Field ot the Invention
The present invention provides acylide derivatives which can be used as antibacterial
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 such as Staphylococci Streptococci, Enter ococci Haemophilus
Moiaxalla spp Chlamydia spp Mxcoplasm Legionella spp Mycobacterium Helicobactei
Clostridium Bacteioides Coiynebacleimm Bacillus 01 Enteiobactericeae Processes for the
preparation of disclosed compounds pharmaceutical compositions thereof and method of
treating bacterial infections are also provided
Background of the Invention
The first genetation macrohdes erythrom\cin A and the early derivatives are chaiactenzed by bacteriostatic or bacteticidal 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 ate known to be responsible for undesired side effects (Itoh Z et al Am J Physiol 247 688, 1984 Omura S et al, J Med Chem 30 1943 1987) Various etythromycin 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 eiythromycin A Both clatithromycin and azithromycin have proved to be important dtugs in the tieatment and prophylaxis of atypical Mycobactenal infectious in patients with HIV
Macrohdes have proved to be effective drugs in the tieatment of many respiratory tract infections Howevei, incieasing resistance among S pneumoniae has prompted the seaich tor 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
WO 01/10878 01/10879 and 01/10880 disclose novel erythromycin derivatives having potent antibacterial effects on erythromycin-resistant bacteria and Haemophilus influenzae WO 99/21870 discloses eiythromycin A 11 12-carbamate derivatives having antibacterial activity
against not only erythromycin-sensitive bacteria but also erythromycin-resistant bacteria U S Patent No 5 444,051 discloses novel erythromycin compounds, antibiotic composition and a method of combating bacteria infection in warm-blooded animals US Patent No 6,191 118 discloses erythromycin A derivatives having strong antibacterial activity against erythromycin-resistant bacteria US Patent No 5 631,354 discloses 5-0-desosaminylerythronolide derivatives possessing antibacterial activity U S Patent No 6,020 521 discloses a class of macrolide compounds which are antagonists of luteinizing hormone-realising hormone (LHRH)
Summary of the Invention The present invention provides acyhde derivatives 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, 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 ot may be learnt by the practice of the invention
In one aspect provided herein are compounds having the structure of Formula I
(Formula Removed)
pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers piodrugs and polymorphs thereof wherein
R1 can be hydrogen, R: can be CH, R can be C2H, CH2CH=CH2 or CH2CH2F R4 can be ethyl R' can be 2-pyridyl or 3-pyndyl, W can be -(CH2)4 - -NHCCH2)3- or NH, Y can be CH2, Z can be oxygen or NOCH3 R can be selected from hydrogen

(Formula Removed)
wherein X can be N or CH, Ra can be NReRt (wherein Re and Rt can be independently hydrogen methyl or ethyl Re and Rf together with N can also form pyrrole) Rb and Rc can be independently hydrogen thienyl furyl oxazolyl thiazolyl pyridyl or fluoro pyridyl or Rb and Rc can together form phenyl pyridyl OR pyrimidinyl Rd can be thienyl furyl oxazolyl or pyrazinyl
In another aspect provided herein is a method tor tieating or preventing a mammal suffering from a condition caused by or contributed to by gram positive gram negative or anaerobic bacteria compusing administeting to said mammal a therapeutically effective amount of a compound or a pharmaceutical composition disclosed herein
The bacterial infection may be caused by bactenum such as Staphylococci Stieptococci Enteiococci Haemophilus Moiaxalla spp Chlamydia spp Mvcoplasm Legionella spp Mycohacteimm Helicobacter Clostiidium Bacteioides Connebacteiium Bacillus or Entaobactei iceae The said conditions may be tor example community acquired pneumonia upper and lower respiratoiy tract infections skin and soft tissue infections hospital acquired lung infections or bone and joint infections and other bacterial infections such as mastitis catether infection foreign body prosthesis infections 01 peptic ulcer disease
In another aspect provided herein are processes for the preparation of disclosed compounds
As used herein the term polymoiphs includes all crystalline forms and amorphous forms for compounds described heiein The term pharmaceutically acceptable solvates refers to solvates with waters (1 e hydrates) 01 pharmaceutically acceptable organic solvents Such solvates are also encompassed within the scope of this invention The phrase "pharmaceutical!) 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, sulfuric phosphoric acid and
the like Appropriate organic acids include, but not limited to aliphatic, cycloahphonc 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 anthramlic mesylic salicylic p-hydroxybenzoic phenylacetic, mandelic embonic (pamoic) methanesulfonic ethanesulfonic benzenesulfonic pantothenic toluenesulfomc 2-hydroxyethanesulfomc sulfanilic, stearic, algenic beta-hydroxybutync cyclohexylaminosulfonic galactanc 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 matenal 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 enantiomeis diastereomers, geometrical isomers atropisomer and comformational isomers Geometric isomers may occur when a compound contains a double bond or some othei 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 mirroi 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 Conformational isomers (or conformers or rotational isomers or rotamers) are stereoisomers produced by rotation about bonds, and are often rapidly interconverting at 100m temperature Racemic mixtures are also encompassed within the scope of this invention The present invention also includes within its scope prodrugs of these agents In general, such "prodrugs" will be functional derivatives of these compounds which are readily convertible in vivo into the required compound Conventional procedure foi the selection and preparation of suitable prodrug derivatives are described for example in design of prodrugs ed H Bundgaard and Elsevier 1985 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 schemes I II and III
(Formula Removed)
The compound of Formula XII can be piepared accoiding to Scheme I Thus clarithromycin of Foimula II is hydiolyzed to give a compound of Formula III which on protection with a reagent of Formula R12O or R1X (wherein X is halogen) gives a compound of Formula IV (wherein R is -COPh) which on desmethylation at 3'-N-dimethyl group gives a compound of Formula V which on alkylation with a reagent of Formula R'CHO R32CO or R'X gives a compound of Foimula VI (wherein R' is the same as defined earlier) which on reaction with a suitable reagent gives a compound of Formula VII which on reaction with a suitable organic base gives a compound of Foimula VIII which on acylation with a reagent of Formula R'YCOOH (R'YCO)2O R'YCOX or R'YCOOR10 (wherein R10 is leaving group such as
pivaloyl p-toleuensulfonyl isobutoxycarbonyl ethoxycarbonyl or isopropoxycarbonyl) gives a compound of Formula IX (wherein Y and RD are the same as defined earlier) which on reaction with N N'-carbonyl dnmidazole gives a compound of Formula X which on reaction with a compound of Formula R-W-NH2 gives a compound of Formula XI (wherein R and W are the same as defined earlier) which is finally deprotected to give a compound of Formula XII
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 sulphuric acid or dichloroacetic acid
The hydroxyl protection of a compound of Formula III to give a compound of Formula IV can be carried out in a suitable solvent for example dichloromethane, dichloroethane, chloroform or ethyl acetate
The hydroxyl protection of a compound of Formula III to give a compound of Formula IV can be carried out in the presence of an organic base for example triethylamine pyridine tnbutylainine or 4-N-dimethylaminopytidine
The desmethylation of a compound of Formula IV to give a compound of Formula V can be carried out in the presence of a suitable demethylating agent for example N-iodosuccinamide or dusopropyl azodicarboxylate
The desmethylation of a compound of Formula IV can be carried out in a suitable solvent for example acetonitrile tetrahydrofuran dichloromethane dichloroethane ethyl acetate or mixtute thereof
The quenching of desmethylation reaction can be carried out in the presence of a suitable quenching agent, for example sodium bisulphite sodium carbonate or mixture thereof
The alkylation of a compound of Formula V to give a compound of Formula VI can be carried out in a suitable solvent for example dimethylformamide acetonitnle or tetrahydrofuran
The alkylation of a compound of Formula V to give a compound of Formula VI can be carried out in an inorganic or organic base for example, sodium hydrogen carbonate potassium carbonate sodium hydride pyridine tnethylamine or dusopropyl ethylamine
The alkylation of a compound of Formula V can also be carried out with a reagent of Formula R3CHO with a reducing agent for example sodium cyanoborohydride, sodium borohydride or sodium triacetoxyborohydnde in the presence of an organic acid for example
acetic acid or dichloroacetic acid in a suitable solvent for example methanol ethanol propanol oi isopropanol
The reaction of a compound of Formula VI to give a compound of Formula VII can be carried out in the presence of suitable reagent for example triphosgene or ethylene dicarbonate
The leaction of a compound of Formula VI to give a compound of Formula VII can be carried out in a suitable solvent for example chloroform dichloromethane carbon tetrachloride or dichloroethane
The reaction of a compound of Formula VI can be carried out in the presence of an oiganicbase tor example tnethylamine pyridine tiibutylamine or 4-N-dimethylaminopyridine
The reaction of a compound of Formula VII to give a compound of Formula VIII can be carried out in a suitable solvent for example dimethylformamide, tetrahydrofuran or dimethylsulphoxide
