WO2006080954A1 - Ketolide derivatives as antibacterial agents - Google Patents

Ketolide derivatives as antibacterial agents Download PDF

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Publication number
WO2006080954A1
WO2006080954A1 PCT/US2005/027875 US2005027875W WO2006080954A1 WO 2006080954 A1 WO2006080954 A1 WO 2006080954A1 US 2005027875 W US2005027875 W US 2005027875W WO 2006080954 A1 WO2006080954 A1 WO 2006080954A1
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WIPO (PCT)
Prior art keywords
methyl
dideoxy
oxo
fluoro
desmethyl
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PCT/US2005/027875
Other languages
French (fr)
Inventor
Biswajit Das
Mohammad Salman
Atul Kashinath Hajare
Ramadass Venkataramanan
Rita Katoch
Rajesh Kumar
Gobind Singh Kapkoti
Anjan Chakrabarti
Anish Bandyopadhyay
Santosh Haribhau Kurhade
Yogesh Baban Surase
Ashok Rattan
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Ranbaxy Laboratories Limited
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Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Priority to EP05856911A priority Critical patent/EP1794171A2/en
Priority to US11/572,619 priority patent/US20080287376A1/en
Priority to JP2007523900A priority patent/JP2008508322A/en
Priority to BRPI0513903-1A priority patent/BRPI0513903A/en
Publication of WO2006080954A1 publication Critical patent/WO2006080954A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • ketolide derivatives which can be used as antibacterial agents.
  • Compounds described herein can be used for treating or preventing conditions caused by or contributed to by Gram-positive, Gram-negative or anaerobic bacteria, more particularly against, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus, Enterobactericeae or any combination thereof. Also provided are processes for preparating compounds described herein, pharmaceutical compositions containing compounds described herein, and methods of treating bacterial infections.
  • erythromycin A and early derivatives are characterized by bacteriostatic or bactericidal activity for most Gram-positive bacteria, atypical pathogens, and many community-acquired respiratory infections and in patients with penicillin allergy.
  • erythromycin A causes numerous drug-drug interactions, has relatively poor absorption, poor local tolerance, loses its antibacterial activity under acidic conditions by degradation and the degraded products are known to be responsible for undesired side effects (Itoh, Z et ah, Am. J. Physiol, 1984, 247:688; Omura, S et ah, J. Med. Chem., 1987, 30:1943).
  • Various erythromycin A derivatives have been prepared to overcome the acid instability and other problems associated with it.
  • Roxithromycin, clarithromycin and azithromycin were developed to address the limitation of erythromycin A. Both clarithromycin and azithromycin were found to be important drugs in the treatment and prophylaxis of atypical mycobacterial infections in patients with HIV.
  • Macrolides were found to be effective drugs in the treatment of many respiratory tract infections. However, increasing resistance among S. pneumoniae has prompted the search for new compounds that retain favorable safety profiles, retain a spectrum of activity and are confined to respiratory pathogens. Consequently, numerous investigators have prepared chemical derivatives of erythromycin A in an attempt to obtain analogs having modified or improved profiles of antibiotic activity. Ketolides exhibit greater efficacy and safety, have broader spectrum of activities, and are particularly effective against resistant pathogens; hence, ketolides have been developed as next generation macrolides.
  • U.S. Patent No. 5,635,485 discloses erythromycin compounds that are reportedly useful in the treatment of bacterial infections in warm-blooded animals.
  • U.S. Patent No. 5,866,549 discloses semi-synthetic macrolides reportedly having antibacterial activity, as well as 6-0-substituted erythromycin ketolide derivatives and a method of treating bacterial infections.
  • U.S. Patent Nos. 6,458,771 and 6,399,582 and PCT Publication Nos. WO 00/62783 and WO 00/44761 disclose ketolide antibacterials that are reportedly useful in treating bacterial and protozoal infections and in treating other conditions involving gastric motility.
  • U.S. Patent No. 5,747,467 discloses erythromycin and antibacterial composition and a method of treating bacterial infection in warm-blooded animals.
  • U.S. Patent No. 6,433,151 discloses erythromycin derivatives and their use as medicament for treating infections caused by particular Gram-positive bacteria, namely Haemophilus influenzae, and Morraxalla spp.
  • U.S. Patent No. 6,472,372 discloses 6-O-carbamoyl ketolide antibacterials and methods of treating bacterial infections.
  • U.S. Patent Application Nos. 2002/0115621 and 2003/0013665 disclose macrolide compounds that are said to be useful as antibacterial and antiprotozoal agents in mammals, including man, as well in fish and birds.
  • ketolide compounds have also been reported. A. Denis and A. Bonnefoy,
  • ketolide derivatives which can be used in the treatment or prevention of bacterial infection, and processes for the synthesis of these compounds.
  • compositions containing the described compounds together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of bacterial infection are included in pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of bacterial infection.
  • R 1 can be hydrogen or a hydroxyl protecting group
  • R 2 and R 3 can independently be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR 11 , wherein R 11 can be hydrogen, alkyl or aralkyl, with the proviso that R 2 and R 3 are not simultaneously methyl;
  • W can be alkenyl, -G(CH 2 ) q J-, -CR 9 R 10 , -NR 9 - or -SO 2 , wherein
  • q can be an integer of from 2 to 6;
  • G can be no atom, -CO, -CS or -SO 2 ;
  • R 9 and R 10 can independently be hydrogen or alkyl
  • J can be no atom, -CR 9 R 10 or N(R 12 )(CH 2 ) m , wherein m can be an integer of from 0 to 6; R 9 and R 10 can be the same as defined earlier; and R 12 can be hydrogen, alkyl, alkylene, alkynyl, COR 8 or -(CH 2 ) m -R 8 , wherein R 8 can be alkyl, aryl or heterocycle;
  • R can be aryl or heterocycle
  • R 4 can be alkyl, alkenyl or alkynyl
  • R' can be alkyl or -(CH 2 ) r -U, wherein r can be an integer of from 1 to 4 and U can be alkenyl or alkynyl; and
  • Y can be halogen, cyano or alkyl; Z can be oxygen, sulfur or NOR 11 , wherein R 11 can be the same as defined earlier.
  • R can be heterocycle;
  • R 2 can be methyl;
  • R 3 can be alkyl (except methyl), alkenyl, cycloalkyl or COR 11 ;
  • W can be -G(CH 2 ) q J- or CR 9 R 10 , wherein G, q, J, R 9 , R 10 and R 11 can be the same as defined above.
  • R 1 can be hydrogen or a hydroxy "" 3
  • R 2 can be CH 3 ;
  • W can be -(CH 2 ) 4 -J-, wherein J can be CH 2 or (CH 2 ) 0-1 -N(CO)-R a ; and
  • R can be:
  • compositions comprising therapeutically effective amounts of one or more compounds of compounds described herein together with one or more pharmaceutically acceptable carriers, excipients, or diluents.
  • provided herein are methods for treating or preventing conditions caused by or contributed to by bacterial infections comprising administering to a mammal in need thereof therapeutically effective amounts of one or more compounds of compounds described herein.
  • the condition can be selected from community acquired pneumonia, upper or lower respiratory tract infections, skin or soft tissue infections, hospital acquired lung infections, hospital acquired bone or joint infections, mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease.
  • the bacterial infection can be caused by Gram-positive, Gram-negative or anaerobic bacteria.
  • the Gram-positive, Gram-negative or anaerobic bacteria can be selected from Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae.
  • the bacterium is cocci.
  • the cocci is drug resistant.
  • R 3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR 11 (wherein R 11 can be hydrogen, alkyl or aralkyl, with the proviso that R 3 is not methyl);
  • W can be alkenyl, -G(CH 2 ) q J-, -CR 9 R 10 , -NR 9 - or -SO 2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO 2 ;
  • R 9 and R 10 can independently be hydrogen or alkyl; and J can be no atom, -CR 9 R 10 or N(R 12 )(CH 2 ) m ⁇ wherein m can be an integer of from 0 to 6;
  • R 3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR 11 (wherein R 11 can be hydrogen, alkyl or aralkyl, with the proviso that R 3 is not methyl);
  • W can be alkenyl, -G(CH 2 ) q J-, -CR 9 R 10 , -NR 9 - or -SO 2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO 2 ;
  • R 9 and R 10 can independently be hydrogen or alkyl; and J can be no atom, -CR 9 R 10 or N(R 12 )(CH 2 ) m ⁇ wherein m can be an integer of from O to 6;
  • R 3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR 11 , wherein R 11 can be hydrogen, alkyl or aralkyl, with the proviso that R 3 is not methyl;
  • W can be alkenyl, -G(CH 2 ) q J-, -CR 9 R 10 , -NR 9 - or -SO 2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO 2 ;
  • R 9 and R 10 can independently be hydrogen or alkyl; and J can be no atom, -CR 9 R 10 or N(R 12 )(CH 2 ) m ⁇ wherein m can be an integer of from 0 to 6;
  • R 9 and R 10 can independently be hydrogen or alkyl; and J can be no atom, -CR 9 R 10
  • R 3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR 11 , wherein R 11 can be hydrogen, alkyl or aralkyl, with the proviso that R 3 is not methyl;
  • W can be alkenyl, -G(CH 2 ) q J-, -CR 9 R 10 , -NR 9 - or -SO 2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO 2 ;
  • R 9 and R 10 can independently be hydrogen or alkyl; and J can be no atom, -CR 9 R 10 or N(R 12 )(CH 2 ) m ⁇ wherein m can be an integer of from 0 to 6;
  • R , 1Q can be the same as defined earlier; and R 12 c, an be hydrogen, alkyl, alkylene, alkynyl, COR 8 or -(CH 2 ) m -R 8 , wherein R 8 can be alkyl, aryl or heterocycle ⁇ ); and R can be aryl or heterocycle;
  • R 1 can be hydrogen or hydroxyl protecting group
  • R 2 and R 3 can independently be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR 11 (wherein R 11 can be hydrogen, alkyl or aralkyl), with the proviso that R 2 and R 3 are not simultaneously methyl;
  • W can be alkenyl, -G(CH 2 ) q J-, -CR 9 R 10 , -NR 9 - or -SO 2 , wherein
  • q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO 2 ; R 9 and R 10 can independently be hydrogen or alkyl; J can be no atom, -CR 9 R 10 orN(R 12 )(CH 2 ) m , wherein
  • n can be an integer of from 0 to 6; R 9 and R 10 are the same as defined earlier; R 12 can be hydrogen, alkyl, alkylene, alkynyl, COR 8 or -(CH 2 ) m - R t wherein
  • R 8 can be alkyl, aryl or heterocycle
  • R can be aryl or heterocycle
  • R 4 can be alkyl, alkenyl or alkynyl
  • R' can be alkyl or -(CH 2 ) r -U, wherein r can be an integer from 1 to 4 and U can be alkenyl or alkynyl;
  • Y can be halogen, cyano or alkyl
  • Z can be oxygen, sulfur or NOR 11 , wherein R 11 can be hydrogen, alkyl or aralkyl.
  • R can be heterocycle
  • R 2 and R 3 can be respectively methyl and alkyl (except methyl), alkenyl, cycloalkyl or COR 11
  • W can be -G(CH 2 ) q J- or CR 9 R 10 , wherein G, q, J, R 9 , R 10 and R 11 are the same as defined above.
  • R 1 can be hydrogen or a hydroxy protecting group, wherein the hydroxy protecting can be benzoyl, tetrahydropyranyl or a trialkylsilylether;
  • R 2 can be CH 3 ;
  • W can be -(CH 2 ) 4 -J-, wherein J can be CH 2 or (CH 2 ) 0-1 -N(CO)-R a ; and R can be,
  • X 1 -X 3 can independently be CH or N; X 4 -X 8 can independently be CH, CR 4 or N; X 9 can be O, S, N, NH or CH; X 10 can be NH or S; R a can be thienyl, furyl, pyrazolyl, oxazolyl, tetrazolyl, imidazolyl, pyridinyl, fluoropyridinyl, chloropyridinyl, aminopyridinyl, pyrazinyl, pyrimidinyl, aminopyrimidinyl, quinolinyl, pyrrolo-pyridyl, pyrrolo-thiazolyl or optionally substituted phenyl; R'a can be hydrogen or furyl; R b can be hydrogen or amino; R 0 can be hydrogen, thienyl, furyl, pyrazolyl, pyrazinyl, pyridinyl, aminopyridinyl, pyrimidiny
  • provided herein are methods for treating or preventing a mammal suffering from conditions caused by or contributed to by Gram- positive, Gram-negative or anaerobic bacteria comprising administering to a mammal in need thereof therapeutically effective amounts of one or more compounds or one or more pharmaceutical compositions described herein.
  • Bacterial infection may be caused by one or more bacteria, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae.
  • bacteria for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae.
  • the conditions treated or prevented may be, for example, community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, or other bacterial infections, for example, mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease.
  • alkyl refers to a monoradical branched or unbranched saturated hydrocarbon chain having from 1 to 20 carbon atoms.
  • Alkyl groups can be optionally interrupted by atom(s) or group(s) independently selected from oxygen, sulfur, a phenylene, sulfinyl, sulfonyl group or — NR a -, wherein R a can be hydrogen, alkyl, alkenyl, alkynyl cycloalkyl or aryl.
  • This term can be exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-decyl, tetradecyl, and the like.
  • alkenyl refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group having from 2 to 20 carbon atoms with cis, trans, or geminal geometry. It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, phenylene, sulfmyl, sulfonyl and -NR a -, wherein R a can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl.
  • alkynyl refers to a monoradical of an unsaturated hydrocarbon, having from 2 to 20 carbon atoms. It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, phenylene, sulfmyl, sulfonyl and -NR 8 -, where R a can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl. hi the event that alkynyl is attached to a heteroatom, the triple bond cannot be alpha to the heteroatom.
  • Alkynyl groups may be substituted further (referred to herein as "substituted alkynyl") with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, oxo, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkyltliio, aryl, aralkyl, aryloxy, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, where
  • cycloalkyl refers to cyclic alkyl groups of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may optionally contain one or more olefmic bonds, unless otherwise constrained by the definition.
  • Such cycloalkyl groups can include, for example, single ring structures, including cyclopropyl, cyclobutyl, cyclooctyl, cyclopentenyl, and the like, or multiple ring structures, including adamantanyl, and bicyclo [2.2.1] heptane, or cyclic alkyl groups to which is fused an aryl group, for example, indane, and the like. Spiro and fused ring structures can also be included.
  • halogen or halo refers to fluorine, chlorine, bromine or iodine.
  • hydroxyl protected includes, but is not limited to, acyl, aroyl, alkyl, aryl, butyldiphenylsilyl, methoxymethyl and methylthiomethyl, and the like.
  • thio refers to the group -SH.
  • alkoxy denotes the group O-alkyl or O-cycloalkyl, wherein alkyl and cycloalkyl are the same as defined above. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, cyclopentoxy, and the like.
  • thioalkyl refers to -SR 5 wherein R 5 is alkyl or cycloalkyl.
  • haloalkyl refers to alkyl of which one or more hydrogen(s) is/are replaced by halogen.
  • aryl herein refers to aromatic system having 6 to 14 carbon atoms, wherein the ring system can be mono-, bi- or tricyclic and are carbocyclic aromatic groups.
  • the aryl group optionally may be fused with a cycloalkyl group, wherein the cycloalkyl group may optionally contain heteroatoms selected from O, N or S.
  • a cycloalkyl group may optionally contain heteroatoms selected from O, N or S.
  • Groups such as phenyl, naphthyl, anthryl, biphenyl, and the like exemplify this term.
  • aralkyl refers to alkyl-aryl linked through an alkyl portion (wherein alkyl is as defined above) and the alkyl portion contains 1-6 carbon atoms and aryl is as defined above.
  • alkyl is as defined above
  • alkyl portion contains 1-6 carbon atoms and aryl is as defined above.
  • aralkyl include, but are not limited to, benzyl, napthylmethyl, phenethyl and phenylpropyl, and the like.
  • Carbonyl or sulfonyl group can replace carbon atom(s) of heterocyclyl.
  • the substituents are attached to the ring atom, i.e., carbon or heteroatom in the ring.
  • the heterocyclyl ring optionally may contain one or more olefinic bond(s).
  • heterocycles include, but not limited to, azabicyclohexyl, azetidinyl, benzoimidazolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, benzoxazolyl, benzothiazolyl, benzothiazinyl, benzotriazolyl, benzoxazinyl, carbaxolyl, dihydrobenzofuryl, dihydroimidazolyl, dihydropyranyl, dihydrofuranyl, dihydroindolyl, dihydroisoxazolyl, dihydropyridinyl, dioxanyl, dioxolanyl, furyl, homopiperidinyl, imidazolyl, imidazolinyl, imidazolidinyl, imidazopyridinyl, indolinyl, indolyl, isoindole 1,3-dione, isoquinolinyl,
  • heterocyclylalkyl refers to heterocycle which is bonded to an alkylene chain, wherein heterocyclyl and alkyl are the same as defined above.
  • heterocycle alkyl include, but are not limited to, isothiazolidinyl ethyl, isothiazolyl propyl, pyrazinyl methyl, pyrazolinyl propyl and pyridyl butyl, pyridyl methyl and the like.
  • polymorphs refers to all crystalline forms and amorphous forms of the compounds described herein, hi addition, some of the compounds described herein may form solvates with water (i.e., hydrate, hemihydrate or sesquihydrate) or common organic solvents. Such solvates are also encompassed within the scope of this invention.
  • Suitable pharmaceutically acceptable salts denotes salts of the free base, which possess the desired pharmacological activity of the free base and which are neither biologically nor otherwise undesirable.
  • Suitable pharmaceutically acceptable salts may be prepared from an inorganic or organic acid.
  • inorganic acids include, but not limited to, hydrochloric, hydrobromic, hydroiodic, nitrous (nitrite salt), carbonic, sulfuric, phosphoric acid and like.
  • organic acids include, but not limited to, aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of organic acids, for example, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, tumeric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic
  • pharmaceutically acceptable carriers is intended to include non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
  • the compounds of present invention include stereoisomers.
  • stereoisomer refers to compounds, which have identical chemical composition, but differ with regard to arrangement of the atoms and the groups in space. These include enantiomers, diastereomers, geometrical isomers, atropisomer and comformational isomers. Geometric isomers may occur when a compound contains a double bond or some other feature that gives the molecule a certain amount of structural rigidity.
  • An enantiomer is a stereoisomer of a reference molecule that is the nonsuperimposable mirror image of the reference molecule.
  • a diastereomer is a stereoisomer of a reference molecule that has a shape that is not the mirror image of the reference molecule.
  • An atropisomer is a conformation 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 room temperature. Racemic mixtures are also encompassed within the scope of this invention.
  • Compounds of Formula XIII can be prepared according to Scheme I.
  • clarithromycin of Formula II can be hydro lyzed to form a compound of Formula III.
  • the compound of Formula IV can be desmethylated at the 3'-N-dimethyl group to form a compound of Formula V.
  • the compound of Formula V can be alkylated by reacting with one or more reagents of Formula R 3 CHO, R 3 2 CO or R 3 X (wherein X is halogen) to form a compound of Formula VI (wherein R 3 is the same as defined earlier).
