-N-{3-[4-(4-(6-bromo-3H-imidazole[4,5-b]pyridinl-2-ylsulfanyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(6-bromo-3H-imidazole[4,5-b]pyridinl-2ylsulfanyl)-4-hydroxy-piperidin-
1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(6-bromo-3H-imidazole[4,5-b]pyridinl-2ylsulfanyl)-4-hydroxy-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1 -methyl-5-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-1 H-imidazol-2-
ylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-hydroxy-(1 -methyl-1 H-tetrazol-5-ylsufanylmethyl)-piperidin-1 -yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1 -methyl-1 H-tetrazol-5-ylsulfanyl)-piperidin-1 -yl)-3,5-difluoro-phenyl]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1 -methyl-1 H-tetrazol-5-ylsulfanyl)-piperidin-1 -yl)-3-fluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1 -methyl-1 H-tetrazol-5-ylsulfanylmethyl)-piperidin-1 -yl)-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-acetoxy-4-(1 -methyl-1 H-tetrazol-5-ylsulfanylmethyl)-piperidin-1 -yl)-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazo[4,5-c]pyridinl-2-ylsulfanylmethyl)-piperidin-1-
yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazo[4,5-c]pyridin-2-ylsulfanylmethyl)-piperidin-1-yl)-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-acetoxy-4-(4-methyl-4H-[1,2,4]-triazol-3-ylsulfanylmethyl)-piperidin-1-
yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-thiocyanatomethyl-piperidin-1-yl)-3,5-ifluorophenyl]-2-oxo-
oxazolidin -5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-methyl-4-(1-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-
piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
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(S)-N-{3-[4-(4-hydroxy-4-thiocyanatomethyf-pip9ridin-1-yl)-3-fluorqphenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-acetoxy-(1 -methyl-1 H-tetrazol-5-ylsufanylmethyl)-piperidin-1 -yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-fluoro-4-thiocyanatomethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin -5-ylmethyl}-acetamide;
(S)-N-{3-[4-(acetylsulfanylmathylpiperidine-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-1yl)-3,5-
difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-acetylamino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-
1yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-1yl)-3-
fluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide
(S)-N-{3-[4-(4-(5-acetylamino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-
1yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-A/-(tert-butyloxycarbonyl-L-alaninylamino)-1,3,4-thiadiazole-2-
thiomethyl)-4-hydroxypiperidine-1yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-
ylmethyl]-acetamide
(S)-N-{3-[4-(4-(6-aminobenzimidazol-2-yl-thiomethyl)-4-hydroxypiperidin-1yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3-amino-1,2,4-triazol-5-yl-thiomethyl)-4-hydroxypiperidin-1-yl-3-
fluoro)phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-1,3,4-thiadiazol-2-sulfanylmethyl)-4-hydroxy)-3-
fluoropiperidin-1-yl)-3,5-difluorophanyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(2'S,5S)-N-{3-[4-(4-(5-(L-ala)amino-1,3,4-thiadiazol-2-yl)sulfanylmethyl-4-
hydroxypiperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide
methanesulfonate;
(S)-N-{3-[4-(4-(5-aminobenzimidazole-2-thiomethyl)-4-hydroxypiperidine-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(4-amino-2,3,5-triazole-5-sulfanylmethyl)-4-hydroxypiperidin-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide.
12

A further embodiment of the invention is to provide methods of preparation of the compound of the invention.
Following schemes describe the preparation of compounds of Formula-1 of the present invention. All of the starting materials are prepared by procedures described in US Patent 5,668,286 and in our pending PCT patent application PCT/IN03/00237, PCT/IN03/00238, PCT/IN04/00276 or by procedures that would be well known to one of ordinary skill in organic chemistry. The variables used in the following Schemes are as defined above. Optically pure material could be obtained either by one of a number of asymmetric synthesis or alternatively by resolution from a racemic mixture.
13
Oxazolidinone compounds bearing substituted thiopiperidino phenyloxazolidinone compounds may be prepared as per schemes described below: The 4-substituted piperidinyl oxazolidinone compound of Formula-1 is treated with an appropriate reagent of formula R3SH in presence of a base for example triethylamine, potassium carbonate to afford thiopiperidinyl oxazolidinone compound of formula 2. The oxidation of compound 2 with sodium metaperiodate in aqueous methanol at room temperature afforded the corresponding sulphoxide of formula 3. The further oxidation of the sulphoxide resulted in the formation of the sulphone of formula 3 as shown in scheme 1.


The 4-oxirainyl piperidinophenyl oxazolidinone of formula 4 was treated with an appropriate reagent of formula R3SH in presence of a base for example triethylamine, potassium carbonate to afford thiopiperidinyl oxazolidinone compound of formula 5. The oxidation of compound 5 with sodium metaperiodate in aqueous methanol afforded the corresponding sulphoxide of formula 6. the further oxidation of the sulphoxide with sodium metaperiodate gave the sulphone of formula 6 as shown in scheme 2.

The compounds of formula 5 when treated with DAST in a halogenated solvent for example dichloromethane at a temperature range between -10 °C to +50 °C for 10 min. to 24 h, provided the thiosubstituted 4-fluoro-piperidino phenyl oxazolidinones of formula 7.

14
The compounds of formula 5 when treated with alkyl anhydride or mixed anhydride in a presence of a base such as triethylamine in halogenated solvent for example dichloromethane at a temperature range between -10 °C to +50 °C for 10min. to 24 h, afforded the thiosubstituted 4-acetoxy-piperidino phenyl oxazolidinones of formula 7.

The 4-pydinyl piperidinylphenyl oxazolidinone compound of formula 8 is treated with an appropriate reagent of formula R3SH in presence of a base for example triethylamine, potassium carbonate to afford thiopiperidinyl oxazolidinone compound of formula 9. The oxidation of compound 9 with sodium metaperiodate in aqueous methanol at room temperature afforded the corresponding sulphoxide of formula 10. The further oxidation of the sulphoxide resulted in the formation of the sulphone of formula 10 as shown in scheme 4.

