WO2020234636A1

WO2020234636A1 - Novel compounds for the treatment of mammalian infections

Info

Publication number: WO2020234636A1
Application number: PCT/IB2019/060511
Authority: WO
Inventors: Ranjit Desai; Vrajesh PANDYA; Anshul SATYANAND; Bhavesh VORA; Jignesh JOSHI; Mehul Pujara; Anil ARGADE
Original assignee: Cadila Healthcare Limited
Priority date: 2019-05-17
Filing date: 2019-12-06
Publication date: 2020-11-26

Abstract

Present invention relates to the novel heterocyclic compounds of the general formula (I) their tautomeric forms, their stereoisomers and their pharmaceutically acceptable salts etc. The invention also relates to pharmaceutical compositions containing compounds of general formula (I) that are useful in the treatment of bacterial infection.

Description

NOVEL COMPOUNDS FOR THE TREATMENT OF MAMMALIAN

INFECTIONS FIELD OF INVENTION

The present invention relates to novel compounds of the general formula (I) having an excellent antibacterial activity against tuberculosis bacteria, their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

BACKGROUND OF THE INVENTION

Tuberculosis (TB) is one of the leading cause of human death from infectious disease in the world. About 33% of world’s population is thought to be infected with Mycobacterium tuberculosis (Mtb), the pathogen that causes TB disease (WHO “Global Tuberculosis Report 2016”, World Health Organization, 2017). Current treatment has a potential to cure drug-sensitive TB, however treatment of drug- resistant or multi drug-resistant TB (MDR-TB) is challenging and needs a two years of combination chemotherapy (WHO“Multidrug-Resistant Tuberculosis (MDR-TB) 2016 Update”, World Health Organization, 2016). Resistance to current treatment for MDR-TB and extensively resistant TB (XDR-TB) highlights the need of new drugs with novel mechanism of actions.

Linezolid is approved antibiotic for gram positive bacterial infections. It has also shown anti-bacterial activity against mycobacterium tuberculosis pathogens. Linezolid and other oxazolidinone class of agents inhibit bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit and interfering with the placement of the aminoacyl-tRNA. They do not bind to mammalian cytoplasmic ribosomes, but do bind to mitochondrial ribosomes which are responsible for bone marrow toxicity associated with Linezolid and other oxazolidinones. Treatment of TB is lengthy which makes Linezolid not suitable for its treatment. Hence, novel oxazolidinones with improves safety profile is required which can be utilized for the treatment of TB. WO2017015106 describes substituted phenyl oxazolidinones for the treatment of tuberculosis. KR101271224 describes oxazolidinone derivatives containing bicyclic group having antibacterial activity against gram positive bacteria including various resistant strains. WO2005054234 describes novel substituted piperidino phenyloxazolidinone derivatives as active ingredients and methods of treating bacterial infection. The other documents that describe oxazolidinone class of inhibitors includes, WO9613502, WO9635691, WO9615130, WO9710223, WO02/080841, WO2001042242, WO2003064415, WO2009020616, CN107400126, WO2017070024, WO2005054234, WO02/051819, WO2017156519, WO2013044865, and WO 2006059221 the contents of which are incorporated herein as reference. SUMMARY OF THE INVENTION

The present invention discloses novel compounds of the general formula (I) having an excellent antibacterial activity against tuberculosis bacteria. The compounds of the present invention are useful in the treatment of the human or animal body, by regulation of bacterial protein synthesis. The compounds of this invention are therefore suitable for the treatment of tuberculosis or Mycobacterium infection.

The main objective of the present invention is to provide novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures suitable for the treatment of tuberculosis or Mycobacterium infection.

In an embodiment is provided a process for the preparation of novel compounds of general formula (I), their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutical compositions containing them.

In another embodiment is provided pharmaceutical compositions containing compounds of general formula (I), their tautomeric forms, their pharmaceutically acceptable salts, solvates and their mixtures having pharmaceutically acceptable carriers, solvents, diluents, excipients and other media normally employed in their manufacture.

In a further embodiment is provided the use of the novel compounds of the present invention for the treatment of mammalian infections such as tuberculosis, by administering a therapeutically effective & non-toxic amount of the compound of formula (I), or their pharmaceutically acceptable compositions to the mammals.

In yet another embodiment is provided the use of the novel compounds of the present invention for the treatment of mammalian infections such as tuberculosis, by administering a therapeutically effective & non-toxic amount of the compound of formula (I), or their pharmaceutically acceptable compositions to the mammals.

In yet another embodiment is provided a pharmaceutical composition comprising the compound of formula (I) and second therapeutic agent for the treatment of mammalian infections such as tuberculosis. DETAILED DESCRIPTION OF THE INVENTION

Accordingly, the present invention relates to compounds of the general formula (I),

wherein,

‘Y’ represents OH, NR₂R₃, NHC(O)R₄;

In one of the embodiment‘X’ is:

wherein, p represents integers from 0-2;

In another embodiment‘X’ is

wherein‘T’ represents O or NR₆R₇;

‘A’ represents either a bond or is absent;

In an embodiment, when‘A’ represents a bond, then‘T’ is directly connected to central 5-membered pyrrolidine ring and forms the following structure:

when‘A’ is absent, then‘T’ represents NR₆R₇ and forms the following structure:

R₁ at each occurrence independently groups selected from H, F, Cl, CH₃, CN and OCH₃;

m = is an integer from 1-4;

Each of R₂ and R₃ are independently selected from H, (C₁-C₆)alkyl, (C₃- C₆)cycloalkyl, aryl, heterocyclyl and heteroaryl groups each of which may be further optionally substituted; in an alternative embodiment, R₂ and R₃ taken together with the nitrogen to which they are attached may form a 4- to 8- membered heterocyclyl or heteroaryl ring, optionally with 1 to 3 additional heteroatoms selected from O, S, or N and may be further be optionally substituted;

R₄ is independently selected from (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, heterocyclyl, aryl, heteroaryl and (C₁-C₆)alkoxy group, each of which may be further optionally substituted;

In an embodiment, when any of the (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, aryl, heterocyclyl and heteroaryl groups are optionally substituted, the substituents may be selected from halo, hydroxyl, (C1-C6)alkyl, (C3-C6)cycloalkyl, heterocyclyl, (C1- C₆)alkoxy, haloalkyl, NO₂, CN and NH₂;

Each of R_5, R₆ and R₇ are independently selected from the group comprising of hydrogen, haloalkyl, optionally substituted groups selected from (C₁-C₆)alkyl, (C₃- C₆)cycloalkyl, heterocyclyl;

In an alternate embodiment, R₆ and R₇ together with the common N atom to which they are attached may form a -5 to -8 membered cyclic ring optionally with 1 to 3 additional heteroatoms selected from O, S, or N and may be further be optionally substituted;

Each of R₈ and R₉ are independently selected from H, optionally substituted groups selected from (C₁-C₆)alkyl and (C₃-C₆)cycloalkyl, wherein substitutions on (C₁-C₆)alkyl and (C₃-C₆)cycloalkyl are as defined earlier;

Further preferred embodiments are those disclosed below: Preferred‘Y’ may be selected from the group consisting of NR₂R₃ and NHC(O)R₄;

Preferred R₁ is fluorine;

In a further embodiment the groups, radicals described above may be selected from:

- the“alkyl” group used either alone or in combination with other radicals, denotes a linear or branched radical containing one to six carbons, selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, amyl, t-amyl, n-pentyl, n-hexyl, and the like;

- the“cycloalkyl”, or“alicyclic” group used either alone or in combination with other radicals, is selected from a cyclic radical containing three to six carbons, more preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like; - the“haloalkyl” group is selected from an alkyl radical, as defined above, suitably substituted with one or more halogens; such as fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, mono or polyhalo substituted methyl, ethyl, propyl, butyl, pentyl or hexyl groups;

- the“aryl” or“aromatic” group used either alone or in combination with other radicals, is selected from a suitable aromatic system containing one, two or three rings wherein such rings may be attached together in a pendant manner or may be fused, more preferably the groups are selected from phenyl, naphthyl, tetrahydronaphthyl, indane, biphenyl, and the like;

