KETOLIDE DERIVATIVES AS ANTIBACTERIAL AGENTS
Field of the Invention
The present invention provides ketolide derivatives in the macrolide family, which can be used as anti-bacterial agents.
Compounds disclosed herein can be used for the treatment or prevention of a condition caused by or contributed to by gram positive, gram negative or anaerobic bacteria, more particularly against bacterium, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae. Processes for the preparation of disclosed compounds, intermediates used in their synthesis, pharmaceutical compositions containing the disclosed compounds, and method of treating bacterial infections are also provided.
Background of the Invention
The first generation macrolides erythromycin A and the early derivatives are characterized by bacteriostatic or bactericidal activity for most gram-positive bacteria, atypical pathogens, and many community acquired respiratory infections and in patients with penicillin allergy. However, erythromycin A causes numerous drug-drug interactions, has relatively poor absorption, poor local tolerance, loses its antibacterial activity under acidic conditions by degradation and the degraded products are known to be responsible for undesired side effects (Itoh, Z et al, Am. J. Physiol, 1984, 247: 688; Omura, S et al, J. Med. Chem, 1987, 30, 1943). Various Erythromycin A derivatives have been prepared to overcome the acid instability and other problems associated with it.
Roxithromycin, clarithromycin and azithromycin have been developed to address the limitation of erythromycin A. Both clarithromycin and azithromycin have proved to be important drugs in the treatment and prophylaxis of atypical mycobacterial infections in patients with HIV.
Macrolides have proved to be effective drugs in the treatment of many respiratory tract infections. However, increasing resistance among S. pneumoniae has prompted the search for new compounds that retain the favorable safety profile, and a spectrum of activity and are confined to respiratory pathogens. Consequently, numerous investigators have prepared chemical derivatives of Erythromycin A in an attempt to obtain analogs having modified or improved profiles of antibiotic activity. Ketolides exhibit greater efficacy and

safety, have broader spectrum of activities, and are particularly effective against resistant pathogens, hence have been developed as next generation macrolides.
U.S. Patent No. 5, 635, 485 discloses erythromycin compounds that are useful in the treatment of bacterial infections in warm-blooded animals.
U.S. Patent No. 5, 866, 549 discloses novel semi-synthetic macrolides having antibacterial activity, more particularly, 6-O-substituted erythromycin ketolide derivatives and method of treating bacterial infections.
U.S. Patent No. 6,472,372 discloses 6-O-carbamoyl ketolide antibacterials and methods of treating bacterial infections.
WO 2004/029066 discloses bifunctional heterocyclic compounds useful as anti-infective, anti-proliferative, anti-inflammatory and prokinetic agents.
WO 00/62783 discloses ketolide antibacterials that are useful in the treatment of bacterial and protozoal infections and in the treatment of other conditions involving gastric motility.
WO 00/44761 discloses ketolide antibiotics useful as antibacterial and antiprotozoal agents in mammals.
U.S. Patent No. 5,747,467 discloses and novel antibacterial composition and method of treating bacterial infections of Gram bacteria in warm-blooded animals.
U.S. Patent No. 6,433,151 discloses demethylated ketolide derivatives and their use as medicament for the treatment of infection caused by gram positive bacteria, Haemophilus influenzae, Moraxalla spp.
U.S. Patent Nos. 6,458,771 and 6,399,582 disclose ketolide antibacterials useful in the treatment of bacterial and protozoal infections and in the treatment of other conditions involving gastric motility
U.S. Patent Application Nos. 2002/0115621 and 2003/0013665 disclose macrolide compounds that are useful as antibacterial and antiprotozoal agents in mammals, including man, as well in fish and birds.
EP 1114 826 discloses macrolide compounds that are useful antibacterial, antiprotozoal and/or prokinetic agents, also, it relates to a method of treating cancer or atherosclerosis.
U.S. Patent No. 6,313,101 and 6,407,257 discloses derivatives of erythromycin that have good antibiotic activity on gram-positive bacteria.

Other references disclosing ketolide compounds include Alexis Denis and Alain Bonnefoy, Drugs of the Future, 26 (10), 975-84 (2001), Champney W. S., et al., Current Microbiology, 42, 203-10 (2001)
Summary of the Invention
The present invention provides ketolide derivatives in the macrolide family, which can be used in the treatment or prevention of bacterial infection and processes for the synthesis of these compounds.
Pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, metabolites, prodrugs, polymorphs of these compounds having same type of activity are also provided.
Pharmaceutical compositions containing the disclosed compounds together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of bacterial infection.
Other object will be set forth in accompanying description which follows and in part will be apparent from the description or may be learnt by the practice of the invention.
In accordance with one aspect, there are provided compounds having the structure of Formula I, as shown in the accompanied drawings, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof, wherein:
R1 can represent
• hydrogen
• hydroxyl protecting group R2 and R3 can be independently
• hydrogen
• alkyl (with the provisio that R2 and R3 simultaneously are not methyl)
• alkenyl
• alkynyl
• cycloalkyl
• aryl
• (heterocyclyl)alkyl
• -COR ' , wherein R11 can represent
O hydrogen

O alkyl O aryl O NR9R10
wherein R9 and R10 are independently hydrogen - alkyl alkenyl alkynyl O alkoxy
W can represent O -NH
O -(CH2)m- wherein m can represent an integer 2-6, -(CH2)m- group can be optionally interrupted by group(s) independently chosen from unsaturated bond, oxygen, sulfur, -NRa-, where Ra can be hydrogen, alkyl, cycloalkyl, alkenyl, heterocyclyl, (heterocyclyl)alkyl, alkynyl or aryl, or one of the hydrogen atom of-(CH2)m- group can be optionally replaced by
halogen - alkyl hydroxyl alkoxy with the provisio that R is hydrogen when W is -(CH2)m-, wherein m can represent an integer 2-6 R can represent
• hydrogen
• hydroxy
• alkyl
• aryl
• heterocyclyl
• cycloalkyl
• cycloalkenyl R can represent
• hydrogen
• alkyl

• alkenyl
• alkynyl
• aryl
• cycloalkyl
• heterocyclyl
• amidoarylalkyl
• amidoarylalkynyl R' can represent
• hydrogen
• aryl
• alkyl
• -(CH2)r-U
wherein r can represent an integer 1 to 4 U can represent
O alkenyl
O alkynyl
O alkylalkenyl
O alkylalkynyl
O arylalkenyl
O arylalkynyl
O heterocyclylalkenyl
O heterocyclylalkynyl OR' can be replaced by hydrogen Y can represent
• hydrogen
• halogen
• cyano
• alkyl
• aryl
• heterocyclyl
• hydroxy
• amino
• PhSe
• -NR9R10 wherein R9 and R10 are the same as defined earlier

• Alkenyl
• Alkynyl
Z can represent
• oxygen
• sulphur
• NOR11 wherein R11 is the same as defined earlier.
In accordance with a second aspect, there is provided a method for treating or preventing a subject suffering from a condition caused by or contributed to by gram positive, gram negative or anaerobic bacteria, comprising administering to said subject, a therapeutically effective amount of a compound or a pharmaceutical composition disclosed herein.
The bacterial infection may be caused by bacterium, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae
The said conditions may be, for example, community acquired pneumonia, upper and lower respiratory tract infections, otitis media, sinusitis, bronchitis, tonsillitis, mastoiditis, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, and other bacterial infections, for example, mastitis, catheter infection, foreign body, prosthesis infections, odontogenic infection or peptic ulcer disease.
In accordance with a third aspect, there is provided a process for the preparation of disclosed compounds.
The compounds disclosed herein can also be used as anti-inflammatory and prokinetic agents.
As used herein the term "alkyl" refers to straight or branched saturated hydrocarbon having one to six carbon atom(s). One or more hydrogen atom (s) of the said alkyl can optionally be replaced by halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl, (heterocyclyl)alkyl, cycloalkoxy, -CH=N-O(C1-6alkyl), -CH=N-NH-(C1-6alkyl), -C(=N-NH-(C1-6alkyl)-C1-6alkyl, -NHCOR8, -NHCOOR8, -OCOR8 or -COR8, wherein R8 is hydrogen, alkyl, alkoxy, aryl or heterocyclyl. Examples of alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl and butyl, and the like.

As used herein the term "alkylene" refers a divalent group derived from a straight or branched chain saturated hydrocarbon having from 1 to 6 carbon atoms by the removal of two hydrogen atoms, for example, methylene, 1,2 ethylene and the like.
As used herein the term "alkenyl or alkynyl" stands for unsaturated hydrocarbon having two to six carbon atoms. One or more hydrogen atom(s) of said alkenyl or alkynyl can be replaced by alkyl, halogen, hydroxy, mercapto, alkoxy, thioalkyl, cycloalkyl, aryl or heteroaryl. Examples of alkenyl and alkynyl include, but are not limited to, ethylene, propylene, ethynyl and propynyl, and the like.
As used herein the term "alkenylene or alkynylene" refers to a divalent group derived from a straight or branched unsaturated hydrocarbon chain having from 1 to 6 carbon atoms by the removal of two hydrogen atoms, for example, vinylene, and the like.
As used herein the term "cycloalkyl" refers to saturated carbocyclic ring having three to seven carbon atoms. One or more hydrogen atom(s) of said cycloalkyl can be replaced by halogen, hydroxy, mercapto, alkoxy or thioalkyl. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl and cyclopentyl, and the like.
As used herein the term "halogen or halo" refers to fluorine, chlorine, bromine or iodine.
"Amidoarylalkyl", "Amidoarylalkenyl" refer to substituents wherein an aryl group is linked to the substituted moiety through an amido and an alkyl or alkenyl respectively.
As used herein the term "hydroxyl protected" includes, but are not limited to, trialkylsilyl, benzyloxycarbonyl. acid remainder, acyl, aroyl, alkyl, aryl, butyldiphenylsilyl, methoxymethyl and methylthiomethyl, and the like.
Acid remainder can be acetic acid, propionic acid, maleic acid, tartaric acid, methane-sulfonic acid, benzene-sulphonic acid, p-toluenesulphonic acid, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, stearic acid, ethylsuccinic acid or laurylsulphonic acid.
As used herein the term "thio" refers to the group -SH.
As used herein the term "alkoxy" stands for a group O-R5 wherein R5 refers to alkyl, aryl or cycloalkyl. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, cyclopentoxy, phenoxy and the like.
As used herein the term "thioalkyl" refers to -SR5 wherein R5 is alkyl or cycloalkyl.
As used herein the term "haloalkyl" refers to alkyl of which one or more hydrogen(s) is/are replaced by halogen.