The reaction of a compound of Formula VII to give a compound of Formula VIII can be carried out in the presence of an organic base for example tetiamethyl guanidine pyridine or tnmethylamine
The leaction of a compound of Formula VIII to give a compound IX can be carried out in a suitable solvent, for example dichloromethane dichloroethane acetone ethyl acetate or tetrahydrofuran
The reaction of a compound of Formula VIII to give a compound IX can be carried out in the presence of an inoi game or organic base foi example sodium bicarbonate potassium carbonate tnethylamine pyridine tnbutvlamine or 4-N-dimethylaminopyridine
The leaction of a compound of Formula VIII to give a compound IX can be carried out in the presence of an activating agent for example dic)clohexylcarbodnmide 01 l-ethyl-3-(3-dimethylaminopropyl) carbodrimide hydrochloride
The reaction of a compound of Formula IX with N N'-carbonyl diimidazole to give a compound of Formula X can be carried out in a suitable solvent for example dimethylformamide tetrahydrofuran or mixture thereof
The reaction of a compound of Formula IX can be carried out in the presence of an inoiganic base tot example sodium hydrogen carbonate potassium carbonate or sodium hvdride
The reaction of a compound of Formula X with a compound of Formula R-W-NFFto give a compound of Formula XI can be carried out in a suitable solvent, for example acetomtrile water, dimethylformamide or mixture theieof
The deprotection of a compound of Formula XI to give a compound of Formula XII can be carried out in an alcohol for example methanol ethanol propanol or isopropanol
The compound of Formula XII can further be converted into its salt by following the conventional method well known in the prior art
(Formula Removed)
The compounds of Formula XV and XVII can be prepared according to Scheme II Thus a compound of Formula X (from scheme I) is reacted with hydrazine hydrate to give a compound of Formula XIII which on deprotection gives a compound of Formula XIV
(a) which is finally reacted with a compound of Formula R (CH;)mCHO to give a compound of Formula XV ( wherein R and m are the same as defined earlier)
(b) which on reaction with a compound of Formula RsONFT hydrochloride gives a compound of Formula XVI (wherein Rs is the same as defined earlier) which is finally reacted with a compound of Formula R (CH2)mCHO to give a compound of Formula XVII ( wherein R and m are the same as defined earlier)
The reaction of a compound of Formula X with hydrazine hydrate to give a compound of Formula XIII can be carried out in a solvent for example dimethylformamide tetrahydrofuran or dimethylsulphoxide
The deprotection of a compound of Formula XIII to give a compound of Formula XIV can be carried out in a solvent for example, methanol ethanol propanol or isopropanol
The reaction of a compound of Formula XIV with a compound of Formula R(CH2)mCHO to give a compound of Formula XV can be carried out in a solvent, for example, methanol, ethanol, propanol or isopropanol
The reaction of a compound of Formula XIV to give a compound of Fotmula XV can be carried out in the presence of an organic acid for example acetic acid or dichloroacetic acid
The reaction of a compound of Formula XIV to give a compound of Formula XV can be carried out in the presence of a reducing agent for example sodium borohydride sodium cyanoborohydnde or sodium triacetoxyborohydride
The reaction of a compound ot Formula XIV with a compound of Formula R8ONH2 hydrochloride to give a compound of Formula XVI can be carried out in a solvent for example methanol ethanol, propanol or isopropanol
The reaction ot a compound of Formula XVI with a compound of Formula R(CH:)mCHO to give a compound of Formula XVII can be carried out in a solvent for example methanol, ethanol propanol or isopropanol
The reaction of a compound of Formula XVI to give a compound of Formula XVII can be cairied out in the presence of a reducing agent for example sodium borohydride sodium cyanoborohydnde or sodium triacetoxyborohydnde
The compounds of Formula XV and XVII can further be converted into their salt by following the conventional method well known in the prior art
(Formula Removed)
A compound of Formula XII can also be prepaied according to Scheme III Thus
leaction of a compound of Formula IV (wherein R1 is -COPh) with a reagent gives a compound of Formula XVIII which on reaction with an oiganic base gives a compound of Formula XIX which on desmethylation at 3'-N-dimethyl group gives a compound of Formula XX which on alkylation with a reagent of Formula R'CHO R32CO of R'X gives a compound of Formula VIII (wherein RJ is the same as defined earlier) which on acylation with a reagent of Formula R'YCOOH (R'YCO)2O R5YCOX or R3YCOOR10 (wheiem R10 is leaving group such as pivaloyl p-toleuensulfonyl isobutoxycarbonyl ethoxycarbonyl or isopropoxycaibonyl) gives a compound of Formula IX (wherein Y and R are the same as defined earlier) which on reaction with N N'-caibonyl dumidazole gives a compound of Formula X which on reaction with a compound of Formula R-W-NH2 gives a compound of Formula XI (wherein R and W are the same as defined earhei) which is finally deprotected to give a compound of Formula XII
The reaction of a compound of Formula IV to give a compound of Formula XVIII can be carried out in the presence of a reagent for example triphosgene or ethylene carbonate
The reaction of a compound of Formula IV to give a compound of Formula XVIII can be carried out in a solvent for example chloroform dichloromethane carbon tetrachloride or dichloroethane
The reaction of a compound of Formula IV can be carried out in the presence of an organic base for example, triethylamine pyridine tributylamine, 4-N-dimethylaminopyridine or dusopropyl ethyl amine
The reaction of a compound of Formula XVIII to give a compound of Formula XIX can be carried out in a solvent for example, dimethylformamide tetrahydrofuran or dimethylsulphoxide
The reaction of a compound of Formula XVIII to give a compound of Formula XIX can be carried out in the presence of an organic base for example tetramethyl guanidine pyridine trimethylamine or dusopropyl ethyl amine
The desmethylation of a compound of Formula XIX to give a compound of Formula XX can be carried out in the presence of a demethylating agent for example N-iodosuccinamide iodine in acetic acid or dusopropyl azodicarboxylate
The desmethylation of a compound of Formula XIX can be carried out in a solvent for example acetomtrile tetrahydrofuran, dichloromethane dichloroethane, chloroform carbon tetrachloride ethyl acetate or mixture thereof
The quenching of desmethylation teaction can be carried out in the presence of a quenching agent for example sodium bisulphite potassium caibonate sodium acetate, sodium carbonate or mixture thereof
The alkylation of a compound of Formula XX with a teagent of Formula R X to give a compound of Formula VIII can be carried out in a solvent for example, dimethylformamide, acetonitrile or tetrahydrofuran
The alkylation of a compound of Formula XX to give a compound of Formula VIII can be carried out in an inorganic or organic base for example sodium hydrogen carbonate potassium carbonate sodium acetate sodium thiosulfate sodium hydride pyridine triethylamine or dusopropyl ethyl amine
The alkylation of a compound of Formula XX can also be carried out with a reagent of Formula R3CHO or R32 O with a reducing agent for example sodium cyanoborohydride sodium borohydnde or sodium triacetoxyborohydnde in the presence of an organic acid for example acetic acid or dichloroacetic acid in a solvent for example methanol, ethanol propanol or isopropanol
The reaction of a compound of Formula VIII to give a compound IX can be carried out in a suitable solvent for example dichloromethane dichloroethane acetone ethyl acetate or tetrahydrofuran
The reaction of a compound of Formula VIII to give a compound IX can be carried out in the presence of an inorganic or organic base for example sodium bicarbonate potassium carbonate triethylamine pyridine tributylamine or 4-N-dimethylaminopyridine
The ieaction of a compound of Formula VIII to give a compound IX can be carried out in the presence of an activating agent for example dicyclohexylcarbodnmide or l-ethyl-3- (3-dimethylaminopiopyl) carbodumide hydrochloride
The ieaction of a compound of Formula IX with N N'-carbonyl dumidazole to give a compound of Formula X can be carried out in a suitable solvent for example, dimethylformamide tetrahydrofuran or mixture theieof
The reaction of a compound of Formula IX can be carried out in the presence of an inorganic base for example sodium hydrogen carbonate potassium carbonate or sodium hydride
The reaction of a compound of Formula X with a compound of Formula R-W-NH2 to give a compound of Formula XI can be carried out in a suitable solvent for example acetomtrile water dimethylformamide or mixture thereof
The deprotection of a compound of Formula XI to give a compound of Formula XII can be carried out in an alcohol for example methanol ethanol propanol or isopropanol
The compound of Formula XII can further be converted into its salt by following the conventional method well known in the priot art
In the above schemes where the specific bases activating agents solvents etc are mentioned it is to be understood that bases activating agents solvents etc known to those skilled in the ait may be used Similarly the reaction temperature and duration may be adjusted according to the desried needs The compounds of invention or the intermediates can be converted to epimers during the course of reaction and such epimers are also encompassed within the scope of this invention
The compounds disclosed herein possess antibacterial activity against gram-positive giam-negative and anaerobic bacteria They are useful as antibacterial agents for the treatment of
bacterial infections in human and animal Compounds of the present invention useful for such
purpose are listed below