- the“heterocyclyl” or“heterocyclic” group used either alone or in combination with other radicals, is selected from suitable saturated, partially saturated or unsaturated aromatic or non-aromatic mono, bi or tricyclic radicals, containing one or more heteroatoms selected from nitrogen, sulfur and oxygen, more preferably selected from aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, 2-oxopiperidinyl, 4-oxopiperidinyl, 2-oxopiperazinyl, 3- oxopiperazinyl, morpholinyl, thiomorpholinyl, 2-oxomorpholinyl, azepinyl, diazepinyl, oxapinyl, thiazepinyl, oxazolidinyl, thiazolidinyl, dihydrothiophene, dihydropyran, dihydrofuran, dihydrothiazole, benzopyranyl, benzopyranonyl, benzodihydrofuranyl, benzodihydrothienyl, pyrazolopyrimidonyl, azaquinazolinoyl, thienopyrimidonyl, quinazolonyl, pyrimidonyl, benzoxazinyl, benzoxazinonyl, benzothiazinyl, benzothiazinonyl, thieno piperidinyl, and the like; In one embodiment, the heterocycle group, wherever applicable, may consists of appropriate number of carbon atoms and include from 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, p = 0-2; - the“heteroaryl” or“heteroaromatic” group used either alone or in combination with other radicals, is selected from suitable single or fused mono, bi or tricyclic aromatic heterocyclic radicals containing one or more hetero atoms selected from O, N or S, more preferably the groups are selected from pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, isothiazolyl, imidazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, benzofuranyl, benzothienyl, indolinyl, indolyl, azaindolyl, azaindolinyl, pyrazolopyrimidinyl, azaquinazolinyl, pyridofuranyl, pyridothienyl, thienopyrimidyl, quinolinyl, pyrimidinyl, pyrazolyl, quinazolinyl, pyridazinyl, triazinyl, benzimidazolyl, benzotriazolyl, phthalazynil, naphthylidinyl, purinyl, carbazolyl, phenothiazinyl, phenoxazinyl, benzoxazolyl, benzothiazolyl and the like;

Suitable groups and substituents on the groups may be selected from those described anywhere in the specification.

Preferred compounds according to the present invention include but are not limited to:

N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol- 5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)acetamide; N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5-difluorophenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3-fluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(3-fluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3-fluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

5-(2,6-difluoro-4-((S)-5-((isoxazol-3-ylamino)methyl)-2-oxooxazolidin-3- yl)phenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

ethyl (((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(3aR,6aS)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

(3aR,6aS)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

N-(((S)-3-(3-fluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((S)-3-(3,5-difluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((S)-3-(3-fluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3,5-difluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol- 5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(3aS,6aR)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one; (3aS,6aR)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

N-(((5S)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4- d]imidazol-5(1H)-yl)phenyl)oxazolidin-2-one;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3,5-difluoro-4-(2- oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)oxazolidin-2-one;

N-(((S)-3-(3-fluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((S)-3-(3-fluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((S)-3-(3-fluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3-fluoro-4-((3aS,6aR)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3,5-difluoro-4-((3aS,6aR)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(3aR,6aS)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)-3-methylhexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

(3aR,6aS)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)-3-methylhexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

(3aS,6aR)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)-3-methylhexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

(3aS,6aR)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)-3-methylhexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

N-(((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)-3- fluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide; methyl (((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)- 3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)- 3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)-3- fluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(3-fluoro-4-(6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3,5-difluoro-4-(6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(3-fluoro-4-(6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3,5-difluoro-4-(6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

5-(2-fluoro-4-((R)-5-(hydroxymethyl)-2-oxooxazolidin-3-yl)phenyl)hexahydro-2H- pyrrolo[3,4-d]oxazol-2-one;

5-(2,6-difluoro-4-((R)-5-(hydroxymethyl)-2-oxooxazolidin-3-yl)phenyl)hexahydro- 2H-pyrrolo[3,4-d]oxazol-2-one;

N-(((5S)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3-fluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3-fluorophenyl)- 2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3-fluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3- fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate; methyl (((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3-fluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3- fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5- c]pyrrol-2-yl)phenyl)oxazolidin-2-one;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(6-oxidooctahydro-2H- thiepino[4,5-c]pyrrol-2-yl)phenyl)oxazolidin-2-one;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5- c]pyrrol-2-yl)-3-fluorophenyl)oxazolidin-2-one;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5- c]pyrrol-2-yl)phenyl)oxazolidin-2-one;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H- thiepino[4,5-c]pyrrol-2-yl)phenyl)oxazolidin-2-one;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5- c]pyrrol-2-yl)-3,5-difluorophenyl)oxazolidin-2-one;

(5S)-5-(aminomethyl)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)oxazolidin-2-one;

(5S)-5-(aminomethyl)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3- fluorophenyl)oxazolidin-2-one;

N-(((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3-fluorophenyl)-2- oxooxazolidin-5-yl)methyl)acetamide; methyl (((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5-difluorophenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)pyrrolidin- 3-yl)morpholine-4-carboxamide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)morpholine-4-carboxamide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)pyrrolidin- 3-yl)thiomorpholine-4-carboxamide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)thiomorpholine-4-carboxamide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)pyrrolidin- 3-yl)thiomorpholine-4-carboxamide 1,1-dioxide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)thiomorpholine-4-carboxamide 1,1-dioxide;

N-(((5S)-3-(3-fluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3-fluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)oxetane-3-carboxamide;

N-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

N-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

ethyl (((S)-3-(3-fluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((S)-3-(3,5-difluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate; N-(((5S)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

ethyl (((5S)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

methyl (((5S)-3-(3-fluoro-4-(3-methyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3,5-difluoro-4-(3-methyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol- 5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((S)-3-(3-fluoro-4-((3aR,6aS)-6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((S)-3-(3-fluoro-4-((3aR,6aS)-6a-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-6a-methyl-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(4-((3aR,6aS)-6a-cyclopropyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(4-((3aR,6aS)-6a-cyclopropyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3-methyl-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3-methoxy-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol- 5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((S)-3-(3-cyano-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(5R)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)-5- (hydroxymethyl)oxazolidin-2-one; N-(((5S)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3-fluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3-fluorophenyl)- 2-oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(3-fluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3-fluorophenyl)- 2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide;

(5R)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-5- (hydroxymethyl)oxazolidin-2-one;

(5R)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-5- (hydroxymethyl)oxazolidin-2-one;

(5R)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3-fluorophenyl)-5- (hydroxymethyl)oxazolidin-2-one;

(5R)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5-difluorophenyl)- 5-(hydroxymethyl)oxazolidin-2-one;

N-(((5S)-3-(3-fluoro-4-(3-ureidopyrrolidin-1-yl)phenyl)-2-oxooxazolidin-5- yl)methyl)acetamide;

N-(((5S)-3-(3,5-difluoro-4-(3-ureidopyrrolidin-1-yl)phenyl)-2-oxooxazolidin-5- yl)methyl)acetamide; N-(((5S)-3-(3-fluoro-4-(3-(1,3,3-trimethylureido)pyrrolidin-1-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3,5-difluoro-4-(3-(1,3,3-trimethylureido)pyrrolidin-1-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2-fluorophenyl)pyrrolidin- 3-yl)pyrrolidine-1-carboxamide;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)pyrrolidine-1-carboxamide;

3-(1-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)-1,1-dimethylurea;

methyl (((5S)-3-(3-fluoro-4-(3-(1,3,3-trimethylureido)pyrrolidin-1-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3,5-difluoro-4-(3-(1,3,3-trimethylureido)pyrrolidin-1-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

N-(((S)-3-(4-((R)-3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5-difluorophenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-(((S)-3-(4-((S)-3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5-difluorophenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-((R)-1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6-difluorophenyl) pyrrolidin-3-yl)morpholine-4-carboxamide;

N-((S)-1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6-difluorophenyl) pyrrolidin-3-yl)morpholine-4-carboxamide. The novel compounds of this invention may be prepared using the reactions and techniques as shown in scheme below and described in this section. The reactions are performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being affected. It is understood by those skilled in the art that the nature and order of the synthetic steps presented may be varied for the purpose of optimizing the formation of the compounds of the present invention. It will also be well appreciated that one or more of the reactants may be protected and deprotected for facile synthesis by techniques known to persons skilled in the art. It will also be appreciated that one or more of the compounds of the present invention may exist in stereoisomeric and/or diastereomeric forms. Such stereoisomers and/or diastereoisomers as well as their optical antipodes are to be construed to be within the scope of the present invention. It will also be well appreciated that one or more of these compounds may be converted to their salts and other derivatives based on the specific groups present on the compounds, which can be well comprehended by persons skilled in the art. Such salts and/or other derivatives, as the case may be should also be construed to be within the scope of the present invention. Scheme 1: Synthesis of compounds of general formula (I)