The oxazolidinone antibacterial agents of this invention have potential for treatment of specially Gram-positive infections including multi-resistant strains. In contrast to compounds of the prior art, they demonstrate bactericidal activity against different resistant microorganisms and in particular different strains of Enterococcus faecalis. In addition they display activity against linezolid-resistant S. aureus strains, linezolid-resistant E. faecalis strains and in particular linezolid-resistant S. pneumoniae strains. These compounds are useful for the treatment of Gram-positive or Gram-negative microbial infections in humans and other warm-blooded animals by either parenteral, oral or topical administration. The infection in human and other warmblooded animals can be systemic or topical.
The compounds of this invention may be used to prevent infections caused by Gram-positive and Gram-negative bacteria by administering the compound to a subject that is at risk for developing an infection caused by Gram-positive or Gram-negative bacteria. A subject at risk for developing an infection may be a health care worker, surgical patient and the like.
15

The compositions of the present invention include compositions such as suspensions, solutions, elixirs, aerosols, and solid dosage forms. Carriers as described in general above are commonly used in the case of oral solid preparations (such as powders, capsules and tablets), with the oral solid preparations being preferred over the oral liquid preparations. The most preferred oral solid preparation is tablets.
Because of their ease of administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are employed. Examples of suitable carriers include excipients such as lactose, white sugar, sodium chloride, glucose solution, urea, starch, calcium carbonate, kaolin, crystalline cellulose and silicic acid, binders such as water, ethanol, propanol, simple syrup, glucose, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate and polyvinyl pyrrolidone, disintegrants such as dried starch, sodium alginate, agar powder, laminaria powder, sodium hydrogen carbonate, calcium carbonate, Tween (fatty acid ester of polyoxyethylenesorbitan), sodium lauryl sulfate, stearic acid monoglyceride, starch, and lactose, disintegration inhibitors such as white sugar, stearic acid glyceryl ester, cacao butter and hydrogenated oils, absorption promoters such as quaternary ammonium bases and sodium lauryl sulfate, humectants such as glycerol and starch, absorbents such as starch, lactose, kaolin, bentonite and colloidal silicic acid, and lubricants such as purified talc, stearic acid salts, boric acid powder, polyethylene glycol and solid polyethylene glycol.
The tablet, if desired, can be coated, and made into sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, or tablets comprising two or more layers.
If desired, tablets may be coated by standard aqueous or non-aqueous techniques. In molding the pharmaceutical composition into pills, a wide variety of conventional
carriers known in the art can be used. Examples of suitable carriers are excipients such as glucose, lactose, starch, cacao butter, hardened vegetable oils, kaolin and
16

talc, binders such as gum arabic powder, tragacanth powder, gelatin, and ethanol, and disintegrants such as laminaria and agar.
In molding the pharmaceutical composition into a suppository form, a wide variety of carriers known in the art can be used. Examples of suitable carriers include polyethylene glycol, cacao butter, higher alcohols, gelatin, and semi-synthetic glycerides.
A second preferred method is parenterally for intramuscular, intravenous or subcutaneous administration.
A third preferred route of administration is topically, for which creams, ointments, shampoos, lotions, dusting powders and the like are well suited. Generally, an effective amount of the compound according to this invention in a topical form is from about 0.1% w/w to about 10% w/w of the total composition. Preferably, the effective amount of the compound of the invention is 1% w/w of the total composition. In addition to the common dosage forms set out above, the compounds of the present invention may also be administered by controlled release means and/or delivery devices such as those described in U.S. Patent Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123 and 4,008,719; the disclosures of which are hereby incorporated by reference.
Desirably, each tablet contains from about 200 mg to about 1500 mg of the active ingredient. Most preferably, the tablet, cachet or capsule contains either one of three dosages, about 200 mg, about 400 mg, or about 600 mg of the active ingredient. When the pharmaceutical composition is formulated into an injectable preparation, in formulating the pharmaceutical composition into the form of a solution or suspension, all diluents customarily used in the art can be used. Examples of suitable diluents are water, ethyl alcohol, polypropylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, and sorbitan esters. Sodium chloride, glucose or glycerol may be incorporated into a therapeutic agent.
17

The antimicrobial pharmaceutical composition may further contain ordinary dissolving aids, buffers, pain-alleviating agents, and preservatives, and optionally coloring agents, perfumes, flavors, sweeteners, and other drugs.
For topical application, there are employed as non-sprayable forms, viscous to semisolid or solid forms comprising a carrier compatible with topical application and having a dynamic viscosity preferably greater than water. Suitable formulations include but are not limited to solutions, suspensions, emulsions, creams, ointments, powders, liniments, salves, aerosols, etc., which are, if desired, sterilized or mixed with auxiliary agents, e.g. preservatives, antioxidants, stabilizers, wetting agents, buffers or salts for influencing osmotic pressure, etc. For topical application, also suitable are sprayable aerosol preparations wherein the active ingredient preferably in combination with a solid or liquid inert carrier material.
A specific embodiment of the invention is the preparation of storage stable compositions of the compounds of the invention of formula I. Such stable compositions can be advantageously made through the use of selective stabilizers. Different stabilizers are known to those skilled in the art of making pharmaceutical compositions. Of special utility for making storage stable compositions of the compound of the invention of formula I, stabilizers such as disodium ethylenediaminetetraacetic acid (EDTA), tromethamine, cyclodextrins such as gamma-cyclodextrin, hydroxy-propyl-gamma-cyclodextrin have been found to be useful.
In a specific embodiment of the invention, the pharmaceutical compositions contain an effective amount of the active compounds of the invention, its derivatives, salts or hydrates thereof described in this specification as hereinbefore described in admixture with a pharmaceutical^ acceptable carrier, diluent or excipients, and optionally other therapeutic ingredients.
The invention is further defined by reference to the following examples describing in detail the preparation of the composition of the present invention as well as their utility. It will be apparent to those skilled in the art that many modifications, both to
1
18

materials and methods may be practiced without departing from the purpose and scope of this invention.
The compounds of this invention are useful antimicrobial agents effective against various humans and veterinary pathogens specially including Linezolid-resistant strains.
For the purpose of this invention the pharmaceutical compositions may contain the active compounds of the invention, their derivatives, salts and hydrates thereof, in a form to be administered alone, but generally in a form to be administered in admixture with a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice. Suitable carriers which can be used are, for example, diluents or excipients such as fillers, extenders, binders, emollients, wetting agents, disintegrants, surface active agents and lubricants which are usually employed to prepare such drugs depending on the type of dosage form. Any suitable route of administration may be employed for providing the patient with an effective dosage of the compound of the invention their derivatives, salts and hydrates thereof. For example, oral, rectal, vaginal, parenteral (subcutaneous, intramuscular, intravenous), nasal, transdermal, topical and like forms of administration may be employed. Dosage forms include (solutions, suspensions, etc) tablets, pills, powders, troches, dispersions, suspensions, emulsions, solutions, capsules, injectable preparations, patches, ointments, creams, lotions, shampoos and the like.
The prophylactic or therapeutic dose of the compounds of the invention, their derivatives, salts or hydrates thereof, in the acute or chronic management of disease will vary with the severity of condition to be treated, and the route of administration. In addition, the dose, and perhaps the dose frequency, will also vary according to the age, body weight and response of the individual patient. In general, the total daily dose range, for the compounds of the invention, the derivatives, salts or hydrates thereof, for the conditions described herein, is from about 200 mg to about 1500 mg, in single or divided closes. Preferably, a daily dose range should be between about 400 mg to 1200 mg, in single or divided dosage, while most preferably a daily dose
19