  • the compound of Formaul VI can be reacted with one or more reagents, for example, triphosgene, ethylene dicarbonate or a mixture thereof, to form a compound of Formula VII.
  • the compound of Formula VII can be reacted with one or more organic bases (for example, tetramethyl guanidine, trimethylamine or mixtures thereof) to form a compound of Formula VIII.
  • the compound of Formula VIII can be oxidized to form a compound of Formula IX.
  • the compound of Formula IX can be reacted with N,N'-carbonyldiimidazole to form a compound of Formula X.
  • the compound of Formula X can be reacted with a compound of Formula R-W-NH 2 to form a compound of Formula XI (wherein W and R are the same as defined earlier).
  • the compound of Formula XI can be fluorinated to form a compound of Formula XII.
  • the compound of Formula XII can be deprotected to form a compound of Formula XIII.
  • Clarithromycin of Formula II can be hydrolyzed in the presence of an inorganic or organic acid, for example, hydrochloric acid, sulfuric acid or dichloroacetic acid.
  • an inorganic or organic acid for example, hydrochloric acid, sulfuric acid or dichloroacetic acid.
  • the compound of Formula III can be hydroxyl protected by reacting with one or more reagents of Formula R ⁇ O or R 1 X in one or more solvents, for example, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixtures thereof.
  • the protection reactions can also be carried out in the presence of one or more organic bases, for example, triethylamine, diisopropylethylamine, pyridine, tributylamine, 4-(N-dimethylamino)pyridine or mixtures thereof.
  • Compounds of Formula IV can be desmethylated in the presence of one or more desmethylating agents, for example, N-iodosuccinimide iodine in acetic acid, diisopropylazodicarboxylate or mixtures thereof.
  • desmethylating agents for example, N-iodosuccinimide iodine in acetic acid, diisopropylazodicarboxylate or mixtures thereof.
  • desmethylation reactions can also be carried out in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixtures thereof.
  • Desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • quenching agents for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • Compounds of Formula V can be alkylated with one or more reagents of Formula R 3 CHO, R 3 2 CO or R 3 X in one or more solvents, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof.
  • Alkylation reactions can also be carried out in the presence of one or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof.
  • inorganic or organic bases for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof.
  • Alkylation reactions can also be carried out in the presence of one or more reducing agents (for example, sodium cyanoborohydride, sodium borohydride, sodium triacetoxyborohydri.de or mixtures there) and in the presence of one or more organic acids (for example, acetic acid or dichloroacetic acid in a solvent, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof).
  • one or more reducing agents for example, sodium cyanoborohydride, sodium borohydride, sodium triacetoxyborohydri.de or mixtures there
  • organic acids for example, acetic acid or dichloroacetic acid in a solvent, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
  • Compounds of Formula VI can be reacted to form compounds of Formula VII in one or more solvents, for example, chloroform, dichloromethane, carbon tetrachloride, dichloroethane or mixtures thereof. These reactions can also be carried out in the presence of one or more organic bases, for example, triethylamine, diisopropyl ethylamine, pyridine, tributylamine, 4-(N-dimethylamino)pyridine or mixtures thereof.
  • solvents for example, chloroform, dichloromethane, carbon tetrachloride, dichloroethane or mixtures thereof.
  • organic bases for example, triethylamine, diisopropyl ethylamine, pyridine, tributylamine, 4-(N-dimethylamino)pyridine or mixtures thereof.
  • Compounds of Formula VII can be reacted with one or more organic bases in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof.
  • Compounds of Formula VIII can be oxidized by reacting with one or more oxidizing agents, for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), Jones Oxidation reagent (chromic acid, aqueous sulfuric acid and acetone), pyridinium dichromate, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or mixtures thereof.
  • oxidizing agents for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide),
  • N-Chlorosuccinamide can be used in combination with dimethyl sulfide and 1- ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride can be used in combination with dimethylsulfoxide.
  • Compounds of Formula VIII can also be oxidized in one or more solvents, for example, chloroform, dichloromethane, carbon tetrachloride, dimethylsulfoxide, dichloroethane or mixtures thereof.
  • Compounds of Formula IX can be reacted with N,N'-carbonyldiimidazole in one or more solvents, for example, dimethylforrnamide, acetonitrile, tetrahydrofuran or mixtures thereof. This reaction can also be carried out in the presence of one or more inorganic bases, for example, sodium hydrogen carbonate, sodium acetate, sodium thiosulfate, potassium carbonate, cesium carbonate or sodium hydride.
  • Compounds of Formula X can be reacted with compounds of Formula R-W-NH 2 in one or more solvent systems, for example, acetonitrile/water, dimethylformamide/water, dimethylformamide or combinations thereof.
  • Compounds of Formula XI can be fluorinated in the presence of one or more fluorinating agents, for example, N-fluorobenzene sulfonimide, selectfluor or mixtures thereof.
  • the fluorination reactions can also be carried out by procedures described in G.Sankar LaI and Syvret R.G., Chem. Rev., 96:1737-1755 (1996).
  • the fluorination reactions can also be carried out in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof.
  • the fluorination reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, sodium hydride, sodium acetate, sodium thiosulfate, potassium fert-butoxide, sodium tert-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, lithium carbonate or mixtures thereof.
  • inorganic bases for example, potassium carbonate, sodium hydride, sodium acetate, sodium thiosulfate, potassium fert-butoxide, sodium tert-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, lithium carbonate or mixtures thereof.
  • Compounds of Formula XII can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
  • Compounds of Formula XIII can also be prepared according to Scheme II.
  • compounds of Formula IV can be reacted with one or more reagents, for example, triphosgene, ethylene dicarbonate or mixtures thereof, to form compounds of Formula XIV.
  • compounds of Formula XIV can be reacted with one or more organic bases, for example, tetramethyl guamdine, trimethyl amine or mixtures thereof, to form compounds of Formula XV.
  • Compounds of Formula XV can be oxidized to form compounds of Formula XVI.
  • Compounds of Formula XVI can be desmethylated at the 3'-N-dimethyl group to form compounds of Formula XVII.
  • Compounds of Formula XVII can be alkylated with one or more reagents of Formula R 3 CHO, R 3 2 CO or R 3 X (wherein X is a halogen) to form compounds of Formula IX (wherein R 3 is the same as defined earlier).
  • Compounds of Formula IX can be fluorinated to form compounds of Formula XVIII.
  • Compounds of Formula XVIII can be reacted with N,N'-carbonyldiimidazole to form compounds of Formula XIX.
  • Compounds of Formula XIX can be reacted with compounds of Formula R-W-NH 2 to form compounds of Formula XII (wherein W and R are the same as defined earlier).
  • Compounds of Formula XII can be deprotected to form compounds of Formula XIII.
  • Compounds of Formula IV can be reacted to form compounds of Formula XTV in one or more solvents, for example, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or mixtures thereof. These reactions can also be carried out in the presence of one or more organic bases, for example, triethylamine, pyridine, diisopropylethylamine, 4-(N-dimethylamino)pyridine or mixtures thereof. ,
  • Compounds of Formula XV can be oxidized in the presence of one or more oxidizing agents, for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), Jones Oxidation reagent (chromic acid, aqueous sulfuric acid and acetone), pyridinium dichromate, l-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride or mixtures thereof.
  • oxidizing agents for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide),
  • Compounds of Formula XVI can be desmethylated in the presence of one or more desmethylating agents, for example, N-iodo succinimide, iodine in acetic acid, diisopropyl azodicarboxylate or mixtures thereof.
  • the desmethylation reactions can also be carried out in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbontetrachloride, ethyl acetate or mixtures thereof.
  • Desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • Compounds of Formula XVII can be alkylated with one or more reagents of Formula R 2 CHO, R 2 2 CO or R 2 X in one or more solvents, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof.
  • Alkylation reactions can also be carried out in the presence of one or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropylethylamine or mixtures thereof.
  • Compounds of Formula XVII can be fluorinated in the presence of one or more fluorinating agents, for example, N-fluorobenzene sulfonimide, selectfluor or mixtures thereof.
  • the fluorination reactions can also be carried out by procedures described in G.Sankar LaI and Syvret R.G., Chern. Rev., 96:1737-1755 (1996).
  • the fluorination reactions can also be carried out in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof.
  • the fluorination reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, cesium carbonate, sodium hydride, sodium acetate, sodium thiosulfate, potassium t ⁇ 't-butoxide or mixtures thereof.
  • inorganic bases for example, potassium carbonate, cesium carbonate, sodium hydride, sodium acetate, sodium thiosulfate, potassium t ⁇ 't-butoxide or mixtures thereof.
  • R-W-NH 2 in one or more solvent systems, for example, dimethylformamide/water, acetonitrile/water, dimethylformamide or combinations thereof.
  • Compounds of Formula XII can be deprorected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
  • Compounds of Fo ⁇ nula XIII can also be prepared according to Scheme III.
  • Compounds of Formula XVI can be fluorinated to form compounds of Formula XX.
  • Compounds of Formula XX can be reacted with N,N'-carbonyldiimidazole to form compounds of Formula XXI.
  • Compounds of Formula XXI can be reacted with compounds of Formula R-W-NH 2 to form compounds of Formula XXII (wherein R and W are the same as defined earlier).
  • Compounds of Formula XXII can be deprotected to form compounds of Formula XXIII.
  • Compounds of Formula XXIII can be desmethylated at the 3'-N-dimethyl group to form compounds of Formula XXIV.
  • Compounds of Formula XXIV can be alkylated with one or more reagents of Formula R 3 CHO, R 3 2 CO or R 3 X (wherein X is halogen) to form compounds of Formula XIII (wherein R 3 is the same as defined earlier).
  • Compounds of Formula XVI can be fiuorinated in the presence of one or more fluorinating agents, for example, N-fluorobenzene sulfonimide, selectfluor or mixtures thereof.
  • the fluorination reactions can also be carried out by procedures described in G.Sankar LaI and Syvret R.G., Chem. Rev., 96:1737-1755 (1996).
  • the fluorination reactions can also be carried out in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethyl sulfoxide or mixtures thereof.
  • the fluorination reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, sodium hydride, sodium acetate, sodium hydrogen carbonate, cesium carbonate, sodium thiosulfate, potassium tert-butoxide, sodium tert-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, lithium carbonate or mixtures thereof.
  • inorganic bases for example, potassium carbonate, sodium hydride, sodium acetate, sodium hydrogen carbonate, cesium carbonate, sodium thiosulfate, potassium tert-butoxide, sodium tert-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, lithium carbonate or mixtures thereof.
  • Compounds of Formula XXI can be reacted with compounds of Formula R-W-NH 2 in one or more solvent systems, for example, acetonitrile/water, dimethylformamide/water or combinations thereof.
  • Compounds of Formula XXII can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
  • Compounds of Formula XXIII can be desmethylated in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbontetrachloride, ethyl acetate or mixtures thereof.
  • solvents for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbontetrachloride, ethyl acetate or mixtures thereof.
  • desmethylation reactions can also be carried out in the presence of one or more desmethylating agents, for example, N-iodosuccinimide, iodine in acetic acid, diisopropyl azodicarboxylate or mixtures thereof.
  • the desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • quenching agents for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • Compounds of Formula XXIV can be alkylated with one or more reagents of Formula R 3 CHO, R 3 2 CO or R 3 X in one or more solvents, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof.
  • solvents for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof.
  • These alkylation reactions can be carried out in the presence of oen or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof.
  • Compounds of Fo ⁇ nula XIII can also be prepared according to Scheme IV.
  • compounds of Formula XX (wherein R 1 is COPh) can be deprotected to form compounds of Formula XXV.
  • Compounds of Formula XXV can be desmethylated at the 3'-N- dimethyl group to form compounds of Formula XXVI.
  • Compounds of Formula XXVI can be alkylated with one or more reagents of Formula R 3 CHO, R 3 2 CHO or R 3 X (X is halogen) to form compounds of Formula XXVII (R 3 is the same as defined earlier).
  • Compounds of Formula XXVII can be protected with one or more reagents of Formula R !
  • Compounds of Formula XX can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
  • Compounds of Formula XXV can be desmethylated in the presence of one or more desmethylating agents, for example, N-iodosuccinimide, iodine in acetic acid, diisopropyl azodicarboxylate or mixtures thereof.
  • Desmethylation reactions can also be carried out in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixtures thereof.
  • the desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • quenching agents for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
  • Compounds of Formula XXVI can be alkylated by reaction with one or more reagents of Formula R 3 CHO, R 3 2 CO on R 3 X in one or more solvents, for example, dimethylformamide, acetonitrile, tetrahydrofuran, acetone, methanol or mixtures thereof.
  • Alkylation reactions can also be carried out in the presence of one or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof.
  • Compounds of Formula XXVII can be hydroxyl protected by reaction with one or more reagents of Formula R ⁇ O or R 1 X in one or more solvents, for example, dichloromethane, dichloroethane, carbontetrachloride, chloroform, acetone or mixtures thereof. Hydroxyl protection reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, cesium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate or mixtures thereof.
  • Compounds of Formula XIX can be reacted with compounds of Formula R-W-NH 2 in one or more solvent systems, for example, acetonitrile/water, dimethylformamide/water, dimethyformamide or combinations thereof.
  • Compounds of Formula XII can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
  • the compounds described herein are pharmacologically active against Gram-positive, Gram-negative and anaerobic bacteria and accordingly, are useful as antibacterial agents for treating bacterial infections in a patient in need thereof, for example, in a human or an animal. Because of their antibacterial activity, the compounds described herein may be administered to an animal for treatment orally, topically, rectally, internasally, or by parenteral route.
  • Pharmaceutical compositions described herein comprise pharmaceutically effective amounts of compounds described herein formulated together with one or more pharmaceutically acceptable carriers, excipients or diluents.
  • Solid form preparations for oral administration include capsules, tablet, pills, powder, granules, cachets and suppositories.
  • active compounds can be mixed with one or more inert, pharmaceutically acceptable excipients or carrier, for example, sodium citrate, dicalcium phosphate and/or fillers or extenders (for example, starches, lactose, sucrose, glucose, mannitol, silicic acid or mixtures thereof); binders, for example, carboxymethylcellulose, alginates, gelatins, polyvinylpyrrolidinone, sucrose, acacia or mixtures thereof; disintegrating agents, for example, agar-agar, calcium carbonate, potato starch, alginic acid, certain silicates, sodium carbonate or mixtures thereof; absorption acceletors, for example, quaternary ammonium compounds; wetting agents, for example, cetyl alcohol, glycerol mono stearate or mixtures thereof; adsorbants, for example, Ka
  • Capsules, tablets or pills may also comprise buffering agents.
  • Tablets, capsules, pills or granules can be prepared using one or more coatings or shells, for example, enteric coatings or other coatings known to one of ordinary skill in the art.
  • Liquid form preparations for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or elixirs, hi such liquid fonn preparations, active compounds can be mixed with water or one or more other solvents, solubilizing agents or emulsifiers, for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, for example, cottonseed, groundnut, corn, germ, olive, castor and sesame oil), glycerol, fatty acid esters of sorbitan or mixtures thereof.
  • Oral compositions can also include one or more adjuants, for example, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavouring agents, perfuming agents or mixtures thereof.
  • aqueous suspensions may be formulated according to methods known to one of ordinary skill in the art, and in particular, using one or more suitable dispersing or wetting and suspending agents.
  • Acceptable vehicles and solvents include one or more of water, Ringer's solution, isotonic sodium chloride or mixtures thereof.
  • Dosage forms for tropical or transdermal administration of a compound of the present invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches.
  • Active compounds can be admixed under sterile condition with one or more pharmaceutically acceptable carriers and optionally any preservatives or buffers as may be required.
  • Ophthalmic formulations, eardrops, eye ointments, powders and solutions are also encompassed within the scope of this invention.
  • Pharmaceutical preparations may be in unit dosage form. In unit dosage form, the preparations can be subdivided into unit doses containing appropriate quantities of active components.
  • Unit dosage forms can be packaged preparations containing discrete capsules, powders, in vials or ampoules, ointments, capsules, sachets, tablets, gels, creams or any combination and number of such packaged forms.
  • 4-(3H)-imidazol[4,5-b]pyridin-3-yl-butylamine was prepared according to a procedure described in U.S. Patent No. 5,635,485, which is incorporated herein in its entirety, hi particular, 10.3 g of potassium carbonate were added to a solution of 5.95 g of 4-azabenzimidazole and 15.5 g of N-4-bromobutyl-phthalimide in 30 mL of dimethylformamide and the mixture was stirred for 20 hours at ambient temperature. The insoluble part was filtered off and rinsed with methylene chloride. The organic phase was washed with water, then dried over magnesium sulfate and evaporated.
  • Step II Preparation of 2-[2-(methylpyridin-4-ylmethylamino) ethylisoindole-l,3-dione
  • Step III Preparation of N* 1 *-methyl-N* 1 *-pyridm-4-ylmethylethane-l , 2-diamine
  • Clarithromycin (25 g, 33.4 mmol) was added in portions to an aqueous solution of hydrochloric acid at ambient temperature.
  • the reaction mixture was neutralized with solid sodium bicarbonate and the aqueous layer was extracted with ethyl acetate.
  • the organic layer was washed successively with water and then brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
  • the crude product was crystallized from ethyl acetate and hexane to yield the title compound.
  • Benzoic anhydride (2.5 equiv.) followed by triethylamine (6 equiv.) was added to a solution of compound of Formula III (1 equiv.) in dichloromethane and stirred at ambient temperature for about 40 hours. The reaction was quenched by adding sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane, washed successively with water and then brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product. The crude product obtained was crystallized from ethyl acetate and hexane to yield the title compound.
  • N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula IV (1 equiv.) in dry acetonitrile:dichloromethane (2:1) at about 0 0 C.
  • the reaction mixture was allowed to come to ambient temperature while being stirred.
  • a sodium bisulfite solution was added to the reaction mixture with stirring followed by adding a sodium carbonate solution with further stirring of the reaction mixture.
  • Dichloromethane was evaporated under reduced pressure.
  • the aqueous layer was extracted with ethyl acetate, washed successively with water and then brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
  • the crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 17-25% acetone in hexane to yield the title compound.
  • Solid sodium hydrogen carbonate (5 equiv.) and ethyl iodide (6 equiv.) were added to a solution of compound of Formula V (1 equiv.) in acetonitrile under argon at ambient temperature and stirred for about 24 hours.
  • the reaction was quenched by adding water.
  • the reaction mixture was then diluted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield a crude product.
  • the crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-15 % acetone in hexane to yield the title compound.
  • the compound of Formula V (1 equiv.) in acetone and methanol was stirred at ambient temperature. A solution of acetic acid was added with stirring and sodium cyanoborohydride (2 equiv.) was then added with continued stirring. The solvent was evaporated under reduced pressure and a crude product was extracted with ethyl acetate. The ethyl acetate layer was combined and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-20 % acetone in hexane to yield the title compound.