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-imino)]erythromycin A (Compound No 1),
11 12-dideoxy-3-O-decladinosyI-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(quinohn-8-yl)-butyl)-imino)]erythromycin A (Compound No
2),
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(quinolin-4-yl)-butyl)-imino)]erythromycin A (Compound No
3)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-( 1 -methyl-1 H-pyrrolo[2,3-b]pyndin-3-yl)-butyl)-immo)]erythromycin A (Compound No 4)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yI)-imino)]erythromycin A (Compound No 5)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-triethyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)] erythromycin A (Compound No 6)
11 12-dideoxy-3-O-decladinosyI-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinohn-5-yl)-butyl)-imino)]erythromycin A (Compound No 7)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-imino)]erythromycin A (Compound
No 8)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-1H-imidazol-l-yl)-butyl)-imino)]erythromycin A (Compound No 9)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3,-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-imidazol-1 -yl)-butyl)-imino)]erythromycin A hydrochloride salt (Compound No 10)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)-imino)]erythromycin A (Compound No 11)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(6-pyrrol-l-yl-punn-9-yl)-butyl)-imino)] erythromycin A (Compound No 12)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-putin-6-yl)-diethyl)-immo)]erythromycin A (Compound No 13)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-ethyl)-imino)]erythromycin A (Compound No 14)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3,-N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)-dimethyl)-imino)]erythromycm A (Compound No 15)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purm-6-yl)-dimethyl)-imino)]erythromycin A (Compound No 16)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-methyl)-imino)]erythromycin A (Compound No 17)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyndyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-meth>l-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-methyl)-imino)]erythromycin A (Compound No 18)
11 12-dideoxy-3-O-decladmosyl-3-O-(2-pyndyl acetyl)-5-O-(3 -N-desmethyl-3'-N-2-tluoioethyl)-6-O-methyl-12 1 l-[oxycaibonyl-((4-(3H-imidazo[4 5-b]pyndin-3-yl)-butyl)-imino)]eiythiomycin A (Compound No 19)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[ox>carbon>l-((4-(lH-imidazo[4 5-b]pyndin-l-yl)-butyl)-immo)]erythromycin A (Compound No 20)
11 12-dideoxy-3-O-decladmosyl-3-O-(2-pyndyl acetyl)-5-O-(3'-N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12,11 -[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)-immo)]erythromycin A (Compound No 21)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyndyl acetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butvl)-9H-purin-6-yl)-imino)] erythromycin A (Compound No 22)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-2-fluoioethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazo[4 5-b]pyndin-l-yl)-butyl)-imino)] erythromycin A (Compound No 23)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyndin-3-yl)-butyl)-imino)] erythromycin A (Compound No 24)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)- imino)]erythromycin A (Compound No 25)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethylo'-N-ethyO-e-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purm-6-yl)-ethyl)-imino)]erythromycin A (Compound No 26)
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(purin-9-yl)-butyl)-immo)]erythromycin A (Compound No 27)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-
methyl-12 1 l-[oxycarbonyl-((4-(purin-9-yl)-butyl)-imino)]eiythromycin A (Compound No 28)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazo[4 5-c]pyndin-l-yl)-butyl)-imino)]erythromycin A (Compound No 29)
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4 5-c]pyndin-3-yl)-butyl)-imino)]erythromycin A (Compound No 30)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-
methyl-12 11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-imidazol-1 yl)-butyI)-imino)]erythromycin
A (Compound No 31)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazol[4,5-c]pyndin-l-yl)-butyl)-imino)]erythromycin A (Compound No 32)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazol[4 5-c]pyndin-3-yl)-butyl)-imino)]erythromycin A (Compound No 33)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-aIlyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinohn-5-yl)-butyl)-imino)]erythromycin A (Compound
No 34),
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyI-((4-(4-oxazoI-5-yI-l H-imidazoI-lyl)-butyl)-butyl)-imino)]erythromycm A (Compound No 35)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-2-yl-1H-imidazol-lyl)-butyl)-imino)] erythromycin A (Compound No 36)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3,-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-2-yl-1H-imidazol-lyl)-butyl)-imino)] erythromycin A hydrochloride salt (Compound No 37),
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pynd>lacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-1H-imidazol-lyl)-butyl)-imino)]erythromycin A (Compound No 38)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acet>l)-5-O-(3 -N-desmethyl^-N-allyl)^-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-3-yl-1H-imidazol-lyl)-butyl)-imino)]erythromycm A (Compound No 39)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-2-yl-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A (Compound No 40)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-fuian-2-yl-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A (Compound No 41)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-turan-2-yl-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A (Compound No 42)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pytidyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-2->l-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A (Compound No 43)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmeth>l-3'-N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)-immo)]erythromycin A (Compound No 44)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-imino)]erythromycin A (Compound No
45)
I l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-
methyl-12 1 l-[oxycarbonyl-((4-(quinohn-3-yl)-butyl)-imino)]erythromycin A (Compound No
46)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-
methyl-12 1 l-[oxycarbonyl-((4-([l 4']bipyrazolyl-l'-yl)-butyl)- imino)] erythromycin A
(Compound No 47)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3,-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4(4-thiazol-2-yl-1H-imidazol-l-yl)-butyl)-imino)]erythromycin A (Compound No 48)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3,-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiazol-2-yl-1H-imidazol-l-yl)-butyl)-imino)]erythromycin A (Compound No 49)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-3-yl-1H-pyrazol-lyl)-imino)]erythromycin A (Compound No 50)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A (Compound No 51)
11, 12-dideoxy-3-O-decladmosyl-3-O(3-pyridylacetyl)-5-O-(3-N-desmethyl-3'-N-allyl)-6-O-methyl-12,1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A (Compound No 52)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-3-yl-1H-pyrazol-1yl)-butyl)-imino)]erythromycin A (Compound No 53)
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((3-(4-pyndin-3-yl-1H-imidazol-l-yl)-propyl)-hydrazo)]erythromycin A (Compound No 54)
11 12-dideoxy-3-O-decladmosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-
methyl-12 1 l-[oxycarbonyl-(3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A
(Compound No 55)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((3-(4-pyridin-3-yl-1 H-imidazol-1 yl)-propyl)-hydiazo)]erythromycin A (Compound No 56)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((3-(4-pyndin-3-yl-1H-imidazol-l-yl)-propyl)-hydrazo)]erythromycin A (Compound No 57)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methy I-12 11 -[oxycarbonyl-(3-(4-py ndin-3-yl-1 H-imidazol-1 -vl)-propyl)-hvdrazo)]eiythromycm A (Compound No 58)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-pyndin-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A (Compound No 59)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pynd}lacetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-pyndin-3-yl-1H-imidazol-lyl)-propyl)-hydrazo)]eiythrom>cin A (Compound No 60)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-(9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycm A (Compound No 61)
11 12-dideoxv-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiophen-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A (Compound No 62)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyndvl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-isoquinolin-5-yl)-propyl)-hydrazo)]erythromycm A (Compound No 63)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-purin-9-yl)-propyl)-hydrazo)]eiythromycin A (Compound No
64)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((3-punn-9-yl)-piopvl)-hydrazo)]erythromycin A (Compound No 65)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-furan-2-yl-1H-imidazol-l-yl)propyl)-hydrazo)]erythromycm A (Compound No 66)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-(9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycm A (Compound No 67)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-furan-3-yl-1H-imidazol-l-yl)propyl)-hydrazo)]erythromycin A (Compound No 68)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyO-S-O-(3'-N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-furan-3-yl-1H-imidazol-l-yl)propyl)-hydrazo)]erythromycm A (Compound No 69),
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycin A (Compound No 70)
1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-thiophen-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A (Compound No 71)