range should be between about 500 mg to about 1000 mg in divided dosage. While intramuscular administration may be a single dose or up to 3 divided doses, intravenous administration can include a continuous drip. It may be necessary to use dosages outside these ranges in some cases as will be apparent to those skilled in the art.
Further, it is noted that the clinician or treating physician will know how and when to interrupt, adjust, or terminate therapy in conjunction with individual patient's response. The term "an amount sufficient to eradicate such infections but insufficient to cause undue side effects" is encompassed by the above - described dosage amount and dose frequency schedule. "Antibacterially effective amount" is the amount required to provide a desirable biological effect of restricting the growth of bacteria or killing bacteria.
Pharmaceutical compositions of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets, or tablets, or aerosol sprays, each containing a predetermined amount of the active ingredient, as a powder or granules, or as a solution or a suspension in an aqueous liquid, a nonaqueous liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion. Such compositions may be prepared by any of the methods of pharmacy, but all methods include the step of bringing into association the active ingredient with the carrier, which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation.
BIOLOGICAL ACTIVITY:
The compounds of this invention are useful antimicrobial agents, effective against various human and veterinary pathogens, including multiple-resistant staphylococci
and streptococci, as well as anaerobic organisms such bacteroides and Clostridia species, and acid resistant organisms such as Mycobacterium tuberculosis and Mycobacterium avium.
20

TEST EXAMPLE 1: MIC TEST METHOD
Overnight grown cultures of S. aureus organisms in Tryptic Soya broth were diluted in Mueller Hinton Broth to give optical density matching with MacFarland tube 0.5 standard. Cultures were further diluted 1:10 in Mueller Hinton broth. Using Denley's mutipoint inoculator, 104 cells were deposited on Mueller Hinton agar (Difco) containing range of 2 fold dilutions of test compounds. These plates were incubated for 24 hrs at 35° C and MIC results recorded. MIC is defined as minimum drug concentration that inhibits test organisms. For determining MIC of test compounds against Streptococcus pneumoniae, Mueller Hinton agar containing 5% sheep blood was employed.
Results: The MIC values of the selected oxazolidinone compounds of the invention have displayed antibacterial activity for MSSA-25923 strain 0.5- 8 mcg/ml, MRSA -32 strain ranging from 0.5 to 8 mcg/ml, Linezolid resistant MRSA strain 8 to 32 mcg/ml, SPN ATCC 49619 strain <0.25 to 8 mcg/ml and H. influenzae 2-32 mcg/ml. The following examples are provided to further illustrate this invention but they should not be taken as limiting.
EXPERIMENTAL
All of the starting materials are prepared by procedures described in US Patent 5,668,286 and in our pending PCT patent application PCT/IN03/00237, PCT/IN03/00238, PCT/IN04/00276 or by procedures that would be well known to one of ordinary skill in organic chemistry. Mass spectra were recorded on Waters Micromass Quatro- II instrument.
Example-1: (S)-N-(3-r4-(4-(1 H-Benzothiazol-2-vlsulfanvn-piperidin-1-vl)-3.5-
difluorophenvl1-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[4-(4-methanesulphonyloxy-piperidin-1-yl)-3,5-difluoro
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.11mmol) in N,N-dimethyl
formamide (5 ml), 2-mercaptobenzothiazole (1.66 mmol) and potassium carbonate
(1.66mmol) were added. The resulting mixture was stirred at 90 °C for 12 h. The reaction mixture was poured onto crushed ice. The separated solid was filtered and
21

purified by column chromatography over silica gel to obtain the product as a white solid in 53% yield. Mp.192-195 °C and MS 519 (M+1) for C24H24F2N4O3S2.
Using the above procedure following examples were synthesized from (S)-N-(3-l4-
(4-methanesulphonyloxy-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl]-acetamide and following reagents.

Example Reagent Mp. (°C) Mass (M+1)
2 Thiophenol 213-217 462
3 1 -Methyl-1 H-imidazole-2-thiol 122-124 578
4 6-Bromo-3H-imidazole [4,5-b] pyridine 221-223 581
5 5-Pyridin-4-yl-[1,3,4]oxadiazole-2-thiol 190-192 531
6 5-Amino-[1,3,4] thiadiazole-2-thiol >200 485
7 5-Methyl-[1,3,4] thiadiazole-2-thiol 160-162 484
8 2-Mercaptopyridine 124-126 463
9 Thiophenol 244-246 472
10 2-Mercapto-benzimidazole 212-214 502
11 2-Mercaptoethanol 210-212 430
12 4-Methyl benzenethiol 204-206 476
13 2-Mercapto-benzoxazole 192-194 503
14 Thiophenol 232-235 472
Example 15: (S)-N-f3-f4-(4-(3.4-Difluoro phenvlsulfanvn-piperidin-1-vl)-3-fluoro
phenvll-2-oxo-oxazolidin-5-ylmethyl)-acetamide
A solution of (S)-N-{3-[4-(4-methanesulphonyloxy-piperidin-1 -yl)-3-fluoro
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (10mmol) in N,N-dimethyl
formamide (10 ml) was reacted with 3,4-difluoro benzenethiol (15 mmol) in presence
of potassium carbonate (16mmol) at 85 °C for 14h. The reaction mixture was
poured onto foe-water. The separated solid was purified by column Chromatography
22

over silica-gel to the obtain product in 65 % yield. Mp. 143-144 °C and MS (M+1) 480 ((M+1), 100%) for C23H24F3N3O3S.
Using the above procedure following examples were synthesized from (S)-N-{3-[4-
(4-methanesulphonyloxy-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide and following reagents.

Example Reagent Mp. (°C) Mass (M+1)
16 Thiophenol 162-164 444
17 2-Mercapto-benzothiazole 130-132 501
18 2-Mercapto-benzoxazole 152-154 485
19 2-Mercaptoethanol 144-146 412
20 4-Methyl benzenethiol 150-152 458
21 2-Mercaptopyridine 153-156 445
22 5-Pyridin-4-yl-[1,3,4] oxadiazole-2-thiol 130-132 513
23 5-Amino-[1,3,4] thiadiazole-2-thiol 190-192 467
24 5-Methyl-[1,3,4] thiadiazole-2-thiol 146-148 466
25 5-Mercapto-1 -methyl-1 H-tetrazole 168-170 450
Example-26: (S)N-(3-r4-(4-Thiocvnato-piperidin-1-vl)-3.5-difluorophenyl)-2-oxo-oxazolidin-5-ylmethyl)-acetamide
To a solution of (S)-N-{3-[4-(4-methanesulphonyloxy -piperidin-1 -yl)-3,5-difluoro phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.11mmol) in N,N-dimethyl formamide (5 ml), potassium thiocyanate (1.66 mmol) was added. The resulting mixture was stirred at 90 °C for 12 h The reaction mixture was poured on to crushed ice. The separated solid was filtered and purified by column chromatography over silica gel to obtain the product as a white solid in 31% yield. Mp. 232-234 °C; Mass m/z 411 (M+1) for C18H20F2N4O3S.
23