  • Triphosgene (1.5 equiv.) was added to a solution of compound of Formula VI (1 equiv.) in dichloromethane. Pyridine (15 equiv.) was then slowly added. After complete addition, the reaction mixture was stirred for about 4 hours and then quenched by adding ice-cold water. The reaction mixture was diluted with dichloromethane, washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • Tetramethyl guanidine (2.2 equiv.) was added to a solution of compound of
  • Dess-Martine Periodinane (2.5 equiv.) was added to a solution of compound of Formula VIII (1 equiv.) in dichloromethane .
  • the reaction mixture was refluxed for about one hour, cooled to ambient temperature, quenched by adding a saturated aqueous potassium carbonate solution followed by a saturated sodium thiosulfate solution, and the reaction mixture was then stirred.
  • the aqueous layer was separated and extracted with dichloromethane.
  • the dichloromethane layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula IX (1 equiv.) in dimethylformamide: tetrahydrofuran (3:2) at ambient temperature.
  • the reaction mixture was cooled, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred.
  • the reaction mixture was quenched by adding water. It was extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the desired product.
  • Triphosgene (1.5 equiv) was added to a solution of compound of Formula IV (1 equiv) in dichloromethane and pyridine (15 equiv) was then slowly added. After complete addition, the reaction mixture was stirred for about 3-4 hours at 0 0 C. The reaction mixture was quenched by adding ice-cold water. The reaction mixture was diluted with dichloromethane and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • Tetramethyl guanidine (2.2 equiv.) was added to a solution of compound of Formula XIV (1 equiv.) in dimethylformamide. The reaction mixture was heated to 65-70 0 C for about 3-4 hours and then cooled to ambient temperature. The organic layer was extracted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • Dess-Martine Periodinane (2.5 equiv.) was added to a solution of compound of Formula XV (1 equiv.) in dichloromethane and the reaction mixture was stirred at 30 0 C for about 1 hour.
  • the reaction mixture was quenched by adding saturated aqueous potassium carbonate solution followed by saturated sodium thiosulfate solution and the reaction mixture was stirred.
  • the resulting aqueous layer was separated and extracted with dichloromethane.
  • the dichloromethane layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula XVI (1 equiv.) in dry acetonitrileidichloromethane (2: 1).
  • the reaction mixture was allowed to reach ambient temperature and stirred for about 3-4 hours.
  • a sodium bisulfite solution was then added to the reaction mixture and stirred.
  • sodium carbonate solution was added to the reaction mixture and stirring.
  • Dichloromethane was evaporated under reduced pressure. The aqueous layer was extracted with ethyl acetate, washed successively with water followed by brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
  • N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula XVIII (1 equiv.) in dimethylformamide:tetrahydrofuran (3:2) at ambient temperature.
  • the reaction mixture was cooled to 0 0 C, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred for about 30 minutes.
  • the reaction mixture was quenched by adding water and then extracted with ethyl acetate. The ethyl acetate layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula XX (1 equiv.) in dimethylformamide:tetrahydrofuran (3:2) at ambient temperature.
  • the reaction mixture was cooled to 0 0 C, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred for about 30 minutes.
  • the reaction was quenched by adding water and extracted with ethyl acetate. The ethyl acetate layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • the compound of Formula XXI (1 equiv.) and R-W-NH 2 (2 equiv.) were taken in a mixture of 10 % water in acetonitrile and heated to 65-70 0 C for about 14 hours.
  • the reaction mixture was cooled to ambient temperature and acetonitrile-water was removed under reduced pressure.
  • the resulting residue was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound.
  • N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula
  • the compound of Formula XX was taken in methanol and reflux ed. The reaction mixture was cooled to attain an ambient temperature and methanol was evaporated under reduced pressure. The crude product was purified by column chromatography.
  • N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula XXV (1 equiv.) in dry acetonitrile and the reaction mixture was allowed to attain ambient temperature and stirred for about 4 hours.
  • a sodium bisulfite solution was added to the reaction mixture with stirring followed the addition of sodium carbonate solution with stirring.
  • the aqueous layer was extracted with ethyl acetate, washed successively with water followed by brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
  • Solid sodium hydrogen carbonate (5 equiv.) and ethyl iodide (6 equiv.) was added to a solution of compound of Formula XXVI (1 equiv.) in acetonitrile under argon at ambient temperature and stirred for about 20 hours.
  • the reaction mixture was quenched by adding water.
  • the reaction mixture was diluted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield a crude product.
  • the crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 20-25 % acetone in hexane to yield the title compound.
  • N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula XVIII (1 equiv.) in dimethylformamide: tetrahydrofuran (3:2) at ambient temperature.
  • the reaction mixture was cooled to 0 0 C, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred for about 30 minutes.
  • the reaction mixture was quenched by adding water. This was extracted with ethyl acetate. Ethyl acetate layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
  • the compound of Formula XIX (1 equiv.) and R-W-NH 2 (2 equiv.) were taken in a mixture of 10 % water in acetonitrile and heated to 65-70 0 C for about 14 hours.
  • the reaction mixture was cooled to ambient temperature and acetonitrile-water was removed under reduced pressure.
  • the resulting residue was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound.
  • the compound of Formula XII was taken in methanol and refluxed. The reaction mixture was cooled to ambient temperature and methanol was removed under reduced pressure. The resulting solid crude product was purified by silica gel chromatography using 2-6 % methanol in dichloromethane to yield the title compound.
  • Compounds described herein displayed antibacterial activity in vitro especially against strains that are resistant to macrolides either due to efflux (mef strains) or ribosomal modification (erm) strains. These compounds are useful in treating community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections, bone and joint infections, and other bacterial infections, for example, mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease. - I ll -
  • MIC Minimum inhibitory concentration
  • TSA Trypticase Soya Agar
  • NCCLS National Committee for Clinical Laboratory Standards
  • 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 0 C in a CO 2 incubator. The results were noted comparing with the control plates.
  • 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.

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Abstract

The present invention provides ketolide derivatives, which can be used as antibacterial agents. In particular, compounds described herein can be used for treating or preventing conditions caused by or contributed to by Gram-positive, Gram-negative or anaerobic bacteria, more particularly against, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae. Also provided are processes for preparing siuch ketolide derivatives, pharmaceutical compositions thereof, and methods of treating bacterial infections.

Description

KETOLIDE DERIVATIVES AS ANTIBACTERIAL AGENTS
Field of Invention
The present invention provides ketolide derivatives, which can be used as antibacterial agents. Compounds described herein can be used for treating or preventing conditions caused by or contributed to by Gram-positive, Gram-negative or anaerobic bacteria, more particularly against, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus, Enterobactericeae or any combination thereof. Also provided are processes for preparating compounds described herein, pharmaceutical compositions containing compounds described herein, and methods of treating bacterial infections.
Background of the Invention
First generation macrolides erythromycin A and early derivatives are characterized by bacteriostatic or bactericidal activity for most Gram-positive bacteria, atypical pathogens, and many community-acquired respiratory infections and in patients with penicillin allergy. However, erythromycin A causes numerous drug-drug interactions, has relatively poor absorption, poor local tolerance, loses its antibacterial activity under acidic conditions by degradation and the degraded products are known to be responsible for undesired side effects (Itoh, Z et ah, Am. J. Physiol, 1984, 247:688; Omura, S et ah, J. Med. Chem., 1987, 30:1943). Various erythromycin A derivatives have been prepared to overcome the acid instability and other problems associated with it.
Roxithromycin, clarithromycin and azithromycin were developed to address the limitation of erythromycin A. Both clarithromycin and azithromycin were found to be important drugs in the treatment and prophylaxis of atypical mycobacterial infections in patients with HIV.
Macrolides were found to be effective drugs in the treatment of many respiratory tract infections. However, increasing resistance among S. pneumoniae has prompted the search for new compounds that retain favorable safety profiles, retain a spectrum of activity and are confined to respiratory pathogens. Consequently, numerous investigators have prepared chemical derivatives of erythromycin A in an attempt to obtain analogs having modified or improved profiles of antibiotic activity. Ketolides exhibit greater efficacy and safety, have broader spectrum of activities, and are particularly effective against resistant pathogens; hence, ketolides have been developed as next generation macrolides.
U.S. Patent No. 5,635,485 discloses erythromycin compounds that are reportedly useful in the treatment of bacterial infections in warm-blooded animals.
U.S. Patent No. 5,866,549 discloses semi-synthetic macrolides reportedly having antibacterial activity, as well as 6-0-substituted erythromycin ketolide derivatives and a method of treating bacterial infections.
U.S. Patent Nos. 6,458,771 and 6,399,582 and PCT Publication Nos. WO 00/62783 and WO 00/44761 disclose ketolide antibacterials that are reportedly useful in treating bacterial and protozoal infections and in treating other conditions involving gastric motility.
U.S. Patent No. 5,747,467 discloses erythromycin and antibacterial composition and a method of treating bacterial infection in warm-blooded animals.
U.S. Patent No. 6,433,151 discloses erythromycin derivatives and their use as medicament for treating infections caused by particular Gram-positive bacteria, namely Haemophilus influenzae, and Morraxalla spp.
U.S. Patent No. 6,472,372 discloses 6-O-carbamoyl ketolide antibacterials and methods of treating bacterial infections.
U.S. Patent Application Nos. 2002/0115621 and 2003/0013665 disclose macrolide compounds that are said to be useful as antibacterial and antiprotozoal agents in mammals, including man, as well in fish and birds.
Other ketolide compounds have also been reported. A. Denis and A. Bonnefoy,
Drugs of the Future, 26(10):975-84 (2001), Champney W. S., et al, Current Microbiology, 42 :203-10 (2001). However, there remains a need for novel ketolide derivatives, which can be used as antibacterial agents on a wide variety of Gram-positive, Gram-negative or anaerobic bacteria.
Summary of the Invention
The present invention provides ketolide 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, enantiomers, diastereomers, polymorphs of these compounds having same type of activity are also provided.
Pharmaceutical compositions containing the described compounds together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of bacterial infection.
Thus in one aspect, provided herein are compounds having the structure of Formula I,
Figure imgf000004_0001
Formula I
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers or polymorphs thereof, wherein
R1 can be hydrogen or a hydroxyl protecting group; - A -
R2 and R3 can independently be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 can be hydrogen, alkyl or aralkyl, with the proviso that R2 and R3 are not simultaneously methyl;
W can be alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein
q can be an integer of from 2 to 6;
G can be no atom, -CO, -CS or -SO2;
R9 and R10 can independently be hydrogen or alkyl; and
J can be no atom, -CR9R10 or N(R12)(CH2)m, wherein m can be an integer of from 0 to 6; R9 and R10 can be the same as defined earlier; and R12 can be hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 can be alkyl, aryl or heterocycle;
R can be aryl or heterocycle;
R4 can be alkyl, alkenyl or alkynyl;
R' can be alkyl or -(CH2)r-U, wherein r can be an integer of from 1 to 4 and U can be alkenyl or alkynyl; and
Y can be halogen, cyano or alkyl; Z can be oxygen, sulfur or NOR11, wherein R11 can be the same as defined earlier.
These compounds can include one or more of the following embodiments. For example, R can be heterocycle; R2 can be methyl; R3 can be alkyl (except methyl), alkenyl, cycloalkyl or COR11 ; W can be -G(CH2)q J- or CR9R10, wherein G, q, J, R9, R10 and R11 can be the same as defined above. In another embodiment, R1 can be hydrogen or a hydroxy "" 3
protecting group (wherein the hydroxy protecting can be benzoyl, tetrahydropyranyl or a trialkylsilylether); R2 can be CH3; R3 can be C2H5, -CH2-CH=CH2 or -CH2CH2F; W can be -(CH2)4-J-, wherein J can be CH2 or (CH2)0-1-N(CO)-Ra; and R can be:
Figure imgf000006_0001
wherein X1-X3 can independently be CH or N; X4-X8 can independently be CH, CR4 or N; Xg can be O, S, N, NH or CH; X10 can be NH or S; Ra can be thienyl, furyl, pyrazolyl, oxazolyl, tetrazolyl, imidazolyl, pyridinyl, fluoropyridinyl, chloropyridinyl, aminopyridinyl, pyrazinyl, pyrimidinyl, aminopyrimidinyl, quinolinyl, pyrrolo-pyridyl, pyrrolo-thiazolyl or optionally substituted phenyl; R'a can be hydrogen or furyl; Rt, can be hydrogen or amino; R0 can be hydrogen, thienyl, furyl, pyrazolyl, pyrazinyl, pyridinyl, aminopyridinyl, pyrimidinyl, pyrrolyl, imidazolyl or optionally substituted phenyl; and Rd can be thienyl, pyrazolyl, imidazolyl, triazolyl, pyrrolyl or tetrahydrofuryl.
hi another aspect, provided herein are compounds selected from:
2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^S-^midazol-l-y^-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-b]-pyridin-l- yl)-butyl)-immo)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-b]-pyridin-l- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)- imino)] erythromycin A, 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-(imidazol-l-yl)-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-(imidazol-l-yl)-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-propyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-(imidazol-l-yl)-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-propyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosam.inyl-l l,12-dideoxy-3-O- decladmosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo-[2,3-b]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladmosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyrrolo-[2,3-b]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(benzoimidazol- l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-n-propyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-(pyrrolo-[2,3-b]pyridin- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11,12-dideoxy-3 -O- decladmosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-b]-pyridin-l- yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(purin-9-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3l-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]-pyridin-3- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-3-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2α-Fluoro-5 -O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(((N'-methyl-N'-quinolin-4- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((N'-methyl-N'-pyridine-3- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(((N'-methyl-N-pyridine-4-ylmethyl)- 2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,H-[oxycarbonyl-(((N'-methyl-N'-pyridine-2- ylmethyl)-2-aminoethyl)-imino)]erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^OST'-methyl-N'-pyridine^- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-θ-O-methyl-S-oxo-πjl-foxycarbonyl-C^'-methyl-N'-pyridine-S- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((N'-methyl-N'-pyridine-4- ylmethyl)-2-aminoethyl)-imino)]erythromycinA,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(((N'-methyl-N'-quinoline-4- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3t-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(((N'-pyridine-3-ylmethyl)-2- aminoethyl)-imino)] erythromycin A, a-α-Fluoro-S-O- CS'-N-desniethyl-S'-N-allyO-desosaminyl-ll^Z-dideoxy-S-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((N'-acetyl-N'-pyridine-3-ylmethyl)- 2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-0- (3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((N'-pyridine-3-ylmetliyl)-2- aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo- 12,11 -[oxycarbonyl-(((N'-acetyl-N'-pyridine-3-ylmethyl)- 2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-(((N',N'-di-pyridine-3 -yl-methyl)-2- ammoethyl)-imino)]erythromycm A,
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-(((N',N'-di-pyridine-3 -yl-methyl)-2- aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(quinolin-8-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo-^jll-foxycarbonyl-^-φyridin-S-y^-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)- desosaminyl-1 l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-4-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(pyridm-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-4-yl)-butyl)- imino)] erythromycin A, 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12, 11 -[oxycarbonyl-((4-(pyridin-3-yl)-pentyl)- imino)] erythromycin A,
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladmosyl-6-O-m6thyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-3-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(indol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladmosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-phenylimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-c]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-Q-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-c]pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaniinyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11- [oxycarbonyl-((4-(4-phenylimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-toxycarbonyl-^-φenzotriazol-l-y^-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyO-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH)-imdazo[4,5-b]pyridin-l-yl)- butyl)-imino)] erythromycin A, 2-α-Fluoro-5-0-(3l-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-0-methyl-3-oxo- 12,11- [oxycarbonyl-((4-(indol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(benzotriazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-0-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-phenylimidazol-l-yl)-butyl)- imino)]erytliromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(indol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyty-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(5-fluoroindol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3I-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)- imino)] erythromycin A, 2-α-Fluoro-5-0-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-metliylbenzoimidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-etriylbenzoimidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-(2-ethylbenzoimidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(pyridin-3-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A,
l-α-Fluoro-S-O-CS'-N-desmethyl-S'-N-allyO-desosaminyl-l ^^-dideoxy-S-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-methylbenzoimidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(pyrrolo [2,3-b]pyridin- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladmosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-b]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3l-N-desmethyl-3l-N-2-fluoroethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-(pyridin-3-ylmethyl)- benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-(pyridin-3-yl-methyl)- benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A, 2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(2-phenylimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmetliyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-fluoroindol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(5,6-dimethyl-benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(5,6-dimethylbenzoimidazol- 1 - yl)-butyl)-imino)]erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-c]pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-methyl-3H-imidazo[4,5- b]pyridin-3-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1 ,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-methyl-3H-imidazo[4,5- b]pyridin-3 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-c]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(6-amino-9H-purin-9-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-phenylimidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12, 11 -[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3- yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)- imino)] erythromycin A, 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(pyrrolo [2,3 -b]pyridin- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 - [oxycarbonyl-((4-(pyrrolo [2,3-b]pyridin- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)- imino)]erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-phenyl-imidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-trifluoromethyl- benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosatninyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4,5-diphenyl-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4,5-diphenyl-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l512-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-phenyl-imidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-ll,12-dideoxy-3- O-decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-phenyl-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl methyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzotriazol- 1 -yl)-butyl)- imino)] erythromycin A, 2-α-Fluoro-5-O-(3'-N-desmetliyl-3'-N-cyclopropyl methyl)-desosaminyl-ll,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-3-yl)-imidazol-l- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3I-N-acetyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)-desosarninyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-phenyl-imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-b]pyridin-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3l-N-desmethyl-3'-N-acetyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(3 ,5-diphenyl)-pyrazol- 1 -yl)- butyl)-imino)]erytlτromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridn-3 -yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(lH-imidazo[4,5-b]pyridin- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3,5-diphenyl)-pyrazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-b] pyridin-1- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyridin-3 -yl)-imidazo- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(2,4-difluoro-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-2-ethyl)-desosaminyl-ll,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(2,4-difluorophenyl)-imidazol- l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2,4-difluoro-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(furan-3-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-3-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A hydrochloride salt,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-phenyl-2H-pyrazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(pyridm-3-yl)-lH-imidazol-l- yl)-pentyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyridin-4-yl)- 1 H-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyridin-4-yl)- lH-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosammyl-l lJ12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-phenyl-2H-pyrazol- 1 -yl)- butyl)-imino) erythromycin A3
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-indazol-2-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-indazol-2-yl)-butyl)-imino)] erytliromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridin-3-yl)-2H-pyrazol- 1 - yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(l H-indazol- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyrazin-2-yl)- lH-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(thiophen-3 -yl)- 1 H-imidazol- l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(thiophen-3 -yl)- 1 H-imidazol- l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(quinolin-3 -yl)- 1 H-imidazol- l-yl)-butyl)-imino)] erythromycin A,
2-α-FluoiO-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(l H-indazol- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyrimin-5-yl)- lH-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5 -O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosammyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(pyrimin-5-yl)- lH-imidazol-1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-l 2, 11 -[oxycarbonyl-((4-(4-(furan-2-yl)- lH-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(thiophen-2-yl)-lH-imidazol- l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(4-chloro-phenyl)~ 1 H- imidazol-l-yl)-butyl)-imino)] erythromycin A5 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-chloro-phenyl)-lH- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridin-2-yl)- 1 H-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyridin-2-yl)- 1 H-imidazol- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-allyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(pyridin-3-yl)-lH-pyrazol-l- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(4-chloro-phenyl)- 1 H- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridin-2-yl)- 1 H-imidazol- 1 - yl)-butyl)-imino)] erytliromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]pyridine-2- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(tetrazol- 1 -yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-benzoimidazol-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(6-fluoro-pyridin-3-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-c]pyridine-2- yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-([ 1 ,2,4] trizol- 1 -yl)-phenyl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(imidazol- 1 -yl)-phenyl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(6-chloro-pyridin-3-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(3-(l-(4-aminobutyl)-lH-imidazol-4- yl)-phenyl)imino] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(pyridin-3-yl)-thiazol-2-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(3-(2-(4-aminobutyl)-thiazol-4-yl)- phenyl)imino] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyrazol- 1 -yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-^l^^-bipyrazolyl-r-y^-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(imidazol- 1 -yl)-pyrazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(pyrazol- 1 -yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-([3,3']bithiophenyl-5-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-([2,3']bithiophenyl-5'-yl)-butyl)- imino)] erythromycin A, 2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-etliyl)-desosaininyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-2-yl)-thiophen-2-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(oxazol-5-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3-(pyrrol-l-yl)-[l,2,4]triazol-l- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(thiophen-2-yl)-tetrazol-2-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(thiophen-3 -yl)-pyrazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(furan-3 -yl)-pyrazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(JEuran-2-yl)-pyrazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-phenyl-tetrazol-2-yl)- butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosammyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(4-methoxy-phenyl)-tetrazol- 2-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(furan-3-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(6-pyrazol- 1 -yl-pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridin-3 -yl)-pyrazol- 1 -yl)- butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(5-tliioplien-2-yl-pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-phenyl-thioph.en-2-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(N-(4-amino-butyl)-N-thiazol-2-yl- nicotinimido)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(N-(4-amino-butyl)-N-thiazol-2-yl- nicotinimido)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(6-pyrrol-l-yl-pyridin-3-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(6-pyrrol-l-yl-pyridin-3-yl)- butyl)-imino)] erythromycin A,
2-oc-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(2-pyrrol- 1 -yl-thiazol-5-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(6-imidazol- 1 -yl-pyridin-3 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(tetrahydro-furan-2-yl)- pyridin-3-yl]-butyl)imino] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-tolyl-imidazol- 1 -yl)-butyl)-imino)] erythromycin A,
l-α-Fluoro-S-O-CS'-N-desmethyl-S'-N-ethy^-l ^^-dideoxy-S-O-decladinosyl-ό-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-aminophenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(4-methyl-3-aminophenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A, 2-α-Huoro-5-O-(3'-N-(tesmethyW'-N-e%l)4142-dideoxy-3-O-decladiiiosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3-(imidazol-lyl)-phenyl)imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-πιιoro-5-0-(3'-N-desmelhyl-3'-N-ethyl)4142^deoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3-(N,N-dicyclopropyl-amino)-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N,N-dimethyl-amino)phenyl)-imidazol-l- yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3-(tetrazol- 1 yl)-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2-(pyrrol-lyl)-thiozol-5-yl)-imidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(3 -trifluoromethyl-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3 '-N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(N-(thiazol-2-yl)-benzimido)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2-amino-pyrimidin-5-yl)-imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-(pyrrol- 1 yl)-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3-(pyrrol-lyl)-phenyl)-imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3 -(N-acetyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(3-(N-isopropyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3-nitrophenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N-benzoyl-amino)-phenyl)-imidazol-l-yl)- butyl)-imino)J erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3,4-dimethyl-phenyl)-imidazol-l-yl)-butyl)- imino)] erythromycin A,
5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l 1 , ^-dideoxy-S-O-decladinosyl-ό-O-methyl-S-oxo- 12,1 l-[oxycarbonyl-((4-(4-Pyridin-3-yl-thiazol-2-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l 1 , 12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-fluorophenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(4-methoxy-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(N-(benzthiazol-2-yl)-benzimido)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(N-(thiazol-2-yl)-nicotinaimdo)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-(4-(3-(N-methyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2-aminopyridin-4-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A3
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(2-aminopyridin-5-yl)- 2H- tetrazol-5-yl)-butyl)-imino)] erythromycin A,
2-α-Fhioro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(3 ,4-difluorophenyl)-imidazol- l-yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(2-chloropyridin-4-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)desosaminyl-l 1 , 12-dideoxy-3-O- decladmosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(6-aminopyridin-3-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A, or
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(2-Chloro-pyridin-4-yl)- tetrazol-2-yl])-butyl)-imino)] erythromycin A,
or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers or polymorphs thereof.