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-thiophen-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A (Compound No 72)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-
methyl-12 11 -[oxycarbonyl-(3-(4-thiophen-3-yl-1 H-imidazol-1 -yl)-propyl)-
hydrazo)]erythromycin A (Compound No 73)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-imidazo[4 5-b]pyndin-l-yl)-propyl)-hydrazo)] erythromycin A (Compound No 74)
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethylo'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-imidazo[4 5-b]pyndin-3-yl)-propyl)-hydrazo)] erythromycin A (Compound No 75)
11 12-dideoxy-3-O-decladmosyl-3-O-(2-pvndyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-
methyl-12 11 -[oxycarbonyl-(3-(4-thiazol-2-yl-1 H-imidazol-1 -y l)-propyl)-hydrazo)]erythromycin
A (Compound No 76)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyO-S-O-O'-N-desmethyl-S'-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-thiazol-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A (Compound No 77)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythromycin A (Compound No 78)
11 12-dideoxy-3-O-decladmosyl-3-O-(2-pyndyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythiomycin A (Compound No 79)
1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-ethyl)-6-O-
methyl-12 1 l-[oxycarbonyl-hydrazo)]erythromycin A (Compound No 80)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-
methyl-12 1 l-[oxycarbonyl-((3-(4-pyndin-3-yl-1H-imidazol-l-yl)-propyl)-
hydrazo)]erythromycin A 9-(0-methyl)oxime (Compound No 81)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythromycin A, 9-(0-methyl)oxime (Compound No 82)
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-(4-fluoio-pvndin-3-yl)-l H-imidazol-l-yl)-butyI)-immo)]erythromycin A (Compound No 83)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-(4-fluoto-pyridin-3-yl)-1H-irnidazol-l-yl)-butyl)-imino)]eiythromycin A (Compound No 84)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-(1H-imidazol-l-yl)phenyl)-butyl)-imino)]erythromycin A (Compound No 85)
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(5-(3-aminophenyl)-thiazol-2-yl)-butyl)-imino)]erythromycin A (Compound No 86)
their pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs or polymorphs
In another aspect, there is provided pharmaceutical composition which may be admimstered to an animal for treatment orally topically rectally internasally or by parenteral toute The pharmaceutical compositions of disclosed compounds comprise a pharmaceutically effective amount of a compound described heiein formulated together with one or more pharmaceutically acceptable carriers
Solid form prepaiation for oral administration includes capsules, tablet pills powder granules cachets and suppository For solid form preparation the active compound is mixed with at least one inert pharmaceutically acceptable exciprents 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 polyvinylpyrrohdinone 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 adsorbants ,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 bufferring agents
The solid preparation of tablets capsules pills and gianules can be prepared with coating and shells for example enteric coating and othei coatings well known in the pharmaceutical formulating art
Liquid form preparation for oral administration includes pharmaceutically acceptable emulsions solutions suspensions syrups and elixirs Foi liquid form preparation the active compound is mixed with water or other solvent, solubilizing agents and emulsifiers for example ethyl alcohol isopropyl alcohol ethyl carbonate ethyl acetate benzyl alcohol, benzyl benzoate piopylene glycol 1 3-butylene glycol, dimethyiformamide oils, for example, cottonseed groundnut corn geim olive, castorand 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 flavouring agents and perfuming agents
Injectable preparations, for example, sterile injections 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 powder and solution 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 01 it can be the appropriate number of any of these packaged forms
The quantity of active compound in unit dose of prepaiation may be varied or adjusted from less than 1 mg to several grams according to the particular application and potency of the active ingredient
In therapeutic use as agents for treating bacterial infections the compounds utilizing in the pharmaceutical method of this invention are administered at the initial dosage of about 3 mg to about 40 mg per kilogiam daily The dosages however may be varied depending upon the lequirements of the patients and the compound being employed
Determination of the propel dosage for a particular situation is within the smaller dosages which are less than the optimum dose Small increments until the optimum effect under the daily dosage may be divided and administered in portion during the day if desired
Examples set forth below demonstrate the general synthetic procedure for the preparation of repiesentative 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 Scheme 1 Preparation of compound of Formula 111
To a solution of hydrochloric acid was added clarithromycin of Formula 11 (25g 33 4 mmol) The teaction mixtuie was neutralized with solid sodium bicarbonate and the aqueous layei was extiacted with ethyl acetate Organic layei was washed with water brine and dned over anhydrous sodium sulphate The solvent was lemoved under reduced pressure to give the desired product The ciude product was crystallized by using ethyl acetate- hexane mixture Pieparation of compound of Formula IV
To a solution of compound of Formula I11 (I equiv) in diy dichloromethane was added benzoic anhydride (2 5 equiv) triethylamine (6 equiv) and stirred at ambient temperature Reaction was quenched by aqueous sodium bicarbonate solution The aqueous layer was extiacted with dichloromethane washed successively with water brine and dried over anhydrous sodium sulphate and then the solvent was lemoved under reduced pressure to give a crude product The crude product was crystallized by using ethyl acetate - hexane mixture
Preparation of compound of Formula V
To a solution of compound of Formula IV (1 equiv) in dry acetonitrile dichloromethane (2 1) was added N-iodosuccinimide (2 equiv) The reaction mixture was stirred with sodiumbisulphite solution tollowed by stirring with sodium carbonate solution Dichloromethane was evaporated under reduced pressure The aqueous matter was extracted with ethyl acetate washed successively with water brine and dried over anhydrous sodiumsulphate and then the solvent was removed under reduced pressure to yield a crude product The crude product was purified by silica gel column chromatogiaphy (thoroughly neutralized with triethylamine) using 10-20% acetone in hexane Preparation of compound of Formula VI
To a solution of compound of Formula V (1 equiv) in acetonitnle was added solid sodium bicarbonate (5 equiv) and a reagent of Formula R3X (6 equiv) under argon at ambient temperature The reaction mixture was diluted with ethyl acetate and washed with water followed by brine dried over anhydrous sodium sulphate and concentrated under reduced pressure to yleld a crude product The crude product was purified by silica gel column chromatogiaphy (thoroughly neutralized with triethylamine) using 10-20% acetone in hexane Pieparation of compound of Formula V11
To a solution of compound of Formula VI (1 equiv) in dichloromethane was added triphosgene (1 5 equiv) with stirring Then to it was added pyridine (15 equiv) slowly After complete addition, reaction mixture was stirred under inert atmosphere Reaction was quenched by addition of water Reaction mixture was diluted with dichloromethane and washed with water brine dried over anhydious sodium sulphate and concentrated under reduced pressure to afford the desired product Pieparation of compound of Formula VIII
To a solution of a compound of formula VII (1 equiv) in dimethylformamide was added tetramethyl guanidine (2 2 equiv) and reaction mixture was heated Reaction mixture was cooled to an ambient temperature and water was added and extracted with ethyl acetate Organic layer was washed with water followed by brine dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain the desired product Preparation of compound of Formula IX
To a solution of compound of Formula VI11 (1 equiv) in dichloromethane was added a leagent of Fotmula RDYCOOH (2 5 equiv) 4-N-dimethylaminopyndine (2 5 equiv) and N, N -dicyclohexylcarbodumide (2 5 equiv) was added Pyridine (4 equiv) was added to it The whole leaction mixture was stirred and then filtered through celite bed Filtrate was washed with water brine dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the desued product The crude product was purified by silica gel column chromatography (thoioughly neutralized with triethylamine) using 10-20% acetone in hexane Pieparation of compound of Formula X
To a solution of compound of Formula IX (1 equiv) in dimethylfonnamide tetrahydiofuran (3 2) was added N N'-caibonyldiimidazole (3 equiv) followed by sodium hydride in portions Reaction was quenched by addition of ice cold water and extracted with ethyl acetate Ethyl acetate layer was washed with water, brine dried over anhvdrous sodium sulphate and concentrated under reduced pressure to afford the desired product Pieparation of compound of Formula XI
A compound of Formula X (1 equiv) and a compound of Formula R-W-NFF (3 equiv) were taken in 10% watet in acetonitrile and heated Reaction mixture was cooled to an ambient temperatuie acetonitrile was evaporated under leduced pressure The resulting residue was taken in ethyl acetate washed with water brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure The resulting residue was purified by column chromatogiaphy using 25-30% acetone in hexane to affoid the desired product Preparation of compound of Formula X11