Example-27: (S)-N-(3-f4-(4-Thiocvnato-piperidin-1 –yl)-3-fluorophenvn-2-oxo-
oxazolidin-5-vlmethvl)-acetamide
Using the above procedure and ((S)-N-{3-[4-(4-methanesulphonylQxy-piperidin-1-y1)-
3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide) the title compound was syntheised in 31% yield. Mp. 184-186 °C; Mass m/z 393.1 (M+1) for C18H21FN4O3S.
Example-28: (S)-N-(3-f4-(4-Thioacetvl-piperidin-1-vl)-3-fluorophenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
A solution of (S)-N-{3-[4-(4-methanesulphonyloxy-piperidin-1-yl)-3-fluoro phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.0mmol) in acetone (10ml) was reacted with potassium thioacetate (1.5mmol) in presence of potassium carbonate (1.6mmol) at reflux temperature for 14h. The reaction mixture was poured onto ice-water. The separated solid was purified by column chromatography over silica-gel to the obtain product in 85% yield. Mp. 208-210 °C; Mass m/z 410 (M+1) for
C19H24FN3O4S.
Example-29: (S)-N-(3-r4-(4-Thioacetvl-piperidin-1-vl)-3.5-difluorophenvll-2-oxo-
oxazolidin-5-vl methyl acetamide
Using the above procedure title compound was synthesized from ((S)-N-{3-[4-(4-
methanesulphonyloxy-piperidin-1 -yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-acetamide). Mp. 204-206 °C; Mass m/z 428 (M+1) for C19H23F2N3O4S.
Example-30: (S)-N-(3-r4-(4-Mercapto-piperidin-1-vl)-3-fluorophenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
A solution of (S)-N-{3-[4-(4-methanesulphonyloxy-piperidin-1-yl)-3-fluoro phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.0mmol) in methanol (10ml) was reacted with potassium carbonate (1.6mmol) at reflux temperature for 4 hr. The solvent was evaporated and the residue partitioned between water and ethyl acetate. The ethyl acetate layer was concentrated and the residue chromatographed on a column of silica-gel to obtain the product in 83% yield. Mp. 134-136 °C; Mass m/z
368 (M+1) for C17H22FN303S.
24

Example-31: (S)-N-(3-f4-(Acetvlsulfanvtmethvtoiperidine-1 -vh-3-fluorophenvn-2-oxo-
oxazolidin-5-vlmethvl)-acetamide
(S)-N-{3[4-(4-methanesulphonyloxymethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide (1.0 mmol) was reacted with potassium thioacetate(1.5mmol) in presence of potassium carbonate(1.6mmol) in DMF (10 ml) at 85° C for 11 hr. The product was obtained by silica gel column chromatography, in 68% yield. Mp. 182-184° C; Mass m/z 424 (M+1) for C20H26FN3O4S.
Using the above procedure following examples were synthesized using the following reagents.

Example Reagent Mp. (°C) Mass (M+1)
32 2-Mercapto-pyridine 148-149 459
33 5-Methyl-[1,3,4]thiadazole-2-thiol 140-142 480
34 4-Methyl-4H-[1,2,4]-triazole-3-thiol 140-142 480
Example-35: (S)-N-(3-[4-(Phenvlsulfinvl-piperidin-1-vn-3-fluoroDhenvn-2-oxo-oxazolidin-5-vlmethyl)-acetamide
To a solution of (S)-N-{3-[4-phenylsulfanyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.12mmol), in 10 ml methanol: water (8:2), sodium metaperiodate (1.41 mmol) was added and the resulting mixture was stirred at 25° C for 14 h. The reaction mixture was concentrated and the residue suspended in water, stirred and extracted with chloroform. The organic layer was concentrated and the residue was purified by column chromatography over silica gel to obtain the product in 78 % yield. Mp. 172-174 °C; Mass m/z 460.1 (M+1) for C23H26FN3O4S.
Using the above procedure following examples were synthesized, from the respective starting materials.

Example Starting material Mp. (°C) Mass (M+1)
36 (S)-N-{3-[4-phenylsulfanyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}- 178-180 478
25

Acetamide
37 (S)-N-{3-[4-[4-(1H-Benzothiazol-2-ylsulfanyl)-piperidin-1 -yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 192-195 535
38 (S)-N-{3[4-(4-toluenesulfanyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 134-136 473
39 (S)-N-{3-[4[4(3,4-Difluorophenylsulfanyl)-piperidin-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 145-148 496
40 (S)-N-{3-[4-[4-(pyridin-2-ylsulfanyl)-piperidin-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl-acetamide 166-168 461
41 (S)-N-{3-[4-(4-hydroxy-4-phenylsulphanylmethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 162-164 490
42 (S)-N-{3-[4-(4-hydroxy-4-phenylsulphanylmethyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 221-223 508
Example-43: (S)-N-(3-r4-(Phenvlsulfonyl-piperidin-1-vh-3-fluorophenvll-2-oxo-oxazolidin-5-vlmethvl}-acetamide
To a solution of (S)-N-{3-[4-phenylsulfinyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.12mmol) in 10 ml methanol:water (8:2), sodium metaperiodate (1.41mmol) was added and the resulting mixture was stirred at 25° C for 14 h. The reaction mixture was concentrated and residue was dissolved in water and extracted with chloroform. The organic layer was concentrated and the residue was purified by column chromatography over silica gel to obtain the product in 69 % yield. Mp. 204-206 °C; Mass m/z 476.1 (M+1) for C23H26FN3O5S.
26

Example-44: (S)-N-(3-r4-(4-Hvdroxv-4-phenvlsulfanvlmethvl-piperidin-1 -vh-3-fluoro
Dhenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[4-(4-hydroxy-4-methanesulphonyloxymethyl-piperidin-1-yl)
3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (0.56 mmol) in N,N dimethylformamide (5 ml) sodium salt of thiophenol (1.12mmol) were added. The resulting mixture was stirred at 120 °C for 12 h. The reaction mixture was poured on to crushed ice. The separated solid was filtered and purified by column chromatography over silica gel to obtain the product as a white solid in 57% yield. Mp. 147-149° C; MS m/z 474.1 ((M+1), 100%) for C24H28FN3O4S.
Example-45: (S)-N-(3-r4-(4-Hydroxv-4-phenvlsulfanvlmethvl-piperidin-1-vl)-3.5-
difluorophenvl1-2-oxo-oxazolidin-5-vlmethvl)-acetamide
Using the above procedure title compound was synthesized from (S)-N-{3-[4-(4-
hydroxy-4-methanesulphonyl-oxymethyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide. Mp. 232-235° C; Mass m/z 492 ((M+1), 100%) for
C24H27F2N3O4S.
Example-46: (S)-N-(3-4-(4-Hvdroxv-4-(5-methvl-f1.3.41thiadiazol-2-vlsulfanvlmeth vnpiperidin-1-vl)-3-fluorophenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
(S)-N-{3-[4-(1-oxo-6-azaspiro[2,5]oct-6-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1 .Ommol) was reacted with 5-methyl-[1,3,4] thiadiazole-2-thiol (1.5mmol) in presence of potassium carbonate (1.6mmol) in methanol (10ml) at 25° C for 3h stirring. The solvent was evaporated under reduced pressure and the residue suspended in water. The separated solid was purified by column chromatography over silica-gel to the obtain product in 94% yield. Mp. 150-152° C; Mass m/z 496 ((M+1), 100%) for C24H27F2N3O4S.
Using the above procedure following examples were synthesized,