In yet another aspect, provided herein are pharmaceutical compositions comprising therapeutically effective amounts of one or more compounds of compounds described herein together with one or more pharmaceutically acceptable carriers, excipients, or diluents.
In another aspect , provided herein are methods for treating or preventing conditions caused by or contributed to by bacterial infections comprising administering to a mammal in need thereof therapeutically effective amounts of one or more compounds of compounds described herein.
The methods may include one or more of the following embodiments. For example, the condition can be selected from community acquired pneumonia, upper or lower respiratory tract infections, skin or soft tissue infections, hospital acquired lung infections, hospital acquired bone or joint infections, mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease. In another embodiment, the bacterial infection can be caused by Gram-positive, Gram-negative or anaerobic bacteria.
In yet another embodiment, the Gram-positive, Gram-negative or anaerobic bacteria can be selected from Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae. In a preferred embodiment, the bacterium is cocci. In another preferred embodiment, the cocci is drug resistant. In another aspect, provided herein are processes for preparing compounds of Formula XIII,
Figure imgf000025_0001
Formiia XIII
(Formila I wherein, Ri = H, R= R? = CH3, Z = O1 R^ = C2H51 Y=F)
or their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers or polymorphs, wherein R3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11 (wherein R11 can be hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl); W can be alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO2; R9 and R10 can independently be hydrogen or alkyl; and J can be no atom, -CR9R10 or N(R12)(CH2)m {wherein m can be an integer of from 0 to 6; R9 and R10 can be the same as defined earlier; and R12 can be hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 can be alkyl, aryl or heterocycle}); and R can be aryl or heterocycle;
which processes comprise the steps of:
(a) hydrolyzing clarithromycin of Formula II,
Figure imgf000025_0002
Formula II to foπn a compound of Formula III,
Figure imgf000026_0001
Formula III
(b) protecting the compound of Formula III by reacting with one or more reagents of Formula R! 2O or R1X (wherein X can be halogen) to form a compound of Formula IV,
Figure imgf000026_0002
Formula IV
(c) desmethylating the compound of Formula IV at the 3'-N-dimethyl group to form a compound of Formula V,
Figure imgf000026_0003
Foπrula V
(d) alkylating the compound of Formula V with one or more reagents of Formula R3CHO, R2 3CO or R3X (wherein X can be halogen) to form a compound of Formula VI (wherein R3 can be the same as defined earlier),
Figure imgf000027_0001
Formula VI
(e) converting the compound of Formula VI with one or more suitable reagents to form a compound of Formula VII,
Figure imgf000027_0002
Formula VII
CD reacting the compound of Formula VII with one or more organic bases to form a compound of Formula VIII,
Figure imgf000027_0003
Formula Vm
(g) oxidizing the compound of Formula VIII to form a compound of Formula IX,
Figure imgf000028_0001
Foimula K
(h) reacting the compound of Formula IX with N,N'-carbonyldimidazole to form a compound of Formula X,
Figure imgf000028_0002
Formula X
(i) reacting the compound of Formula X with a compound of Formula R-W-
NH2 to form a compound of Formula XI (wherein W and R can be the same as defined earlier),
Figure imgf000028_0003
Formula XI
(j) fluorinating the compound of Formula XI to form a compound of Formula XII, and
Figure imgf000029_0001
Formula XII
(k) deprotecting the compound of Formula XII to form a compound of Formula XIII.
In another aspect, provided herein are processes for preparing compounds of Formula XIII,
Figure imgf000029_0002
Formula XDI
(Formula I wherein, R1 = H, R2 = CH3, Z = O^ = C2H5, Y= F)
or their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugSjStereoisomers or polymorphs, wherein R3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11 (wherein R11 can be hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl); W can be alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO2; R9 and R10 can independently be hydrogen or alkyl; and J can be no atom, -CR9R10 or N(R12)(CH2)m {wherein m can be an integer of from O to 6; R9 and R10 can be the same as defined earlier; and R12 can be hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 can be alkyl, aryl or heterocycle}); and R can be aryl or heterocycle; which processes comprise the steps of:
(a) reacting a compound of Formula IV with a suitable reagent,
Figure imgf000030_0001
Formula IV
to form a compound of Formula XIV,
Figure imgf000030_0002
Formula XW
(b) reacting the compound of Formula XIV with one or more organic bases to form a compound of Formula XV,
Figure imgf000030_0003
Formula XV
(c) oxidizing the compound of Formula XV to form a compound of Formula XVI,
Figure imgf000031_0001
Formula XYI
(d) desmethylating the compound of Formula XVI at the 3'-N-dimethyl group to form a compound of Formula XVII,
Figure imgf000031_0002
Formula XVH
(e) alkylating the compound of Formula XVII with one or more reagents of Formula R3CHO, R3 2 CO or R3X (wherein X can be halogen) to form a compound of Formula IX,
Figure imgf000031_0003
Formula DC
(f) fluorinating the compound of Formula IX to form a compound of Formula XVIII,
Figure imgf000032_0001
(g) reacting the compound of Formula XVIII with N,N'-carbonyldiimidazol to form a compound of Formula XIX,
Figure imgf000032_0002
(li) reacting the compound of Formula XIX with a compound of Formula R-W- NH2 to form a compound of Formula XII, and
Figure imgf000032_0003
Formula Xn
(i) deprotecting the compound of Formula XII to form a compound of Formula XIII. In another aspect, provided herein are processes for preparing compounds of Formula XIII,
Figure imgf000033_0001
Formula Xm (Formula I, wherein, R'=R2=CH3; R4 =q,H5; R1=H,Z=O,Y=F)
or their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs or polymorphs, wherein R3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 can be hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl; W can be alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO2; R9 and R10 can independently be hydrogen or alkyl; and J can be no atom, -CR9R10 or N(R12)(CH2)m {wherein m can be an integer of from 0 to 6; R9 and R10 can be the same as defined earlier; and R12 can be hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 can be alkyl, aryl or heterocycle}); and R can be aryl or heterocycle;
which processes comprises the steps of:
(a) fluorinating the compound of Formula XVI,
Figure imgf000034_0001
FoimulaXVI
to form a compound of Formula XX,
Figure imgf000034_0002
(b) reacting the compound of Formula XX with N5N'- carbanoyldiimidazole to form a compound of Formula XXI,
Figure imgf000034_0003
FomiulaXXI
(c) reacting the compound of Formula XXI with a compound of Formula R-W- NH2 to form a compound of Formula XXII,
Figure imgf000035_0001
(Φ deprotecting the compound of Formula XXII to form a compound of Formula XXIII,
Figure imgf000035_0002
(e) desmethylating the compound of Formula XXIII at the 3'-N-dimethyl group to form a compound of Formula XXIV, and
Figure imgf000035_0003
Formula XXIV
(f) alkylating the compound of Formula XXIV with one or more reagents of F Foorrmmuullaa RR33CCHHOO,, RR33 22CCOO oorr : R3X (wherein X can be halogen) to form a compound of Formula XIII. In another aspect, provided herein are processes for preparing compounds of Formula XIII,
Figure imgf000036_0001
Formula XIII
(Formula I wherein, R1 = H, R? = R' = CH3, Z = O, R4 = q,H5; Y= F)
or their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs or polymorphs, wherein R3 can be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 can be hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl; W can be alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2 (wherein q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO2; R9 and R10 can independently be hydrogen or alkyl; and J can be no atom, -CR9R10 or N(R12)(CH2)m {wherein m can be an integer of from 0 to 6; R9 and
R , 1Q can be the same as defined earlier; and R 12 c, an be hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 can be alkyl, aryl or heterocycle}); and R can be aryl or heterocycle;
which processes comprise the steps of:
(a) deprotecting the compound of Formula XX (wherein R1 can be COPh),
Figure imgf000037_0001
Formula XX to form a compound of Formula XXV,
Figure imgf000037_0002
Formula XXV
(b) desmethylating the compound of Formula XXV at 3-N'-dimethyl group to form a compound of Formula XXVI,
Figure imgf000037_0003
Formula XXVI
(c) alkylating the compound of Formula XXVI with one or more reagents of Formula R3CHO, R3 2CHO or R3X (wherein X can be halogen) to form a compound of Formula XXVII,
Figure imgf000038_0001
Formula XXVn
(d) protecting the compound of Formula XXVII with one or more reagents of Formula R 20 or R1X (wherein X can be halogen) to form a compound of Formula XVIII (wherein R1 can be COCH3),
Figure imgf000038_0002
Formula XVπi
(e) reacting the compound of Formula XVII with N,N'-carbonyldiimidazole to form a compound of Formula XIX,
Figure imgf000038_0003
(f) reacting the compound of Formula XIX with a compound of Formula R-W- NH2 to form a compound of Formula XII, and
Figure imgf000039_0001
(g) deprotecting the compound of Formula XII to form a compound of Formula XIII.
Detailed Description of the Invention
In accordance with one aspect, provided herein are compounds having the structure of Formula I,
Figure imgf000039_0002
their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs or polymorphs wherein,
R1 can be hydrogen or hydroxyl protecting group;
R2 and R3 can independently be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11 (wherein R11 can be hydrogen, alkyl or aralkyl), with the proviso that R2 and R3 are not simultaneously methyl;
W can be alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein
q can be an integer of from 2 to 6; G can be no atom, -CO, -CS or -SO2; R9 and R10 can independently be hydrogen or alkyl; J can be no atom, -CR9R10 orN(R12)(CH2)m, wherein
m can be an integer of from 0 to 6; R9 and R10 are the same as defined earlier; R12 can be hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m- R t wherein
R8 can be alkyl, aryl or heterocycle;
R can be aryl or heterocycle;
R4 can be alkyl, alkenyl or alkynyl;
R' can be alkyl or -(CH2)r-U, wherein r can be an integer from 1 to 4 and U can be alkenyl or alkynyl;
Y can be halogen, cyano or alkyl; and
Z can be oxygen, sulfur or NOR11, wherein R11 can be hydrogen, alkyl or aralkyl.
hi one embodiment, R can be heterocycle; R2 and R3 can be respectively methyl and alkyl (except methyl), alkenyl, cycloalkyl or COR11; W can be -G(CH2)qJ- or CR9R10, wherein G, q, J, R9, R10 and R11 are the same as defined above.
In another embodiment, R1 can be hydrogen or a hydroxy protecting group, wherein the hydroxy protecting can be benzoyl, tetrahydropyranyl or a trialkylsilylether; R2 can be CH3; R3 can be C2H5, -CH2-CH=CH2 or -CH2CH2F; W can be -(CH2)4-J-, wherein J can be CH2 or (CH2)0-1-N(CO)-Ra; and R can be,
Figure imgf000041_0001
wherein
X1-X3 can independently be CH or N; X4-X8 can independently be CH, CR4 or N; X9 can be O, S, N, NH or CH; X10 can be NH or S; Ra can be thienyl, furyl, pyrazolyl, oxazolyl, tetrazolyl, imidazolyl, pyridinyl, fluoropyridinyl, chloropyridinyl, aminopyridinyl, pyrazinyl, pyrimidinyl, aminopyrimidinyl, quinolinyl, pyrrolo-pyridyl, pyrrolo-thiazolyl or optionally substituted phenyl; R'a can be hydrogen or furyl; Rb can be hydrogen or amino; R0 can be hydrogen, thienyl, furyl, pyrazolyl, pyrazinyl, pyridinyl, aminopyridinyl, pyrimidinyl, pyrrolyl, imidazolyl or optionally substituted phenyl; and Rd can be thienyl, pyrazolyl, imidazolyl, triazolyl, pyrrolyl or tetrahydrofuryl.
In accordance with a second aspect, provided herein are methods for treating or preventing a mammal suffering from conditions caused by or contributed to by Gram- positive, Gram-negative or anaerobic bacteria comprising administering to a mammal in need thereof therapeutically effective amounts of one or more compounds or one or more pharmaceutical compositions described herein.
Bacterial infection may be caused by one or more bacteria, for example, Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae.
The conditions treated or prevented may be, for example, community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections or bone and joint infections, or other bacterial infections, for example, mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease.
In accordance with a third aspect, provided herein are processes for preparing the described compounds.
The term "alkyl," unless otherwise specified, refers to a monoradical branched or unbranched saturated hydrocarbon chain having from 1 to 20 carbon atoms. Alkyl groups can be optionally interrupted by atom(s) or group(s) independently selected from oxygen, sulfur, a phenylene, sulfinyl, sulfonyl group or — NRa-, wherein Ra can be hydrogen, alkyl, alkenyl, alkynyl cycloalkyl or aryl. This term can be exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, n-decyl, tetradecyl, and the like. Alkyl groups may be substituted further (referred herein as "substituted alkyl") with one or more substituents selected from alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, oxo, thiocarbonyl, carboxy, carboxyalkyl, aryl (for R6-R9, alkyl is not substituted with aryl), heterocyclyl, heteroaryl, arylthio, thiol, alkylthio, aryloxy, nitro, aminosulfonyl, aminocarbonylamino, -NHC(=O)Rk, -NRpRq, -C(=O)NRpRq, -NHC(=O)NRpRq,, -C(=O)heteroaryl, C(=O)heterocyclyl, -O-C(=O)NRpRq {wherein Rp and Rq are independently selected from alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, aralkyl, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl}, nitro, hydroxyamino, alkoxyamino or S(O)mR66 (wherein m is an integer from 0-2 and R66 is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl, aryl, heterocyclyl, heteroaryl, heteroarylalkyl or heterocyclylalkyl). Unless otherwise constrained by the definition, alkyl substituents may be further substituted by 1-3 substituents selected from alkyl, alkenyl, alkynyl, carboxy, -NRpRq, -C(=O)NRpRq, -OC(=O)NRpRq, -NHC(=O)NRφRq (wherein Rp and Rq are the same as defined earlier), hydroxy, alkoxy, halogen, CF3, cyano, and S(O)1nR66 (wherein m is an integer from 0-2 and R66 are the same as defined earlier); or an alkyl group also may be interrupted by 1-5 atoms of groups independently selected from oxygen, sulfur or -NRa- {wherein Ra is selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, acyl, aralkyl,-C(=O)ORp (wherein Rp is the same as defined earlier), S(O)mR66 (wherein m is an integer from 0-2 and R66 is as defined earlier), or -C(=O)NRpRq (wherein Rp and Rq are as defined earlier)}. Unless otherwise constrained by the definition, all substituents may be substituted further by 1-3 substituents selected from alkyl, carboxy, carboxyalkyl, -NRpRq, -C(=O)NRpRq, -O-C(=O)NRpRq (wherein Rp and Rq are the same as defined earlier) hydroxy, alkoxy, halogen, CF3, cyano, and S(O)mR66 (wherein m is an integer from 0-2 and R66 is same as defined earlier); or an alkyl group as defined above that has both substituents as defined above and is also interrupted by 1-5 atoms or groups as defined above.