The compound (IV) can be obtained by reacting compounds of the formula (II) with (III) (prepared by following the general process described in WO2009153554) in the presence of base such as sodium carbonate, potassium carbonate, sodium hydride etc. in solvents such as THF, DMF, methanol etc. The compounds of general formula (V) can be obtained by reduction using stannous chloride dihydrate in ethyl acetate. The compounds of the general formula (VI) can be obtained by reacting (V) with benzyloxycarbonyl chloride using sodium bicarbonate as a base in solvents such as water, ethyl acetate, acetonitrile, THF or mixture thereof. Compounds of the formula (I, when Y = OH) can be obtained by treating it with n-butyl lithium and R-glycidyl butyrate in THF. The compound of formula (I, when Y = OH) was then converted into mesylate derivatives (VII), which was then reacted with sodium azide in DMF to get compounds of the formula (VIII). Reduction of (VIII) using sodium borohydride and palladium charcoal as a catalyst or treatment with PPh₃ and water gave further compounds of formula (I, when Y = NH₂). Compounds of formula (I, when Y = -NHCOR₄) can be obtained by reacting the above obtained amino compounds of formula (I, when Y = NH₂) with appropriate acid chlorides in solvents such as DCM, THF etc. in presence of base such as TEA, pyridine etc. Compounds of the formula (VIII) can also be converted in to compound of formula (I, when Y = triazole), by reacting it with Bicyclo[2.2.1]hepta-2,5-diene in dioxane at reflux temperature. Scheme 2: Synthesis of compounds of general formula (I)

Alternatively, compounds of the general formula (I) can be prepared using scheme 2. The compound (V) can be reacted with (IX) under refluxing conditions in protic solvents such as MeOH, EtOH, water etc. to get compounds of general formula (X). The compounds of the general formula (XI) can be obtained by heating (X) with N,N’-carbonyl diimidazole using chloroform as solvent. Subsequent deprotection can be carried out using aqueous methylamine in methanol or ethanol to get compounds of the formula (I, when Y = NH₂). Compounds (I, when Y = -NHCOR₄) can be obtained by reacting above amino compound with appropriate acid chlorides or acid anhydrides in suitable solvents such as DCM, THF etc. in presence of suitable base such as TEA, pyridine etc. The novel compounds of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known. Pharmaceutical composition comprising the compounds of the present invention may comprise a suitable binder, suitable bulking agent and/or diluent and any other suitable agents as may be necessary. Novel compounds of the present invention can be used for the treatment of mammalian infections such as tuberculosis by administrating therapeutically active and non-toxic amount of compounds of formula (I) or pharmaceutically acceptable compositions thereof. These compounds may be used to treat infection of Gram positive bacteria. A method of treating anti-tuberculosis infection in a subject that comprising administering to a patient in need thereof an effective amount of a compound of formula (I) or its suitable pharmaceutical composition is also provided hereinafter. The pharmaceutical compositions according to this invention can exist in various forms. In some embodiments, the pharmaceutical composition is suitable for topical, oral or parenteral administration. One or more additional pharmaceutical agents or treatment methods can be used in combination with the compounds of the present invention for treatment or prevention of mammalian infection. The therapeutic agents such as anti-TB agent and antibiotics can be combined with the present compounds in a single dosage form, or the agents can be administered simultaneously or sequentially in separate dosage forms. Thus, the compound of formula (I) can be administered in combination with other therapeutic agents such as isoniazide, rifampin, rifapentine, rifabutin, ethambutol, pyrazinamide, streptomycin, amikacin, levofloxacin, ofloxacin, p- aminosalicylic acid. Following is a list of abbreviations used in the description of the preparation of the compounds of the present invention

DMF : N,N-Dimethyl formamide

DMSO : Dimethyl sulfoxide

EtOH : Ethanol

EtOAc : Ethyl acetate

h : hours

HCl : Hydrochloric acid

IPA : Isopropyl alcohol

MeOH : Methanol

mCPBA : meta-Chloro perbenzoic acid MsCl : Methane sulfonylchlorode

NH₃ : Ammonia

Na₂CO₃ : Sodium carbonate

Na₂SO₄ : Sodium sulfate

NaHCO₃ : Sodium bicarbonate/sodium hydrogen carbonate

TEA : Triethylamine

TFA : Trifluoro acetic acid

THF : Tetrahydrofuran

TLC : Thin layer chromatography The invention is further exemplified by the following non-limiting examples which discloses the preferred means of carrying out the invention and should not be construed to be limiting the scope of the invention from what has been disclosed elsewhere in the specification. EXAMPLES Example 1

Preparation of N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: (3aR,6aS)-5-(2,6-difluoro-4-nitrophenyl)hexahydro-2H-pyrrolo[3,4- d]oxazol-2-one

To a stirring solution of (3aR,6aS)-hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one hydrochloride (0.440 g, 2.67 mmol, prepared as per general process described in WO2009153554) in DMF (20 ml) was added 1,2,3-trifluoro-5-nitrobenzene (0.430 g, 2.428 mmol) followed by K₂CO₃ (0.839 g, 6.07 mmol). Reaction mixture was stirred at 70-80 ^oC for 12 h. Reaction mixture was then poured into water and extracted with DCM:MeOH (7:3). Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get title product. ESI-MS (m/z): 286.05 [M+H]⁺. Step 2: (3aR,6aS)-5-(4-amino-2,6-difluorophenyl)hexahydro-2H-pyrrolo[3,4- d]oxazol-2-one

To a stirring solution of product of step 1 (0.680 g, 2.384 mmol) in DCM (75 ml) and methanol (25 ml) was added Palladium on Carbon (10 % wet) (1.26 g, 11.29 mmol) and reaction was stirred under H₂ pressure at 25-30^oC for 6 h. After complete conversion of starting material, the reaction mixture was filtered over Celite bed and filtrate was dried over sodium sulfate, distilled under vacuum to get the titled product as solid. ESI-MS (m/z): 256.07 [M+H]⁺. Step 3: 2-((R)-3-((3,5-difluoro-4-((3aR,6aR)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)amino)-2-hydroxypropyl)isoindoline-1,3-dione

To a stirring solution of product of step 2 (0.600 g, 2.351 mmol) in ethanol (13.50 ml) and Water (1.5 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (0.836 g, 4.11 mmol, prepared as per teachings in Tetrahedron Asymmetry, 7(6), 1641-1648; 1996) at 25-30^oC. Reaction mixture was stirred at 70-80°C for 16 h. After complete conversion of starting material, the reaction mixture was cooled to 10°C and precipitate was filtered and dried under vacuum to get title product as solid. ESI-MS (m/z): 459.12 [M+H]⁺. Step 4: 2-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)isoindoline-1,3-dione

To a stirring solution of product of step 3 (0.830 g, 1.811 mmol) in chloroform (20 ml) was added N,N’-carbonyl diimidazole (1.174 g, 7.24 mmol). Reaction mixture was stirred at 70°C for 5 h. After complete conversion of starting material, solvent was distilled and reaction mixture was acidified using 35 % HCl up to pH =2. Product was extracted with DCM:methanol (7:3). Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get the titled product. ESI-MS (m/z): 485.11 [M+H]⁺. Step 5 : (3aR,6aS)-5-(4-((S)-5-(aminomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one

To a stirring solution of product of step 4 (0.740 g, 1.528 mmol) in ethanol (10 ml) was added aq. methyl amine (40% solution) (1.186 ml, 15.28 mmol) at 25-30 ^oC. Reaction mixture was stirred at 80°C for 3 h. After complete conversion of starting material, the reaction mixture was diluted with DCM (100 ml) and washed with cold water (20 ml). Organic layer was dried over sodium sulfate and distilled to get the titled product as solid. ESI-MS (m/z): 355.10 [M+H]⁺. Step 6 : N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

To a stirring solution of product of step 5 (0.500 g, 1.411 mmol) in DCM (10 ml) was added pyridine (0.171 ml, 2.117 mmol) followed by acetic anhydride (0.186 ml, 1.976 mmol) and stirred for 2 h at 25-30^oC. After complete conversion of starting material the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by preparative HPLC to get titled product as white solid. ¹H NMR (MeOD): 7.25-7.22 (d, J = 12 Hz, 2H), 5.20 (m, 1H), 4.88 (m, 1H), 4.42 (m, 1H), 4.13 (m, 1H), 3.80 (m, 1H), 3.70-3.67 (d, J = 13.24 Hz, 2H), 3.57-3.56 (d, J = 4.40 Hz, 1H), 3.50-3.48 (d, J = 10.40 Hz, 1H), 3.39- 3.36 (m, 1H), 3.34-3.27 (m, 1H), 2.71 (s, 3H), ESI-MS (m/z) : 397.09 [M+H]⁺. Example 2