A solution of compound of Formula XI (560mg, 0 6mmol) in methanol was refluxed Reaction mixture was cooled to an ambient tempetature and methanol was evaporated under reduced pressure Purification of the solid mass was done over silica gel (thoroughly neutialized triethylamine) using 30-35% acetone in hexane or 2-8% methanol in dichloromethane Scheme 11 Pieparation of compound of Formula XI11
A solution of compound of Formula X (1 mmol) in dry dimethylformamide and hydrazine hydtate (2 0 mmol) was added to it The reaction mixture was stirred at room temperature for about 1 5 hour It was quenched with watei and extracted in ethyl acetate The
solvent was removed under reduced pressure and the residue was redissolved in tetrahyrofuran Potassium -t-butoxide (2 354 mol) was added to it at 0°C and the reaction mixture was stirred for about 2 hr It was extracted with ethyl acetate washed with water and brine and dried over sodium sulphate to give the desired isomer Preparation of compound of Formula XIV
A solution of compound of Formula XI11 in methanol was heated at 70°C for about 20 hours The solvent was removed and the residue was purified over silica gel column to afford the product Preparation of compound of Formula XV
A compound of Formula XIV (1 0 mmol) and heterocyclyl alkyl aldehyde (5 0 mmol (prepared by following the procedure given in WO 00/17218), a compound of Formula R(CH2)mCHO (5 0 mmol) were dissolved in methanol Glacial acetic acid (5 0 mmol) was added The resulting mixture was stirred at room temperature for about 1-2 hour Sodium cyanoborohydnde (5 0 mmol) and glacial acetic and (5 0 mmol) were added to it The mixture was stirred at room temperature for about 12 hours solvent was removed, the reaction mixture was extacted with dichloromethane washed with watei brine and dried over sodium sulphate The solvent was removed under reduced piessuie and the residue was purified over silica gel column to afford the product Preparation of compound of Formula XVI
A compound of Formula XIV (0 298 mmol) and a compound of Formula R8ONH2 hydiochlonde (4 471 mmol) in ethanol were stiired at 80°C for about 48 hours The solvent was evaporated The reaction mixture was redissolved into ethyl acetate washed with water and biine dried over sodium sulphate and solvent was evaporated get the product Preparation of compound of Formula XV11
A compound of Formula XVI (1 0 mmol) and heterocyclyl alkyl aldehyde a compound of Formula R(CH2)mCHO (5 0 mmol) (piepaied by following the procedure given in WO 00/17218) were dissolved in methanol Glacial acetic acid (5 0 mmol) was added The resulting mixture was stined at room temperature for about 1-2 hour Sodium cyanoborohydnde (5 0 mmol) and glacial acetic and (5 0 mmol) were added to it The mixture was stirred at room temperature for about 12 houis solvent was removed, the reaction mixture was extracted with dichloromethane washed with water brine and dned over sodium sulphate The solvent was
removed under reduced pressure and the residue was purified over silica gel column to afford the
product
Scheme 111
Preparation of compound of Formula XV111
To a solution of compound of Formula IV (1 equiv) in dichloromethane at 0°C was added tnphosgene (1 5 equiv) with stirring Then to it was added pyridine (15 equiv) slowly After complete addition reaction mixture was stirred for about 3h at 0-5°C Reaction was quenched by drop wise addition of water was diluted with dichloromethane and washed with water brine, dried over anhydrous sodium sulphate and concentrated under leduced pressure to afford the desired product Piepaiation of compound of Formula XIX
To a solution of a compound of formula XVI11 (1 equiv) in dimethyltormamide was added tetiamethyl guanidine (2 2 equiv) and reaction mixtuie was heated at 90°C for about 8 hours Reaction mixture was cooled to an ambient temperature and water was added and extracted with ethyl acetate Organic layer was washed with water followed by brine dried over anhydrous sodium sulphate and concentrated undei reduced pressure to obtain the desired product Preparation of compound of Formula XX
To a solution of compound of Formula VI (1 equiv) in dry acetonitnle dichloromethane (2 1) cooled to 0°C was added N-iodosuccinimide (2 equiv) The reaction mixtuie was stirred with sodium bisulphite solution followed by stilting with sodium carbonate solution Dichloromethane was evaporated under reduced pressure The aqueous residue was extracted with ethyl acetate washed successively with watei, brine and dried over anhydrous sodium sulphate and then the solvent was removed undei reduced pressure to obtain the crude product which was punfied by silica gel column chromatography (thoroughly neutialized with triethyl amine) using 10-20% acetone in hexane to give the product Preparation of compound of Formula VI11
To a solution of a compound of formula V11 (1 equiv) in dimethylformamide was added tetramethyl guanidine (2 2 equiv) and reaction mixture was heated Reaction mixture was cooled to an ambient temperature and water was added and extracted with ethyl acetate Organic layer
was washed with water followed by brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain the desired product Preparation of compound of Formula IX
To a solution of compound of Formula VI11 (1 equiv) in dichloromethane was added a reagent of Formula R3YCOOH (2 5 equiv), 4-N-dimethylaminopyridine (2 5 equiv) and N, N -dicyclohexylcarbodnmide (2 5 equiv) was added Pyndine (4 equiv) was added to it The whole leaction mixture was stirred and then filtered through celite bed Filtrate was washed with water brine dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the desired product The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-20% acetone in hexane Pieparation of compound of Formula X
To a solution of compound of Formula IX (1 equiv) in dimethylformamide tetrahydrofuran (3 2) was added N N'-carbonyldiimidazole (3 equiv) followed by sodium hydride in portions Reaction was quenched by addition of ice cold water and extracted with ethyl acetate Ethyl acetate layei was washed with water brine dried over anhydrous sodium sulphate and concentiated under reduced pressure to afford the desired product Preparation of compound of Formula XI
A compound of Formula X (1 equiv) and a compound of Formula R-W-NHi (3 equiv) were taken in 10% watet in acetonitrile and heated Reaction mixture was cooled to an ambient temperature acetonitrile was evaporated under reduced pressure The resulting residue was taken in ethyl acetate, washed with water brine dried over anhydrous sodium sulphate and concentrated under reduced pressure The resulting residue was purified by column chromatography using 25-30% acetone in hexane to afford the desired product Pieparation of compound of Formula X11
A solution of compound of Formula XI (560mg 0 6mmol) in methanol was refluxed Reaction mixture was cooled to an ambient temperature and methanol was evaporated under leduced pressure Purification of the solid mass was done over silica gel (thoroughly neutralized triethylamine) using 30-35% acetone in hexane of 2-8% methanol in dichloromethane The following compounds were prepared by following the above general procedures
Compound No 1 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acet>l)-5-O-(3 -N-desmethyl-3'-N-ethyl)-6-O-methyl-12,l l-[oxycarbonyl-((4-(qumolm-8-yl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 931 44 [M+1 ]
Compound No 2 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(quinolm-8-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 943 40 [M+l],
Compound No 3 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((4-(quinolin-4-yl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 943 44 [M+l]
Compound No 4 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmeth\l-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((4-(l-methyl-1H-pyrrolo[2 3-b]pyndin-3-yl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 946 86 [M+l]
Compound No 5 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)]eiythromycin A MS (+ion mode) m/z 949 62 [M+l],
Compound No 6 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)] eiythromycin A MS (+ion mode) m/z 937 62 [M+l]
Compound No 7 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-imino)]erythrornycin A MS (+ion mode) m/z 943 62 [M+l]
Compound No 8 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinolin-5-yl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 931 59 [M+l]
Compound No 9 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-1H-imidazol-l-yl)-butyl)-imino)]eiythiomycin A MS (+ion mode) m/z 964 59 [M+l]
Compound No 10 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-((4-(4-thiophen-3-yl-1H-imidazol-l-yl)-butvl)-imino)]eiythromvcin A hvdrochlonde salt
Compound No 11 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-ammo-butyl)-9H-punn-6-yl)-dimethyl)-immo)]erythromycin A MS (+ ion mode) m/z 977 65 [M+l]
Compound No 12 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(6-pyrrol-l-yl-purm-9-yl)-butyl)-lmino)] erythromycin A, MS (+ ion mode) m/z 999 64 [M+l]
Compound No 13 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3,-N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purm-6-yl)-diethvl)-imino)]erythromycin A, MS (+ ion mode) m/z 1005 62 [M+l],
Compound No 14 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-ethyl)-imino)]erythromycin A, MS (+ ion mode) m/z 978 72 [M+l],
Compound No 15 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3,-N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)-imino)]erythromycin A, MS (+ ion mode) m/z 965 43 [M+l]
Compound No 16 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)-imino)]erythromycin A MS (+ ion mode) m/z 977 45 [M+l]
Compound No 17 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-methyl)-imino)]ervthromycin A MS (+ion mode) m/z 963 33 [M+l]
Compound No 18 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyudyl acetyl)-5-O-(3-N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)-methyl)-imino)]erythromycin A MS (+ ion mode) m/z 963 39 [M+l],