The term "alkenyl," unless otherwise specified, refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group having from 2 to 20 carbon atoms with cis, trans, or geminal geometry. It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, phenylene, sulfmyl, sulfonyl and -NRa-, wherein Ra can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl. hi the event that alkenyl is attached to a heteroatom, the double bond cannot be alpha to the heteroatom. Alkenyl groups may be substituted further (referred to herein as "substituted alkenyl") with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, -NHC(=O)RP, -NRpRq, -C(=O)NRpRq, -NHC(=O)NRpRq, -O-C(=O)NRpRq (wherein Rp and Rq are the same as defined earlier), alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, keto, carboxyalkyl, thiocarbonyl, carboxy, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, heterocyclyl, heteroaryl, heterocyclyl alkyl, heteroaryl alkyl, aminosulfonyl, aminocarbonylamino, alkoxyamino, hydroxyamino, alkoxyamino, nitro, or SO2R66 (wherein R66 are is same as defined earlier). Unless otherwise constrained by the definition, alkenyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, carboxy, hydroxy, alkoxy, halogen, -CF3, cyano, -NRpRq, -C(=O)NRpRq, -O-C(=O)NRpRq (wherein Rp and Rq are the same as defined earlier) and -SO2R66 (where R66 is same as defined earlier). Groups such as ethenyl or vinyl (CH=CH2), 1 -propylene or allyl (-CH2CH=CH2), iso-propylene (-C(CH3)=CH2), bicyclo[2.2.1]heptene, and the like, exemplify this term.
The term "alkynyl," unless otherwise specified, refers to a monoradical of an unsaturated hydrocarbon, having from 2 to 20 carbon atoms. It can be optionally interrupted by atom(s) or group(s) independently chosen from oxygen, sulfur, phenylene, sulfmyl, sulfonyl and -NR8-, where Ra can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl. hi the event that alkynyl is attached to a heteroatom, the triple bond cannot be alpha to the heteroatom. Alkynyl groups may be substituted further (referred to herein as "substituted alkynyl") with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, oxo, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkyltliio, aryl, aralkyl, aryloxy, aminosulfonyl, aminocarbonylamino, hydroxyamino, alkoxyamino, nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl,
-NHC(=O)RP, -NRpRq, -NHCO=O)NRpRq, -C(=O)NRpRq, -0-C(=O)NRpRq (wherein Rp and Rq are the same as defined earlier), S(O)mR66 (wherein m is an integer from 0-2 and R66 is as defined earlier). Unless otherwise constrained by the definition, alkynyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, carboxy, carboxyalkyl, hydroxy, alkoxy, halogen, CF3, -NRpRq, -C(=O)NRpRq,
-NHC(=O)NRpRq,
Figure imgf000044_0001
(wherein Rp and Rq are the same as defined earlier), cyano, or S(O)1nR66 (wherein m is an integer from 0-2 and R66 is same as defined earlier). Groups such as ethynyl, (-C ≡€H), propargyl (or propynyl, -CH2C ≡€H), and the like exemplify this term. The term "cycloalkyl," unless otherwise specified, refers to cyclic alkyl groups of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may optionally contain one or more olefmic bonds, unless otherwise constrained by the definition. Such cycloalkyl groups can include, for example, single ring structures, including cyclopropyl, cyclobutyl, cyclooctyl, cyclopentenyl, and the like, or multiple ring structures, including adamantanyl, and bicyclo [2.2.1] heptane, or cyclic alkyl groups to which is fused an aryl group, for example, indane, and the like. Spiro and fused ring structures can also be included. Cycloalkyl groups may be substituted further with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, carboxy, carboxyalkyl, arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl, aminocarbonylamino, -NRpRq, -NHC(=O)NRpRq, -NHC(=O)RP,
Figure imgf000044_0002
-O-C(=O)NRpRq (wherein Rp and Rq are the same as defined earlier), nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, or S(O)mR66 (wherein m is an integer from 0-2 and R66 is same as defined earlier). Unless otherwise constrained by the definition, cycloalkyl substituents optionally may be substituted further by 1-3 substituents selected from alkyl, carboxy, hydroxy, alkoxy, halogen, CF3, -NRpRq, -C(=O)NRpRq, -NHC(=O)NRpRq, -O-C(=O)NRpRq (wherein Rp and Rq are the same as defined earlier), cyano or S(O)mR66 (wherein m is an integer from 0-2 and R66 is same as defined earlier). As used herein the term "halogen or halo" refers to fluorine, chlorine, bromine or iodine.
As used herein the term "hydroxyl protected" includes, but is not limited to, acyl, aroyl, alkyl, aryl, butyldiphenylsilyl, methoxymethyl and methylthiomethyl, and the like.
As used herein the term "thio" refers to the group -SH.
The term "alkoxy" denotes the group O-alkyl or O-cycloalkyl, wherein alkyl and cycloalkyl are the same as defined above. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, cyclopentoxy, and the like.
As used herein the term "thioalkyl" refers to -SR5 wherein R5 is alkyl or cycloalkyl.
As used herein the term "haloalkyl" refers to alkyl of which one or more hydrogen(s) is/are replaced by halogen.
The term "aryl" herein refers to aromatic system having 6 to 14 carbon atoms, wherein the ring system can be mono-, bi- or tricyclic and are carbocyclic aromatic groups. For example, aryl groups include, but are not limited to, phenyl, biphenyl, anthryl or naphthyl ring and the like, optionally substituted with 1 to 3 substituents selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, acyl, aryloxy, CF3, cyano, nitro, COORS (wherein Rs is hydrogen, alkyl, alkenyl, cycloalkyl, aralkyl, heterocyclylalkyl, heteroarylalkyl), NHC(=O)RP, -NRpRq,
Figure imgf000045_0001
-NHC(=O)NRpRq,
Figure imgf000045_0002
(wherein Rp and Rq are the same as defined earlier), S(O)01R66 (wherein m is an integer from 0-2 and R66 is same as defined earlier), carboxy, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl or amino carbonyl amino. The aryl group optionally may be fused with a cycloalkyl group, wherein the cycloalkyl group may optionally contain heteroatoms selected from O, N or S. Groups such as phenyl, naphthyl, anthryl, biphenyl, and the like exemplify this term.
The term "aralkyl," unless otherwise specified, refers to alkyl-aryl linked through an alkyl portion (wherein alkyl is as defined above) and the alkyl portion contains 1-6 carbon atoms and aryl is as defined above. Examples of aralkyl include, but are not limited to, benzyl, napthylmethyl, phenethyl and phenylpropyl, and the like. The terms "heterocycle" or "heterocyclyl," unless otherwise specified, refers to a non-aromatic monocyclic or bicyclic cycloalkyl group having 5 to 10 atoms wherein 1 to 4 carbon atoms in a ring are replaced by heteroatoms selected from O, S or N, and optionally are benzofused or fused heteroaryl having 5-6 ring members and/or optionally are substituted, wherein the substituents are selected from halogen (e.g., F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, acyl, amino, optionally substituted aryl, alkoxy, alkaryl, cyano, nitro, oxo, carboxy, guanidine, haloalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, heteroaryl, -CORP, -O-C(=O)RP, -O-C(=O)ORP) -C(=O)NRpRq, S(O)1nR66, -O-C(=O)NRpRq, nitro, -NHC(=O)NRpRq, -NRpRq (wherein m, R66, Rp and Rq are as defined earlier), -NHCORP, -NHSO2Rp3 and -SO2NHRP, mercapto or thioalkyl.
Carbonyl or sulfonyl group can replace carbon atom(s) of heterocyclyl. Unless otherwise constrained by the definition, the substituents are attached to the ring atom, i.e., carbon or heteroatom in the ring. Also, unless otherwise constrained by the definition, the heterocyclyl ring optionally may contain one or more olefinic bond(s). Examples of heterocycles include, but not limited to, azabicyclohexyl, azetidinyl, benzoimidazolyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, benzoxazolyl, benzothiazolyl, benzothiazinyl, benzotriazolyl, benzoxazinyl, carbaxolyl, dihydrobenzofuryl, dihydroimidazolyl, dihydropyranyl, dihydrofuranyl, dihydroindolyl, dihydroisoxazolyl, dihydropyridinyl, dioxanyl, dioxolanyl, furyl, homopiperidinyl, imidazolyl, imidazolinyl, imidazolidinyl, imidazopyridinyl, indolinyl, indolyl, isoindole 1,3-dione, isoquinolinyl, isothiazolidinyl, isothiazolyl, isoxazolidinyl, isoxazolyl, morpholinyl, napthyridinyl, oxazolidinyl, oxazolyl, phenoxazinyl, phenothiazinyl, piperazinyl, piperidinyl, purinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, pyrrolopyridinyl, quinolinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrazolyl, thiazolidinyl and thiazolyl, and thienyl and the like.
As used herein the term "(heterocyclyl)alkyl" refers to heterocycle which is bonded to an alkylene chain, wherein heterocyclyl and alkyl are the same as defined above. Examples of heterocycle alkyl include, but are not limited to, isothiazolidinyl ethyl, isothiazolyl propyl, pyrazinyl methyl, pyrazolinyl propyl and pyridyl butyl, pyridyl methyl and the like. As used herein the term "polymorphs" refers to all crystalline forms and amorphous forms of the compounds described herein, hi addition, some of the compounds described herein may form solvates with water (i.e., hydrate, hemihydrate or sesquihydrate) or common organic solvents. Such solvates are also encompassed within the scope of this invention.
The phrase "pharmaceutically acceptable salts" denotes salts of the free base, which possess the desired pharmacological activity of the free base and which are neither biologically nor otherwise undesirable. Suitable pharmaceutically acceptable salts may be prepared from an inorganic or organic acid. Example of such inorganic acids include, but not limited to, hydrochloric, hydrobromic, hydroiodic, nitrous (nitrite salt), carbonic, sulfuric, phosphoric acid and like. Appropriate organic acids include, but not limited to, aliphatic, cycloaliphatic, aromatic, heterocyclic, carboxylic and sulfonic classes of organic acids, for example, formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, tumeric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic
(pamoic), methanesulfonic, ethanesulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, stearic, algenic, beta-hydroxybutyric, cyclohexylaminosulfonic, galactaric and galacturonic acid and the like.
The term pharmaceutically acceptable carriers" is intended to include non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
The compounds of present invention include stereoisomers. The term "stereoisomer" refers to compounds, which have identical chemical composition, but differ with regard to arrangement of the atoms and the groups in space. These include enantiomers, diastereomers, geometrical isomers, atropisomer and comformational isomers. Geometric isomers may occur when a compound contains a double bond or some other feature that gives the molecule a certain amount of structural rigidity. An enantiomer is a stereoisomer of a reference molecule that is the nonsuperimposable mirror image of the reference molecule. A diastereomer is a stereoisomer of a reference molecule that has a shape that is not the mirror image of the reference molecule. An atropisomer is a conformation 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 σ bonds, and are often rapidly interconverting at room temperature. Racemic mixtures are also encompassed within the scope of this invention.
Compounds described herein may be prepared by techniques well known to one of ordinary skill in the art. In addition, compounds described herein may also be prepared by the following reaction sequences as depicted in Schemes I, II, III or IV below.
Figure imgf000049_0001
Figure imgf000049_0002
Figure imgf000049_0003
Figure imgf000049_0004
(Foimila I whcrcm Rl - H R= RJ = CH3 Z -O W -C2H5 Y- F)
Compounds of Formula XIII can be prepared according to Scheme I. Thus, clarithromycin of Formula II can be hydro lyzed to form a compound of Formula III. The compound of Formula II can be protected by reacting with one or more reagents of Formula R^2O or R1X (wherein X is halogen) to form a compound of Formula IV (wherein R1=COPh). The compound of Formula IV can be desmethylated at the 3'-N-dimethyl group to form a compound of Formula V. The compound of Formula V can be alkylated by reacting with one or more reagents of Formula R3CHO, R3 2CO or R3X (wherein X is halogen) to form a compound of Formula VI (wherein R3 is the same as defined earlier). The compound of Formaul VI can be reacted with one or more reagents, for example, triphosgene, ethylene dicarbonate or a mixture thereof, to form a compound of Formula VII. The compound of Formula VII can be reacted with one or more organic bases (for example, tetramethyl guanidine, trimethylamine or mixtures thereof) to form a compound of Formula VIII. The compound of Formula VIII can be oxidized to form a compound of Formula IX. The compound of Formula IX can be reacted with N,N'-carbonyldiimidazole to form a compound of Formula X. The compound of Formula X can be reacted with a compound of Formula R-W-NH2 to form a compound of Formula XI (wherein W and R are the same as defined earlier). The compound of Formula XI can be fluorinated to form a compound of Formula XII. The compound of Formula XII can be deprotected to form a compound of Formula XIII.
Clarithromycin of Formula II can be hydrolyzed in the presence of an inorganic or organic acid, for example, hydrochloric acid, sulfuric acid or dichloroacetic acid.
The compound of Formula III can be hydroxyl protected by reacting with one or more reagents of Formula R^O or R1X in one or more solvents, for example, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixtures thereof. The protection reactions can also be carried out in the presence of one or more organic bases, for example, triethylamine, diisopropylethylamine, pyridine, tributylamine, 4-(N-dimethylamino)pyridine or mixtures thereof.
Compounds of Formula IV can be desmethylated in the presence of one or more desmethylating agents, for example, N-iodosuccinimide iodine in acetic acid, diisopropylazodicarboxylate or mixtures thereof. Such desmethylation reactions can also be carried out in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixtures thereof.
Desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof. Compounds of Formula V can be alkylated with one or more reagents of Formula R3CHO, R3 2CO or R3X in one or more solvents, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof. Alkylation reactions can also be carried out in the presence of one or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof. Alkylation reactions can also be carried out in the presence of one or more reducing agents (for example, sodium cyanoborohydride, sodium borohydride, sodium triacetoxyborohydri.de or mixtures there) and in the presence of one or more organic acids (for example, acetic acid or dichloroacetic acid in a solvent, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof).
Compounds of Formula VI can be reacted to form compounds of Formula VII in one or more solvents, for example, chloroform, dichloromethane, carbon tetrachloride, dichloroethane or mixtures thereof. These reactions can also be carried out in the presence of one or more organic bases, for example, triethylamine, diisopropyl ethylamine, pyridine, tributylamine, 4-(N-dimethylamino)pyridine or mixtures thereof.
Compounds of Formula VII can be reacted with one or more organic bases in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof.
Compounds of Formula VIII can be oxidized by reacting with one or more oxidizing agents, for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), Jones Oxidation reagent (chromic acid, aqueous sulfuric acid and acetone), pyridinium dichromate, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or mixtures thereof. N-Chlorosuccinamide can be used in combination with dimethyl sulfide and 1- ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride can be used in combination with dimethylsulfoxide. Compounds of Formula VIII can also be oxidized in one or more solvents, for example, chloroform, dichloromethane, carbon tetrachloride, dimethylsulfoxide, dichloroethane or mixtures thereof. Compounds of Formula IX can be reacted with N,N'-carbonyldiimidazole in one or more solvents, for example, dimethylforrnamide, acetonitrile, tetrahydrofuran or mixtures thereof. This reaction can also be carried out in the presence of one or more inorganic bases, for example, sodium hydrogen carbonate, sodium acetate, sodium thiosulfate, potassium carbonate, cesium carbonate or sodium hydride.
Compounds of Formula X can be reacted with compounds of Formula R-W-NH2 in one or more solvent systems, for example, acetonitrile/water, dimethylformamide/water, dimethylformamide or combinations thereof.
Compounds of Formula XI can be fluorinated in the presence of one or more fluorinating agents, for example, N-fluorobenzene sulfonimide, selectfluor or mixtures thereof. The fluorination reactions can also be carried out by procedures described in G.Sankar LaI and Syvret R.G., Chem. Rev., 96:1737-1755 (1996). The fluorination reactions can also be carried out in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof. Further, the fluorination reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, sodium hydride, sodium acetate, sodium thiosulfate, potassium fert-butoxide, sodium tert-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, lithium carbonate or mixtures thereof.
Compounds of Formula XII can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
Figure imgf000053_0001
Figure imgf000053_0002
Compounds of Formula XIII can also be prepared according to Scheme II. Thus, compounds of Formula IV can be reacted with one or more reagents, for example, triphosgene, ethylene dicarbonate or mixtures thereof, to form compounds of Formula XIV. Compounds of Formula XIV can be reacted with one or more organic bases, for example, tetramethyl guamdine, trimethyl amine or mixtures thereof, to form compounds of Formula XV. Compounds of Formula XV can be oxidized to form compounds of Formula XVI. Compounds of Formula XVI can be desmethylated at the 3'-N-dimethyl group to form compounds of Formula XVII. Compounds of Formula XVII can be alkylated with one or more reagents of Formula R3CHO, R3 2 CO or R3X (wherein X is a halogen) to form compounds of Formula IX (wherein R3 is the same as defined earlier). Compounds of Formula IX can be fluorinated to form compounds of Formula XVIII. Compounds of Formula XVIII can be reacted with N,N'-carbonyldiimidazole to form compounds of Formula XIX. Compounds of Formula XIX can be reacted with compounds of Formula R-W-NH2 to form compounds of Formula XII (wherein W and R are the same as defined earlier). Compounds of Formula XII can be deprotected to form compounds of Formula XIII.
Compounds of Formula IV can be reacted to form compounds of Formula XTV in one or more solvents, for example, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or mixtures thereof. These reactions can also be carried out in the presence of one or more organic bases, for example, triethylamine, pyridine, diisopropylethylamine, 4-(N-dimethylamino)pyridine or mixtures thereof. ,
Compounds of Formula XIV can be reacted with one or more organic bases in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof/
Compounds of Formula XV can be oxidized in the presence of one or more oxidizing agents, for example, Dess-Martin periodinane, N-chlorosuccinimide, pyridinium chlorochromate, Swern Oxidation reagent (oxalyl chloride and dimethylsulfoxide), Pfitzner-Moffatt Oxidation reagent (dicyclohexylcarbodiimide and dimethylsulfoxide), Jones Oxidation reagent (chromic acid, aqueous sulfuric acid and acetone), pyridinium dichromate, l-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride or mixtures thereof. Such oxidation reactions can also be carried out in one or more solvents, for example, chloroform, dichloromethane, carbon tetrachloride, dimethylsulfoxide, dichloroethane or mixtures thereof.
Compounds of Formula XVI can be desmethylated in the presence of one or more desmethylating agents, for example, N-iodo succinimide, iodine in acetic acid, diisopropyl azodicarboxylate or mixtures thereof. The desmethylation reactions can also be carried out in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbontetrachloride, ethyl acetate or mixtures thereof. Desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
Compounds of Formula XVII can be alkylated with one or more reagents of Formula R2CHO, R2 2 CO or R2 X in one or more solvents, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof. Alkylation reactions can also be carried out in the presence of one or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropylethylamine or mixtures thereof.