Preparation of N-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: (3aR,6aS)-5-(2-fluoro-4-nitrophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol- 2-one

To a stirring solution of (3aR,6aS)-hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one hydrochloride (0.6 g, 3.65 mmol) in DMF (10 ml) was added 1,2-difluoro-4- nitrobenzene (0.527 g, 3.31 mmol) followed by K₂CO₃ (1.14 g, 8.29 mmol). Reaction mixture was stirred at 70-80^oC for 12 h. Reaction mixture was then poured in to water and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get titled product. ESI-MS (m/z): 268.08 [M+H]⁺. Step 2: (3aR,6aS)-5-(4-amino-2-fluorophenyl)hexahydro-2H-pyrrolo[3,4- d]oxazol-2-one

To a stirring solution of product of step 1 (0.730 g, 2.73 mmol) in EtOAc (20 ml) was added SnCl₂.2H₂O (3.08 g, 13.66 mmol) and reaction stirred at 80^oC for 2 h. After complete conversion of starting material, the reaction mixture was cooled and basified with NH₃ solution. EtOAc layer was decanted and dried over sodium sulfate and distilled under vacuum to get the titled product as solid. Step 3: 2-((R)-3-((3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)amino)-2-hydroxypropyl)isoindoline-1,3-dione

To a stirring solution of product of step 2 (0.670 g, 2.82 mmol) in ethanol (13.5 ml) and water (1.5 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (1.04 g, 4.94 mmol) at 25-30^oC. Reaction mixture was stirred at 70-80°C for 16 h. After complete conversion of starting material, the reaction mixture was cooled to 10°C and precipitate was filtered and dried under vacuum to get titled product as solid. Step 4: 2-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)isoindoline-1,3-dione

To a stirring solution of product of step 3 (1.10 g, 2.49 mmol) in Chloroform (20 ml) was added N,N’-carbonyl diimidazole (1.62 g, 9.99 mmol). Reaction mixture was stirred at 70°C for 5 h. After complete conversion of starting material, solvent was distilled and reaction mixture was acidified by 35 % HCl up to pH = 2. Product was extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get the titled product. Step 5: (3aR,6aS)-5-(4-((S)-5-(aminomethyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one

To a stirring solution of product of step 4 (1.16 g, 2.48 mmol) in Ethanol (10 ml) was added aq. Methyl amine (40 % solution) (1.9 ml, 24.80 mmol) at 25-30^oC. Reaction mixture was stirred at 80°C for 3 h. After complete conversion of starting material, the reaction mixture was diluted with DCM (100 ml) and washed with cold water (20 ml). Organic layer was dried over sodium sulfate and distilled to get the titled product as solid. ESI-MS (m/z): 337.12 [M+H]⁺. Step 6: N-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

To a stirring solution of product of step 5 (0.200 g, 595 mmol) in DCM (10 ml) was added pyridine (0.072 ml, 0.892 mmol) followed by acetic anhydride (0.079 ml, 0.833 mmol) and stirred for 2 h at 25-30^oC. After complete conversion of starting material, the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by preparative HPLC to get titled product as white solid. ¹H NMR (DMSO-d₆): 8.23 (t, J = 5.6 Hz, 1H), 7.85 (s, 1H), 7.46 (dd, J = 2.8 and 15.6 Hz, 1H), 7.15 (dd, J = 2.0 and 8.8 Hz, 1H), 6.95 (t, J = 9.4 Hz, 1H), 5.17-5.13 (m, 1H), 4.72-4.68 (m, 1H), 4.39-4.36 (m, 1H), 4.08 (t, 1H), 3.71-3.68 (m, 2H), 3.52-3.50 (m, 1H), 3.42-3.39 (m, 2H), 2.98-2.94 (m, 1H), 2.87- 2.83 (m, 1H), 1.83 (s, 3H), ESI-MS (m/z): 379.14 [M+H]⁺. Example 3

Preparation of methyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate

To a stirring solution of product of step 5 of example 1 (0.125 g, 0.353 mmol) in DCM (10 ml) was added pyridine (0.049 ml, 0.600 mmol) followed by methyl chloroformate (0.041 ml, 0.592 mmol) and stirred for 2 h at 25-30 ^oC. After complete conversion of starting material the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by column to get titled product as white solid. ¹H NMR (DMSO-d₆): 7.79 (s, 1H), 7.52 (t, J = 5.8 Hz, 1H), 7.31-7.24 (m, 2H), 5.10-5.07 (m, 1H), 4.74-4.70 (m, 1H), 4.32-4.29 (m, 1H), 4.08 (t, J = 8.8 Hz, 1H), 3.74-3.71 (m, 1H), 3.56-3.53 (m, 4H), 3.35 (m, 4H), 3.17-3.13 (m, 1H). ESI-MS (m/z) : 413.07 [M+H]⁺. Example 4

Preparation of methyl (((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate

Prepared following similar procedure as described for example 3 using product of step 5 from example 2.¹H NMR (DMSO-d₆): 7.86 (s, 1H), 7.54-7.49 (m, 1H), 7.45 (d, J = 2.4 Hz, 1H), 7.15 (dd, J = 2.0 and 8.8 Hz, 1H), 6.95 (t, J = 9.4 Hz, 1H), 5.17- 5.14 (m, 1H), 4.71-4.67 (m, 1H), 4.39-4.36 (m, 1H), 4.08 (t, 1H), 3.75-3.68 (m, 2H), 3.54-3.50 (m, 4H), 3.35 (m, 2H), 2.98-2.94 (m, 1H), 2.87-2.83 (m, 1H). ESI-MS (m/z): 395.08 [M+H]⁺. Example 5

Preparation of N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Prepared using hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one hydrochloride by following similar procedure as described for example 1.¹H NMR (DMSO-d₆): 8.23 (t, J = 5.6 Hz, 1H), 7.79 (s, 1H), 7.30-7.24 (m, 2H), 5.10-5.07 (m, 1H), 4.76-4.69 (m, 1H), 4.32-4.29 (m, 1H), 4.08 (t, 1H), 3.71-3.67 (m, 1H), 3.56-3.53 (m, 1H), 3.41-3.38 (m, 2H), 3.30-3.29 (m, 1H), 3.27-3.26 (m, 1H), 3.17-3.13 (m, 1H), 1.83 (s, 3H). ESI- MS (m/z) : 397.19 [M+H]⁺. Example 6

Preparation of methyl (((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate

Prepared by following similar procedure as described for example 3. ESI-MS (m/z): 413.19 [M+H]⁺. Example 7

Preparation of N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro- 5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: (3aR,6aS)-5-(2,6-difluoro-4-nitrophenyl)-3-methylhexahydro-2H- pyrrolo[3,4-d]oxazol-2-one

To a stirring solution of sodium hydride (0.185 g, 7.71 mmol) in DMF (20 ml) at 0 ^°C was added (3aR,6aS)-5-(2,6-difluoro-4-nitrophenyl)hexahydro-2H-pyrrolo[3,4- d]oxazol-2-one (0.440 g g, 2.67 mmol) followed by iodomethane (1.991 g, 14.02 mmol) at 0^°C. Reaction mixture was stirred at 25-30 ^oC for 1 h. Reaction mixture was then poured in to water and precipitated compound was filtered and dried to get titled product. ESI-MS (m/z): 300.08 [M+H]⁺. Step 2: (3aR,6aS)-5-(4-amino-2,6-difluorophenyl)-3-methylhexahydro-2H- pyrrolo[3,4-d]oxazol-2-one

To a stirring solution of product of step 1 (1 g, 3.51 mmol) in THF (25 ml) was added palladium on carbon (10 % wet) (1.26 g, 11.29 mmol) and reaction stirred under H₂ pressure at 25-30^oC for 6 h. After complete conversion of starting material, the reaction mixture was filtered over celite bed and the filtrate was dried over sodium sulfate and distilled under vacuum to get the tilted product as solid. ESI-MS (m/z): 270.06 [M+H]⁺. Step 3: 2-((R)-3-((3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)amino)-2-hydroxypropyl)isoindoline-1,3-dione