Compound No 19 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4 5-b]pyndin-3-yl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 939 30 [M+l]
Compound No 20 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazo[4 5-b]pyndin-l-yl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 939 37 [M+l]
Compound No 21 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)]eiythromycin A MS (+ion mode) m/z 955 30 [M+l]
Compound No 22 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)] erythromycin A, MS (+ ion mode) m/z 955 39 [M+l]
Compound No 23 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-2-fluoroethyl)-6-O-methyl-12 11-[oxycarbonvl-((4-(1H-imidazo[4 5-b]pyndin-l-yl)-butyl)-imino)] erythromycin A MS (+ ion mode) m/z 939 38 [M+l]
Compound No 24 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4 5-b]pyndin-3-yl)-butyl)-imino)] erythromycin A MS (+ion mode) m/z 939 38 [M+l]
Compound No 25 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)- imino)]erythromycin A MS (+ ion mode) m/z 965 39 [M+l],
Compound No 26 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-ethyl)-imino)]erythromycin A MS (+ion mode) m/z 965 37 [M+l]
Compound No 27 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allvl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(purm-9-yl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 934 37 [M+l]
Compound No 28 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(purm-9-yl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 934 34 [M+l]
Compound No 29 11 12-dideoxy-3-O-decladmosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazo[4 5-c]pyndin-l-yl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 933 37 [M+1]
Compound No 30 11 12-dideoxy-3-O-decladmosyI-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4 5-c]pyndin-3-yl)-butyI)-imino)]erythromycin A MS (+ion mode) m/z 933 35 [M+l]
Compound No 31 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-2-yl-1H-imidazol-lyl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 964 40 [M+l]
Compound No 32 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazol[4 5-c]pyridin-1-yl)-butyl)-immo)]erythromycin A MS (+ion mode) m/z 933 35 [M+l]
Compound No 33 11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazol[4 5-c]pyndin-3-yl)-butyl)-imino)]erythromycm A MS (+ion mode) m/z 933 44 [M+l]
Compound No 34 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3,-N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinohn-5-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 943 39 [M+l],
Compound No 35 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-oxazol-5-yl-1H-imidazol-lyl)-butyl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 949 62 [M+l],
Compound No 36 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((4-(4-furan-2-yl-1H-imidazol-lyl)-butyl)-imino)] erythromycin A MS (+ion mode) m/z 948 67 [M+l]
Compound No 37 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-2-yI-1H-imidazol-lyl)-butyl)-imino)] erythromycin A hydrochloride salt
Compound No 38 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-1H-imidazol-lyl)-butyl)-imino)]erythromycm A MS (+ ion mode) m/z 948 67 [M+l]
Compound No 39 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyI-((4-(4-furan-3-yl-1H-imidazol-lyl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 948 53 [M+l]
Compound No 40 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-2-yl-l H-pyrazol-lyl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 964 56 [M+l]
Compound No 41 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-2-yl-l H-pyrazol-l>l)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 948 73 [M+l]
Compound No 42 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethy 1-3 '-N-al ly l)-6-O-methyl-12 11 -[oxy carbony l-((4-(4-furan-2-y 1-1 H-pyrazol-1 y l)-buty 1 )-imino)]eiythromycin A, MS (+ ion mode) m/z 948 57 [M+l]
Compound No 43 1 l,12-dideoxy-3-O-decladinosyI-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyI)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 964 70 [M+l],
Compound No 44 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-ethyl)-6-O-methyl-12 1 l-[oxycaibonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)]erythromycin A MS (+ ion mode) m/z 937 50 [M+l]
Compound No 45 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-ethyl)-6-O-methyl-12,l l-[oxycarbonyl-((4-(quinohn-3-yl)-butyl)-imino)]erythromycm A, MS (+ ion mode) m/z931 50 [M+l]
Compound No 46 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethylo'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 943 50 [M+l]
Compound No 47 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-((4-([l,4 ]bipyrazolyl-l -yl)-butyl)-immo)] erythromycin A, MS (+ ion mode) m/z 948 77 [M+l]
Compound No 48 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-al]yl)-6-O-methyl-12 1 ]-[oxycarbonyl-((4(4-thiazol-2-yI-1H-imidazol-l-yl)-butyl)-imino)]erythromycm A MS (+ion mode) m/z 965 68 [M+l]
Compound No 49 11 12-dideoxy-3-O-decladmosyl-3-O-(3-pytidyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycaibon>l-((4-(4-thiazol-2-yl-1H-imidazol-l-yl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 965 68 [M+l]
Compound No 50 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[ox}carbonyl-((4-(4-furan-3-y 1-1 H-pyrazol-lyl)-imino)]eiythromycin A MS (+ ion mode) m/z 948 73 [M+l]
Compound No 51 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbon]l-((4-(4-thiophen-3-yl-1H-pyrazol-lyl)-butyl)-imino)]erythromycin A MS (+ ion mode) m/z 964 77 [M+l]
Compound No 52 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethylo'-N-allyl)-O-methyl-12 11 -[oxycarbony l-((4-(4-thiophen-3-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 964 81 [M+l]
Compound No 53 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-furan-3-yl-l H-pyrazol-lyl)-butyl)-imino)]ervthromycin A MS (+ion mode) m/z 948 83 [M+l]
Compound No 54 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 11-[oxycarbonyl-((3-(4-pyndin-3-yl-1H-imidazol-1-yl)-propyl)-hydrazo)]erythromycm A MS (+ ion mode) m/z 960 44 [M+l]
Compound No 55 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3,-N-allyl)-6-O-methyl-12 11 -[oxycarbony l-(3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A MS (+ion mode) m/z 933 41 [M+l],
Compound No 56 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((3-(4-pyndin-3-yl-1H-imidazol-lyl)-ptopyl)-hydrazo)]erythromycin A, MS (+ ion mode) m/z 960 63 [M+l]
Compound No 57 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyi-3'-N-allyl)-6-O-methyl-12 1 ]-[oxycarbonyl-((3-(4-pyndin-3-yl-1H-irnidazol-]-yl)-propyl)-hydrazo)]erythromycin A 9-(0-methyl)oxime MS (+ion mode) m/z 989 68 [M+l]
Compound No 58 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((3-(4-pyndin-3-y!-1H-imidazol-l-yl)-propyl)-hydrazo)]erythromycin A MS (+ion mode) m/z 960 64 [M+l]
Compound No 59 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyi-3 '-N-ethyl)-6-O-methyl-12,11 -[oxycai bonyl-(3-(4-pyndin-3-yl-1 H-imidazol-1 -yl)-propyl)-hydtazo)]erythromycm A MS (+ ion mode) m/z 948 72 [M+l]
Compound No 60 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-pyndin-3-yl-1H-imidazol-lyl)-piopyl)-hydrazo)]erythiomycin A, MS (+ ion mode) m/z 960 24 [M+l],
Compound No 61 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-pyndin-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A MS (+ ion mode) m/z 948 25 [M+l],
Compound No 62 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-(9-(3-hydrazo-propyl-9H-purm-6-yl-amine)]erythromycin A MS (+ ion mode) m/z 938 36 [M+l]
Compound No 63 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-thiophen-3-yl-1H-imidazol-lyl)-propyl)-hydrazo)]erythromycin A, MS (+ ion mode) m/z 965 39 [M+l]
Compound No 64 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-(3-isoquinolin-5-yl)-propyl)-hydrazo)]erythromycin A, MS (+ ion mode) m/z 944 54 [M+l],
Compound No 65 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12,11-[oxycarbonyl-(3-punn-9-yl)-propyl)-hydrazo)]erythromycin A MS (+ ion mode) m/z 935 49 [M+l]
Compound No 66 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((3-punn-9-yl)-propyl)-hydrazo)]erythromycin A, MS (+ ion mode) m/z 935 49 [M+l]
Compound No 67 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-(3-(4-furan-2-yl-1H-imidazol-l-yl)propyl)-hydrazo)]erythromvcin A MS (+ ion mode) m/z 949 54 [M+l]
Compound No 68 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-(9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycin A MS (+ ion mode) m/z 950 70 [M+l]
Compound No 69 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyndyI acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-furan-3-yl-1H-imidazol-l-yl)propyl)-hydrazo)]erythromycin A MS (+ion mode) m/z 949 62 [M+l],
Compound No 70 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3,-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-(3-(4-furan-3-yl-1H-imidazol-l-yl)propyl)-hydrazo)]erythromycin A MS (+ ion mode) m/z 949 66 [M+l]
Compound No 71 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycin A MS (+ion mode) m/z 950 67 [M+l]
Compound No 72 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-(3-(4-thiophen-2-yl-1H-imidazol-l-yl)-propyl)-hydrazo)]erythromycin A, MS (+ ion mode) m/z 965 57 [M+l]
Compound No 73 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-thiophen-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A MS (+ ion mode) m/z 965 63 [M+l]
Compound No 74 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 '-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiophen-3-y 1-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A MS (+ ion mode) m/z 965 58 [M+l]
Compound No 75 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-imiddzo[4 5-b]pyndin-l-yl)-propyl)-hydrazo)] erythromycin A MS (+ ion mode) m/z 934 65 [M+l]
Compound No 76 11 12-dideoxy-3-O-decladmosyl-3-O-(3-pyridyl acetyl)-5-O-(3'-N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-imidazo[4 5-b]pyndm-3-yl)-propyl)-hydrazo)] erythromycin A MS (+ion mode) m/z 934 79 [M+l]