Example Reagent Mp. (°C) Mass (M+1)
47 2-Mercapto-1 H-benzoimidazole 198-200 513
48 2-Mercapto-H-benzothiazote 200-202 531
27

49 3-Fluoro-4-morpholin-4-yl-benzenethiol 136-138 577
50 3,4-Difluoro-benzenethiol 172-174 510
51 4-Methyl-benzenethiol 160-162 488
52 3-Mercapto-propan-1 -ol 140-142 456
53 2-Mercaptopyridine 169-172 475
54 2-Mercaptoimidazole 118-120 464
55 2-Mercapto-N-methyl imidazole 127-130 478
56 2-Mercaptothiophene 145-147 480
57 5-Amino-[1,3,4] thiadiazole-2-thiol 124-126 497
58 2-Mercaptothiazoline 162-164 483
59 2-Mercapto-1-methyl-1H-1, 3,4-triazole 192-194 479
60 6-Bromo-3H-imidazole [4,5-b] pyridine 186-188 593
61 5-mercapto-1 -methyl-1 H-tetrazole 166-168 480
62 3H-lmidazo[4,5-c]pyridine-2-thiol 168-170 515
Example-63: (S)-N-(3-r4-Acetoxv-(1 -methvl-1 H-tetrazol-5-vlsufanvlmethvO-piperidin-1-vl)-3-fluorophenvll-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[4-hydroxy-(1-methyl-1H-tetrazol-5-ylsufanylmethyl)-piperidin-1 -yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1 .00mmoles) in 15 ml dichloromethane was added triethyl amine (2.00mmoles), dimethylamino pyridine (2.00 mmoles) and acetic anhydride (1.2 mmoles) and the reaction mixture was stirred at ambient temperature for 16 hrs. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain the product in 74 % yield. Mp. 166-168 °C; Mass m/z 522.1((M+1), 100%) for C22H28FN7O5S.
Example-64: (S)-N-(3-r3-Fluoro-4-(4-(5-acetamido-1.3.4-thiadiazole-2-thiomethvn-4-hvdroxv piperidine-1vl) phenvll-2-oxo-oxazolidin-5-vl methyl-acetamide
To a solution of (S)-N-{3-[3-fluoro-4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-1yl)phenyl]-2-oxo-oxazolidin-5-yl methyl}-acetamide (0.3 mmol) in ethyl acetate (10 ml), was added acetic anhydride (0.6 mmol) at 50° C under stirring.
28

After 2 hours, the contents were cooled to 5-10° C and stirred overnight. The separated solid was filtered, washed with chilled ethyl acetate (2 x 5 ml) and dried to obtain the acetylated product in 74% yield. Mp. 242-246 °C; Mass m/z 539 ((M+1),
100%) for C22H27FN6O5S2.
Example-65: (S)-N-{3-r4-(4-Hvdroxv-4-thiocvanatomethvl-piperidin-1-vh-3-fluoro phenvll-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[4-(1-oxa-6-aza-spiro[2,5]oct-6-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}}-piperidin-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.11mmol) in acetonitrile (5 ml) ammonium thiocynate (2.20 mmol) and selectfluor (0.15mmol) were added the resulting mixture was stirred at 25° C for 4 h .The reaction mixture was concentrated and the residue purified by column chromatography over silica gel to obtain the product as a white solid in 43% yield. Mp. 165-167 °C; Mass m/z 423.2 ((M+1), 100%) for C19H23FN4o4S.
Example-66: (S)-N-(3-r4-(4-Hvdroxv-4-thiocvanatomethvl-piperidin-1-vl)-3.5-fluoro
phenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
Using the above procedure title compound was synthesized using (S)-N-{3-[4-(1-
oxa-6-aza-spiro[2,5]oct-6-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}}-piperidin-1-yl]-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide to obtain the product as a
white solid in 48% yield. Mp. 132-134 °C; Mass m/z 441 ((M+1), 100%) for
C19H22F2N4O4S.
Example-67: (S)-N-{3-r4-(4-Fluoro-4-thiocvanatomethvl-piperidin-1-vl)-3-fluoro phenvll-2-oxo-oxazolidin -5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[4-(4-hydroxy-4-thiocyanatomethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.37 mmol) in dichloromethane (10 ml), DAST (2.20 mmol) was added at 0 °C resulting mixture was stirred at 25° C for 1h. The solvent was evaporated and the residue chromatographed on a silica-gel column to obtain the product in 38% yield. Mp. 162-
164 °C; Mass m/z 425.2 ((M+1), 100%) for C19H22F2N4O4S.
29

Example-68: (S)-N-(3-r4-(4-( 1 H-Benzothiazoi-2-vlsulphanvlmethvlV4-hvdroxv-
piperidin-1-vl)-3.5-difluorophenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[4(1-oxa-6-aza-spiro [2,5] oct-6-yl)- 3,5-difluoro-phenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide (1.11mmol) in methanol (5 ml) 2-mercapto
1 H-benzothiazole (1.66 mmol) and potassium carbonate (1.66mmol) were added the
resulting mixture was stirred at room temperature for 12 h The reaction mixture was
concentrated. The residue was purified by column chromatography over silica gel to
obtain the product as a white solid in 73% yield.
Mp. 217-219 °C; Mass m/z 549 ((M+1), 100%) for C25H26F2N4O4S.
Using the above procedure following examples were synthesized,

Example Reagent Mp. (°C) Mass (M+1)
69 2-Mercapto 1 H-benzoimidazole 204-206 532
70 2-Mercaptoimidazole 155-158 482
71 2-Mercapto-N-methyl imidazole 136-138 496
72 2-Mercaptopyridine 165-168 493
73 5-Methyl-[1,3,4] thiadiazole-2-thiol 186-188 514
74 5-Furan-2-yl [1,3,4] oxadiazole-2-thiol 178-180 550
75 6-Bromo-3H-lmidazole [4,5-b] pyridine 190-192 611
76 5-Mercapto-1 -methyl-1 H-tetrazole 178-180 498
77 3H-lmidazo [4,5-c] pyridine-2-thiol 176-178 533
78 2-Mercapto-1 -methyl-1 H-1,3,4 triazole 154-134 497
Example-79: (S)-N-(3-r4-(4-acetoxv-4-(1 -Methyl-1 H-tetrazol-5-vlsulfanvlmethvh-
piperidin-1-vn-3.5-difluorophenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-N-{3-[3,5-Difluoro-4-[4-hydroxy-4-(1 -methyl-1 H-tetrazol-5-
ylsulfanylmethyl)-piperidin-1-yl]-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-
acetamide (1.00mmoles) in 15 ml dichloromethane was added triethyl
amine(2.00mmoles), dimethyl aminopyridine (2.00 mmoles) and acetic anhydride
30