To a stirring solution of product of step 2 (600 mg, 2.228 mmol) in ethanol (13.5 ml) and water (1.5 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (679 mg, 3.34 mmol) at 25-30^oC. Reaction mixture was stirred at 70-80°C for 16 h. After complete conversion of starting material, the reaction mixture was cooled to 10°C and precipitate was filtered, dried under vacuum to get titled product as solid. ESI- MS (m/z): 473.10 [M+H]⁺. Step 4: 2-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)isoindoline-1,3- dione

To a stirring solution of product of step 3 (1 g, 2.117 mmol) in chloroform (20 ml) was added N,N’-carbonyl diimidazole (1.716 g, 10.58 mmol). Reaction mixture was stirred at 70°C for 5 h. After complete conversion of starting material, solvent was distilled and reaction acidified by 35 % HCl up to pH = 2. Product was extracted with DCM:methanol (7:3). Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get the titled product. ESI-MS (m/z): 499.07 [M+H]⁺. Step 5: (3aR,6aS)-5-(4-((S)-5-(aminomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)-3-methylhexahydro-2H-pyrrolo[3,4-d]oxazol-2-one

To a stirring solution of product of step 4 (0.8 g, 1.605 mmol) in Ethanol (10 ml) was added aq. Methyl amine (40 % solution) (0.498 ml, 16.05 mmol) at 25-30^oC. Reaction mixture was stirred at 80°C for 3 h. After complete conversion of starting material, the reaction mixture was diluted with DCM (100 ml) and washed with cold water (20 ml) Organic layer was dried over sodium sulfate and distilled to get the titled product as solid. ESI-MS (m/z): 369.13 [M+H]⁺. Step 6: N-(((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

To a stirring solution of product of step 5 (120 mg, 0.326 mmol) in DCM (10 ml) was added Pyridine (0.04 ml, 0.489 mmol) followed by Acetic anhydride (0.046 ml, 0.326 mmol) and stirred for 2 h at 25-30^oC. After complete conversion of starting material the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by preparative HPLC to get titled product as white solid. ¹H NMR (DMSO-d₆): 8.25-8.22 (m, 1H), 730-7.24 (m, 2H), 5.05 (m, 1H), 4.85 (m, 1H), 4.43 (m, 1H), 4.13 (m, 1H), 3.83 (m, 1H), 3.76-3.65 (m, 2H), 3.51-3.53 (m, 1H), 3.51-3.48 (m, 1H), 3.30-3.31(m, 1H), 3.34-3.27 (m, 1H), 2.75 (s, 3H), 1.95 (s, 3H). ESI-MS (m/z) : 411.15 [M+H]⁺. Example 8

Preparation of methyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-3-methyl-2- oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5- yl)methyl)carbamate

To a stirring solution of product of step 5 of example 7 (100 mg, 0.271 mmol) in DCM (10 ml) was added pyridine (0.038 ml, 0.380 mmol) followed by methyl chloroformate (0.036 ml, 0.380 mmol) and stirred for 2.0 h at 25-30 ^oC. After complete conversion of starting material, the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by preparative HPLC to get titled product as white solid. ¹H NMR (DMSO- d₆): 7.54-7.51 (m, 1H), 730-7.25 (m, 2H), 5.04 (m, 1H), 4.82 (m, 1H), 4.44 (m, 1H), 4.15 (m, 1H), 3.81 (m, 1H), 3.71-3.66 (m, 2H), 3.71 (s, 3H), 3.55-3.52 (m, 1H), 3.52- 3.49 (m, 1H), 3.30-3.31 (m, 1H), 3.34-3.27 (m, 1H), 2.79 (s, 3H). ESI-MS (m/z) : 427.14 [M+H]⁺. Example 9

Preparation of N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4- d]imidazol-5(1H)-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: 5-(2,6-difluoro-4-nitrophenyl)hexahydropyrrolo[3,4-d]imidazol-2(1H)- one

To a stirring solution of tert-butyl 2-oxohexahydropyrrolo[3,4-d]imidazole-5(1H)- carboxylate (3.50 g, 15.40 mmol, prepared by following generally the process described in WO2009153554) in DCM (25 ml) was added 2,2,2-trifluoroacetic acid (5.93 ml, 77 mmol) at 0°C and stirred for 3 h at 25-30°C. After completion of reaction DCM was evaporated under reduced pressure to get the crude product which was taken without further purification for next step. To the above crude product in DMF (30 ml) was added K₂CO₃ (6.20 g, 44.80 mmol) and 1,2,3-trifluoro-5- nitrobenzene (2.65 g, 14.94 mmol) was stirred for 4 h at 80°C. After completion of reaction, water (150 ml) was added to get solid which was filtered and dried to get titled product. ESI-MS (m/z) : 285.08 [M+H]⁺. Step 2: 5-(4-amino-2,6-difluorophenyl)hexahydropyrrolo[3,4-d]imidazol-2(1H)- one

To a stirring solution of product of step 1 (2.50 g, 8.80 mmol) in THF (50 ml) and Ethanol (20 ml) was added Palladium on charcoal (0.936 g, 8.80 mmol) and stirred under H₂ balloon for 16 h at 25°C. The reaction mixture was filtered through celite and washed with THF:EtOH. Filtrate was evaporated to get the titled product. ESI- MS (m/z): 255.11 [M+H]⁺. Step 3: 2-((2R)-3-((3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)amino)-2-hydroxypropyl)isoindoline-1,3-dione

To a stirring solution of product of step 2 (1.10 g, 4.33 mmol) in Ethanol (25 ml) and Water (3 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (1.319 g, 6.49 mmol) at 25-30^oC. Reaction mixture was stirred at 70-80°C for 16 h. After complete conversion of starting material, the reaction mixture was cooled to 10°C and precipitate was filtered and dried under vacuum to get titled product as solid. ESI-MS (m/z): 456.14 [M+H]⁺. Step 4: 2-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)isoindoline-1,3-dione

To a stirring solution of product of step 3 (1.70 g, 3.72 mmol) in Chloroform (20 ml) was added N,N’-carbonyl diimidazole (2.47 g, 14.87 mmol). Reaction mixture was stirred at 70°C for 5 h. After complete conversion of starting material, solvent was distilled and reaction mixture was acidified by 35 % HCl up to pH = 2. Product was extracted with DCM:Methanol (7:3). Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get the titled product. ESI-MS (m/z): 484.07 [M+H]⁺. Step 5: (5S)-5-(aminomethyl)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4- d]imidazol-5(1H)-yl)phenyl)oxazolidin-2-one

To a stirring solution of product of step 4 (1.0 g, 2.069 mmol) in Ethanol (15 ml) was added aq. Methyl amine (40 % solution) (0.803 ml, 10.34 mmol) at 25-30^oC. Reaction mixture was stirred at 80°C for 3 h. After complete conversion of starting material, the reaction mixture was diluted with DCM (100 ml) and washed with cold water (20 ml). Organic layer was dried over sodium sulfate and distilled to get the titled product as solid. ESI-MS (m/z): 354.09 [M+H]⁺. Step 6: N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

To a stirring solution of product of step 5 (0.400 g, 1.32 mmol) in DCM (30 ml) was added Pyridine (0.137 ml, 1.69 mmol) followed by Acetic anhydride (0.139 ml, 1.472 mmol) and stirred for 2 h at 25-30^oC. After complete conversion of starting material, the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by preparative HPLC to get titled product as white solid. ¹H NMR (DMSO-d₆): 8.24-8.21 (t, J = 5.80 Hz, 1H), 7.28-7.22 (dd, J = 5.80 Hz, 2H), 6.43 (s, 2H), 4.74-4.70(m, 1H), 4.17 (s, 2H), 4.09- 4.05 (t, J = 9.0 Hz, 1H), 3.70-3.67 (m, 1H), 3.41-3.38 (m, 2H), 3.36-3.32 (m, 2H), 3.32-3.18 (m, 2H), 1.83 (s, 3H). ESI-MS (m/z) : 396.09 [M+H]⁺. Example 10

Preparation of N-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: 2,2'-(1-(tert-butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic acid

To stirring solution of t-butyl 1,3,3a,4,7,7a-hexahydro-2H-isoindole-2-carboxylate (15 g, 67.2 mmol, prepared by the general procedure described in WO201704434) in ethyl acetate (400 mL) was added Ruthenium(IV) oxide (0.203 g, 1.343 mmol) at 0- 5^oC followed by drop wise addition of solution of sodium metaperiodate (115 g, 537 mmol) dissolved in water (1.2 L) and stirred for 2 h at 0-5°C. After completion of reaction it was diluted with ethyl acetate (500 ml). The organic layer was dried over Na₂SO₄, and concentrated under reduce pressure to get the titled product. ESI-MS (m/z): 232.04 [M-56]. Step 2: dimethyl 2,2'-(1-(tert-butoxycarbonyl)pyrrolidine-3,4-diyl)diacetate