As used herein the term "aryl" stands for an aromatic radical having 6 to 14 carbon atoms. Examples of aryl include, but are not limited to, phenyl, napthyl, anthryl and biphenyl, and the like.
As used herein the term "aralkyl" stands for an aryl radical having 7 to 14 carbon atoms, which is bonded to an alkylene chain. Examples of aralkyl include, but are not limited to, benzyl, napthylmethyl, phenethyl and phenylpropyl, and the like.
As used herein the term "heterocyclyl" refers to non-aromatic or aromatic ring system having one or more heteroatom(s) wherein the said hetero atom(s) is/are selected from the group comprising of nitrogen, sulphur and oxygen, ring system is attached through heteroatom or carbon and the ring system includes mono, bi or tricyclic. Examples of heterocyclyls include, but not limited to, benzoimidazolyl, 3H-Imidazo[4,5-b]pyridine, isoquinolinyl, pyridyl, lH-Pyrrolo[2,3-b]pyridine, and the like.
As used herein the term "(heterocyclyl)alkyl" stands for heterocyclyl which is bonded to an alkylene chain. Examples of heterocyclyl alkyl include, but are not limited to, isothiazolidinyl ethyl, isothiazolyl propyl, pyrazinyl methyl, pyrazolinyl propyl and pyridyl butyl, pyridyl methyl and the like.
The said aryl and heterocyclyl may optionally be substituted with one or more substituent(s) independently selected from the group comprising of amino, hydroxy, halogen, nitro, mercapto, cyano, alkyl, haloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclyl alkyl, alkoxy, thioalkyl, -NR6R7, -CONR6R7, -COOR7, -CONHR7, -OCOR7, -COR7, -NHSO2R7, and -SO2NHR7, wherein R6 and R7 are independently selected from the group comprising of hydrogen and alkyl. Examples of substituted heterocyclyl include, but not limited to, 4-Pyridyl-3-yl-imidazol-l-yl, 4-Phenyl-imidazol-1-yl, 4-Thiophen-3-yl-imidazol-l-yl, and the like.
As used herein the term "polymorphs" includes all crystalline form and amorphous form for compounds described herein. In addition, some of the compounds described herein may form solvates with water (i.e. hydrate, hemihydrate or sesquihydrate) or common organic solvents. Such solvates are also encompassed within the scope of this invention.
As used herein the term "prodrugs" refers to the compounds that are rapidly transformed in vivo to yield the parent compound of the previous formula.
The phrase "pharmaceutically acceptable salts" denotes salts of the free base, which possess the desired pharmacological activity of the free base and which are neither biologically nor otherwise undesirable. Suitable pharmaceutically acceptable salts may be prepared from an inorganic or organic acid. Example of such inorganic acids include, but not

limited to, hydrochloric, hydrobromic, hydroiodic, carbonic, sulfuric, phosphoric acid and like. Appropriate organic acids include, but not limited to, aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of organic acids, for example, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumeric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, stearic, algenic, beta-hydroxybutyric, cyclohexylaminosulfonic, galactaric and galacturonic acid and the like.
The term "pharmaceutically acceptable carriers" is intended to include non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
The compounds of present invention include stereoisomers. The term "stereoisomer" refers to compounds, which have identical chemical composition, but differ with regard to arrangement of the atoms and the groups in space. These include enantiomers, diastereomers, geometrical isomers, atropisomer and comformational isomers. Geometric isomers may occur when a compound contains a double bond or some other feature that gives the molecule a certain amount of structural rigidity. An enantiomer is a stereoisomer of a reference molecule that is the nonsuperimposable mirror image of the reference molecule. A diastereomer is a stereoisomer of a reference molecule that has a shape that is not the mirror image of the reference molecule. An atropisomer is a conformational of a reference compound that converts to the reference compound only slowly on the NMR or laboratory time scale. Conformation isomers (or conformers or rotational isomers or rotamers) are stereoisomers produced by rotation about a bonds, and are often rapidly interconverting at room temperature. Racemic mixtures are also encompassed within the scope of this invention.
The term "drug resistance" or "drug resistant" refers to the characteristics of a microbe to survive in presence of a currently available antimicrobial agent such as an antibiotic at its effective concentration.
The term "subject" includes any animal or artificially modified animal. As a particular embodiment, the subject is a human.
The term "administering" includes the treatment of the various disorders described with the compounds specifically disclosed or with a compound which may not be specifically

disclosed, but which converts to the specified compound in vivo after administration to the patient.
The term "treating" means reversing, alleviating, inhibiting the progress of or preventing the disorder or condition to which such term applies, or one or more symptoms of such disorder or condition. The term "treatment" refers to the act of treating, as treating is defined above.
Detailed Description of the Invention
The compounds disclosed herein may be prepared by techniques well known in the art and familiar to the average synthetic organic chemist. In addition, the compounds of the present invention may be prepared by the following reaction sequences as depicted in Scheme I, IA, II and III.
The compound of Formula XIII can be prepared according to Scheme I, as shown in the accompanied drawings. Thus, hydrolyzing Clarithromycin of Formula II to give a compound of Formula III, which on protection with a reagent of Formula R12O or R'X (wherein X is halogen and R1 is as defined earlier) gives a compound of Formula IV, which is reacted with a suitable reagent to give a compound of Formula V, which on reaction with a organic base, gives a compound of Formula VI, which on oxidation gives a compound of Formula VII, which on desmethylation at 3'-N-dimethyl group gives a compound of Formula VIII, which on alkylation with a reagent of Formula R3CHO, R32 CO or R3X (wherein X, halogen) gives a compound of Formula IX (wherein R3 is the same as defined earlier), which on fluorination gives a compound of Formula X, which on reaction with N,N'-carbonyl diimidazole gives a compound of Formula XI, which on reaction with a compound of Formula R-W-NH2 gives a compound of Formula XII (wherein W and R are the same as defined earlier), which is finally deprotected to give a compound of Formula XIII.
The hydrolysis of clarithromycin of Formula II to give a compound of Formula III can be carried out in the presence of an inorganic or organic acid, for example, hydrochloric acid, sulfuric acid or dichloroacetic acid.
The hydroxyl protection of a compound of Formula III with a reagent of Formula R12O or R'X to give a compound of Formula IV can be carried out in a solvent, for example, dichloromethane, dichloroethane, chloroform, carbon tetrachloride or ethyl acetate.
The hydroxyl protection of a compound of Formula III with a reagent of Formula R12O or R'X can be carried out in the presence of an organic base, for example,

triethylamine, pyridine, tributylamine, diisopropylethylamine or 4-(N-dimethylamino)pyridine.
The reaction of a compound of Formula IV to give a compound of Formula V can be carried out in presence of a reagent, for example, phosgene, diphosgene, triphosgene or ethylene carbonate.
The reaction of a compound of Formula IV to give a compound of Formula V can be carried out in a solvent, for example, dichloromethane, chloroform, carbon tetrachloride, or dichloroethane.
The reaction of a compound of Formula IV to give a compound of Formula V can be carried out in the presence of an organic base, for example, triethylamine, pyridine, tributylamine, 4-(N-dimethylamino) pyridine or diisopropylethylamine.
The reaction of a compound of Formula V to give a compound of Formula VI can be carried out in a solvent, for example, dimethylformamide, tetrahydrofuran or dimethylsulphoxide.
The oxidation of a compound of Formula VI to give a compound of Formula VII can be carried out with an oxidizing agent, for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), pyridinium dichromate or l-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride.
The oxidation of a compound of Formula VI to give a compound of Formula VII can be carried out in a solvent, for example, chloroform, dichloromethane, carbon tetrachloride, dimethylsulphoxide or dichloroethane.
The desmethylation of a compound of Formula VII to give a compound of Formula VIII can be carried out in the presence of a desmethylating agent, for example, iodine in acetic acid, N-iodo succinimide, 1-chloroethyl chloroformate or diisopropyl azodicarboxylate.
The desmethylation of a compound of Formula VII to give a compound of Formula VIII can be carried out in a solvent, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixture thereof.
The quenching of desmethylation reaction can be carried out in the presence of a quenching agent, for example, sodium bisulphite, sodium carbonate, cesium carbonate, potassium carbonate, sodium acetate or mixture thereof.

The alkylation of a compound of Formula VIII with a reagent of Formula R3CHO, R2 3CO or R X to give a compound of Formula IX can be carried out in a solvent, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixture thereof.
The alkylation of a compound of Formula VIII can be carried out in the presence of an inorganic or organic base, for example, sodium hydrogen carbonate, potassium carbonate, sodium hydride, pyridine, triethylamine, sodium carbonate, sodium acetate, sodium thiosulphate or diisopropylethylamine.
The fluorination of a compound of Formula IX to give a compound of Formula X can be carried out with a fluorinating agent, for example, selectfluor, N-fluorobenzene sulfonamide (also as described by G.Sankar Lai and Syvret R.G in Chem.Rev. 1996, 96, 1737-1755).
The fluorination of a compound of Formula IX can be carried out in a solvent, for example, dimethylformamide, tetrahydrofuran or dimethylsulphoxide.
The fluorination of a compound of Formula IX can be carried out in the presence of an inorganic base, for example, potassium carbonate, sodium hydride, sodium acetate, sodium thiosulphate, potassiunm-t-butoxide, sodium-t-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide or lithium carbonate.
The reaction of a compound of Formula X with N,N'-carbonyldiimidazole to give a compound of Formula XI can be carried out in a solvent, for example, dimethylformamide, acetonitrile, tetrahydrofuran or mixture thereof.
The reaction of a compound of Formula X with N,N'-carbonyldiimidazole can be carried out in the presence of an inorganic base, for example, sodium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium acetate, potassium-/-butoxide, sodium thiosulphate or sodium hydride.
The reaction of a compound of Formula XI with a compound of Formula R-W-NH2 to give a compound of Formula XII can be carried out in a solvent or solvent system, for example, dimethylformamide, acetonitrile/water or dimethylformamide/water.
The deprotection of a compound of Formula XII to give a compound of Formula XIII can be carried out in an alcohol, for example, methanol, ethanol, propanol or isopropanol.