Compound No 77 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethylo'-N-allyl)-6-O-methyl-^ 1 l-[oxvcarbon>l-(3-(4-thiazol-2-yl-1H-imidazol-l-yl)-propyl)-hydrazo)]ervthromycm A MS (+ion mode) m/z 966 66 [M+l],
Compound No 78 1 l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 '-N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-thiazol-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A, MS (+ ion mode) m/z 966 66 [M+l],
Compound No 79 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3,-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythromycin A, MS (+ ion mode) m/z 775 52 [M+l]
Compound No 80 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3'-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-hydrazo]erythromycin A, MS (+ ion mode) m/z 775 52 [M+l]
Compound No 81 11 12-dideoxy-3-O-decladinosyI-3-O-(2-pyridyl acetyi)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythromycin A 9-(0-methyl)oxime, MS (+ ion mode) m/z 804 58 [M+l]
Compound No 82 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3-N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbon]l-hydrazo)]erythromycin A MS (+ ion mode) m/z 763 59 [M+l]
Compound No 83 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-(4-fluoro-pyndin-3-yl)-1H-imidazol-l-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 977 63 [M+l]
Compound No 84 1 l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3,-N-allyl)-6-O-methyl-12,l l-[oxycarbonyl-((4-(4-(4-fluoro-pyndin-3-yl)-1H-imidazol-l-yI)-butyl)-imino)]eiythromycin A MS (+ ion mode) m/z 977 40 [M+l]
Compound No 85 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pytidyl acetyl)-5-O-(3'-N-desmethylo'-N-allyl)^-O-methyl-^ 1 l-[oxycarbonyl-((4-(4-(1H-imidazol-l-yl)phenyl)-butyl)-imino)]erythromycin A MS (+ion mode) m/z 958 64 [M+l]
Compound No 86 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(5-(3-aminophenyl)-thiazol-2-yl)-butyl)-imino)]erythromycin A, MS (+ ion mode) m/z 960 50 [M+l]
Pharmacological activity
Compounds disclosed herein displayed antibacterial activity in vitio especially against stiains which are resistant to macrohdes 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 respiratoiy tract infections skin and soft tissue infections hospital acquired lung infections bone and joint infections and othei bacterial infections tor example mastitis catether infection foreign body prosthesis infections or peptic ulcer disease
Minimum inhibitory concentration (MIC) has been an indicator of w 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 aeiobic cultuies and MHA with 5% sheep blood for fastidious cultures Aerobic cultures were incubated at 37 °C for about 18-24 hours Fastidious cultures weie incubated CO2 incubation (5% CO2) at 37 °C for about 18-24 hours Three to four well isolated colonies weie taken and saline suspensions 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) The cultures were diluted 10 fold in saline to get inoculum size of approximately 1-2 x 107 organisms/ml Preparation of drug concentration
1 mg/ml concentiation of stock solution of drugs was prepared in dimethylsulfoxide/distilled water/solvent given in National Committee for Clinical Laboratory Standaids (NCCLS) manual Serial two fold dilutions of the compounds and standard drugs were prepared as per NCCLS manual
Stock solution was changed according to the need of the expenment 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 µglml- 16 u.g/ml For fastidious cultures 1 ml of sheep blood was added in Molten Mueller Hinton agar
For conttol MHA and MHA with 5% sheep blood plates without antibiotic for each set were piepaied One MHA and MHA with 5% sheep blood plate without antibiotic for determining quality check for media was prepared Prepaiation of Teflon template
1 µl 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 comparing 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 tor purity
Media Control NCCLS disc diffusion assay using 10µg discs of Gentamicin (Difco) against Pseudomonas aeruginosa ATCC 27853 A zone diameter of 16-21 mm was considered for optimum cation (Magnesium and Calcium) content of the media The diameter was plotted in the media QC chart
Results The MICs of compounds of Formula I against some bacterium are shown in Tables I11 and IV and V References
o National Committee tor Clinical Laboratory Standaids (NCCLS) Methods for Dilution Antimicrobial Susceptibility Tests tor Bacteria That Grow Aerobically -Fifth Edition Approved Standard M7-A5 Vol 20 No 2 (January 2000)
o National Committee tor Clinical Laboratory Standards, Performance Standards for Antimicrobial Susceptibility Testing-Twelfth informational supplement M 100-S12 Vol 22 No 1 (January 2002)
Table I
(Table Removed)

WE CLAIM
1 Compounds having the structure of Formula I

(Formula Removed)
pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs and polymorphs thereof wherein
R1 is hydrogen R2 is CH3 R3 is C2H, CH2CH=CH2 or CH2CH2F, R4 is ethyl, R is 2-pyridyl or 3-pyridyl, W is -(CH2)4- -NH(CH2),- 01 NH Y is CH2, Z is oxygen or NOCHj, R is selected from hydrogen
(Formula Removed)
wherein X is N or CH R1 IS NReRt (wheiein Re and Rt are independently hydrogen methyl or ethyl Re and Rt together with N form pyrrole) Rb and RL are independently hydrogen thienyl furyl oxazolyl thiazolyl pyridyl or fluoro pyridyl or Rb and Rc together form phenyl pyridyl or pyrimidinyl Rd is thienyl furyl oxazolyl or pyrazinyl
2 A compound which is
11,12-dideoxy-3-0-decladinosyl-3-0-(2-pyndyl acetyl)-5-0-(3 -N-desmethyl-3 -N-ethyl)-6-0-methyl-12 1 l-[oxycarbonyl-((4-(quinohn-8-yl)-butyl)-imino)]erythromycin A
11 12-dideo\y-3-0-decladinosyl-3-0-(2-pyndyl acetyl)-5-0-(3 -N-desmethyl-3 -N-allyl)-6-0-methvl-12 1 l-[oxycarbonyl-((4-(quinohn-8-yl)-butyl)-imino)]erythromycin A
(Table Removed)
E ErythromucinA C Clarithromycin T Telithromycin Cl Clindamycin A Azithromycin S pneum Streptococcus pneumoniae, H influ Haemophilus influenzae , MRSA Methiullin resistant staphylococcus aureus E faecal is Enteiococci faecalis E taecium Enterococu faecium S pyo Streptococcus pyogenes Ribosomal modification (mutation) eim genes
T Target organ assay (cfu log reduction) All MIC are in µg/ml

11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-
allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(quinolin-4-yl)-butyl)-imino)]erythromycin
A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(l-methyl-lH-pyrrolo[2 3-b]pyndin-3-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-nnino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12,l l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)] erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,ll-[oxycarbonyl-((4-(isoquinohn-5-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinohn-5-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3'-N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-lH-imidazol-l-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-imidazol-1 -yl)-butyl)-imino)]erythromycin A hydrochloride salt
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 ll-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)-imino)]erythromycin A
I l,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-S'-N-
allyl)-6-O-methyl-12 11 -[oxycaibonyl-((4-(6-pyi rol-1 -yl-punn-9-yl)-butyl)-imino)]
erythromycin A
II 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-
allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-diethyl)-
imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-ethyl)-imino)]erythromycin A
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 ll-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 ll-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-methyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-methyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4 5-b]pyndin-3-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(lH-imidazo[4 5-b]pyndin-l-yl)-butyl)- imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 ll-[oxycaibonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 11 -[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-lmino)] erythromycin A
11 12-dideo\y-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(lH-imidazo[4 5-b]pyndin-l-yl)-butyl)-nnino)] eiythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-2-fluoroethyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazo[4 5-b]pyndin-3-yl)-butyl)-imino)] erythromycin A,
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 ll-[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-dimethyl)- imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycaibonyl-((9-(4-amino-butyl)-9H-punn-6-)'l)-ethyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3"-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(punn-9-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11-[oxycarbonyl-((4-(punn-9-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-( 1 H-imidazo[4 5-c]pyndin-1 -yl)-butyl)-imino)]erythromycin A
1l,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 "-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(3H-imidazo[4,5-c]pyndin-3-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-S'-N-
allyl)-6-O-methyl-12,11- [oxycarbonyl-((4-(4-thiophen-2-y 1-1 H-imidazol-1 yl)-butyl)-
imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(1H-imidazol[4 5-c]pyndin-l-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(3H-imidazol[4 5-c]pyndin-3-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(isoquinolm-5-yl)-butyl)-imino)]erythromycin A,
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-oxazol-5-yl-1 H-imidazol-1 yl)-butyl)-butyl)-imino)]erythromycin A,
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-imidazol-1 yl)-butyl)-lmino)] erythromycin A,
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-imidazol-1 yl)-butyl)-lmino)] erythromycin A hydrochloride salt
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-S'-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-imidazol-1 yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ally l)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-imidazol-1 yl)-butyl)-imino)]erythromycin A