To a stirring solution of product of step 1 (5.0 g, 17.40 mmol) in DMF (50 ml) was added K₂CO₃ (14.57 g, 105 mmol) followed by methyl iodide (3.30 ml, 52.7 mmol) at 0°C and stirred it for 24 h at 25-30^oC. After completion of reaction, the reaction mixture was quench in to water (100mL) and extracted with EtOAc (50 mL). The organic layer was dried over sodium sulphate and concentrated to get titled product. ESI-MS (m/z): 260.01 [M-56]. Step 3: tert-butyl 3,4-bis(2-hydroxyethyl)pyrrolidine-1-carboxylate

To a stirring solution of product of step 2 (3.2 g, 10.15 mmol) in THF (40 ml) was added lithium borohydride (0.884 g, 40.6 mmol) portion wise at 0°C then stirred for 2 h at 25-30^oC. After completion of reaction, the reaction mixture was quench with water (80 mL) and extracted with EtOAc (40 mL). The organic layer was dried over sodium sulphate and concentrated to get the product. ESI-MS (m/z): 204.13 [M-56]. Step 4: tert-butyl 3,4-bis(2-((methylsulfonyl)oxy)ethyl)pyrrolidine-1-carboxylate

To a stirring solution of product of step 3 (3.0 g, 11.75 mmol) in DCM (30 ml) was added triethylamine (9.67 ml, 69.4 mmol) and methanesulfonyl chloride (2.70 ml, 34.7 mmol) at 0°C. The reaction mixture was stirred for 2 h at 25-30 °C. After completion of reaction it was diluted with DCM (30 mL).and washed with water (30 mL). DCM layer was dried over sodium sulphate and distilled out to get the titled product. ESI-MS (m/z) : 360.10 [M-56]. Step 5: tert-butyl octahydro-2H-thiepino[4,5-c]pyrrole-2-carboxylate

To a stirring solution of product of step 4 (4 g, 9.63 mmol) in EtOH (40 ml) was added sodium sulfide nonahydrate (2.77 g, 11.55 mmol) and reaction mixture was refluxed for 1 h. After completion of reaction, the reaction mixture was concentrated. and quench with water (80 mL). Product was extracted with ethyl acetate (40 mL). Organic layer was dried over sodium sulphate and concentrated to get crude product which was purified by column chromatography to get pure product. ESI-MS (m/z): 202.10 [M-56]. Step 6: octahydro-1H-thiepino[4,5-c]pyrrole

To a stirring solution of product of step 5 (0.75 g, 2.91 mmol) in DCM (10 ml) was added Trifluoroacetic acid (1.122 ml, 14.57 mmol) at 0-5^oC. After completion of reaction, the reaction mixture was diluted with DCM and washed with aq. sodium bicarbonate. Organic layer was dried over sodium sulphate and concentrated to get product. ESI-MS (m/z) : 158.10 [M+H]⁺. Step 7: 2-(2,6-difluoro-4-nitrophenyl)octahydro-1H-thiepino[4,5-c]pyrrole

To a stirring solution of product of step 6 (0.8 g, 3.15 mmol) in DMF (10 ml) was added K₂CO₃ (1.304 g, 9.44 mmol) and 1,2,3-trifluoro-5-nitrobenzene (0.557 g, 3.15 mmol). It was stirred for 2 h at 80°C. After completion of reaction, water (40 ml) was added to get solid product. ESI-MS (m/z) : 315.11[M+H]⁺. Step 8: 3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)aniline

To a stirring solution of product of step 7(0.75 g, 2.393 mmol) in Methanol (10 ml) was added palladium charcoal (0.6 g, 0.564 mmol) and stirred at 25-30^oC for 16 h under H₂ atmosphere. After completion of reaction, the reaction mixture was filtered through celite bed and washed with methanol (100 mL). The filtrate was concentrated to get product. ESI-MS (m/z) : 285.11 [M+H]⁺. Step 9: 2-((2R)-3-((3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)amino)-2-hydroxypropyl)isoindoline-1,3-dione

To a stirring solution of product of step 8 (0.7 g, 2.462 mmol) in 9:1 EtOH:water (25 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (1.000 g, 4.92 mmol) and stirred at 90°C for 16 h. After completion of reaction, water (10 ml) was added to get solid product ESI-MS (m/z) : 488.16 [M+H]⁺. Step 10: 2-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)isoindoline-1,3-dione

To a stirring solution of product step 9(0.2 g, 0.411 mmol) in CHCl₃ (10 ml) was added N,N’-carbonyl diimidazole (0.333 g, 2.055 mmol). Reaction mixture was stirred at 60°C for 1 h After completion of reaction the reaction mixture was concentrated and acidified with 10% dil. HCl to get solid product. ESI-MS (m/z) :514.16 [M+H]⁺. Step 11: (5S)-5-(aminomethyl)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5- c]pyrrol-2-yl)phenyl)oxazolidin-2-one

To a stirring solution of product of step 10 (0.15 g, 0.293 mmol) in EtOH (10 ml) was added aq. Methyl amine (0.099 g, 1.463 mmol) and reaction mixture was stirred at 60°C for 1 h. After completion of reaction, the reaction mixture was concentrated to get product. ESI-MS (m/z) : 384.15 [M+H]⁺. Step 12: N-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide.

To stirring solution of product of step 11 (0.1 g, 0.261 mmol) in DCM (5 ml) .was added pyridine (0.034 ml, 0.417 mmol) and acetic anhydride (0.030 ml, 0.313 mmol) at 0°C. Reaction mixture was stirred at 25-30^oC for 1 h. Reaction mixture was diluted with DCM and washed with water. Organic layer was dried over sodium sulfate and concentrated to get crude product which was purified by column chromatography.¹H NMR (DMSO-d6): 8.23 (t, J = 5.8 Hz, 1H), 7.17 (dd, J = 7.2 and 20 Hz, 2H), 4.72- 4.69 (m, 1H), 4.08-4.03 (t, J = 9.2 Hz, 1H), 3.69-3.65 (m, 1H), 3.61-3.57 (m, 2H), 3.40-3.38 (m, 2H), 3.00-2.96 (m, 2H), 2.73-2.68 (m, 2H), 2.65-2.58 (m, 2H), 2.51- 2.33 (m, 2H), 2.12-2.07 (m, 2H), 1.87-1.83 (m, 5H). ESI-MS (m/z) : 426.16 [M+H]⁺. Example 11

Preparation of N-(((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5- c]pyrrol-2-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

To a stirring solution of N-(((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5- c]pyrrol-2-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide (0.015 g, 0.035 mmol) in DCM was added m-CPBA (6.08 mg, 0.035 mmol) at 0°C and stirred for 3 h. Reaction mixture was diluted with DCM and washed with sodium bicarbonate solution to get crude product which was purified by column chromatography. ¹H NMR (MeOD): 7.17 (d, J =12.4 Hz, 2H), 4.79-4.61 (m, 1H), 4.11 (s, 1H), 4.11-4.09 (t, J = 8.8 Hz, 1H), 3.78-3.64 (m, 5H), 3.33-3.32 (m, 2H), 3.06-3.03 (m, 2H), 2.89- 2.62 (m, 5H), 2.12-2.07 (m, 2H), 1.97-1.71 (m, 1H), 1.75-1.71 (m, 2H). ESI-MS (m/z) : 442.18 [M+H]⁺. Example 12

Preparation of N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2- yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: tert-butyl octahydro-2H-thiepino[4,5-c]pyrrole-2-carboxylate 6,6-dioxide

To a stirring solution of tert-butyl octahydro-2H-thiepino[4,5-c]pyrrole-2-carboxylate (0.4g, 1.554 mmol) in Acetone (10 ml) was added oxone (3.34 g, 5.44 mmol) at 0°C. Reaction mixture was stirred at 25-30^oC for 24 h. After completion of reaction, the reaction mixture was filtered. Filtrate was added to water (40 mL) and extracted with ethyl acetate (30 mL x 3). Organic layer was dried over sodium sulfate and distilled out to get product. ESI-MS (m/z): 234.09 [M-56]. Step 2: octahydro-1H-thiepino[4,5-c]pyrrole 6,6-dioxide