Compounds of the present invention useful for such purpose are listed below (also shown in Table I).
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(3-pyridin-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 2),
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(3-pyridin-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No.3),
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(pyridin-3-yloxy)-propyl)-imino)]erythromycin A (Compound
No. 4),
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(3-thiophen-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 5),
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof.
The compound of Formula XIVA can be prepared according to Scheme IA, as shown in the accompanied drawings. Thus, desmethylation at 3'-N-dimethyl group of Formula XII gives a compound of Formula XIIIA, which is deprotected to give a compound of Formula XIVA.
The desmethylation of a compound of Formula XII to give a compound of Formula XIIIA can be carried out in a solvent, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixture thereof.
The quenching of desmethylation reaction can be carried out in the presence of a quenching agent, for example, sodium bisulphite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixture thereof.
The deprotection of a compound of Formula XIIIA to give a compound of Formula XIVA can be carried out in an alcohol, for example, methanol, ethanol, propanol or isopropanol.

A compound of the present invention useful for such purpose is listed below (also shown in
Table I).
2-α-Fluoro-5-0-(3'-N-didesmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-imidazol[4,5-b]pyridin-3-yl)-butyl)-imino] erythromycin A (Compound No. 1),
The compound of Formula XVI can be prepared according to Scheme II, as shown in the accompanied drawings. Thus, a compound of Formula XI, which on reaction with hydrazine hydrate results into unsubstituted carbazate derivative, which on epimerization gets converted into desired isomer of Formula XIV, which on deprotection gives a compound of Formula XV, which on reaction with a compound of Formula R-W-CHO gives a compound of Formula XVI (wherein W and R are the same as defined earlier).
The reaction of a compound of Formula XI with hydrazine hydrate to give carbazate epimers of Formula XIVA can be carried out in a solvent, for example, dimethylformamide, acetonitrile, tetrahydrofuran, ethanol or methanol.
The epimers of Formula XIVA are treated with a base for example, potassiun-t-butoxide or sodiun-t-butoxide to give a desired isomer of Formula XIV.
The reaction of epimers with a base can be carried out in a solvent, for example, tetrahydrofuran, dimethylformamide, acetonitrile, ethanol or methanol.
The reaction of compound of Formula XIV with a compound of Formula R-W-CHO to give a compound of Formula XV can be carried out in an alcoholic solvent for example, methanol, ethanol, propanol, isopropanol or t-butyl alcohol.
The reaction of compound of Formula XIV to give a compound of Formula XV can be carried out in presence of a reducing agent, for example, sodium cyanoborohydride, sodium borohydride or sodium triacetoxyborohydride.
The reaction of compound of Formula XIV to give a compound of Formula XV can be carried out in presence of an organic acid, for example, acetic acid, formic acid or trifluoroacetic acid.
The deprotection of a compound of Formula XV to give a compound of Formula XVI can be carried out in an alcohol, for example, methanol, ethanol, propanol or isopropanol.
In the above scheme, where specific bases, acids, solvents etc. are mentioned, it is to be understood that other bases, acids, solvents etc., known to those skilled in the art may also

be use. Similarly, the reaction temperature and duration of the reactions may be adjusted according to the desired needs.
Compounds of the present invention useful for such purpose are listed below (also shown in
Table I).
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-hydrazo]erythromycin A (Compound No. 6),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-hydrazo]erythromycin A (Compound No. 7),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-pyrrolo[2,3-b]pyridin-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 8),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-phenylpropyl)-hydrazo)]erythromycin A (Compound No. 9),
2-α-Fluoro-5-O-(3'-N-desmethyl-3,-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-isoquinolin-5-yl-propyl)-hydrazo)]erythromycin A (Compound No. 10),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-phenylpropyl)-hydrazo)]erythromycin A (Compound No. 11),
2-aα-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-phenyl-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A (Compound No. 12),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-phenyl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 13),
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)- ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 14),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 15),

2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 16),
2-α-Fluoro-5-O-(3,-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 17),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-thiophen-3-yl-imidazol-1 -yl)propyl)-hydrazo)] erythromycin A (Compound No. 18),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-l-yl)-butyl)-hydrazo)] erythromycin A (Compound No. 22),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-phenyl-imidazol-l-yl)-butyl)-hydrazo)] erythromycin A (Compound No. 23),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-phenyl-allyl)-hydrazo)]erythromycin A (Compound No. 24),
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof.
The compound of Formula XVIII can be prepared according to Scheme III, as shown in the accompanied drawings. Thus, treating a compound of Formula XV with a reagent of Formula H2NOR11 (wherein R11 is the same as defined earlier) gives a compound of Formula XVII, which on reaction with a compound of Formula R-W-CHO (wherein M and R are the same as defined earlier) gives a compound of Formula XVIII.
The reaction of a compound of Formula XV to give a compound of Formula XVII can be carried out in a solvent, for example ethanol, methanol or isopropanol.
The reaction of a compound of Formula XVII to give a compound of Formula XVIII can be carried out in a solvent, for example, ethanol, methanol, isopropanol, tetrahydrofuran or dimethylformamide.
The reaction of a compound of Formula XVII to give a compound of Formula XVIII can be carried out in presence of a reducing agent, for example, sodium cyanoborohydride, sodium borohydride or sodium triacetoxyborohydride.

The reaction of compound of Formula XVII to give a compound of Formula XVIII can be carried out in presence of an organic acid, for example, acetic acid, formic acid or trifluoroacetic acid.
Compounds of the present invention useful for such purpose are listed below (also shown in
Table I).
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-phenyl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A-9-(O-methyl)oxime (Compound No. 19),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A-9-(0-methyl)oxime (Compound No. 20),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-thiophen-3-yl-imidazol-1 -yl)propyl)-hydrazo)] erythromycin A-9-(O-methyl)oxime (Compound No. 21),
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof.
In the above schemes, where specific bases, acids, solvents etc. are mentioned, it is to be understood that other bases, acids, solvents etc., known to those skilled in the art may also be use. Similarly, the reaction temperature and duration of the reactions may be adjusted according to the desired needs. All the epimers, unless otherwise specified in the above schemes, are also encompassed within the scope of this invention.
(Formula Removed)

Table I: Formula 1 (wherein R'=R2= CH3 ,R4= C2H5,R'=H, Z=O, Y=F)

(Table Removed)
*R is Hydrogen, ** Z is NOMe, —• is point of attachment
Because of their antibacterial activity, the compounds described herein may be administered to an animal for treatment orally, topically, rectally, intemasally, intracisternally, intravaginally, intraperitoneally, buccally or by parenteral route. The pharmaceutical compositions of the present invention comprise a pharmaceutically effective
amount of compounds described herein formulated together with one or more pharmaceutically acceptable carriers.
Solid form preparations for oral administrations include capsules, tablet, pills, powder, dragees, granules, cachets and suppository. For solid form preparation, the active compound is mixed with at least one inert, pharmaceutically acceptable excipients or carrier, for example, sodium citrate, dicalcium phosphate and/or a filler or extenders, for example, starches, lactose, sucrose, glucose, mannitol and silicic acid; binders, for example, carboxymethylcellulose, alginates, gelatins, polyvinylpyrrolidinone, sucrose, acacia; disintegrating agents, for example, agar-agar, calcium carbonate, potato starch, alginic acid, certain silicates and sodium carbonate; absorption acceletors, for example, quaternary ammonium compounds; wetting agents, for example, cetyl alcohol, glycerol mono stearate; adsorbents, for example, Kaolin; lubricants, for example, talc, calcium stearate, magnesium stearate, solid polyethyleneglycol, sodium luaryl sulphate and mixture thereof. In the case of capsules, tablets, pills, the dosage form may also comprise buffering agents.
The solid preparation of tablets, capsules, pills and granules can be prepared with coating and shells, for example, enteric coating and other coatings well known in the pharmaceutical formulating art.
Liquid form preparation for oral administration includes pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. For liquid form preparation, the active compound is mixed with water or other solvent, solubilizing agents and emulsifiers, for example, ethyl alcohol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol, dimethylformamide, oils, for example, cottonseed, groundnut, corn, germ, olive, castor and sesame oil), glycerol, and fatty acid esters of sorbitan and mixture thereof. Besides inert diluents, the oral composition can also include adjuants, for example, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavoring agents and perfuming agents.
Injectable preparations, for example, sterile injections, injectable depot forms, aqueous suspensions may be formulated according to the art using suitable dispersing or wetting and suspending agent. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride.
Dosage form for tropical or transdermal administration of a compound of the present invention includes ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active compound is admixed under sterile condition with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be
required. Ophthalmic formulations, eardrops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention.
The pharmaceutical preparation is in unit dosage form. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be packaged preparation, the package containing discrete capsules, powders, in vials or ampoules, and ointments capsule, sachet, tablet, gel, cream itself or it can be the appropriate number of any of these packaged forms.
Examples set forth below demonstrate the general synthetic procedure for the preparation of representative compounds. The examples are provided to illustrate particular aspect of the disclosure and do not constrain the scope of the present invention as defined by the claims.
Experimental Details General Procedure
Preparation of compound of Formula R-W-NH2
(a) When W= -O(CH2)3-
Example 1: Preparation of 3-(4-pyridin-3-yl phenoxy) propan-1-amine
Step I: Preparation of pyridin-3-boronic acid
3-bromo pyridine (5 g) was dissolved in about 20 ml dry tetrahydrofuran, cooled to -78°C and to it tri-isopropyl borate (14.6 ml) was added, followed by addition of butyl lithium (15% in hexane, 21ml). The reaction mixture was stirred at -78°C for about 4 hours, pH was adjusted to about 7, it was extracted with ethyl acetate and concentrated to get white solid. Yield: 1.2 g
Step 2: Preparation of 2-[3-(3-bromo-phenoxy)-propyl]-isoindole-1,3-dione
To 3-bromo phenol (0.03178 mol, 1 equiv.), about 30 ml of dry dimethylformamide was added. It was cooled to 0°C. Then sodium hydride (0.0476 mol, 1.5 equiv.) was added in portions. After 30 minutes, N-3-bromopropyl phthalimide (0.0381 mol, 1.2 equiv.) was added. The reaction mixture was stirred for about 3 hours. It was quenched by pouring reaction mixture into ice cold water. The precipitate was filtered and vacuum dried. Yield: 9 g
Step 3: Preparation of 2-{3-[3-(pyridin-3-yl)-phenoxyl-propyll-isoindole-1,3-dione
Pyridin-3-boronic acid (6.11mmol, l.lequiv.), 2-[3-(3-bromo-phenoxy)-propyl]-isoindole-l, 3-dione (5.5 mmol, 1 equiv.) and potassium carbonate (22.2 mmol, 4 equiv.) were taken in a round bottom flask and degassed for about 1 hour. Dry dimethylformamide of about 15 ml was added. The reaction mixture was than flushed with argon for about 15 minutes. Tetrakis (triphenylphosphine) palladium (0) (0.27 mol, 0.05 equiv.) was added to it. The reaction mixture was heated at 80°C for about 12 hours. It was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over anhydrous sodium sulfate. Yield: 0.2 g
Step 4: Preparation of 3-(4-pyridin-3-ylphenoxy)-propan-l-amine
2-{3-[3-(pyridin-3-yl)-phenoxy]-propyl}-isoindole-1,3-dione (0.2 g) was taken in about 10
ml of ethanol and hydrazine monohydrate (0.2 ml) was added to it . The reaction mixture
was heated at 60°C for about 4 hours. It was cooled to room temperature and solid obtained
was filtered through celite bed. The filtrate was concentrated to get the crude product, which
was purified using dichloromethane and methanol as eluent.
Yield: 0.13 g
The following compounds were prepared similarly
3-[4-(3-Thienyl) phenoxy]propan-l-amine
The title compound was prepared by a procedure analogous to the one described step 3 by
substituting pyridin-3-ylboronic acid with 3-thienylboronic acid
3 -(Pyridin-3 -yl-oxy)propan-1 -amine
The title compound was prepared by a procedure analogous to the one described in step 2 by
substituting 3-bromophenol with Pyridin-3-ol
(ii) when W= -(CH2)4 -
Example 2: Preparation of 4-(3H-imidazor4,5-6]pyridin-3-yl)butan-l-amine
It was prepared by following the procedure given in US Patent No. 5,635,485.
Preparation of compound of Formula RWCOH