Compounds of Formula XVII can be fluorinated in the presence of one or more fluorinating agents, for example, N-fluorobenzene sulfonimide, selectfluor or mixtures thereof. The fluorination reactions can also be carried out by procedures described in G.Sankar LaI and Syvret R.G., Chern. Rev., 96:1737-1755 (1996). The fluorination reactions can also be carried out in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethylsulfoxide or mixtures thereof. The fluorination reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, cesium carbonate, sodium hydride, sodium acetate, sodium thiosulfate, potassium tø't-butoxide or mixtures thereof.
Compounds of Formula XVIII can be reacted with N,N'-carbonyldiimidazole in one or more solvents, for example, dimethylformamide, acetonitrile, tetrahydrofuran or mixtures thereof. These reactions can also be carried out in the presence of one or more inorganic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium acetate, sodium thiosulfate, sodium hydride or mixtures thereof.
Compounds of Formula XIX can be reacted with compounds of Formula
R-W-NH2 in one or more solvent systems, for example, dimethylformamide/water, acetonitrile/water, dimethylformamide or combinations thereof.
Compounds of Formula XII can be deprorected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
Figure imgf000056_0001
Compounds of Foπnula XIII can also be prepared according to Scheme III. Thus, Compounds of Formula XVI can be fluorinated to form compounds of Formula XX. Compounds of Formula XX can be reacted with N,N'-carbonyldiimidazole to form compounds of Formula XXI. Compounds of Formula XXI can be reacted with compounds of Formula R-W-NH2 to form compounds of Formula XXII (wherein R and W are the same as defined earlier). Compounds of Formula XXII can be deprotected to form compounds of Formula XXIII. Compounds of Formula XXIII can be desmethylated at the 3'-N-dimethyl group to form compounds of Formula XXIV. Compounds of Formula XXIV can be alkylated with one or more reagents of Formula R3CHO, R3 2CO or R3X (wherein X is halogen) to form compounds of Formula XIII (wherein R3 is the same as defined earlier).
Compounds of Formula XVI can be fiuorinated in the presence of one or more fluorinating agents, for example, N-fluorobenzene sulfonimide, selectfluor or mixtures thereof. The fluorination reactions can also be carried out by procedures described in G.Sankar LaI and Syvret R.G., Chem. Rev., 96:1737-1755 (1996). The fluorination reactions can also be carried out in one or more solvents, for example, dimethylformamide, tetrahydrofuran, dimethyl sulfoxide or mixtures thereof. The fluorination reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, sodium hydride, sodium acetate, sodium hydrogen carbonate, cesium carbonate, sodium thiosulfate, potassium tert-butoxide, sodium tert-butoxide, lithium diisopropylamide, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium isopropoxide, potassium isopropoxide, lithium carbonate or mixtures thereof.
Compounds of Formula XX can be reacted with N,N'-carbonyldiimidazole in one or more solvents, for example, dimethylformamide, tetrahydrofuran, acetonitrile or mixtures thereof. These reactions can also be carried out in the presence of one or more inorganic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium acetate, sodium thiosulfate, sodium hydride or mixtures thereof.
Compounds of Formula XXI can be reacted with compounds of Formula R-W-NH2 in one or more solvent systems, for example, acetonitrile/water, dimethylformamide/water or combinations thereof.
Compounds of Formula XXII can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
Compounds of Formula XXIII can be desmethylated in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbontetrachloride, ethyl acetate or mixtures thereof. These desmethylation reactions can also be carried out in the presence of one or more desmethylating agents, for example, N-iodosuccinimide, iodine in acetic acid, diisopropyl azodicarboxylate or mixtures thereof.
The desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
Compounds of Formula XXIV can be alkylated with one or more reagents of Formula R3CHO, R3 2 CO or R3X in one or more solvents, for example, dimethylformamide, acetonitrile, methanol, acetone, tetrahydrofuran or mixtures thereof. These alkylation reactions can be carried out in the presence of oen or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof.
Figure imgf000058_0001
R-W-NH2
Figure imgf000058_0002
Compounds of Foπnula XIII can also be prepared according to Scheme IV. Thus, compounds of Formula XX (wherein R1 is COPh) can be deprotected to form compounds of Formula XXV. Compounds of Formula XXV can be desmethylated at the 3'-N- dimethyl group to form compounds of Formula XXVI. Compounds of Formula XXVI can be alkylated with one or more reagents of Formula R3CHO, R3 2CHO or R3X (X is halogen) to form compounds of Formula XXVII (R3 is the same as defined earlier). Compounds of Formula XXVII can be protected with one or more reagents of Formula R! 2O or R1X (wherein X is halogen) to form compounds of Formula XVIII (wherein R1 is COCH3). Compounds of Formula XVIII can be reacted with N,N'-carbonyldiimidazole to form compounds of Formula XIX. Compounds of Formula XIX can be reacted with compounds of Formula R-W-NH2 to form compounds of Formula XII (R is the same as defined earlier). Compounds of Formula XII can be deprotected to form compounds of Formula XIII.
Compounds of Formula XX can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
Compounds of Formula XXV can be desmethylated in the presence of one or more desmethylating agents, for example, N-iodosuccinimide, iodine in acetic acid, diisopropyl azodicarboxylate or mixtures thereof. Desmethylation reactions can also be carried out in one or more solvents, for example, acetonitrile, tetrahydrofuran, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate or mixtures thereof.
The desmethylation reactions can be quenched in the presence of one or more quenching agents, for example, sodium bisulfite, sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate or mixtures thereof.
Compounds of Formula XXVI can be alkylated by reaction with one or more reagents of Formula R3CHO, R3 2CO on R3X in one or more solvents, for example, dimethylformamide, acetonitrile, tetrahydrofuran, acetone, methanol or mixtures thereof. Alkylation reactions can also be carried out in the presence of one or more inorganic or organic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydride, pyridine, triethylamine, sodium acetate, sodium thiosulfate, diisopropyl ethylamine or mixtures thereof. Compounds of Formula XXVII can be hydroxyl protected by reaction with one or more reagents of Formula R^O or R1X in one or more solvents, for example, dichloromethane, dichloroethane, carbontetrachloride, chloroform, acetone or mixtures thereof. Hydroxyl protection reactions can also be carried out in the presence of one or more inorganic bases, for example, potassium carbonate, cesium carbonate, sodium carbonate, sodium bicarbonate, potassium bicarbonate or mixtures thereof.
Compounds of Formula XVIII can be reacted with N, N'-carbonyldiimidazole in one or more solvents, for example, dimethylformamide, tetrahydrofuran, acetonitrile or mixtures thereof. Such reactions can also be carried out in the presence of one or more inorganic bases, for example, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium acetate, sodium thiosulfate, sodium hydride or mixtures thereof.
Compounds of Formula XIX can be reacted with compounds of Formula R-W-NH2 in one or more solvent systems, for example, acetonitrile/water, dimethylformamide/water, dimethyformamide or combinations thereof.
Compounds of Formula XII can be deprotected in one or more alcohols, for example, methanol, ethanol, propanol, isopropanol or mixtures thereof.
In the above sechemes, where specific reagents, for example, bases, acids oxidizing agents, solvents, etc., are described, it is to be understood that other reagents, e.g., bases, acids, oxidizing agents, solvents, etc., known to one of ordinary skill in the art may be used. Similarly, reaction temperatures and durations may be adjusted according to the desired needs without undue experimentation and well within the abilities of one of ordinary skill in the art. All the epimers, unless otherwise specified in the above schemes, are also encompassed within the scope of the invention.
Compounds of the present invention useful for such purpose are listed below: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3!-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((3-imidazol-l-yl)-propyl)-imino] erythromycin A (Compound No. 1),
2-α-Fluoro-5-0-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoχy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo(4,5-b)-ρyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 2), 2-α-HιuMO-5-O-(3I-N-desmethyl-3l-N-ettiyl)-l lJ2-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((3H)-imidazo(4,5-b)-pyridin- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 3),
2-a-Fluoro-5-O-(3l-N-desmethyl-3I-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 4),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l 1 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 5),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((3-imidazol- 1 -yl)-propyl)-imino] erythromycin A (Compound No. 6),
2-α-Fluoro-5-O-(3'-N-desmethyl-3 '-N-isopropyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((3-imidazol-l-yl)-propyl)-imino] erythromycin A (Compound No. 7), 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-n-propyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((3-imidazol- 1 -yl)-propyl)-imino] erytliromycin A (Compound No. 8),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-n-propyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)-imino)] erytliromycin A (Compound No. 9),
2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-cyclopropyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyrrolo-(2,3-b)pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 10),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isoρroρyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo-(2,3-b)pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 11),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 12),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 13),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-n-propyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 14), 2-α-Fluoro-5-O-(3!-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(ρyrrolo-(2,3-b)-pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 15),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((lH)-imidazo(4,5-b)-pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 16),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(purin-9-yl)-butyl)-imino)] erythromycin A (Compound No. 17),
2-α-Fluoro-5-O-(3I-N-desmethyl-3'-N-cyclopropyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((3H)-imidazo(4,5-b)-pyridin- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 18),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-pyridin-3-yl-imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 19),
2α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-O-methyl- 3-oxo-12,l l-[oxycarbonyl-((Nl-methyl-N'-quinolin-4-ylmethyl)-2-aminoethyl)-imino] erythromycin A (Compound No. 20 ),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((N'-methyl-N'-pyridine-3 -ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 21 ),
2-α-Fluoro-5-O-(3l-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((N'-methyl-N-pyridine-4-ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 22 ),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((N'-methyl-N'-pyridine-2-ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 23 ),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((N'-methyl-N'-pyridine-2-ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 24),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((N'-methyl-N'-pyridine-3-ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 25),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((N'-methyl-N'-pyridine-4-ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 26), 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((N'-metliyl-NI-quinolme-4-ylmethyl)-2-aminoetliyl)- imino] erythromycin A (Compound No. 27),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-etliyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((N'-pyridine-3-ylmethyl)-2-aminoetliyl)-imino] erythromycin A (Compound No. 28),
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-l 1 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((N'-acetyl-N'-pyridine-3-ylmethyl)-2-ammoethyl)- imino] erythromycin A (Compound No. 29),
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladmosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((N'-pyridine-3 -ylmethyl)-2-aminoethyl)-imino] erythromycin A (Compound No. 30),
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((N'-acetyl-Nl-pyridine-3-ylmethyl)-2-aminoethyl)- imino] erythromycin A (Compound No. 31),
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((N',N'-di-pyridine-3-ylmethyl)-2-aminoethyl)-imino] erythromycin A (Compound No. 32),
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((N',N'-di-pyridine-3-ylmethyl)-2-aminoethyl)-imino] erythromycin A (Compound No. 33),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 34),
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-imino)] erythromycin A (Compound No. 35),
2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-2-yl)-butyl)-imino)] erythromycin A (Compound No. 36),
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 37),
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-ethyl)- 1 l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-4-yl)-butyl)-imino)] erythromycin A (Compound No. 38), 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-2-yl)-butyl)-imino)] erythromycin A (Compound No. 39),
2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-aHyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-4-yl)-butyl)-imino)] erythromycin A (Compound No. 40),
2-α-Fluoro-5-0- (3t-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridm-3-yl)-pentyl)-imino] erythromycin A (Compound No. 41),
2-α-Fluoro-5-O- (3'-N-desmethyl-3l-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 42),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(indol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 43),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 44),
2-α-Fluoro-5-0-(3'-N-desmethyl-3l-N-ethyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((5-nitro)-indol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 45),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((lH)-imidazo[4,5-c]pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 46),
2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)-imino)] erythromycin A (Compound No. 47),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-c]pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 48),
2-α-Fluoro-5-O-(3 -N-desmethyl-3 '-N-cyclopropyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 49),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 50), 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)-imino)] erythromycin A (Compound No. 51),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 -N-cyclopropyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 - [oxycarbonyl-((4-(( 1 H)-imdazo [4,5 -bjpyridin- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 52),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(indol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 53),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 54),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 55),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 56),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 57),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)-imino)] erytliromycin A (Compound No. 58),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(indol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 59),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 60),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,ll-[oxycarbbnyl-((4-((5-nitro)-indol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 61),
2-α-Fluoro-5-O-(3 -N-desmethyl-3 -N-cyclopropyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((5-nitro)-indol- l-yl)-butyl)-imino)] erythromycin A (Compound No. 62), 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 !-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((5-fluoro)-indol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 63),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 64),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((2-methyl)-benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 65),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((2-ethyl)-benzoimidazol-l -yl)-butyl)-imino)] erythromycin A (Compound No. 66),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)] erytliromycin A (Compound No. 67),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-ethyl)-benzoimidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 68),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-pyridin-3 -yl-imidazol)- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 69),
2-α-Fluoro-5-O-(3'-N-desmethyl-3t-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((2-methyl)-benzoimidazol-l -yl)-butyl)-imino)] erythromycin A (Compound No. 70),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 71),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3'-N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((lH)-imidazo[4,5-b]pyridin- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 72),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 T-N-2-fluoroethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6- O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3-yl)-butyl)-immo)] erythromycin A (Compound No. 73),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)- 11,12-dideoxy-3 -O-decladinosyl-6- O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((5-nitro)-indol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 74), 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l 1 , 12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-pyridin-3-ylmetnyl)-benzoimidazol-l-yl)- butyl)-imino)] erythromycin A (Compound No. 75),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l 1 , 12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-((2-pyridin-3-ylmethyl)-benzoimidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 76),
2-α-Fluoro-5-O-(3t-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyi-3 -oxo- 12,11 -[oxycarbonyl-((4-((2-phenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 77),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((5-fluoro)-indol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 78),
2-α-Fluoro-5-0-(3l-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((5,6-dimethyl)-benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 79),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((5,6-dimethyl)-benzoimidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 80),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-c]pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 81),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-((2-methyl)- (3H)-imidazo[4,5-b]pyridin-3-yl)- butyl)-imino)] erythromycin A (Compound No. 82),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((2-methyl)-(3H)-imidazo[4,5-b]pyridin-3-yl)- butyl)-imino)] erythromycin A (Compound No. 83),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((lH)-imidazo[4,5-c]pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 84),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)-imino] erythromycin A (Compound No. 85),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((2-phenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 86), 2-α-Fluoro-5-O-(3I-N-desmethyl-3I-N-acetyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 87), 2-α-Fluoro-5-O-(3'-N-desmetliyl-3'-N-cycloproρyl methyl)- 11,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3- yl)-butyl)-imino)] erythromycin A (Compound No. 88),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl methyl)- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 89),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-yl)- butyl)-imino)] erythromycin A (Compound No. 90),
2-α-Fluoro-5-O-(3 ?-N-desmethyl-3 '-N-2-fluoroethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6- 0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 91),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)- 11,12-dideoxy-3 -O-decladinosyl-6- O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)]erythromycin A (Compound No. 92),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l l,12-dideoxy-3-O-decladinosyl-6- O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 93),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6- O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 94),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladmosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-trifluoromethyl)-benzoimidazol-l-yl)-butyl)- imino)] erythromycin A (Compound No. 95),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4,5-diphenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 96),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4,5-diphenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 97),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 98), 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl methyl)- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-phenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A (Compound No. 99),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 100),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-3-yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 101),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 102),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 103),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo[4,5-b]pyridin-l-yl)-butyl)-imino)] erythromycin A (Compound No. 104),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3-yl)-butyl)-imino)] erythromycin A (Compound No. 105),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3,5-diphenyl)-pyrazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 106),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6- O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-pyridn-3-yl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 107),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l l,12-dideoxy-3-O-decladinosyl-6- O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(( 1 H)-imidazo [4,5-b]pyridin- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 108),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3,5-diphenyl)-pyrazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 109),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl methyl)-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo[4,5-b]pyridin-l- yl)-butyl)-imino)] erythromycin A (Compound No. 110), 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-3-yl)-imidazo)-l -yl)-butyl)-imino)] erythromycin A (Compound No. 111),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l l,12-dideoxy-3-O-decladinosyl-6- O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-(2,4-difluoro)-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 112),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-(2,4-difluoro)-phenyl)-imidazol)- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 113),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-(2,4-difluoro)-phenyl)-imidazol)-l -yl)-butyl)- imino)] erythromycin A (Compound No. 114),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-furan-3 -yl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 115),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11- [oxycarbonyl-((4-((4-furan-3 -yl)-imidazol- 1 -yl)-butyl)-imino)] erythromycin A hydrochloride salt (Compound No. 115a),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 - [oxycarbonyl-((4-((4-phenyl-pyrazol- 1 -yl)-butyl)-imino))] erythromycin A (Compound No. 116),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-pyridin-3-yl-lH-imidazol-l-yl)-pentyl)-imino)] erythromycin A (Compound No. 117),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((4-pyridin-4-yl- 1 H-imidazol- 1 -yl)-butyl)-imino))] erytliromycin A (Compound No. 118)