To a stirring solution of product of step 1(0.270 g, 0.933 mmol) in DCM (5 ml) was added trifluoroacetic acid (0.072 ml, 0.933 mmol) at 0°C. After completion of reaction, the reaction mixture was diluted with DCM and washed with aq. sodium bicarbonate. Organic layer was dried over sodium sulphate and concentrated to get product. ESI-MS (m/z) : 190.10 [M+H]⁺. Step 3: 2-(2,6-difluoro-4-nitrophenyl)octahydro-1H-thiepino[4,5-c]pyrrole 6,6- dioxide

To a stirring solution of product of step-2 (0.4 g, 1.397 mmol) in DMF (5 ml) was added potassium carbonate (0.579 g, 4.19 mmol) followed by 1,2,3-trifluoro-5- nitrobenzene (0.247 g, 1.397 mmol) and stirred for 2 h at 80°C. After completion of reaction, water (20 ml) was added to get solid product. ESI-MS (m/z) : 347.12 [M+H]⁺. Step 4: 2-(4-amino-2,6-difluorophenyl)octahydro-1H-thiepino[4,5-c]pyrrole 6,6- dioxide

To a stirring solution of product of step 3 (0.4 g, 1.397 mmol) in Methanol (10 ml) was added palladium charcoal (0.16 g, 1.50 mmol). Reaction mixture was stirred at 25-30^oC for 16 h under H₂ atmosphere. After completion of reaction, reaction mixture was filtered through celite bed and washed with methanol (50 mL). The filtrate was concentrated to get product. ESI-MS (m/z) : 317.13 [M+H]⁺. Step 5: 2-((2R)-3-((4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)amino)-2-hydroxypropyl)isoindoline-1,3-dione

To a stirring solution of step 4 (0.3 g, 0.948 mmol) in 9:1 EtOH:water (10 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (0.385 g, 1.897 mmol). Reaction mixture was stirred at 90°C for 24 h. After completion of reaction, water (4 ml) was added to get solid product. ESI-MS (m/z) : 520.19 [M+H]⁺. Step 6: 2-2-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)isoindoline-1,3-dione

To a stirring solution of product of step 5 (0.3 g, 0.577 mmol) in chloroform (10 ml) was added N,N’-carbonyl diimidazole (0.468 g, 2.89 mmol) and stirred at 60°C for 1 h After completion of reaction, the reaction mixture was concentrated and acidified with 10% diluted HCl to get solid which was filtered to get titled product. ESI-MS (m/z) : 546.13 [M+H]⁺. Step 7: (5S)-5-(aminomethyl)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5- c]pyrrol-2-yl)-3,5-difluorophenyl)oxazolidin-2-one

To a stirring solution of product of step 6 (0.2g, 0.385 mmol) in ethanol (10 ml) was added aq. methylamine (0.130 g, 1.925 mmol) and reaction mixture was stirred at 60°C for 2 h. After completion of reaction, the reaction mixture was concentrated to get titled product. Step 8: N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide.

To stirring solution of product of step 7 (0.150 g, 0.361 mmol) in DCM (10 ml) was added pyridine (0.047 ml, 0.578 mmol) and acetic anhydride (0.044 ml, 0.469 mmol) at 0°C. Reaction mixture was stirred at 25-30^oC for 1 h. Reaction mixture was diluted with DCM and washed with water. Organic layer was dried over sodium sulfate and concentrated to get crude product which was purified by column chromatography ¹H NMR (DMSO-d₆): 8.22 (t, J = 5.6 Hz, 1H), 7.20 (d, J =12.4 Hz, 2H), 4.71 (t, J =8.4 Hz, 1H), 4.06 (t, J = 9.2 Hz, 1H), 3.69-3.58 (m, 4H), 3.42-3.33 (m, 5H), 3.29-3.27 (m, 2H), 3.13-3.10 (m, 2H), 1.88-1.83(m, 7H). ESI-MS (m/z): 558.16 [M+H]⁺. Example 13

Preparation of N-(((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Step 1: tert-butyl 3-(3,3-dimethylureido)pyrrolidine-1-carboxylate

To a stirring solution of tert-butyl 3-aminopyrrolidine-1-carboxylate (2.3 g, 12.35 mmol) in DCM (23 ml) was added triethylamine (2.58 ml, 18.52 mmol) and dimethylcarbamic chloride (1.461 g, 13.58 mmol) at 0°C and reaction mixture was stirred for 2 h at 25-30°C. After completion of reaction it was diluted with DCM (50 ml) and water (25 ml). Organic layer was separated, , dried over Na₂SO₄, concentrated under reduced pressure to get the titled product. Step 2: 3-(1-(2,6-difluoro-4-nitrophenyl)pyrrolidin-3-yl)-1,1-dimethylurea

To a stirring solution of product of step 1 (3.0 g, 11.66 mmol) in Dioxane (15 ml) was added dioxane:HCl (3 ml) at 0°C and stirred it for 3 h 25°C. After completion of reaction Dioxane was evaporated under reduced pressure to get the crude product which was taken without further purification for next step. To the above crude product in DMF (15 ml) was added K₂CO₃ (3.51 g, 25.4 mmol) and 1,2,3-trifluoro-5- nitrobenzene (1.5 g, 8.47 mmol) and stirred for 4 h at 80°C. After completion of reaction, water (40 ml) was added to get solid ESI-MS (m/z) : 315.12 [M+H]⁺. Step 3: 3-(1-(4-amino-2,6-difluorophenyl)pyrrolidin-3-yl)-1,1-dimethylurea

To a stirring solution of product of step 2 (654 mg, 2.081 mmol) in Ethanol (10 ml) was added palladium charcoal (22 mg) and stirred under hydrogen atmosphere for 5 h. After completion of reaction it was filtered through hyflow and filtrate was concentrated under reduced pressure to get titled product. ESI-MS (m/z) : 285.14 [M+H]⁺. Step 4: 3-(1-(4-(((R)-3-(1,3-dioxoisoindolin-2-yl)-2-hydroxypropyl)amino)-2,6- difluorophenyl)pyrrolidin-3-yl)-1,1-dimethylurea

To a stirring solution of product of step 3 (400 mg, 1.407 mmol) in Ethanol (10 ml) and Water (1 ml) was added (S)-2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (572 mg, 2.81 mmol) at 25-30^oC. Reaction mixture was stirred at 100°C for 16 h. After complete conversion of starting material, the reaction mixture was cooled to 10°C and precipitate was filtered and dried under vacuum to get titled product. ESI-MS (m/z) : 488.20 [M+H]⁺. Step 5: 3-(1-(4-((S)-5-((1,3-dioxoisoindolin-2-yl)methyl)-2-oxooxazolidin-3-yl)- 2,6-difluorophenyl)pyrrolidin-3-yl)-1,1-dimethylurea

To a stirring solution of product of step 4 (700 mg, 1.436 mmol) in Chloroform (20 ml) was added N,N’-carbonyl diimidazole (1.1 g, 7.18 mmol). Reaction mixture was stirred at 70°C for 5 h. After complete conversion of starting material, solvent was distilled and reaction acidified by 35 % HCl up to pH = 2. Product was extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get the title product. ESI-MS (m/z): 514.17 [M+H]⁺. Step 6: 3-(1-(4-((S)-5-(aminomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)-1,1-dimethylurea

To a stirring solution of product of step 5 (730 mg, 1.422 mmol) in Ethanol (14 ml) was added aq. Methyl amine (552 mg, 7.11 mmol) at 25-30^oC. Reaction mixture was stirred at 80°C for 10 h. After complete conversion of starting material, the reaction mixture was diluted with DCM (25 ml) and washed with water (20 ml). The organic layer was dried over sodium sulfate and distilled to get the titled product. Step 7: N-(((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

To a stirring solution of product of step 6 (300 mg, 0.782 mmol) in DCM (5 ml) was added pyridine (93 mg, 1.174 mmol) followed by acetic anhydride (112 mg, 1.095 mmol) and stirred for 2 h at 25-30^oC. After complete conversion of starting material the reaction mixture was quenched with water (10 ml) and extracted with DCM. Organic layer was separated, washed with water, dried over sodium sulfate and distilled out to get crude product which was purified by preparative HPLC to get titled product.¹H NMR (DMSO-d₆): 8.23 (t, J = 5.6 Hz, 1H), 7.22-7.17 (m, 2H), 6.25 (d, J = 6.4 Hz, 1H), 4.74-4.67 (m, 1H), 4.19-4.14 (m , 1H), 4.06 (t, 1H), 3.69-3.65 (m, 1H), 3.54-3.40 (m, 5H), 3.27-3.25 (m, 1H), 2.78 (s, 6H), 2.09-2.02 (m, 1H), 1.88-1.81 (m, 4H). ESI-MS (m/z) : 426.21[M+H]⁺.