When W= -(CH2)3-
Example 3: Preparation of 3-isoquinolin-5-ylpropanal Step I: Preparation of dioxolane derivative of triphenylphosphorane
A solution of 2-bromomethyl-[l,3]dioxolane (60.0 mmol) and triphenylphosphine (60.0 mmol) in toluene (50 ml) was refluxed for 24 hours. The solid formed was filtered at room temperature and the solid was washed with diethyl ether and dried under reduced pressure. Yield: 3.5 g (54%) M.P: 194-195°C
Step II: Preparation of 5-[2-(l,3-dioxolan-2-yl)vinyl~lisoquinoline
A solution of Wittig salt (1.97 mmol) and isoquinoline-2-carboxyaldehyde (7.97 mmol) (commercially available, Biocom) in about 20 ml of tetrahydrofuran was cooled to -35°C and to it potassiunm-t-butoxide (9.9 mmol) was added in portions and stirred at -35°C for about 1 hour. It was then allowed to warm to 10°C and then stirred for about 3 hour, poured into water and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to get the crude product, which on purification over silica gel column using methanol- dichloromethane as eluent, gave the desired product. Yield: lg (55%).
Step III: Preparation of 5-[2-(l,3-dioxolan-2-yl)ethyl"lisoquinoline
5-[2-(l,3dioxolan-2-yl)-vinyl] isoquinoline (100 mg) and Palladium/Carbon (50% wet, 50 mg) was taken in hydrogen bottle, flushed with argon and hydrogenated at 10 psi for about 12 hours, filtered through celite and the filtrate was evaporated to get product. Yield: 70 mg (99%)
Step IV: Preparation of 3-isoquinolin-5-yl-propanal
A solution of 5-(2-[l,3-dioxolan-2-yl-ethyl] isoquinoline (0.9 g) and 2N Hydrochloric acid
(15 ml) in acetone (15 ml) was stirred at 40°C for 4 hour under nitrogen atmosphere. The
solvent was evaporated off and the pH was adjusted to 9-10 by aqueous potassium carbonate
solution and extracted with ethyl acetate, evaporation of ethyl acetate extract gave the
product.
Yield: 0.5 g (68%).

Example 4: Preparation of 3-Pyrrolo[2,3-blpvridine-l-yl-propionaldehyde lH-Pyrrolo[2,3-b]pyridine (8.403 mmol) (commercially available, Lancaster) was dissolved
in tetrahydrofuran (30 ml) and to it was added ethanol (8.403 mmol) and acrolein (33.612
mmol). The reaction mixture was stirred at 60°C for about 6 hours. The volatiles were
removed and the residue was purified over silica gel column using methanol and
dichloromethane as eluent, to give the desired product.
Yield: 31%
The following compounds were prepared similarly.
3-(4-Phenyl-imidazol-1 -yl)-propionaldehyde
The title compound was prepared by a procedure analogous to the one described
above by substituting lH-Pyrrolo[2,3-b]pyridine with 4-Phenyl-lH-imidazole (commercially
available, Lancaster)
3 -(1 -H-Benzimidazol-1 -yl)propanal
The title compound was prepared by a procedure analogous to the one described
above by substituting lH-Pyrrolo[2,3-b]pyridine with l-H-Benzimidazol (commercially
available, Loba Chemie)
3 -(4-Pyridin-3 -yl-1 H-imidazol-1 -yl)propanal
The title compound was prepared by a procedure analogous to the one described
above by substituting lH-Pyrrolo[2,3-b]pyridine with 4-Pyridin-3-yl-1H-imidazole
(commercially available, Argus Chemicals)
3-[4-(3-thienyl)-lH-imidazol-l-yl]propanal
The title compound was prepared by a procedure analogous to the one described
above by substituting lH-Pyrrolo [2,3-b]pyridine with 3-Thienyl-lH-imidazole
Example 5: Preparation of 4-(thienvl-3-yl)imidazole
Step 1: A solution of l-trityl-4-bromo-imidazole (10.28 mmol), thiophene-3-boronic acid (12.33 mmol) and potassium carbonate (41.12 mmol) in dimethylformamide (50 ml) was degassed for 15 minutes with stirring at room temperature followed by addition of tetrakis(triphenylphospine)palladium (1.028 mmol) and reaction mixture was stirred at 90°C for about 20 hours. The reaction mixture was worked up, extracted with ethyl acetate and purified by column, using ethylacetate: hexane (-15%) as eluent. Yield: 2.45 g

Step 2: The product of the above coupling reaction (0.00625 mol) was taken in ethanol, to this hydrochloric acid (IN, 1ml) was added and the resulting solution was heated at 50°C for about 2 hours. The reaction mixture was the cooled to room temperature, the solvent was evaporated and pH was adjusted to 8 with help of sodium bicarbonate solution. The product was extracted with ethyl acetate. Evaporation of ethyl acetate gave the crude product. This was purified by column using dichloromethane: methanol as the eluent. Yield: 0.81g
Scheme I
Preparation of compound of Formula III
To an aqueous solution of hydrochloric acid (IN, 250 ml) was added clarithromycin (33.4 mmol) at an ambient temperature in portion. The reaction mixture was neutralized with solid sodium bicarbonate and the aqueous layer was extracted with ethyl acetate. Organic layer was washed with water, brine, and dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure to afford crude product. The crude product was crystallized by using ethyl acetate and hexane.
Preparation of compound of Formula IV
To a solution of compound of Formula III (1 equiv.) in dry dichloromethane was added benzoic anhydride (2.5 equiv.) followed by triethylamine (6 equiv.) and stirred at an ambient temperature for about 30 hours. The reaction was quenched by addition of sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane, washed successively with water, brine, and dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to give crude product. The crude product obtained was crystallized by using ethyl acetate and hexane mixture.
Preparation of compound of Formula V
To a solution of compound of Formula IV (1 equiv.) in dichloromethane at about 0°C was added triphosgene (1.5 equiv.) with stirring. To it was added pyridine (15 equiv.) slowly, exothermic reaction was observed. After complete addition, reaction mixture was stirred for about 3-4 hours at 0°C. The reaction was quenched by drop wise addition of ice-cold water. Reaction mixture was diluted with dichloromethane and washed with water

followed by brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the desired product. Preparation of compound of Formula VI
To a solution of compound of Formula V (1 equiv.) in dimefhylformamide was added tetramethyl guanidine (2.2 equiv.) and heated at about 80-90°C for about 8 hours. Reaction mixture was cooled to an ambient temperature, water was added and extracted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the desired product.
Preparation of compound of Formula VII
To a solution of compound of Formula VI (1 equiv.) in dichloromethane was added Dess-Martin Periodinane (2.5 equiv.) and stirred at 30°C for about 1 hour. Reaction was quenched by addition of saturated aqueous potassium carbonate solution followed by saturated sodium thiosulphate solution and stirred. The reaction mixture was separated and extracted with dichloromethane. Dichloromethane layer was washed with water, brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the desired product.
Preparation of compound of Formula VIII
To a solution of compound of Formula VII (1 equiv.) in dry acetonitrile: dichloromethane (2:1) was added N-iodosuccinimide (2 equiv.) and the reaction mixture was allowed to attain an ambient temperature and stirred for about 3-4 hours. Then the reaction mixture was stirred with a sodium bisulphite solution followed by stirring with sodium carbonate solution. Dichloromethane was evaporated under reduced pressure. The residue was extracted with ethyl acetate, washed with water, brine, dried over anhydrous sodium sulfate and then the solvent was removed under reduced pressure to yield the product.
Preparation of compound of Formula IX
To a solution of compound of Formula VIII (1 equiv.) in acetonitrile was added solid sodium hydrogen carbonate (5 equiv.) and R3X (6 equiv.) under argon at an ambient temperature and stirred for about 18-20 hours. Reaction was quenched by the addition of water. Reaction mixture was diluted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield

a crude product. Purification of the crude product was done by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-15% acetone in hexane to afford the desired product.
Preparation of compound of Formula X Method-A
To a solution of compound of Formula IX (1 equiv.) in dimethylformamide was added sodium hydride (1.5 equiv.) in portions at 0°C, stirred for about 15 min. Then N-fluorobenzene sulfonimide (1.2 equiv.) was added. Reaction mixture was stirred at 0 C for about 3 hours. Reaction was quenched by addition of water and extracted with ethyl acetate. Organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure.
Method- B
To a solution of compound of Formula IX (1 equiv.) in tetrahydrofuran was added potassium-/-butoxide at about -15 °C, stirred for about 20 min. Then N-fluorobenzene sulfonimide (1.2 equiv.) in tetrahydrofuran was added. Reaction mixture was stirred at -15 °C for about 2 hours, quenched by addition of water and extracted with ethyl acetate. Organic layer was washed with water followed by brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure.
Preparation of compound of Formula XI
A solution of compound of Formula X (1 equiv.) in dimethylformamide: tetrahydrofuran (3:2), cooled to 0°C, to it was added N, N'-carbonyldiimidazole (3 equiv.) and sodium hydride (3 equiv.) and it was stirred for about 30 min. Reaction was quenched by addition of water. This was extracted with ethyl acetate. Ethyl acetate layer was washed with water, brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the desired product.
Preparation of compound of Formula XII
The compound of Formula XI (1 equiv.) and compound of Formula R-W-NH2 (3 equiv.) were taken in 10% water in acetonitrile and heated to 65-70 °C for about 14 hours. Reaction mixture was cooled to attain an ambient temperature; acetonitrile-water was removed under reduced pressure. The resulting residue was purified by silica gel column

chromatography (thoroughly neutralized with triethylamine) using 25-30% acetone in hexane to afford the desired product.
Preparation of compound of Formula XIII
The compound of Formula XII was taken in methanol and refluxed for about 12 hours. Reaction mixture was cooled to attain an ambient temperature and methanol was evaporated under reduced pressure. Purification of the solid mass was done over a silica gel column using 2-6% methanol in dichloromethane.
The following compounds were prepared following the above general procedure
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(3-pyridin-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 2) Mass: m/z 856.40 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(3-pyridin-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 3) Mass: m/z 868.40 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(pyridin-3-yloxy)-propyl)-imino)]erythromycin A (Compound No. 4) Mass: m/z 780.47 [M+l]
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-(3-thiophen-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 5) Mass: m/z 861.82 [M+l]
Scheme 1A
Preparation of compound of Formula XIIIA
To a solution of compound of Formula XII (1 equiv.) in dry acetonitrile: dichloromethane (2:1) was added N-iodosuccinimide (2 equiv.) at 0°C and the reaction mixture was allowed to attain an ambient temperature and stirred for about 3-4 hours. Then the reaction mixture was stirred with a sodium bisulphite solution followed by stirring with sodium carbonate solution. Dichloromethane was evaporated under reduced pressure. The residue was extracted with ethyl acetate, washed with water, brine, dried over anhydrous sodium sulfate and then the solvent was removed under reduced pressure to yield the product.

Preparation of compound of Formula XIVA
The compound of Formula XIIIA was taken in methanol and refluxed for about 12 hours. Reaction mixture was cooled to attain an ambient temperature and methanol was evaporated under reduced pressure. Purification of the solid mass over a silica gel column using 2-6% methanol in dichloromethane yielded the desired product.
The following compound was prepared following the above general procedure
2-a-Fluoro-5-0-(3'-N-didesmethyl-3'-N-ethyl)-ll,12-dideoxy-3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-imidazol[4,5-b]pyridin-3-yl)-butyl)-imino] erythromycin A (Compound No.l) Mass: m/z 804.30 [M+l]
Scheme II
Preparation of compound of Formula XIV
Stepl: To the compound of Formula XI (15 mmol) in dimethylformamide (10 ml) was added
hydrazine hydrate (6.0 mmol) and stirred for about 1.5 hours at room temperature. The
reaction was quenched by pouring into water and extracted with ethyl acetate. The organic
layer was concentrated, washed with brine to give carbazate epimers.
Step 2: A solution of epimers (1.308 mmol) in tetrahydrofuran (10 ml), was cooled to about 0
°C, to which, potassiunm-butoxide (2.354 mmol) was added and stirred for about 2 hours.
The reaction was quenched by pouring into water and extracted with ethyl acetate, which was
then evaporated to give the desired isomer of Formula XIV. This crude product was purified
through the column of silica gel, using hexane: acetone + 2% triethylamine as the eluting
solvent.
Preparation of compound of Formula XV
The compound of Formula XIV was stirred in methanol (20 times) at 65-70° C for about 24-48 hours. The solvent was evaporated and solid obtained was purified through the column of 100-200 mesh silica gel, using dichloromethane: methanol as the eluting solvent.
Preparation of compound of Formula XVI
The compound of Formula XV, R-W-CHO (5equiv.) and acetic acid (5equiv.) were taken in methanol (20 times) and stirred at room temperature for about 2 hours. To it Acetic acid (5equiv.) and sodium cyanoborohydride (5equiv.) were added and stirred for 16-24 hours.

The solvent was evaporated and the residue was purified through column of silica gel, using hexane: acetone + 2% triethyl amine as the eluting solvent.
The following compounds were prepared following the above general procedure
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-11,12-dideoxy-3 -O-decladinosyl-6-O-methyl-3 -oxo-12,1 l-[oxycarbonyl-hydrazo]erythromycin A (Compound No. 6) Mass: m/z 660.46 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-hydrazo]erythromycin A (Compound No.7) Mass: m/z 672.49 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-pyrrolo[2,3-b]pyridin-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 8) Mass: m/z 830.38 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-phenylpropyl)-hydrazo)]erythromycin A (Compound No. 9) Mass: m/z 790.45 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l 1, 12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11-[oxycarbonyl-((3-isoquinolin-5-yl-propyl-hydrazo)]erythromycin A (Compound No. 10) Mass: m/z 841.36 [M+l]
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-11,12-dideoxy-3 -O-decladinosyl-6-O-methyl-3 -oxo-12,1 l-[oxycarbonyl-((3-phenylpropyl)-hydrazo)]erythromycin A (Compound No. 11) Mass: m/z 778.76 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-phenyl-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A (Compound No. 12) Mass: m/z 856.64 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-phenyl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 13) Mass: m/z 844.52 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)- ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 14)

Mass: m/z 818.48 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 15) Mass: m/z 845.45 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 16)
Mass: m/z 857.45 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 17) Mass: m/z 830.41 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3,-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-thiophen-3-yl-imidazol-l-yl)propyl)-hydrazo)] erythromycin A (Compound No. 18) Mass: m/z 862.51 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-l-yl)-butyl)-hydrazo)] erythromycin A (Compound No. 22) Mass: m/z 871.34 [M+l]
2α-Fluoro-5-O-(3,-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-phenyl-imidazol-l-yl)-butyl)-hydrazo)] erythromycin A (Compound No. 23) Mass: m/z 870.44 [M+l]
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-phenyl-allyl)-hydrazo)]erythromycin A (Compound No. 24) Mass: m/z 776.73 [M+l]
Scheme III
Preparation of compound of Formula XVII
The compound of Formula XV (0.742 mmol) and hydrochloride salt of H2NNOR11 (14.84 mmol) in ethanol (6 ml) was stirred at reflux for about 40 hours. The solvent was evaporated, to this was added dichloromethane and pH was adjusted to about 9.0 by addition of 1 N sodium hydroxide. The aqueous layer was extracted with dichloromethane and then the

combined dichloromethane layer was washed with brine dried and concentrated to give the
desired product.
Yield: 0.430 g
Preparation of compound of Formula XVIII
The compound of Formula XVII (0.624 mmol) and R-W-CHO (1.248 mmol) were taken in
methanol (10 ml), glacial acetic acid (53.62 mmol) was added at room temperature and
reaction stirred for about an hour. Then acetic acid (53.62 mmol) followed by sodium
cyanoborohydride (3.12 mmol) was added and reaction was stirred for about 12-18 hours.
The solvent was removed under reduced pressure and residue worked up by extraction with
ethyl acetate and the residue was purified over silica gel column using acetone:hexane:2%
triethylamine as eluent.
Yield: 0.120 g
The following compounds were prepared following the above general procedure
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-11, 12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-(4-phenyl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A-9-(O-methyl)oxime (Compound No. 19) Mass: m/z 885.59 [M+l]
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A-9-(0-methyl)oxime (Compound No. 20) Mass: m/z 874.41 [M+l]
2α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-thiophen-3-yl-imidazol- l-yl)propyl)-hydrazo)] erythromycin A-9-(0-methyl)oxime (Compound No. 21) Mass: m/z 891.55 [M+l]
Microbiological activity
Compounds disclosed herein displayed antibacterial activity in vitro especially against strains which are resistant to macrolides either due to efflux (mef strains) or ribosomal modification (erm) strains. These compounds are useful in the treatment of community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections, bone and joint infections, and other bacterial infections, for example, mastitis, catheter infection, foreign body, prosthesis infections or peptic ulcer disease.
Minimum inhibitory concentration (MIC) has been an indicator of in vitro antibacterial activity widely used in the art.