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11- [oxycarbonyl-((4-((4-pyridin-4-yl- lH-imidazol- 1 -yl)-butyl)-imino))] erythromycin A (Compound No. 119),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-phenyl-pyrazol- 1 -yl)-butyl)-imino)) erythromycin A (Compound No. 120),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,1 l-[oxycarbonyl-((4-((indazol-2-yl)-butyl)-imino))] erythromycin A (Compound No. 121), 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 - [oxycarbonyl-((4-((indazol-2-yl)-butyl)-imino))] erythromycin (Compound No. 122),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-123ll-[oxycarbonyl-((4-((3-pyridin-3-yl-pyrazol-l-yl)-butyl)-imino))] erythromycin A (Compound No. 123),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((indazol-l-yl)-butyl)-imino))] erythromycin A (Compound No. 124),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((4-pyrazin-2-yl- 1 H-imidazol- 1 -yl)-butyl)-imino))] erythromycin A (Compound No. 125),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-thiophen-3-yl-lH-imidazol-l-yl)-butyl)- imino))] erythromycin A (Compound No. 126),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-thiophen-3-yl-lH-imidazol-l-yl)-butyl)- imino))] erythromycin A (Compound No. 127),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-quinolin-3-yl-lH-imidazol-l-yl)-butyl)-imino))] erythromycin A (Compound No. 128),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(indazol-l-yl)-butyl)-imino))] erythromycin A (Compound No. 129),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-pyrimidin-5-yl-lH-imidazol-l-yl)-butyl)- imino))] erythromycin A (Compound No. 130),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-pyrimidin-5-yl-lH-imidazol-l-yl)-butyl)- imino))] erythromycin A (Compound No. 131),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-furan-2-yl- 1 H-imidazol- 1 -yl)-butyl)-imino))] erythromycin A (Compound No. 132), 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-thiophen-2-yl-lH-imidazol-l-yl)-butyl)- imino))] erythromycin A (Compound No. 133),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-(4-cmoro-phenyl)- lH-imidazol-1 -yl)-butyl)- imino))] erythromycin A (Compound No. 134),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-(4-chloro-phenyl)- lH-imidazol- 1 -yl)-butyl)- imino))] erythromycin A (Compound No. 135),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-pyridin-2-yl-lH-imidazol-l-yl)-butyl)-imino))] erythromycin A (Compound No. 136),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)- 11,12-dideoxy-3-0-decladinosyl-6-0- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-pyridin-2-yl- lH-imidazol- 1 -yl)-butyl)-imino))] erythromycin A (Compound No. 137),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo-12,l l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)-imino)] erythromycin A (Compound No. 138),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-allyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3-pyridin-3-yl-lH-pyrazol-l-yl)-butyl)-imino))] erythromycin A (Compound No. 139),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-2-fluoroethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6- 0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(4-chloro-phenyl)-lH-imidazol-l-yl)-butyl)- imino))] erythromycin A (Compound No. 140),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-2-fluoroethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6- O-methyl-3 -oxo- 12,11- [oxycarbonyl-((4-((4-pyridin-2-yl)- 1 H-imidazol- 1 -yl)-butyl)- imino))] erythromycin A (Compound No. 141),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-Imidazo[4,5-b]pyridine-2- yl)-butyl)-imino)erythromycin A (Compound No. 142),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-Tetrazol- 1 -yl-imidazol- 1 -yl)- butyl)-imino)erythromycin A (Compound No. 143),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-Benzoimidazol-2-yl)-butyl)- imino)erythromycin A (Compound No. 144), 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-metliyl-3-oxo- 12,11 -[oxycarbonyl-((4-[4-(6-Fluoro-pyridin-3-yl)- imidazol-l-yl]-butyl)-imino)erythromycin A (Compound No. 145),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-Imidazo[4,5-c]pyridine-2- yl)-butyl) iminoerythromycin A (Compound No. 146),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4-[ 1 ,2,4]Trizol-l -yl-phenyl)- butyl)-imino)erythromycin A (Compound No. 147),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-Imidazol- 1 -yl-phenyl)-butyl)- imino)erythromycin A (Compound No. 148),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-[4-(6-Chloro-pyridin-3-yl)- imidazol-l-yl]-butyl)-imino)erythromycin A (Compound No. 149),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(3-[l-(4-Amino-butyl)-lH-imidazol- 4-yl]-phenyl)iminoerythromycin A (Compound No. 150),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-Pyridin-3-yl-thiazol-2-yl)- butyl)-imino)erythromycin A (Compound No. 151),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-(3 - [2-(4-Amino-butyl)-thiazol-4-yl] - phenyl)iminoerythromycin A (Compound No. 152),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-Pyrazol- 1 -yl-imidazol- 1 -yl)- butyl)-imino)erythromycin A (Compound No. 153),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-([l,4']-Bipyrazolyl-r-yl)-butyl)- imino)erythromycin A (Compound No. 154),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-Imidazol-l-yl-pyrazol-l-yl)- butyl) iminoerythromycin A (Compound No. 155),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-Pyrazol- 1 -yl-imidazol- 1 -yl)- butyl) iminoerythromycin A (Compound No. 156), 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-ό-O-niethyl-S-oxo-πjl l-foxycarbonyl-^-fSjS'JBithiophenyl-S-yl-butyl)- imino)erythromycin A (Compound No. 157),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-etliyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-[2,3I]Bithiophenyl-5I-yl-butyl)- imino)erythromycin A (Compound No. 158),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Furan-2-yl-thiaophen-2-yl)- butyl)-imino)erythromycin A (Compound No. 159),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-(4-Oxazol-5-yl-imidazol- 1 -yl)- butyl)-imino)erythromycin A (Compound No. 160),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-metliyl-3-oxo-12, 11 -[oxycarbonyl-((4-(3-Pyrrol- 1 -yl-[ 1 ,2,4]triazol- 1 - yl)-butyl) iminoerythromycin A (Compound No. 161),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-Thiophen-2-yl-tetrazol-2-yl)- butyl)-imino)erythromycin A (Compound No. 162),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-Thiophen-3 -yl-pyrazol- 1 -yl)- butyl)-imino)erytliromycin A (Compound No. 163),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Furan-3-yl-pyrazol-l-yl)- butyl)-imino)erythromycin A (Compound No. 164),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-Furan-2-yl-pyrazol-l-yl)- butyl)-imino)erythromycin A (Compound No. 165),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(5-Phenyl-tetrazol-2-yl)- butyl)- imino)erythromycin A (Compound No. 166),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-[5-(4-Methoxy-phenyl)-tetrazol- 2-yl]-butyl)-imino)erythromycin A (Compound No. 167),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^J l-foxycarbonyl-^-^-Furan-S-yl-imidazol-l-yl)- butyl)-imino)erythromycin A (Compound No. 168), 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(6-Pyrazol-l -yl-pyridin-3-yl)- butyl)-imino)erytliromycin A (Compound No. 169),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Pyridin-3-yl-pyrazol-l-yl)- butyl)-imino)erythromycin A (Compound No. 170),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycafbonyl-((4-(5-Thiophen-2-yl-pyridin-3-yl)- butyl)-imino)- erythromycin A (Compound No. 171),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-Phenyl-thiophen-2-yl)-butyl)- imino)erythromycin A (Compound No. 172),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-(N-(4- Amino-butyl)-N-thiazol-2-yl- nicotinimido)] erythromycin A (Compound No. 173),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(N-(4-Amino-butyl)-N-thiazol-2-yl- nicotinimido)] erythromycin A (Compound No. 174),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-[4-(6-Pyrrol- 1 -yl-pyridin-3 -yl)- imidazol-l-yl]-butyl)-imino)erythromycin A (Compound No. 175),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(6-Pyrrol- 1 -yl-pyridin-3-yl)- butyl)-imino)erythromycin A (Compound No. 176),
2-oc-Fluoro-5-O-(3 ' -N-desmethyl-3 '-N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-Pyrrol-l-yl-thiazol-5-yl)- butyl)-imino)erythromycin A (Compound No. 177),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(6-Imidazol-l-yl-pyridin-3-yl)- butyl) iminoerythromycin A (Compound No. 178),
2-α-Fluoro-5-O-(3.' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-[4-(Tetrahydro-ruran-2-yl)- pyridin-3-yl] -butyl) iminoerythromycin A (Compound No. 179),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-0- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-p-tolyl-imidazol- 1 -yl)-butyl)-imino)] erythromycin A (Compound No. 180), 2-α-Fluoro-5-O-(3'-N-desmettiyl-3'-N-ethyl)-1142-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-aminophenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 181),
2-a-nuoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-11.12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-methyl-3 -aminophenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 182),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11- [oxycarbonyl-((4-((4-(3 -imidazol- 1 yl)-phenyl)imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 183),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N,N-dicyclopropyl-amino)-phenyl)- imidazol- l-yl)-butyl)-imino)] erythromycin A (Compound No. 184),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3-(N,N-dimethyl-amino)phenyl)-imidazol-l- yl)-butyl)-imino)] erythromycin A (Compound No. 185),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-(3 -(tetrazol- 1 yl)-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 186),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-(2-(pyrrol- 1 yl)-thiozol-5-yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 187),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(3-trifluoromethyl-phenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A (Compound No. 188),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,ll-[oxycarbonyl-((4-((N-(thiazol-2-yl)-benzimido)-butyl)-imino)] erythromycin A (Compound No. 189),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(2-ammo-pyrimidin)-5 -yl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 190),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-(4-(pyrrol- 1 yl)-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 191),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-(3 -(pyrrol- 1 yl)-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 192), 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)41J2-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3 -(N-acetyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 193),
2-α-Huoio-5-0-(3'-N^esmelhyW'-N-eliiyl)-l l,12-dideoxy-3-0-decladiiiosyl-6-0- methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(3-(N-isopropyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erytliromycin A (Compound No. 194),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0-decladinosyl-6-0- methyl-3 -oxo-12,11- [oxycarbonyl-((4-((4-(3 -nitrophenyl)-imidazol- 1 -yl)-butyl)-immo)] erythromycin A (Compound No. 195),
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-0-decladinosyl-6-0- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3-(N-benzoyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 196),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((4-(3 ,4-dimethyl-phenyl)-imidazol- 1 -yl)-butyl)- imino)] erythromycin A (Compound No. 197),
5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo- 12,1 l-[oxycarbonyl-(((4-(4-Pyridin-3-yl-thiazol-2-yl)-butyl)-imino)] erythromycin A (Compound No. 198),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(4-fluoroρhenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A (Compound No. 199),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(4-methoxy-phenyl)-imidazol-l-yl)-butyl)- imino)] erytliromycin A (Compound No. 200),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo-12,l l-[oxycarbonyl-((4-((N-(benzthiazol-2-yl)-benzimido)-butyl)-imino)] erythromycin A (Compound No. 201),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((N-(thiazol-2-yl)-nicotinamido)-butyl)-imino)] erythromycin A (Compound No. 202),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-O- methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3-(N-methyl-amino)-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A (Compound No. 203),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-(2-aminopyridyl)-imidazol- l-yl)-butyl)-imino)] erythromycin A (Compound No. 204), 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12, 1 l-[oxycarbonyl-((4-(4-(5-(2-amiiiopyridyl)- 2H- tetrazol-5-yl)-butyl)-imino)] erythromycin A (Compound No. 205),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3 ,4-difluorophenyl)-imidazol- l-yl)-butyl)-imino)] erythromycin A (Compound No. 206),
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)desosaminyl-l 1 ,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12, 1 l-[oxycarbonyl-((4-(4-(4-(2-chloropyridyl)-imidazol- l-yl)-butyl)-imino)] erythromycin A (Compound No. 207),
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(6-aminopyridyl)-imidazol- l-yl)-butyl)-imino)] erythromycin A (Compound No. 208),
2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(2-Chloro-pyridin-4-yl)- tetrazol-2-yl])-butyl)-imino)] erythromycin A (Compound No. 209), pharamceutically acceptable salts, pharamceutiacally acceptable solvates, stereoisomers, prodrugs, metabolites or polymorphs thereof.
The compounds described herein are pharmacologically active against Gram-positive, Gram-negative and anaerobic bacteria and accordingly, are useful as antibacterial agents for treating bacterial infections in a patient in need thereof, for example, in a human or an animal. Because of their antibacterial activity, the compounds described herein may be administered to an animal for treatment orally, topically, rectally, internasally, or by parenteral route. Pharmaceutical compositions described herein comprise pharmaceutically effective amounts of compounds described herein formulated together with one or more pharmaceutically acceptable carriers, excipients or diluents.
Solid form preparations for oral administration include capsules, tablet, pills, powder, granules, cachets and suppositories. For solid form preparations, active compounds can be mixed with one or more inert, pharmaceutically acceptable excipients or carrier, for example, sodium citrate, dicalcium phosphate and/or fillers or extenders (for example, starches, lactose, sucrose, glucose, mannitol, silicic acid or mixtures thereof); binders, for example, carboxymethylcellulose, alginates, gelatins, polyvinylpyrrolidinone, sucrose, acacia or mixtures thereof; disintegrating agents, for example, agar-agar, calcium carbonate, potato starch, alginic acid, certain silicates, sodium carbonate or mixtures thereof; absorption acceletors, for example, quaternary ammonium compounds; wetting agents, for example, cetyl alcohol, glycerol mono stearate or mixtures thereof; adsorbants, for example, Kaolin; lubricants, for example, talc, calcium stearate, magnesium stearate, solid polyethyleneglycol, sodium luaryl sulfate or mixtures thereof; or mixtures thereof.
Capsules, tablets or pills may also comprise buffering agents.
Tablets, capsules, pills or granules can be prepared using one or more coatings or shells, for example, enteric coatings or other coatings known to one of ordinary skill in the art.
Liquid form preparations for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups or elixirs, hi such liquid fonn preparations, active compounds can be mixed with water or one or more other solvents, solubilizing agents or emulsifiers, for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, for example, cottonseed, groundnut, corn, germ, olive, castor and sesame oil), glycerol, fatty acid esters of sorbitan or mixtures thereof. Oral compositions can also include one or more adjuants, for example, wetting agents, emulsifying agents, suspending agents, sweetening agents, flavouring agents, perfuming agents or mixtures thereof.
Injectable preparations, for example, sterile injections, aqueous suspensions may be formulated according to methods known to one of ordinary skill in the art, and in particular, using one or more suitable dispersing or wetting and suspending agents. Acceptable vehicles and solvents that may be employed include one or more of water, Ringer's solution, isotonic sodium chloride or mixtures thereof.
Dosage forms for tropical or transdermal administration of a compound of the present invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. Active compounds can be admixed under sterile condition with one or more pharmaceutically acceptable carriers and optionally any preservatives or buffers as may be required. Ophthalmic formulations, eardrops, eye ointments, powders and solutions are also encompassed within the scope of this invention. Pharmaceutical preparations may be in unit dosage form. In unit dosage form, the preparations can be subdivided into unit doses containing appropriate quantities of active components. Unit dosage forms can be packaged preparations containing discrete capsules, powders, in vials or ampoules, ointments, capsules, sachets, tablets, gels, creams or any combination and number of such packaged forms.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are included within the scope of the present invention. The examples are provided to illustrate particular aspects of the disclosure and do not limit the scope of the present invention as defined by the claims.
Examples
General Procedure
Example 1. Preparation of R-W-NBb
(a) Preparation of 4-(3H)-imidazol [4,5-b] pyridin-3-yl-butylarnine wherein W = -(CH2)4-
4-(3H)-imidazol[4,5-b]pyridin-3-yl-butylamine was prepared according to a procedure described in U.S. Patent No. 5,635,485, which is incorporated herein in its entirety, hi particular, 10.3 g of potassium carbonate were added to a solution of 5.95 g of 4-azabenzimidazole and 15.5 g of N-4-bromobutyl-phthalimide in 30 mL of dimethylformamide and the mixture was stirred for 20 hours at ambient temperature. The insoluble part was filtered off and rinsed with methylene chloride. The organic phase was washed with water, then dried over magnesium sulfate and evaporated. The oily residue obtained was washed with petroleum ether, then with isopropyl ether to obtain 16.3 g of a yellow solid, which was purified by chromatography on silica, eluting with a methylene chloride: acetone mixture to obtain 4.9 g of product (A) melting at 143 0C.
A mixture of 32.86 g of product (A) obtained above, 697 mL of ethanol and 20 mL of hydrazine was refluxed for 19 hours. The mixture was allowed to return to ambient temperature, filtered, rinsed and evaporated to dryness. The residue was taken up in methylene chloride, filtered, rinsed and evaporated to dryness to obtain 18.87 g of the desired product.
NMR CDCl3 - 250 MHz
1.52 (m)-2.00 (m); 1.63 (wide s); 2.76 (t); 4.33 (t); 7.24 (dd, J= 8 and 5); 8.08 (dd, J=8 and 1.5); 8.40 (dd, J = 5 and 1.5); 8.08 (s).
(b) Preparation of N*l*-pyridin-4-yl-methylethane-l, 2-diamine wherein W = -(CH2)2-NH-CH2-
Pyridin-3-carboxaldehyde (46.7 mmol) was added to a solution of ethylene diamine (467.2 mmol) in methanol (50 mL) at 0-50C. The reaction mixture was allowed to come to ambient temperature, sodium borohydride (46.7 mmol) was added in portions, and the reaction mixture was stirred for about 4 hours. The solvent was removed under reduced pressure to yield 5.2 g of crude product. The crude product was purified by silica gel column chromatography using 10% methanol :dichloromethane using 5 % triethyl amine.
(c) wherein W = -(CH2)2-N (CH3)-CH2-
Step I: Preparation of methylpyridin-4-ylmethylamine
40% methyl amine (68.7 mmol) was added to a solution of pyridine 4- carbaldehyde (57.3 mmol) in methanol (90 mL) at 0-5 0C and stirred for about 15minutes, followed by adding sodium borohydride (57.3 mmol). The reaction mixture was refluxed for about 1 hour, cooled to ambient temperature and solvent was removed under reduced pressure. Water was added to the resulting residue the mixture was extracted with dichloromethane. The dichloromethane layers were combined, mixed and washed successively with water and then brine, and dried over anhydrous sodium sulfate. Solvent was evaporated under reduced pressure to yield a crude product.
Step II: Preparation of 2-[2-(methylpyridin-4-ylmethylamino) ethylisoindole-l,3-dione
Potassium carbonate (55.2 mmol) and 2-bromoethylfthalimide (66.2 mmol) was added to a solution of N* l*-pyridin-4-yl-methylethane-l, 2-diamine (55.2 mmol) in dimethylformamide (50 mL). The reaction mixture was heated to 800C and stirred for about 16 hours. The reaction mixture was cooled to ambient temperature, poured into water and extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title product.
Step III: Preparation of N* 1 *-methyl-N* 1 *-pyridm-4-ylmethylethane-l , 2-diamine
Hydrazine hydrate (202.8 mmol) was added to a solution of 2-[2-(methylpyridin-4- ylmethylamino)ethylisoindole-l,3-dione (20.28 mmol) in methanol (210 mL). The reaction mixture was refluxed for about 2 hours. The reaction mixture was cooled to ambient temperature and a white crystalline solid was filtered, washed with methanol (50 mL), and the solvent was removed under reduced pressure. Diethyl ether was added to the resulting residue and then stirred for about 30 minutes. A resulting solid was filtered and washed with ether. The filtrate was concentrated under reduced pressure to afford oily product.
Example 2. Synthetic Procedure of Scheme I
(a) Preparation of compound of Formula III
Clarithromycin (25 g, 33.4 mmol) was added in portions to an aqueous solution of hydrochloric acid at ambient temperature. The reaction mixture was neutralized with solid sodium bicarbonate and the aqueous layer was extracted with ethyl acetate. The organic layer was washed successively with water and then brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product. The crude product was crystallized from ethyl acetate and hexane to yield the title compound.
(b) Preparation of compound of Formula IV
Benzoic anhydride (2.5 equiv.) followed by triethylamine (6 equiv.) was added to a solution of compound of Formula III (1 equiv.) in dichloromethane and stirred at ambient temperature for about 40 hours. The reaction was quenched by adding sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane, washed successively with water and then brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product. The crude product obtained was crystallized from ethyl acetate and hexane to yield the title compound.
(c) Preparation of compound of Formula V
N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula IV (1 equiv.) in dry acetonitrile:dichloromethane (2:1) at about 0 0C. The reaction mixture was allowed to come to ambient temperature while being stirred. A sodium bisulfite solution was added to the reaction mixture with stirring followed by adding a sodium carbonate solution with further stirring of the reaction mixture. Dichloromethane was evaporated under reduced pressure. The aqueous layer was extracted with ethyl acetate, washed successively with water and then brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 17-25% acetone in hexane to yield the title compound.
(d) Preparation of compound of Formula VI
Compounds of Formula VI can be and were prepared by three different methods.
Method A
Solid sodium hydrogen carbonate (5 equiv.) and ethyl iodide (6 equiv.) were added to a solution of compound of Formula V (1 equiv.) in acetonitrile under argon at ambient temperature and stirred for about 24 hours. The reaction was quenched by adding water. The reaction mixture was then diluted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield a crude product. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-15 % acetone in hexane to yield the title compound.