Using appropriate starting materials and suitable modifications of the processes described in above examples, including suitable addition and/or deletion of steps as may be necessary, well within the scope of a person skilled in the art the following compounds were prepared in an analogues manner.

Table 1:

The following compounds can be prepared by procedure similar to those described above with appropriate variations of reactions, reaction conditions, reagents and quantities of reagents which are within the scope of person skilled in the art.

N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)oxetane-3-carboxamide; N-(((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

ethyl (((S)-3-(3,5-difluoro-4-((3aS,6aR)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(3-fluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

methyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-6a-methyl-2-oxohexahydro-5H- pyrrolo[3,4-d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate; methyl (((S)-3-(4-((3aR,6aS)-6a-cyclopropyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(5R)-3-(3,5-difluoro-4-(2-oxohexahydropyrrolo[3,4-d]imidazol-5(1H)-yl)phenyl)-5- (hydroxymethyl)oxazolidin-2-one;

N-(((5S)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)butyramide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)cyclopropanecarboxamide; (5R)-3-(3-fluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-5- (hydroxymethyl)oxazolidin-2-one;

N-(((5S)-3-(3,5-difluoro-4-(3-ureidopyrrolidin-1-yl)phenyl)-2-oxooxazolidin-5- yl)methyl)acetamide;

N-(((5S)-3-(3-fluoro-4-(3-(1,3,3-trimethylureido)pyrrolidin-1-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

N-((S)-1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6-difluorophenyl) pyrrolidin-3-yl)morpholine-4-carboxamide. Biological evaluation:

Minimum inhibitory concentration (MIC) determination

To assess the bacterial growth inhibitory effect of the compounds of the invention, MABA assay was performed with log phase culture of Mycobacterium tuberculosis H37Rv. Bacterial culture of optical density 0.6-0.8 was diluted to final density of 0.02 in 7H9 medium. 100µl of diluted Mycobacterium tuberculosis H37Rv was incubated with the test compounds in microtiter plate. A drug free control containing DMSO also was also prepared. Following incubation of the compound with culture for 7 days at 37°C, 20µl of 0.02% alamar blue (freshly prepared) was added in each well. The color was allowed to develop for 16 h at 37°C. Blue color in the well indicated no growth whereas pink color signifies growth in the well. MIC value is defined as the lowest concentration that prevents the color change from blue to pink. Fluorescence was measured at excitation at 530 nm and emission at 590 nm. MIC values of the selected compounds are shown in Table 2. Table 2:

Claims

Claims: 1. Compound of general formula (I), their stereoisomers, their tautomeric forms, their pharmaceutically acceptable salts,

Wherein,

‘Y’ represents OH, NR₂R₃, NHC(O)R₄;

‘X’ represents:

wherein,

‘T’ represents O and NR₆R₇; A represents either a bond or is absent;

m represents integers selected from 1-4;

p represents integers selected from 0-2;

R₁ at each occurrence is selected from H, F, Cl, CH₃, CN and OCH₃;

R₂ and R₃ is independently selected from H, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, aryl, heterocyclyl and heteroaryl and R₂ and R₃ taken together with the nitrogen to which they are attached to form a 4- to 8- membered heterocyclyl or heteroaryl with 1 to 3 additional heteroatoms selected from O, S, or N;

R₄ is independently selected from (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, heterocyclyl, aryl, heteroaryl and (C₁-C₆)alkoxy;

R₂, R₃, R₄ are further optionally substituted with (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, aryl, heterocyclyl and heteroaryl groups are optionally substituted, the groups are selected from halo, hydroxyl, (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, heterocyclyl, (C₁- C₆)alkoxy, haloalkyl, NO₂, CN and NH₂;

R_5, R₆ and R₇ are independently selected from the group consisting of hydrogen, haloalkyl, optionally substituted (C₁-C₆)alkyl, (C₃-C₆)cycloalkyl, heterocyclyl, derivatives; R₆ and R₇ together with the common N atom to which they are attached to form a -5 to -8 membered cyclic ring;

R₈ and R₉ is independently selected from H, optionally substituted (C₁-C₆)alkyl and (C₃-C₆)cycloalkyl; wherein substitutions on (C₁-C₆)alkyl and (C₃-C₆)cycloalkyl are as defined earlier.

2. The compound of formula (I) as claimed in claim 1, wherein when A is bond, T is directly connected to 5-membered pyrrolidine ring and forms a following structure:

3. Compound of formula (I) as claimed in claim 1, wherein A is absent, T represents NR6R7 and forms a following structure:

4. The compound of formula (I) as claimed in claim 1, wherein Y is selected from NR₂R₃ and NHC(O)R₄ wherein R₂, R₃ & R₄ are as defined in claim 1. 5. The compound of formula (I) as claimed in claim 1, wherein R₁ is fluorine. 6. The compound of formula (I) as claimed in claim 1, wherein compound is selected from:

methyl (((S)-3-(3-fluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate; N-(((5S)-3-(3,5-difluoro-4-(2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(3,5-difluoro-4-(6-oxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)- 2-oxooxazolidin-5-yl)methyl)acetamide;

N-(((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

ethyl (((S)-3-(3,5-difluoro-4-((3aR,6aS)-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5- yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate; (3aR,6aS)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

(3aS,6aR)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2- fluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

(3aS,6aR)-5-(4-((R)-5-((1H-1,2,3-triazol-1-yl)methyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)hexahydro-2H-pyrrolo[3,4-d]oxazol-2-one;

methyl (((S)-3-(3-fluoro-4-((3aS,6aR)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate; methyl (((S)-3-(3,5-difluoro-4-((3aS,6aR)-3-methyl-2-oxohexahydro-5H-pyrrolo[3,4- d]oxazol-5-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

N-(((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)-3,5- difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(4-(3a,6a-dimethyl-2-oxohexahydro-5H-pyrrolo[3,4-d]oxazol-5-yl)- 3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

5-(2-fluoro-4-((R)-5-(hydroxymethyl)-2-oxooxazolidin-3-yl)phenyl)hexahydro-2H- pyrrolo[3,4-d]oxazol-2-one; 5-(2,6-difluoro-4-((R)-5-(hydroxymethyl)-2-oxooxazolidin-3-yl)phenyl)hexahydro- 2H-pyrrolo[3,4-d]oxazol-2-one;

methyl (((5S)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5-c]pyrrol-2-yl)-3- fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (((5S)-3-(3,5-difluoro-4-(octahydro-2H-thiepino[4,5-c]pyrrol-2-yl)phenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

(5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(6-oxidooctahydro-2H- thiepino[4,5-c]pyrrol-2-yl)phenyl)oxazolidin-2-one; (5R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(6,6-dioxidooctahydro-2H-thiepino[4,5- c]pyrrol-2-yl)-3-fluorophenyl)oxazolidin-2-one;

N-(((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3-fluorophenyl)-2- oxooxazolidin-5-yl)methyl)acetamide;

methyl (((5S)-3-(4-(3-(3,3-dimethylureido)pyrrolidin-1-yl)-3,5-difluorophenyl)-2- oxooxazolidin-5-yl)methyl)carbamate;

N-(1-(4-((S)-5-(acetamidomethyl)-2-oxooxazolidin-3-yl)-2,6- difluorophenyl)pyrrolidin-3-yl)thiomorpholine-4-carboxamide 1,1-dioxide. 7. Pharmaceutical composition comprising compound of general formula (I), their tautomeric forms, their pharmaceutically acceptable salts, solvates and their mixtures having pharmaceutically acceptable carriers, solvents, diluents, excipients and other media normally employed in their manufacture. 8. Use of the compounds as claimed in any preceding claims for the treatment of mammalian infections such as tuberculosis, by administering a therapeutically effective & non-toxic amount of the compound of formula (I), or their pharmaceutically acceptable compositions to the mammals. 9. Method of treating antibacterial infections in a subject which comprising administering to a patient in need thereof an effective amount of a compound of Formula (I) as claimed in any of the preceding claims or its suitable pharmaceutical composition. 10. Compound of formula (I) as claimed in claim 1 or its pharmaceutical compositions in combination with one or more suitable pharmaceutically active agents wherein, pharmaceutically active agents selected from anti-TB and antibiotic class of drugs.