Procedure Medium
a) Cation adjusted Mueller Hinton Agar (MHA-Difco)
b) Trypticase Soya Agar (TSA)
Inoculum preparation
The cultures were streaked on TSA for aerobic cultures and MHA with 5% sheep blood for fastidious cultures.Aerobic cultures were incubated at 37°C for about 18-24 hours. Fastidious cultures were incubated CO2 incubation (5% CO2) at 37°C for about 18-24 hours. Three to four well isolated colonies were taken and saline suspension were prepared in sterile densimat tubes. The turbidity of the culture was adjusted to 0.5-0.7 Mc Farland standard (1.5 x 108 CFU/ml (Colony Forming Unit)/ml). The cultures were diluted 10 fold in saline to get inoculum size of approximately 1-2 x 10 organisms/ml. Preparation of drug concentration
1 mg/ml concentration of stock solution of drugs was prepared in dimethyl sulphoxide/distilled water/solvent given in National Committee for Clinical Laboratory Standards (NCCLS) manual. Serial two fold dilutions of the compounds and standard drugs were prepared as per NCCLS manual.
Stock solution can be changed according to the need of the experiment. Preparation of Agar Plates
Two ml of respective drug concentration was added to 18 ml of Molten Mueller Hinton agar to get the required range, for example 0.015 µg/ml - 16 µg/ml. For fastidious culture added 1 ml of sheep blood in Molten Mueller Hinton agar.
For control MHA and MHA with 5% sheep blood plates without antibiotic for each set were prepared. One MHA and MHA with 5% sheep blood plates without antibiotic for determining quality check for media was prepared. Preparation of Teflon template
1 µg of each culture on each plate was replicated with the help of replicator (Denley's multipoint replicator).The spots were allowed to dry and the plates were incubated for about 18-24 hours at 37°C. Fastidious cultures were incubated at 37 °C in CO2 incubator. The results were noted with the control plates.

Endpoint definition
The concentration of drug at which there was complete disappearance of growth spot or formation of less than 10 colonies per spot was considered as Minimum Inhibitory Concentration (MIC).
The MICs of quality control (QC) strains were plotted on the QC chart for agar dilution method. If the MICs were within the range, the results interpreted by comparing MICs of standards against all organisms with those of test compounds. Precautions & Quality Control Measures Quality Control Strains Staphylococcus aureus ATCC 29213 Enterococcus faecalis ATCC 29212 Eschericia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853 All 60 cultures were visually checked for purity.
Media Control: Performed NCCLS disc diffusion assay using 10ug discs of Gentamicin (Difco) against Ps. aeruginosa ATCC 27853. A zone diameter of 16-21 mm should be considered for optimum cation (Magnesium and Calcium) content of the media. Plotted the diameter in the media QC chart.
Results: The compounds disclosed herein were found to be active against staphylococci, enterococci, Moraxella catarrhalis, Streptococcus pnemoniae, Streptococcus pyogenes, Haemophilus influenzae strains. MIC of the disclosed compounds was <0.004 ->16 µg/ml for Steptococcus pnemoniae; <0.015 - >16 µg/ml for Streptococcus pyogenes; 2 ->16µg/ml for Haemophilus influenzae; 0.03-4 µg/ml for Moraxella catarrhalis; 0.125 ->16µg/ml for staphylococci and 0.06 - >16µg/ml for enterococci. Some of the compounds disclosed herein were found have good activity against erythromycin resistant and telithromycin resistant Streptococcus pyogenes 1721 erm B References:
O National Committee for Clinical Laboratory Standards (NCCLS), Methods for
Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically -
Fifth Edition; Approved Standard. M7-A5, Vol.20. No. 2 (January 2000).

o National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Susceptibility Testing - Twelfth informational supplement, M 100-S12, Vol. 22 No. 1 (January 2002).
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

WE CLAIM:
1. A compound having the structure of Formula I, as shown in the accompanied drawings, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof, wherein: R1 represents
• hydrogen
• hydroxyl protecting group R2 and R3 are independently
• hydrogen
• alkyl (with the provisio that R and R simultaneously are not methyl)
• alkenyl
• alkynyl
• cycloalkyl
• aryl
• (heterocyclyl)alkyl
• -COR11 , wherein R11 represents
O hydrogen
O alkyl
O aryl
O NR9R10, wherein R9 and R10 are selected from
hydrogen - alkyl
alkenyl
alkynyl o alkoxy
W represents
o -NH
o -(CH2)m- wherein m can represent an integer 2-6, -(CH2)m- group can be
optionally interrupted by groups independently chosen from unsaturated bond, oxygen, sulfur, -NRa-, where Ra can be hydrogen, alkyl, cycloalkyl, alkenyl,

heterocyclyl, (heterocyclyl)alkyl, alkynyl or aryl, or one of the hydrogen atom of-(CH2)m- group can be optionally replaced by
- halogen
- alkyl
- hydroxyl
- alkoxy
with the provisio that R is hydrogen when W is -(CH2)m- wherein m represents an integer 2-6 R represents
• hydrogen
• hydroxy . alkyl
• aryl
• heterocyclyl
• cycloalkyl
• cycloalkenyl R4 represents
• hydrogen
• alkyl
• alkenyl
• alkynyl
• aryl
• cycloalkyl
• heterocyclyl
• amidoarylalkyl
• amidoarylalkynyl R' represents

■ hydrogen
■ aryl
■ alkyl
■ -(CH2)r-U
wherein r represents an integer 1 to 4 U can represent o alkenyl

O alkynyl
O alkylalkenyl
O alkylalkynyl
O arylalkenyl
O arylalkynyl
O heterocyclylalkenyl
O heterocyclylalkynyl OR' can be replaced by hydrogen Y represents
alkoxy
hydrogen
halogen
cyano
alkyl
aryl
heterocyclyl
hydroxy
amino
PhSe
-NR9R1o
alkenyl
alkynyl Z represents
• oxygen
• sulphur
• NOR1' wherein R1' is the same as defined earlier.

2. The compound according to claim 1 wherein R1 is hydrogen, R2 is hydrogen or alkyl; R4 is alkyl; Y is halogen and R' is alkyl.
3. The compound according to claim 2 wherein R1 is hydrogen; R2 is hydrogen or methyl; R4 is ethyl, Y is fluorine and R' is methyl.
4. The compound according to claim 1 wherein R3 is alkyl.
5. The compound according to claim 4 wherein R3 is ethyl.
6. The compound according to claim 1 wherein R3 is alkenyl.

7. The compound according to claim 6 wherein R3 is allyl.
8. The compound according to claim 1 wherein Z is oxygen.
9. The compound according to claim 1 wherein Z is -NoR11, wherein R11 is alkyl.
1o. The compound according to claim 9 wherein Z is -NoCH3.
11. The compound according to claim 1 wherein W is -(CH2)m-, wherein m is 4.
12. The compound according to claim 11 wherein -(CH2)m- group is interrupted by oxygen, nitrogen or unsaturated bond.
13. The compound according to claim 12 wherein W is -(CH2)3O-, -NH(CH2)3- or
-NHCH2CH=CH-
14. The compound according to claim 11 wherein one of the hydrogen atom of -(CH2)m- group is replaced by alkyl.
15. The compound according to claim 14 wherein W is -NH-(CH2)2-CH(CH3)-
16. The compound according to claim 1 wherein W is -NH-.
17. The compound according to claim 1 wherein R is selected from hydrogen, aryl, substituted aryl and heterocyclyl.
18. The compound according to claim 17 wherein R is selected from phenyl, 3- (pyridine-3-yl)- phenyl, 3-(thienyl-3-yl)-phenyl, 3-yl-pyridine, 3-yl-imidazo [4,5-b]pyridine, 1-yl-Pyrrolo[2,3 b]pyridine, 5-yl-Isoquinoline and 1-yl-Benzimmidazole, 3-(lH-Imidazol-4-yl)- pyridine, 4-Phenyl-lH-imidazole and 4-Thiophen-3-yl-lH-imidazole.
19. A compound which is:
2-a-Fluoro-5-O-(3'-N-didesmethyl-3'-N-ethyl)-11,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-imidazol[4,5-b]pyridin-3-yl)-butyl)-imino] erythromycin A (Compound No.l),
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(3-pyridin-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 2),
2-a-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-11,12-dideoxy-3 -O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(3-pyridin-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 3),

2-a-Fluoro-5 -O-(3 '-N-desmethyl-3 '-N-ethyl)-11,12-dideoxy-3 -o-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(pyridin-3-yloxy)-propyl)-imino)]erythromycin A (Compound No.4),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-11,12-dideoxy-3 -o-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(3-thiophen-3-yl-phenoxy)-propyl)-imino)] erythromycin A (Compound No. 5),
2-α-Fluoro-5-O-(3 -N-desmethyl-3 -N-ethyl)-l 1,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-hydrazo]erythromycin A (Compound No. 6),
2-α-Fluoro-5-o-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-hydrazo]erythromycin A (Compound No. 7),
2-a-Fluoro-5-o-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-pyrrolo[2,3-b]pyridin-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 8),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-phenylpropyl)-hydrazo)]erythromycin A (Compound No. 9),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-isoquinolin-5-yl-propyl-hydrazo)]erythromycin A (Compound No. 1o),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-phenylpropyl)-hydrazo)]erythromycin A (Compound No. 11),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-phenyl-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A (Compound No. 12),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-phenyl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 13),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)- ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-benzoimidazol-1 -yl)-propyl)-hydrazo)] erythromycin A (Compound No. 14),

2-α-Fluoro-5 -O-(3 '-N-desmethyl-3 '-N-ethyl)-11,12-dideoxy-3 -O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 15),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 16),
2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No. 17),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(4-thiophen-3-yl-imidazol-l-yl)propyl)-hydrazo)] erythromycin A (Compound No. 18),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-o-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-phenyl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A-9-(o-methyl)oxime (Compound No. 19),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-1 -yl)-propyl)-hydrazo)] erythromycin A-9-(o-methyl)oxime (Compound No. 2o),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-thiophen-3-yl-imidazol-1 -yl)propyl)-hydrazo)] erythromycin A-9-(o-methyl)oxime (Compound No. 21),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-11,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(4-pyridyl-3-yl-imidazol-l-yl)-butyl)-hydrazo)] erythromycin A (Compound No. 22),
2-α-Fluoro-5-o-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-o-methyl-3-oxo-12,11 -[oxycarbonyl-((3-(4-phenyl-imidazol-1 -yl)-butyl)-hydrazo)] erythromycin A (Compound No. 23),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l 1,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,1 l-[oxycarbonyl-((3-phenyl-allyl)-hydrazo)]erythromycin A (Compound No. 24),
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof.