(1.2 mmoles) and the mixture stirred at ambient temperature for 16 hrs. The solvent was evaporated under reduced pressure and the residue obtained was purified by column chromatography to obtain the product in 80 % yield. Mp. 138-140 °C; Mass
m/z 540 ((M+1), 100%) for C22H27F2N7O5S.
Example-80: (S)-N-(3-r4-(4-Acetoxv-4-f4-methvl-4H-ri.2.41-triazol-3-vlsulfanvl-methvl)-piperidin-1-vl)-3.5-difluorophenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide Using the above procedure title compound was synthesized using (S)-N-{3-[4-[4-
Hydroxy-4-(4-methyl-4H-[1,2,4]-triazol-3-ylsulfanylmethyl)}-piperidin-1-yl]-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide in 80 % yield.
Example-81: (S)-A/-(3-r3.5-Difluoro-4-(4-(5-acetamido-1.3.4-thiadiazole-2-thiomethvl)-4-hvdroxvpiperidine-1vnphenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide
To a solution of (S)-/V-{3-[3,5-difluoro-4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-1 yl)phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (0.29 mmol) in ethyl acetate (10 ml), was added acetic anhydride (0.58 mmol) at 50°C under stirring. After 2 hours, the contents were cooled to 5-10 °C and stirred overnight. The separated solid was filtered, washed with chilled ethyl acetate (2x5 ml) and dried to obtain the product in 77% yield. Mp. 258-260 °C; Mass m/z 557((M+1), 100%) for C22H26F2N6O5S2.
Example-82: (2'S, 5S)-A/-(3-(3.5-Difluoro-4-r4-r5-f/v-(tert-butvloxvcarbonvl-L-alaninvlamino)1-1.3.4-thiadiazole-2-thiomethvn-4-hvdroxypiperidine-1vnphenvn-2-oxo-oxazolidin-5-vl methyl-acetamide
To a solution of /V-fert-butyloxycarbonyl-L-alanine (1.166 mmol) in THF (3 ml), was added methane sulfonyl chloride (0.777 mmol) and triethylamine (1.943 mmol). The contents were cooled to 5-10°C and (S)-/V-{3-[3,5-difluoro-4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-1yl)phenyl]-2-oxo-oxazolidin-5-yl methyl-acetamide (0.388 mmol) was added under stirring at 5° C. The stirring was further continued at the same temperature for 14h. Water (25 ml) was added and the contents were extracted in ethyl acetate (2 x 25 ml). The combined ethyl acetate layer was dried and the solvent evaporated to obtain the product as a white solid in 64% yield. Mp. 120-124 °C; Mass m/z 686 ((M+1), 100%) for C28H37F2N7O7S2.
31

Examole-83: (S)-N-[3-f3.5-Difluoro-4-f4-f5-amiho-1.3.4-thiadiazole-2-thiomethvl)-4-hvdroxv piperidine -1vl)phenvn-2-oxo-oxazolidin-5-yl methyl-acetamide
To a solution of (5S)-/V-{3-[4-(1-oxa-6-azaspiro[2.5]oct-6-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-yl methyl]-acetamide (2.6 mmol) in THF (20 ml) was added 5-
amino-2-thio-1,3,4-thiadiazole (3.14 mmol) under stirring. The contents were stirred under nitrogen and cooled to 20-22° C. 1.6M solution of n-BuLi (3.14 mmol) in hexane was added slowly and the reaction mixture was stirred for 2 hours. Water (30 ml) was added and the resulting mixture was extracted with ethyl acetate (3x15 ml). The ethyl acetate layer was evaporated and the residue was purified by column chromatography over neutral alumina to obtain the product as a white solid in 27% yield. Mp. 164-167 °C; Mass m/z 515 ((M+1), 100%) for C20H24F2N6O4S2.
Example-84: (S)-A/-(3-f3-Fluoro-4-(4-(5-amino-1.3.4-thiadiazole-2-thiomethvl)-4-hvdroxvpiperidine-1vl)phenvn-2-oxo-oxazolidin-5-vl methyl-acetamide
To a solution of (5S)-/V-{3-[4-(1-oxa-6-azaspiro[2.5]oct-6-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-yl methyl]-acetamide (2.75 mmol) in THF (20 ml) was added 5-amino-2-thio-1,3,4-thiadiazole (3.3 mmol) and the mixture stirred under nitrogen at RT. A 1.6M solution of n-BuLi (4.95 mmol) in hexane was added slowly and stirring continued further. After 3h the solvents were evaporated and water (30 ml) was added to the residue. The separated solid was filtered and further purified by column chromatography over neutral alumina to obtain the product as a white solid in 29% yield. Mp. 146-148 °C; Mass m/z 497 ((M+1), 100%) for C20H25FN6o4S2.
Example-85: (S)-A/-(3-r3.5-Difluoro-4-(3-fluoro-4-(5-amino-1.3.4-thiadiazole-2-thiomethvl)-4-hvdroxvpiperidine-1vl)phenvn-2-oxo-oxazolidin-5-vlmethvl)-acetamide To a solution of 5-amino-2-mercapto-1,3,4-thiadiazole (1.87 mmol) in methanol (25 ml) was added sodium methoxide (2.81 mmol) under stirring and the mixture heated to 35-40° C, for 1 hour. To the clear solution was added (5S)-/V-{3-[4-(1-oxa-6-azaspiro[2.5]oct-4-fluoro-6-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide (1.25 mmol) and the mixture was stirred at 40° C. After 3 hours the
solvent was evaporated and water (50 ml) was added to the residue. The separated solid was filtered, washed with water and purified by column chromatography over
32

silica gel to obtain the product (a mixture of isomers) as a white solid in 27% yield. Mp. 160-164 °C; Mass m/z 533 ((M+1), 100%) for C20H23F3N6O4S2.
Using the above procedure following and using (5S)-A/-{3-[4-(1-oxa-6-azaspiro[2.5] oct-6-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide were synthesized from following reagents.

Example Reagent Mp. (°C) Mass (M+1)
86 5-Amino-2-mercapto-benzimidazole 120-122 547
87 3-Amino-5-mercapto-1,2,4-triazole 108-110 498
Using the above procedure following and using (5S)-N-{3-[4-(1-oxa-6-azaspiro[2.5] oct-6-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-yl methyl-acetamide were synthesized from following reagents.