11 12-dideo\y-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methy 1-12,1 l-[oxycarbonyl-((4-(4-thiophen-2-yl-lH-pyrazol-lyl)-butyl)-imino)]erythromycin A
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((4-(4-furan-2-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-thiophen-2-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-((9-(4-amino-butyl)-9H-punn-6-yl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(quinohn-3-yl)-butyl)-imino)]erythiomycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 ll-[oxycarbonvl-((4-(quinolin-3-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-([l 4 ]bipyrazolyl-l'-yl)-butyl)- imino)] erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4(4-thiazol-2-yl-lH-imidazol-l-yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-thiazol-2-yl-1 H-imidazol-1 -yl)-butyl)-imino)]erythiomycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pynd>l acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-pyrazol-1 yl)-nnino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-thiophen-3-yl-l H-pyrazol- lyl)-butyl)-nnino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-thiophen-3-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((4-(4-furan-3-yl-1 H-pyrazol-1 yl)-butyl)-imino)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((3-(4-pyndin-3-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyO-S-O-Q'-N-desmethyl-3'-N-allyl)-6-O-methyl-12 ll-[oxycarbonyl-(3-benzoimidazol-l-yl)-propyl)-hydrazo)] erythromycin A
11 12-dideoxy-3-O-decladmosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-((3-(4-pyndin-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((3-(4-pyndin-3-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12,11 -[oxycarbonyl-(3-(4-pyndin-3-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-pyndin-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-pyndin-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 1 l-[oxycarbonyl-(9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiophen-3-yl-1 H-imidazol-1 yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosvl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-isoquinohn-5-yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-punn-9-yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosvl-3-O-(2-pyndvl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-((3-purm-9-yl)-piopyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-l 2 11 -[oxycarbonyl-(3-(4-furan-2-yl-1 H-imidazol-1 -yl)propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(9-(3-hydrazo-propyl-9H-punn-6-yl-amine)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pvndyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonvl-(3-(4-furan-3-yl-lH-imidazol-l-yl)propyl)-hydiazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-furan-3-yl-1 H-imidazol-1 -yl)propyl)-hydrazo)]erythromvcin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridylacetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-9-(3-hvdrazo-propyl-9H-purm-6-yl-amine)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-(4-thiophen-2-yl-lH-imidazol-l-yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiophen-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiophen-3-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A
11,12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-imidazo[4 5-b]pyridin-l-yl)-propyl)-hydrazo)] erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-(3-imidazo[4 5-b]pyridin-3-yl)-propyl)-hydiazo)] erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiazol-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A,
11 12-dideoxy-3-O-decladmobyl-3-O-(3-pyridyl acetyl)-5-O-(3"-N-desmethyl-3 -N-allyl)-6-O-methyl-12 11 -[oxycarbonyl-(3-(4-thiazol-2-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A,
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3'-N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-hydrazo]erythromycin A
11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-ethyl)-6-O-methyl-12 ll-[oxycarbonyl-hydrazo)]erythromycin A
11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12,11 -[oxycarbonyl-((3-(4-pyridin-3-yl-1 H-imidazol-1 -yl)-propyl)-hydrazo)]erythromycin A 9-(0-methyl)oxime
11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 ll-[oxycarbonyl-hydrazo]erythromycin A 9-(0-methyl)oxime
Compound No 83 11 12-dideoxy-3-O-decladinosyl-3-O-(3-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-(4-fluoro-pyridin-3-yl)-1 H-imidazol-1 -yl)-butyl)-imino)]erythromycm A
Compound No 84 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycaibonyl-((4-(4-(4-fluoro-pyridin-3-yl)-lH-imidazol-l-yl)-butyl)-imino)]erythiomycin A
Compound No 85 11,12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(4-(lH-imidazol-l-yl)phenyl)-butyl)-imino)]erythromycin A
Compound No 86 11 12-dideoxy-3-O-decladinosyl-3-O-(2-pyridyl acetyl)-5-O-(3 -N-desmethyl-3 -N-allyl)-6-O-methyl-12 1 l-[oxycarbonyl-((4-(5-(3-aminophenyl)-thiazol-2-yl)-butyl)-imino)]erythromycin A
their pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs or polymorphs
3 A pharmaceutical composition comprising a therapeutically effective amount of a
compound of claim 1 or 2 together with pharmaceutically acceptable carrier excipients or diluents
4 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 claim 1 or 2 or a pharmaceutical composition of claim 3
5 The method according to claim 4 wherein the the said bacterium is gram positive gram negative or anaerobic bacteria and the said condition is selected from community acquired pneumonia upper and lower respiratory tract infections skin and soft tissue infections hospital acquired lung infections or bone and joint infections and other bacterial infections selected from mastitis catether infection, foieign body or prosthesis infections
6 The method according to claim 4 wherein the bacterium is selected Staphylococci Stieptocotci Enteiococa Haemophilus Moiaxallaspp Chlamydia spp Mycoplasm Legionella spp M\cobacteimm Helicobactei Clostridium Bacteioides Coiynebacteinim Bacillus andEnteiobactei iceae
7 A method for preparing compounds of Formula XII

(Formula Removed)
pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs and polymorphs thereof wherein RJ R^ Y W and R are the same as defined in claim l which method comprises (a) hydrolyzing clarithromycin of Formula II
(Formula Removed)
to give a compound of Formula III
(Formula Removed)
(b) protecting a compound of Formula III with a reagent of Formula RSO or R'x (wherein X is halogen) to give a compound of Formula IV
(Formula Removed)
(c) desmethylating at 3'-N-dimethyl the compound of Formula IV to give a compound ot Foimula V,
(Formula Removed)
(d) alkylating the compound of Formula V with a reagent of Formula RJCHO R32CO or R3X (wherein X is halogen) to give a compound of Formula VI
(Formula Removed)
(e) reacting the compound of Formula VI with a suitable reagent to give a compound of Formula VII
(Formula Removed)
(f) reacting the compound of Formula VII with a suitable base to give a compound of Formula VIII

(g) reacting the compound of Formula VIII with a compound of Formula R YCOOH (R'YCO)2O R'YCOX or R'YCOOR10 (wherein R10 is leaving group) to give a compound of Formula IX
(Formula Removed)
(h) reacting the compound of Formula IX with N N - carbonyl dnmidazole to give a compound of Formula X
(Formula Removed)
(1) reacting the compound of Formula X with a compound of Formula R-W-NFF to give a compound of Formula XI
(Formula Removed)
(j) deprotectmg the compound of Formula XI to give a compound of Formula XII
8 A method for preparing a compound of Formula XV

(Formula Removed)
pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs and polymorphs thereof wherein R R' R' and Y are the same as defined in claim 1 and m is 3 which method comprises
(a) reacting a compound of Formula X
(Formula Removed)
with hydrazine hydrate to give a compound of Formula XIII
(Formula Removed)
(b) deprotecting the compound of Formula XIII to give a compound of Formula XIV
(Formula Removed)
(c) reacting the compound of Formula XIV with a compound of Formula
R(CH2)mCHO to give a compound of Formula XV
9 A method for preparing a compound of Formula XVII
(FORMULA REMOVED)
pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs and polymorphs thereof wherein R R3 R1 and Y are the same as defined in claim 1 and m is 3 which method comprises
(a) reacting a compound of Formula XIV
with a compound of Formula CH^ONFb HCl to give a compound of Formula XVI

(Formula Removed)
(b) reacting the compound of Formula XVI with a compound of Formula R (CH2)mCHO to give a compound of Formula XVII
10 A method tor preparing a compound ol Formula XII

(Formula Removed)
with a reagent to give a compound of Foimula XVIII
pharmaceutically acceptable salts pharmaceutically acceptable solvates stereoisomers prodrugs and polymorphs theieof wheiein Y W R R3 and R' are the same as defined in claim 1 which method comprises (a) reacting a compound of Formula IV (wherein R is-COPh)
(Formula Removed)
(b) reacting the compound of Formula XVIII with an organic base to give a compound of Formula XIX
(Formula Removed)
(c) desmethylation at 3'-N-dimethyl group of the compound of Formula XIX to give a compound of Formula XX,
(Formula Removed)
(d) alkylating the compound of Formula XX with a reagent of Formula R'CHO R32CO or R'X to give a compound of Formula VIII

(Formula Removed)
(e) acylating the compound of Formula VIII with a reagent of Formula R5YCOOH (R YCO)2O R'YCOX or R'YCOOR10 (wherein R10 is leaving group selected from pivaloyl p-toleuensulfonyl isobutoxycarbonyl ethoxycarbonyl or isopropoxycarbonyl) to give a compound of Formula IX,
(Formula Removed)
(f) reacting the compound of Formula IX with N N'-carbonyl dumidazole to give a compound of Formula X

(Formula Removed)
(g) reaction the compound of Formula X with a compound of Formula R-W-NHi to give a compound of Formula XI

(Formula Removed)
(h) deprotecting the compound of Formula XI to give a compound of Formula XII