2o. A pharmaceutical composition comprising a therapeutically effective amount of a
compound as defined in the preceding claims optionally together with pharmaceutically
acceptable carriers, excipients or diluents.
21. A method for treating or preventing a mammal suffering from a condition caused by or contributed to by bacterial infection, comprising administering to the said mammal a therapeutically effective amount of a compound of any one of the claims 1-19.
22. A method for treating or preventing a mammal suffering from a condition caused by or contributed to by bacterial infection, comprising administering to the said mammal a therapeutically effective amount of a pharmaceutical composition of claim 2o.
23. A method according to claim 21 or 22 wherein the said condition is selected from the group comprising of community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, mastitis, catheter infection, foreign body, prosthesis infections and peptic ulcer disease.
24. A method according to claim 21 or 22 wherein the said bacterium is gram positive, gram negative or anaerobic bacteria.
25. A method according to claim 24 wherein bacterium is selected from the group comprising of Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus and Enterobactericeae.
26. A method according to claim 25 wherein the bacterium is cocci.
27. A method according to claim 26 wherein the cocci is drug resistant.
28. A method for preparing a compound of Formula XIII, as shown in the accompanied drawings, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers and polymorphs thereof, wherein:
R3 represents
■ hydrogen
■ alkyl, (with theprovisio that R3 is not methyl)
■ alkenyl
■ alkynyl
■ cycloalkyl
■ aryl
■ (heterocyclyl)alkyl
■ -CoR11 , wherein R11 represents

O hydrogen O alkyl O aryl
O NR9R1o, wherein R9 and R1o are selected from hydrogen
- alkyl
alkenyl
alkynyl
O alkoxy
W represents O -NH
O -(CH2)m- wherein m can represent an integer 2-6 and -(CH2)m- group can be optionally interrupted by groups independently chosen from unsaturated bond, oxygen, sulfur, -NRa-, where Ra can be hydrogen, alkyl, cycloalkyl, alkenyl, heterocyclyl, (heterocyclyl)alkyl, alkynyl or aryl, or one of the hydrogen atom of-(CH2)m- group can be optionally replaced by halogen
- alkyl
hydroxyl
alkoxy
with the provisio that R is hydrogen when W is -(CH2)m- wherein m represents an integer 2-6 R represents
• hydrogen
• hydroxy
• alkyl
• aryl
• heterocyclyl
• cycloalkyl
• cycloalkenyl, comprising:

hydrolysis of clarithyromycin of Formula II,
(Formula Removed)

to give a compound of Formula III,
(Formula Removed)

which on protection with a reagent of Formula R12O or R1X (wherein X is halogen),
gives a compound of Formula IV,
(Formula Removed)

which on reaction with a suitable reagent gives a compound of Formula V,
(Formula Removed)

which on treatment with an organic base gives a compound of Formula VI,
(Formula Removed)
which on oxidation gives a compound of Formula VII,

(Formula Removed)


which on desmethylation at 3'-N-dimethyl group gives a compound of Formula VIII,
(Formula Removed)

which on alkylation with a reagent of Formula R3CHo, R32 Co or R3X gives a
compound of Formula IX

(Formula Removed)
which on fluorination gives a compound of Formula X,

(Formula Removed)
which on reaction with N,N'-carbonyldiimidazole gives a compound of Formula XI,
(Formula Removed)
which on reaction with a compound of Formula R-W-NH2 gives a compound of Formula XII,

(Formula Removed)
which on deprotection gives a compound of Formula XIII (wherein R, R3 and W are
the same as defined earlier).
29. The method according to claim 28 wherein the hydrolysis of clarithromycin of
Formula II to give a compound of Formula III is carried out in the presence of an
inorganic or organic acid selected from the group comprising of hydrochloric acid,
sulphuric acid and dichloroacetic acid.
3o. The method according to claim 29 wherein the hydrolysis is carried out in hydrochloric
acid.
31. The method according to claim 28 wherein the protection of a compound of Formula III
with a reagent of Formula R12O or R1x to give a compound of Formula IV is carried out in a solvent selected from the group comprising of dichloromethane, dichloroethane, chloroform, carbon tetrachloride and ethyl acetate.
32. The method according to claim 31 wherein the protection is carried out in dichloromethane.
33. The method according to claim 28 wherein the protection of a compound of Formula III with a reagent of Formula R12Oo or R'X is carried out in the presence of an organic base selected from the group comprising of triethylamine, pyridine, tributylamine, diisopropylethylamine and 4-N-(dimethylamino) pyridine.
34. The method according to claim 33 wherein the protection is carried out in triethylamine.
35. The method according to claim 28 wherein the reaction of a compound of Formula IV to give a compound of Formula V is carried out in a solvent selected from the group comprising of dichloromethane, chloroform, carbon tetrachloride and dichloroethane.
36. The method according to claim 35 wherein the reaction is carried out in dichloromethane.
37. The method according to claim 28 wherein the reaction of a compound of Formula IV to give a compound of Formula V is carried out in the presence of an organic base selected from the group comprising of triethylamine, pyridine, tributylamine, diisopropylethylamine and 4-(dimethylamino)pyridine.
38. The method according to claim 37 wherein the reaction is carried out in the presence of pyridine.
39. The method according to claim 28 wherein the reaction of a compound of Formula IV to give a compound of Formula V is carried out in the presence of a reagent selected from the group comprising of phosgene, diphosgene, triphosgene or ethylene carbonate.
4o. The method according to claim 39 wherein the reaction is carried out in the presence of
triphosgene.
41. The method according to claim 28 wherein the reaction of a compound of Formula V to give a compound of Formula VI is carried out in a solvent selected from the group comprising of dimethylformamide, tetrahydrofuran and dimethylsulphoxide.
42. The method according to claim 41 wherein the reaction is carried out in dimethylformamide.

43. The method according to claim 28 wherein the oxidation of a compound of Formula VI to give a compound of Formula VII is carried out with an oxidizing agent selected from the group comprising of Dess-Martin periodinane, Swern oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), N-chlorosuccinimide, pyridinium chlorochromate, pyridinium dichromate and l-ethyl-3 (3 -dimethyl aminopropyl) carbodiimide hydrochloride.
44. The method according to claim 43 wherein the oxidation is carried out with Dess-Martin periodinane.
45. The method according to claim 28 wherein the oxidation of a compound of Formula VI to give a compound of Formula VII is carried out in a solvent selected from the group comprising of chloroform, dichloromethane, carbon tetrachloride, dimethylsulphoxide and dichloroethane.

46. The method according to claim 45 wherein the reaction is carried out in dichloromethane.
47. The method according to claim 28 wherein the desmethylation of a compound of Formula VII to give a compound of Formula VIII is carried out in a solvent selected from the group comprising of acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate and mixture thereof.
48. The method according to claim 47 wherein the reaction is carried out in dichloromethane and acetonitrile mixture.
49. The method according to claim 28 wherein the desmethylation of a compound of Formula VII to give a compound of Formula VIII is carried out in the presence of a desmethylating agent selected from the group comprising of iodine in acetic acid, N-iodosuccinimide, 1-chloroethyl chloroformate and diisopropyl azodicarboxylate.
5o. The method according to claim 49 wherein the desmethylation is carried out in the
presence of N-iodosuccinimide.
51. The method according to claim 28 wherein the quenching of desmethylation reaction is carried out in the presence of a quenching agent selected from the group comprising of sodium bisulphite, sodium carbonate, potassium carbonate, ammonium hydroxide, sodium acetate and mixture thereof.
52. The method according to claim 51 wherein the quenching is carried out in the presence of sodium bisulphite.

53. The method according to claim 28 wherein the alkylation of a compound of
Formula VIII with a reagent of Formula R3CHo, R23Co or R3X to give a
compound of Formula IX is carried out in a solvent selected from the group comprising of dimethylformamide, acetonitrile, acetone, methanol, tetrahydrofuran and mixture thereof.
54. The method according to claim 53 wherein the alkylation is carried out in acetonitrile.
55. The method according to claim 28 wherein the alkylation of a compound of Formula VIII is carried out in an inorganic or organic base selected from the group comprising of sodium hydrogen carbonate, potassium carbonate,
sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulphate or diisopropylethylamine.
56. The method according to claim 55 wherein the alkylation is carried out in the presence of sodium hydrogen carbonate.
57. The method according to claim 28 wherein the fluorination of a compound of Formula IX to give a compound of Formula X is carried out with a fluorinating agent selected from the group comprising of N-fluorobenzene sulfonimide and selectfluor.
58. The method according to claim 57 wherein the fluorination is carried out with N-fluorobenzenesulfonimide.
59. The method according to claim 28 wherein the fluorination of a compound of Formula IX is carried out in a solvent selected from the group comprising of acetonitrile, dichloromethane, chloroform, carbon tetrachloride, dimethylformamide, tetrahydrofuran and dimethylsulphoxide.
6o. The method according to claim 59 wherein the fluorination is carried out in
dimethylformamide.
61. The method according to claim 59 wherein the fluorination is carried out in the
presence of tetrahydrofuran.
62. The method according to claim 28 wherein the fluorination of a compound of Formula IX is carried out in the presence of an inorganic base selected from the group comprising of potassium carbonate, sodium acetate, sodium thiosulphate, sodium hydride and potassium-t-butoxide.
63. The method according to claim 62 wherein the fluorination is carried out in the presence of sodium hydride.
64. The method according to claim 62 wherein the fluorination is carried out in the presence of potassiunm-t-butoxide.