Example Reagent Mp. (°C) Mass (M+1)
88 5-Amino-2-mercapto-benzimidazole 118-120 529
89 3-Amino-5-mercapto-1,2,4-triazole 84-85 480
Example-90: (2'S.5SVA/-(3-(3.5-Difluoro-4-r4-r5-N-(alaninvlamidomethanesulfonic acid)1-1.3.4-thiadiazole-2-thiomethvll-4-hvdroxvDiDeridine-1vnphenvl)-2-oxo-oxazolidin-5-vl methyl-acetamide
To a solution of (2'S,5S)-A/-{3-{3,5-difluoro-4-[4-[5-[A/-(ferf-butyloxycarbonyl-L-alaninylamino)]-1,3,4-thiadiazole-2-thiomethyl]-4-hydroxypiperidine-1yl]phenyl}-2-oxo-oxazolidin-5-yl methyl-acetamide (2.7 mmol) in acetone (5 ml), was added methane sulfonic acid (0.41 mmol) and the mixture stirred for 4 hours at RT. The mixture was filtered and the residue washed with diethyl ether (2 x 25 ml) and dried to obtain the product as a brownish hygroscopic solid, in 65% yield. Mp. 170-172 °C; Mass m/z 586 ((M+1), 100%) for C23H29F2N7O5s2-CH4SO3 (m. wt, = 681).
33

We Claim
1. An oxazolidinone compound of Formula-1,

wherein
X and Y represent a group each and independently selected from CH, CF, CCI, N;
R1 is selected from the group comprising of C1-C6 alkylsulfonyloxy, C1-C6 alkylamido,
substituted C1-C6 alkylamido, C1-C6 thioalkylamido, substituted C1-C6 thioalkylamido,
heteroaryl, substituted heteroaryl, NHR4;
wherein R4 is selected from the group comprising cyano, COORa, CSORa,
CONRbRc, CSNRbRc;
wherein Ra is selected from C1-C6 alkyl, substituted C1-C6 alkyl, cycloalkyl,
heterocyclyl;
Rb, Rc are selected from C1-C6 alkyl, substituted C1-C6 alkyl, 3-6 membered
cycloalkyl or Rb and Rc together form a 5-6 membered cycloalkyl or heterocyclyl
ring;
R2 represents group selected from H, CH3, OH, halogen or OCOR5;
wherein R5 is selected from C1-C6 alkyl, substituted C1-C6 alkyl, 5-6 membered
cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl,
aralkyl;
W is either absent or -CH2-, pyridyl;
"a" is optional double bond;
Q is represents S, SO, S02;
R3 is selected from the group consisting of
hydrogen, cyano, C1-C6 alkylcarbonyl, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6
alkenyl, substituted C2-C6 alkenyl, C1-C6 alkylcarbonyl, aryl, heteroaryl, substituted
aryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl,
substituted heterocyclyl.
34

2. The compound according to claim 1, wherein atleast X or Y is CF.
3. The compound according to claim 1, wherein R1 is C1-C6 alkylsulfonyloxy, C1-C6 alkylamido, C1C6 thioalkylamido, or heteroaryl.
4. The compound according to claim 1, wherein R1 is C1C6 alkylamido or heteroaryl.
5. The compound according to claim 1, wherein R2 is H or OH.
6. The compound according to claim 1, wherein W is absent or -CH2.
7. The compound according to claim 1, wherein wherein atleast X or Y is CF; "a" is single bond; W is absent or CH2; R2 is H or OH; R1 is C1-C6 alkylamido or heteroaryl.
8. A compound selected from
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfanylmethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfanyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfinyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfinylmethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfanyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl]-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfanylmethyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-phenylsulfinylmethyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzimidazole-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzothiazole-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(phenylsulfonyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl]-acetamide;
(S)-N-{3-[4-(phenylsulfinyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl]-acetamide; (S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
35

(S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulfinyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulfanyl)-piperidinr;1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide; (S)-N-{3-[4-(4-(1H-benzothiazol-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(R)-2-{3-[4-(4-phenylsulfanyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-2H-1,2,3-triazole;
(R)-1 -{3-[4-(4-phenylsulfanyl-piperidin-1 -yl)-3,5-difluorophenyl]-2-oxo- oxazolidin-5-
ylmethyl}-1 H-1,2,3-triazole;
(S)-N-{3-[4-(4-(1H-benzimidazole-2-sulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzimidazole-2-ylsulphanylmethyl)-4-hydroxy-piperidin-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(2-hydroxyethylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-toluenesulfanyl-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3-fluoro-4-morpholin-4-yl-phenylsulfanylmethyl)-4-hydroxy-piperidin-
1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3,4-difluoro-phenylsulfanylmethyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-toluenesulfanylmethyl-piperidin-1-yl)-3-fluoro phenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzoxazolyl-2-sulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1H-benzoxazolyl-2-sulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(3-hydroxy-propylsulfanylmethyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide; (S)-N-{3-[4-(4-(2-hydroxyethylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
36

(S)-N-{3-[4-(4-thioacetyl-piperidin-1-yl)-3,5-dlfluorophenyl]-2-oxo-oxazolldin-5-yl
methyl-acetamide;
(S)-N-{3-[4-(4-thiocynato-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-thiocynato-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-
acetamide;
(S)-N-{3-[4-(4-toluenesulfanyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-toluene-sulfinyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-(3,4-difluorophenylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(3,4-difluorobenzenesulfinyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-thioacetyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-
acetamide;
(S)-N-{3-[4-(4-mercapto-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-
acetamide;
(S)-N-{3-[4-(4-(pyridin-2-ylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-(pyridin-2-ylsulfinyI)-piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(pyridin-2-ylsulfanylmethyl)-piperidin-1-yl)-3-fluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(pyridin-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-
oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3,5-difluoro-
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3-fluoro-
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
37

(S)-N-{3-[4-(4-hydroxy-4-(1 -methyl-1 H-imidazol-2-ylsulfanylmethyl)-piperidin-1 -yl)-
3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(pyridin-2-ylsulfanylmethyl)-piperidin-1-yl)-3,5-dlfluoro-
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(thiophen-2-ylsulfanylmethyl)-piperidin-1-yl)-3-fluorophenyl]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-pyridin-4-yl-[1,3,4]oxaadiazole-2-ylsulfanyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(5-m8thyl-[1,3,4]thiadiazol8-2-ylsulfanylmethyl)-piperidin-1-
yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-[1,3,4]thiadiazole-2-ylsulfanyl)-piperidin-1-yl)-3-fluorophenyl]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-4-hydroxy-piperidin-1-
yl)-3-fluoroph8nyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl) piperidin-1 -
yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-methyl-[1,3,4]thiadiazol8-2-ylsulfanyl)-piperidin-1-yl)-3-fluoroph8ny]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4,5-dihydro-thiazol-2-ylsulphanylm8thyl)-4-hydroxy-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-[1,3,4]thiadiazole-2-ylsulfanyl)-piperidin-1-yl)-3,5-difluoro
phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-[3-{3-fIuoro-4-[4-(pyridine-2-ylsulfanylmethyl)-piperidin-1-yl]-phenyl}-2-oxo-
oxazolidin-5-ylmethyl]-acetamide;
(S)-N-{3-[4-(4-(5-furan-2-yl-[1,3,4]oxadiazol-2-ylsulfanylmethyl)-4-hydroxy piperidin-
1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylm8thyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-(1 -methyl-1 H-[1,3,4]triazol-2-ylsufanylmethyl)-piperidin-1 -yl)-
3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-methyl-[1,3,4]thiadiazole-2-ylsulfanyl)-piperidin-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-pyridin-4-yl-[1,3,4]thiadiazole-2-ylsulfanyl)-piperidin-1-yl)-3,5-
difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
38