65. The method according to claim 28 wherein the reaction of a compound of Formula X with N,N'-carbonyldiimidazole to give a compound of Formula XI is carried out in a solvent selected from the group comprising of dimethylformamide, tetrahydrofuran, acetonitrile and mixture thereof.
66. The method according to claim 65 wherein the reaction is carried out in a mixture of dimethylformamide and tetrahydrofuran.
67. The method according to claim 28 wherein the reaction of a compound of Formula X with N,N'-carbonyldiimidazole is carried out in the presence of an inorganic base selected from the group comprising of sodium hydrogen carbonate, potassium carbonate, sodium acetate, sodium thiosulphate and sodium hydride.
68. The method according to claim 67 wherein the reaction is carried out in the presence of sodium hydride.
69. The method according to claim 28 wherein the reaction of a compound of Formula XI
with a compound of Formula R-W-NH2 to give a compound of Formula XII is carried
out in a solvent or solvent system selected from the group comprising of
acetonitrile/water, dimethylformamide/water, and dimethylformamide.
7o. The method according to claim 69 wherein the reaction is carried out in
acetonirile/water.
71. The method according to claim 28 wherein the deprotection of a compound of Formula XII to give a compound of Formula XIII is carried out in an alcohol selected from the group comprising of methanol, ethanol, propanol and isopropanol.
72. The method according to claim 71 wherein the reaction is carried out in methanol.
73. A method for preparing a compound of Formula XIVA, as shown in the accompanied darwings, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs, metabolites and polymorphs thereof, wherein:
R3 represents
■ hydrogen
■ alkyl, (with the provisio that R is not methyl)
■ alkenyl
■ alkynyl
■ cycloalkyl
■ aryl
■ (heterocyclyl)alkyl

■ -CoR11 , wherein R11 represents O hydrogen O alkyl O aryl O NR9R1o wherein R9 and R1o are selected from hydrogen - alkyl alkenyl alkynyl O alkoxy
W represents O -NH
O -(CH2)m- wherein m can represent an integer 2-6 and -(CH2)m- group can be optionally interrupted by groups independently chosen from unsaturated bond, oxygen, sulfur, -NR5-, where R5 can be hydrogen, alkyl, cycloalkyl, alkenyl, heterocyclyl, (heterocyclyl)alkyl, alkynyl or aryl, or one of the hydrogen atom of-(CH2)m- group can be optionally replaced by halogen - alkyl hydoxyl alkoxy with the provisio that R is hydrogen when W is -(CH2)m- wherein m represents an integer 2-6 R represents
• hydrogen
• hydroxy
• alkyl
• aryl
• heterocyclyl
• cycloalkyl
• cycloalkenyl comprising:

desmethylation at 3'-N-dimethyl group of a compound of Formula XII
(Formula Removed)
to give a compound of Formula XIIIA,
(Formula Removed)
which on deprotection gives a compound of Formula XIVA (wherein R, R3 and W are the same as defined earlier).
74. The method according to claim 73 wherein the desmethylation of c compound of Formula XII to give a compound of Formula XIIIA is carried out in a solvent selected from the group comprising of acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetra chloride, ethyl acetate and mixture thereof.
75. The method according to claim 74 wherein the reaction is carried out in dichloromethane and acetonitrile mixture.
76. The method according to claim 73 wherein the desmethylation of compound of Formula XII to give a compound of Formula XIIIA is carried out in the presence of a desmethylating agent selected from the group comprising of N-iodosuccinimide, 1-chloroethyl chloroformate, diisopropylazodicarboxylate and iodine in acetic acid.
77. The method according to claim 76 wherein the desmethylation is carried out in the presence of N-iodosuccinimide.
78. The method according to claim73 wherein the deprotection of a compound of Formula XIIIA to give a compound of Formula XIVA is carried out in an alcohol selected from the group comprising of methanol, ethanol, propanol and isopropanol.

79. The method according to claim 78 wherein the reaction is carried out in methanol.
8o. A method for preparing a compound of Formula XVI, as shown in the accompanied
drawings, pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
tereoisomers, prodrugs, metabolites and polymorphs thereof, wherein:
R3 represents
■ hydrogen
■ alkyl, (with the provisio that R3 is not methyl)
■ alkenyl
■ alkynyl
■ cycloalkyl
■ aryl

■ (heterocyclyl)alkyl
■ -CoR11, wherein R11 represents O hydrogen
O alkyl
O aryl
O NR9R1o
wherein R9 and R1o are selected from
- hydrogen
- alkyl
- alkenyl
- alkynyl o alkoxy
W represents
o -NH
o -(CH2)m- wherein m can represent an integer 2-6 and -(CH2)m- group can be optionally interrupted by groups independently chosen from unsaturated bond, oxygen, sulfur, -NRa-, where Ra can be hydrogen, alkyl, cycloalkyl, alkenyl, heterocyclyl, (heterocyclyl)alkyl, alkynyl or aryl, or one of the hydrogen atom of -(CH2)m- group can be optionally replaced by
- halogen
- alkyl
- hydroxyl
- alkoxy

with the provisio that R is hydrogen when W is -(CH2)m- wherein m represents an integer 2-6 R represents hydrogen hydroxy alkyl aryl
heterocyclyl cycloalkyl cycloalkenyl comprising: reacting a compound of Formula XI,

(Formula Removed)

with hydrazine hydrate to give a compound of Formula XIV,
which on deprotection gives a compound of Formula XV,
(Formula Removed)
which on treatment with a compound of Formula R-W-CHo gives a compound of Formula XVI (wherein R,R3 and W are the same as defined earlier).
81. The method according to claim 8o wherein the reaction of a compound of Formula XI with hydrazine hydrate to give a compound of Formula XIV is carried out in a solvent selected from the group comprising of dimethylformamide, tetrahydrofuran, ethanol, methanol and acetonitrile.
82. The method according to claim 81 wherein the reaction is carried out in dimethylformamide.
83. The method according to claim 81 wherein the reaction is carried out in tetrahydrofuran.
84. The method according to claim 8o wherein the reaction of a compound of Formula XI to give a compound of Formula XIV is carried out in presence of a base selected from the group comprising of potasshmw-butoxide and sodium-/-butoxide.
85. The method according to claim 84 is carried out in presence of potassiun-t-butoxide.
86. The method according to claim 8o wherein the deprotection of a compound of Formula XIV to give a compound of Formula XV is carried out in a solvent selected from the group comprising of dimethylformamide, tetrahydrofuran, ethanol, methanol and acetonitrile.

87. The method according to claim 86 wherein the deprotection is carried out in methanol.
88. The method according to claim 8o wherein the reaction of a compound of Formula XV with a compound of Formula R-W-CHo to give a compound of Formula XVI is carried out in a solvent selected from the group comprising of dimethylformamide, tetrahydrofuran, ethanol, methanol and acetonitrile.
89. The method according to claim 88 wherein the reaction is carried out in methanol.
9o. The method according to claim 8o wherein the reaction of a compound of Formula XV to
give a compound of Formula XVI is carried out in presence of a reducing agent selected

from the group comprising of sodium borohydride, sodium cyanoborohydride and sodium acetoxyborohydride.
91. The method according to claim 9o wherein the reaction is carried out in presence of sodium cyanoborohydride.
92. The method according to claim 8o wherein the reaction of a compound ofFormula XV to give a compound of Formula XVI is carried out in presence of an organic acid selected from the group conmprising of formic acid, acetic acid and trifluoroacetic acid.
93. The method according to claim 92 wherein the reaction is carried out in presence of acetic acid.
94. A method for preparing a compound of Formula XVIII, as shown in the accompanied darwingspharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers and polymorphs thereof, wherein:
R3 represents
■ hydrogen
■ alkyl, (with the provisio that R3 is not methyl)
■ alkenyl
■ alkynyl
■ cycloalkyl
■ aryl
■ (heterocyclyl)alkyl
• -CoR11, wherein R11 represents o hydrogen o alkyl o aryl o NR9R1o wherein R9and R1oare selected from hydrogen - alkyl alkenyl alkynyl o alkoxy
W represents
o -NH
56

O -(CH2)m- wherein m can represent an integer 2-6 and -(CH2)m- group can be optionally interrupted by groups independently chosen from unsaturated bond , oxygen, sulfur, -NR5-, where R5 can be hydrogen, alkyl, cycloalkyl, alkenyl, heterocyclyl, (heterocyclyl)alkyl, alkynyl or aryl, or one of the hydrogen atom of -(CH2)m- group can be optionally replaced by halogen - alkyl hydroxyl alkoxy with the provisio that R2 is hydrogen when Wis -(CH2)m- wherein m represents an integer 2-6 R represents
• hydrogen
• hydroxy . alkyl
• aryl
• heterocyclyl
• cycloalkyl
• cycloalkenyl R11 represents
• hydrogen
• alkyl
• aryl
. NR9R1o wherein R9 and R1o are the same as defined earlier
• alkoxy
comprising:
reacting a compound of Formula XV with a compound of Formula H2NoR11

(Formula Removed)
to give a compound of Formula XVII,
(Formula Removed)
which is further treated with a compound of Formula R-W-CHo to give a compound of Formula XVIII (wherein R, R3 and W are the same as defined earlier).
95. The method according to claim 94 wherein the reaction of a compound of Formula XV to give a compound of Formula XVII is carried out in a solvent selected from the group comprising of ethanol, methanol, isopropanol, tetrahydrofuran and dimethylformamide.
96. The method according to claim 95 wherein the reaction is carried out in ethanol.
97. The method according to claim 94 wherein the reaction of a compound of Formula XVII to give a compound of Formula XVIII is carried out in a solvent selected from the group comprising of ethanol, methanol, isopropanol, tetrahydrofuran and dimethylformamide.
98. The method according to claim 97 wherein the reaction is carried out in methanol.
99. The method according to claim 94 wherein the reaction of a compound of Formula XVII to give a compound of Formula XVIII is carried out in presence of a reducing agent selected from the group comprising of sodium
cyanoborohydride, sodium borohydride and sodium triacetoxyborohydride.

100. The method according to claim 99 wherein the reaction is carried out in presence of sodium cyanoborohydride.
101. The method according to claim 94 wherein the reaction of a compound of Formula XVII to give a compound of Formula XVIII is carried out in presence of an organic acid selected from the group comprising of formic acid, acetic acid and trifluoroacetic acid.
1o2. The method according to claim 1o1 wherein the reaction is carried out in presence of
acetic acid.
1o3. The processes for the preparation of compounds of Formulae XIII, XIVA, XVI and
XVIII, substantially as herein described and illustrated by example herein.