(S)-N-{3-[4-(4-(6-bromo-3H-imidazole[4J5-b]pyridinl-2-ylsulfanyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(6-bromo-3H-imidazole[4,5-b]pyridinl-2ylsulfanyl)-4-hydroxy-piperidin-
1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(6-bromo-3H-imidazole[4,5-b]pyridinl-2ylsulfanyl)-4-hydroxy-piperidin-
1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1 -methyl-5-(1 -methyl-1 H-imidazol-2-ylsulfanyl)-1 H-imidazol-2-
ylsulfanyl)-piperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-hydroxy-(1 -methyl-1 H-tetrazol-5-ylsufanylmethyl)-piperidin-1 -yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1 -methyl-1 H-tetrazol-5-ylsulfanyl)-piperidin-1 -yl)-3,5-difluoro-phenyl]-
2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(1 -methyl-1 H-tetrazol-5-ylsulfanyl)-piperidin-1 -yl)-3-fluorophenyl]-2-
oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanylmethyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-piperidin-1-yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1 -methyl-1 H-tetrazol-5-ylsulfanylmethyl)-piperidin-1 -yl)-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-acetoxy-4-(1 -methyl-1 H-tetrazol-5-ylsulfanylmethyl)-piperidin-1 -yl)-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazo[4,5-c]pyridinl-2-ylsulfanylmethyl)-piperidin-1-
yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-(1H-imidazo[4,5-c]pyridin-2-ylsulfanylmethyl)-piperidin-1-yl)-
3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-acetoxy-4-(4-methyl-4H-[1,2,4]-triazol-3-ylsulfanylmethyl)-piperidin-1-
yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-thiocyanatomethyl-piperidin-1-yl)-3,5-ifluorophenyl]-2-oxo-
oxazolidin -5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-hydroxy-4-methyl-4-(1-methyl-4H-[1,2,4]triazol-3-ylsulfanylmethyl)-
piperidin-1-yl)-3-fluorophenyl]-2-oxo-oxazolidJn-5-ylmethyl}-acetamide;
39

(S)-N-{3-[4-(4-hydroxy-4-thiocyanatomethyl-piperidin-1-yl)-3-fluorophenyl]-2-oxo-
oxazolJdin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-acetoxy-(1 -methyl-1 H-tetrazol-5-ylsufanylm8thyl)-piperidin-1 -yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-fluoro-4-thiocyanatomethyl-pip8ridin-1-yl)-3-fluoroph8nyl]-2-oxo-
oxazolidin -5-ylmethyl}-ac8tamide;
(S)-N-{3-[4-(acetylsulfanylmethylpip8ridine-1-yl)-3-fluorophenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide;
(S)-N-{3-[4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-1yl)-3,5-
difluoro-phenyl]-2-oxo-oxazolidin-5-yl methyl-acetamide;
(S)-N-{3-[4-(4-(5-acetylamino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypiperidine-
1yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide;
(S)-N-{3-[4-(4-(5-amino-1,3,4-thiadiazole-2-thiomethyl)-4-hydroxypip8ridine-1yl)-3-
fluoro-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamid8
(S)-N-{3-[4-(4-(5-acetylamino-1,3,4-thiadiazol8-2-thiomethyl)-4-hydroxypiperidin8-
1yl)-3-fluoro-ph8nyl]-2-oxo-oxazolidin-5-ylm8thyl}-acetamide;
(S)-N-{3-[4-(4-(5-/V-(tert-butyloxycarbonyl-L-alaninylamino)-1)3,4-thiadiazole-2-
thiomethyl)-4-hydroxypiperidine-1yl)-3,5-difluoro-phenyl]-2-oxo-oxazolidin-5-
ylmethyl-acetamide
(S)-N-{3-[4-(4-(6-aminobenzimidazol-2-yl-thiomethyl)-4-hydroxypip8ridin-1yl)-3-
fluorophenyl]-2-oxo-oxazolidin-5-ylm8thyl}-ac8tamide;
(S)-N-{3-[4-(4-(3-amino-1,2,4-triazol-5-yl-thiom8thyl)-4-hydroxypiperidin-1-yl-3-
fluoro)phenyl]-2-oxo-oxazolidin-5-ylm8thyl}-acetamid8;
(S)-N-{3-[4-(4-(5-amino-1,3,4-thiadiazol-2-sulfanylmethyl)-4-hydroxy)-3-
fluoropiperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylm8thyl}-acetamid8;
(2'S,5S)-N-{3-[4-(4-(5-(L-ala)amino-1,3,4-thiadiazol-2-yl)sulfanylmethyl-4-
hydroxypiperidin-1-yl)-3,5-difluorophenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamid8
methanesulfonate;
(S)-N-{3-[4-(4-(5-aminobenzimidazole-2-thiom8thyl)-4-hydroxypiperidine-1-yl)-3,5-
difluorophenyl]-2-oxo-oxazolidin-5-ylm8thyl}-ac8tamide;
(S)-N-{3-[4-(4-(4-amino-2,3,5-triazole-5-sulfanylmethyl)-4-hydroxypiperidin-1-yl)-3,5-
difluoroph8nyl]-2-oxo-oxazolidin-5-ylm8thyl}-ac8tamide.
40

9. A pharmaceutical composition comprising a compound according to claim 1 as an
effective ingredient and a pharmaceutically acceptable carrier, diluent or excipient.
10. A pharmaceutical composition comprising a compound according to claim 8 as
an effective ingredient and a pharmaceutically acceptable carrier, diluent or
excipient.

Dated this 13th day of September 2006 Dr. Mahesh V Patel
Director-Drug Discovery

41

Abstract
The present invention provides compounds having antimicrobial activity for preventing and treating diseases caused by microbial infections. Thus, the present invention provides novel oxazolidinone derivatives, processes for making compounds as well as antimicrobial pharmaceutical compositions containing said derivatives as active ingredient and method of treating microbial infections with the said derivatives.
1 4 SEP Z006
42