Method B
The compound of Formula V (1 equiv.) in acetone and methanol was stirred at ambient temperature. A solution of acetic acid was added with stirring and sodium cyanoborohydride (2 equiv.) was then added with continued stirring. The solvent was evaporated under reduced pressure and a crude product was extracted with ethyl acetate. The ethyl acetate layer was combined and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-20 % acetone in hexane to yield the title compound.
Method C
(l-ethoxycyclopropoxy)trimethylsilane (3 equiv.) followed by glacial acetic acid (10 equiv.) were added to a solution of compound of Formula V (1 equiv.) in methanol at ambient temperature with stirring. The reaction mixture was cooled and sodium cyanoborohydride (5 equiv.) was then added. The reaction mixture was then stirred and refluxed. Methanol was removed under reduced pressure and water was then added. The organic layer was extracted with ethyl acetate. The ethyl acetate layer was combined, washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-20 % acetone in hexane to yield the title compound.
(e) Preparation of compound of Formula VII
Triphosgene (1.5 equiv.) was added to a solution of compound of Formula VI (1 equiv.) in dichloromethane. Pyridine (15 equiv.) was then slowly added. After complete addition, the reaction mixture was stirred for about 4 hours and then quenched by adding ice-cold water. The reaction mixture was diluted with dichloromethane, washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(f) Preparation of compound of Formula VIII
Tetramethyl guanidine (2.2 equiv.) was added to a solution of compound of
Formula VII (1 equiv.) in dimethylformamide. The reaction mixture was heated to 70 0C, stirred for about 10 hours, and then cooled to ambient temperature. The organic layer was extracted with ethyl acetate, washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound. (g) Preparation of compound of Foπnula IX
Dess-Martine Periodinane (2.5 equiv.) was added to a solution of compound of Formula VIII (1 equiv.) in dichloromethane . The reaction mixture was refluxed for about one hour, cooled to ambient temperature, quenched by adding a saturated aqueous potassium carbonate solution followed by a saturated sodium thiosulfate solution, and the reaction mixture was then stirred. The aqueous layer was separated and extracted with dichloromethane. The dichloromethane layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(h) Preparation of compound of Formula X
N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula IX (1 equiv.) in dimethylformamide: tetrahydrofuran (3:2) at ambient temperature. The reaction mixture was cooled, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred. The reaction mixture was quenched by adding water. It was extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the desired product.
(i) Preparation of compound of Formula XI
Compounds of Formula XI can be prepared by two different methods.
Method A
Compound of Formula X (I equiv.) and R-W-NH2 (2 equiv.) were taken in water in acetonitrile, heated at 70 °C and stirred for about 20 hours. The reaction mixture was then cooled to ambient temperature and acetonitrile was removed under reduced pressure. The resulting residue was taken in ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate, and filtered. The filtrate thus obtained was collected and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound. Method B
Compound of Formula X (I equiv.) and R-W-NH2 (2 equiv.) were taken in dimethylformamide and heated at 70 °C and stirred for about 20 hours. The reaction mixture was cooled to ambient temperature and dimethylformamide was removed under reduced pressure. The resulting crude product was taken in ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound.
(j) Preparation of compound of Formula XII
Compounds of Formula XII can be and were prepared by two different methods.
Method A
Sodium hydride (1.5 equiv.) was added in portions to a cold solution of compound of Formula XI (1 equiv.) in dimethylformamide . N-fluorobenzene sulfonimide (1.2 equiv.) was then added to the reaction mixture. The reaction mixture was quenched by adding water and then extracted with ethyl acetate. The oganic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
Method B
Potassium fø't-butoxide (1.5 equiv.) was added to a solution of compound of
Formula XI (1 equiv.) in tetrahydrofuran at -150C. The reaction mixture was stirred for 20 minutes and N-fluorobenzene sulfonimide (1.2 equiv.) in tetrahydrofuran was then added. The reaction mixture was stirred at —150C for about 3 hours, quenched by adding water, and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound. (k) Preparation of compound of Formula XIII
Compound of Formula XII (560 mg, 0.6 mmol) was taken in methanol and refluxed. The reaction mixture was cooled to ambient temperature and methanol was removed under reduced pressure. A resulting solid product was purified over a silica gel column (thoroughly neutralized with triethylamine) using 20-40 % acetone in hexane or 2- 6 % methanol in dichloromethane to yield the title compound.
Example 3 Synthetic Procedure of Scheme II
(a) Preparation of compound of Formula XIV
Triphosgene (1.5 equiv) was added to a solution of compound of Formula IV (1 equiv) in dichloromethane and pyridine (15 equiv) was then slowly added. After complete addition, the reaction mixture was stirred for about 3-4 hours at 0 0C. The reaction mixture was quenched by adding ice-cold water. The reaction mixture was diluted with dichloromethane and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(b) Preparation of compound of Formula XV
Tetramethyl guanidine (2.2 equiv.) was added to a solution of compound of Formula XIV (1 equiv.) in dimethylformamide. The reaction mixture was heated to 65-70 0C for about 3-4 hours and then cooled to ambient temperature. The organic layer was extracted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(c) Preparation of compound of Formula XVI
Dess-Martine Periodinane (2.5 equiv.) was added to a solution of compound of Formula XV (1 equiv.) in dichloromethane and the reaction mixture was stirred at 300C for about 1 hour. The reaction mixture was quenched by adding saturated aqueous potassium carbonate solution followed by saturated sodium thiosulfate solution and the reaction mixture was stirred. The resulting aqueous layer was separated and extracted with dichloromethane. The dichloromethane layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(d) Preparation of compound of Formula XVII
N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula XVI (1 equiv.) in dry acetonitrileidichloromethane (2: 1). The reaction mixture was allowed to reach ambient temperature and stirred for about 3-4 hours. A sodium bisulfite solution was then added to the reaction mixture and stirred. Then sodium carbonate solution was added to the reaction mixture and stirring. Dichloromethane was evaporated under reduced pressure. The aqueous layer was extracted with ethyl acetate, washed successively with water followed by brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
(e) Preparation of compound of Formula IX
Solid sodium hydrogen carbonate (5 equiv.) and ethyl iodide (6 equiv.) was added to a solution of compound of Formula XVII (1 equiv.) in acetonitrile under argon at ambient temperature and the reaction mixture was stirred for about 18-20 hours. The reaction mixture was quenched by adding water. The reaction mixture was then diluted with ethyl acetate, washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield a crude product. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 10-15 % acetone in hexane to yield the title compound.
(f) Preparation of compound of Formula XVIII
Compounds of Formula XVIII can be and were prepared by two different methods.
Method A
Sodium hydride (1.5 equiv.) was added in portions to a solution of compound of Formula IX (1 equiv.) in dimethylformamide at 00C and then stirred for about 15 minutes. N-fluorobenzene sulfonimide (1.2 equiv.) was then added to the reaction mixture and stirred at 00C for about 3 hours. The reaction mixture was quenched by adding water and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
Method B
Potassium tø-t-butoxide was added to a solution of compound of Formula IX (1 equiv.) in tetrahydrofuran at -150C and the reaction mixture was stirred for about 20 minutes. N-fluorobenzene sulfonimide (1.2 equiv.) in tetrahydrofuran was then added added to the reaction mixture and then stirred at -15 0C for about 2 hours, quenched by adding water and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(g) Preparation of compound of Formula XIX
N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula XVIII (1 equiv.) in dimethylformamide:tetrahydrofuran (3:2) at ambient temperature. The reaction mixture was cooled to 00C, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred for about 30 minutes. The reaction mixture was quenched by adding water and then extracted with ethyl acetate. The ethyl acetate layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(h) Preparation of compound of Formula XII
Compound of Formula XIX (1 equiv.) and R-W-NH2 (3 equiv.) were taken in 10
% water in acetonitrile and heated to 65-700C for about 14 hours. The reaction mixture was cooled to ambient temperature and the acetonitrile-water mixture was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound.
(i) Preparation of compound of Formula XIII
Compound of Formula XII was taken in methanol and refluxed for about 12 hours. The reaction mixture was cooled to ambient temperature and methanol was removed under reduced pressure. The resulting solid crude product was purified over a silica gel column using 2-6% methanol in dichloromethane to yield the title compound.
Example 4. Synthetic Procedure of Scheme III
(a) Preparation of compound of Formula XX
Compounds of Formula XX can be and were prepared by two different methods.
Method A
Sodium hydride (1.5 equiv.) was added in portions to a solution of compound of Formula XVI (1 equiv.) in dimethylformamide at 0 0C and the reaction mixture was stirred for about 15 minutes. N-fluorobenzene sulfonimide (1.2 equiv.) was then added and the reaction mixture was stirred at 00C for about 4 hours. The reaction mixture was quenched by adding water and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
Method B
Potassium tert-butoxide (1.5 equiv) was added to a solution of compound of
Formula XVI (1 equiv.) in tetrahydrofuran at -150C and the reaction mixture was stirred for about 20 minutes. N-fluorobenzene sulfonimide (1.2 equiv.) in tetrahydrofuran was then added and the reaction mixture was stirred at -150C for about 3 hours, quenched by adding water and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(b) Preparation of compound of Formula XXI
N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula XX (1 equiv.) in dimethylformamide:tetrahydrofuran (3:2) at ambient temperature. The reaction mixture was cooled to 00C, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred for about 30 minutes. The reaction was quenched by adding water and extracted with ethyl acetate. The ethyl acetate layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(c) Preparation of compound of Formula XXII
The compound of Formula XXI (1 equiv.) and R-W-NH2 (2 equiv.) were taken in a mixture of 10 % water in acetonitrile and heated to 65-700C for about 14 hours. The reaction mixture was cooled to ambient temperature and acetonitrile-water was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound.
(d) Preparation of compound of Formula XXIII
The compound of Formula XXII (560 mg, 0.6 mmol) was taken in methanol and refluxed. The reaction mixture was cooled to ambient temperature and methanol was evaporated under reduced pressure to yield the title compound.
(β) Preparation of compound of Formula XXIV
N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula
XXIII (1 equiv.) in dry acetonitrile and the reaction mixture was allowed to attain ambient temperature and stirred for 4h. A sodium bisulfite solution was added to the reaction with stirring. A sodium carbonate solution was then added with stirring. The aqueous layer was extracted with ethyl acetate, washed successively with water followed by brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
(f) Preparation of compound of Formula XIII
Solid sodium hydrogen carbonate (5 equiv.) and ethyl iodide (6 equiv.) was added to a solution of compound of Formula XXIV (1 equiv.) in acetonitrile under argon at ambient temperature and stirred for about 20 hours. The reaction mixture was quenched by adding water. The reaction mixture was diluted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield a crude product. The crude product was purified bysilica gel column chromatography (thoroughly neutralized with triethylamine) using 30-35 % acetone in hexane to yield the title compound.
Example 5. Synthetic Procedure for Scheme IV
(a) Preparation of compound of Formula XXV
The compound of Formula XX was taken in methanol and reflux ed. The reaction mixture was cooled to attain an ambient temperature and methanol was evaporated under reduced pressure. The crude product was purified by column chromatography.
(b) Preparation of compound of Formula XXVI
N-iodosuccinimide (2 equiv.) was added to a solution of compound of Formula XXV (1 equiv.) in dry acetonitrile and the reaction mixture was allowed to attain ambient temperature and stirred for about 4 hours. A sodium bisulfite solution was added to the reaction mixture with stirring followed the addition of sodium carbonate solution with stirring. The aqueous layer was extracted with ethyl acetate, washed successively with water followed by brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to yield a crude product.
(c) Preparation of compound of Formula XXVII
Solid sodium hydrogen carbonate (5 equiv.) and ethyl iodide (6 equiv.) was added to a solution of compound of Formula XXVI (1 equiv.) in acetonitrile under argon at ambient temperature and stirred for about 20 hours. The reaction mixture was quenched by adding water. The reaction mixture was diluted with ethyl acetate and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield a crude product. The crude product was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 20-25 % acetone in hexane to yield the title compound.
(d) Preparation of compound of Formula XVIII
Potassium carbonate (2 equiv.) was added to a solution of compound of Formula XXVII (1 equiv.) in acetone and the reaction mixture was stirred for about 5 minutes. Aacetic anhydride (5 equiv.) was then added and the reaction mixture was stirred for about 24 hours at ambient temperature. The reaction mixture was poured into a chilled aqueous potassium carbonate solution and extracted with dichloromethane. The dichloromethane layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated to yield the title compound.
(e) Preparation of compound of Formula XIX
N, N'-carbonyldiimidazole (3 equiv.) was added to a solution of compound of Formula XVIII (1 equiv.) in dimethylformamide: tetrahydrofuran (3:2) at ambient temperature. The reaction mixture was cooled to 00C, sodium hydride (3 equiv.) was added in portions and the reaction mixture was stirred for about 30 minutes. The reaction mixture was quenched by adding water. This was extracted with ethyl acetate. Ethyl acetate layer was washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to yield the title compound.
(f) Preparation of compound of Formula XII
The compound of Formula XIX (1 equiv.) and R-W-NH2 (2 equiv.) were taken in a mixture of 10 % water in acetonitrile and heated to 65-700C for about 14 hours. The reaction mixture was cooled to ambient temperature and acetonitrile-water was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (thoroughly neutralized with triethylamine) using 25-30 % acetone in hexane to yield the title compound.
(g) Preparation of compound of Formula XIII
The compound of Formula XII was taken in methanol and refluxed. The reaction mixture was cooled to ambient temperature and methanol was removed under reduced pressure. The resulting solid crude product was purified by silica gel chromatography using 2-6 % methanol in dichloromethane to yield the title compound.
(h) Preparation of a hydrochloride salt of compound of Formula XIII
The compound of Formula XIII (0.09 mol) was taken in ethanol, cooled to 0 0C and 3N ethanolic hydrochloric acid (0.0945 mol) was added. The reaction mixture was stirred at 00C for about 2 hours and ethanol was removed under reduced pressure. The residue was dried under vacuum, triturated with diethyl ether and ether was decantated off to yield the title compound.
The following compounds were prepared following the above general procedures:
Compound No.l : 2-α-Fluoro-5-O-(3'-N-desmemyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-imidazol-l-yl)-propyl)-imino] erythromycin A; MS (+ ion mode): m/z 753.6 [M+l]
Compound No.2: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-((lH)-imidazo(4,5-b)-pyridin- 1 - yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 818.4 [M+l]
Compound No.3: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo(4,5-b)-pyridin-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 818.3 [M+l]
Compound No. 4: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 817.6 [M+l]
Compound No. 5: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(imidazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 767.6 [M+l]
Compound No. 6: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((3-imidazol- 1 -yl)-propyl)-imino] erythromycin A; MS (+ ion mode): m/z 765.6 [M+l]
Compound No.7: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((3-imidazol-l-yl)-propyl)-imino] erythromycin A; MS (+ ion mode): m/z 767.5 [M+l]
Compound No. 8: 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ρroρyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((3 -imidazol- 1 -yl)-propyl)-imino] erythromycin A; MS (+ ion mode): m/z 767.6 [M+l]
Compound No.9: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-propyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-^benzoimidazol-l-y^-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 831.3 [M+l]
Compound No. 10: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-ll,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-φyrrolo-(2,3-b)pyridin-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 829.4 [M+l] Compound No.l 1 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(pyrrolo-(2,3 -b)pyridin- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 831.6 [M+l]
Compound No.12: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isoρropyl)-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzoimidazol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 831.4 [M+l]
Compound No.13: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 829.7 [M+l]
Compound No.14: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-n-propyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(imidazol- 1 -yl)-butyl)-imino)] erythromycin A; MS (+ ion mode) : m/z 781.5 [M+ 1 ]
Compound No. 15: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(pyrrolo-(2,3 -b)pyridin- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 817.6 [M+l]
Compound No.16: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo(4,5-b)-pyridin-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 832.9 [M+l]
Compound No.17: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(purin-9-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 820.0 [M+l]
Compound No.18: 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((3H)-imidazo(4,5-b)-pyridin- l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 830.4 [M+l]
Compound No.19: 2-α-Fluoro-5-O-(3'-N-desmemyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-pyridin-3-yl-imidazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 844.55 [M+l]
Compound No. 20: 2α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((N'-methyl-N'-quinolin-4-ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 843.90 [M+l]
Compound No. 21 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((N'-methyl-N'-pyridine-3-ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 794.00 [M+l]
Compound No. 22: 2-α-Fluoro-5-O-(3'-N-desmemyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((N'-methyl-N-pyridine-4-ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 794.00 [M+l] Compound No. 23: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((N'-metnyl-N'-pyridine-2-ylmethyl)- 2-aminoethyl)-immo] erythromycin A; MS (+ ion mode): m/z 794.01 [M+ 1]
Compound No. 24: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((Nl-methyl-N'-pyridine-2-ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 805.58 [M+l]
Compound No. 25: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo-12,11- [oxycarbonyl-((N'-methyl-N'-pyridine-3 -ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 805.45 [M+l]
Compound No. 26: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((N'-methyl-N'-pyridine-4-ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 805.40 [M+l]
Compound No.27: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladmosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((N'-methyl-N'-quinoline-4- ylmethyl)-2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 855.59 [M+l]
Compound No. 28: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((N'-pyridine-3-ylmethyl)-2- aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 779.71 [M+l]
Compound No.29: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((N'-acetyl-N'-pyridme-3-yhnethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 833.78 [M+l]
Compound No.30: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo-Ojl l-foxycarbonyl-^'-pyridine-S-ylmethyl)^- aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 791.73 [M+l]
Compound No. 31: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladmosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((N'-acetyl-N'-pyridine-3-ylmethyl)- 2-aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 821.76 [M+l]
Compound No. 32: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((N',N'-di-pyridine-3-ylmethyl)-2- aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 870.54 [M+l]
Compound No. 33: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((N',N'-di-pyridine-3-ylmethyl)-2- aminoethyl)-imino] erythromycin A; MS (+ ion mode): m/z 882.69 [M+l]
Compound No. 34: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(quinolin-3-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 840.7 [M+l] Compound No. 35: 2-α-Fluoro-5-O- (S'-N-desmethyl-S'-N-ethylJ-l l.U-dideoxy-S-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 829[M+1]
Compound No.36: 2-α-Fluoro-5-O- (3?-N-desmetiiyl-3 VNh?thyl)-l 1 , 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-2-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 778 [M+l]
Compound No. 37: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-3-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 778 [M+l]
Compound No. 38: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-4-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 778 [M+l]
Compound No. 39: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-123ll-[oxycarbonyl-((4-(pyridin-2-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 789 [M+l]
Compound No. 40: 2-α-Fluoro-5-O- (S'-N-desmethyl-S'-N-allylHl^-dideoxy-S-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-4-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 789 [M+l]
Compound No.41 : 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(pyridin-3-yl)-pentyl)-imino] erythromycin A; MS (+ ion mode): m/z 804.77 [M+l]
Compound No. 42: 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-3-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 790.50 [M+l]
Compound No. 43: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(indol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 816.8 [M+l]
Compound No.44: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-^-pheny^-imidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 843.9 [M+l]
Compound No. 45: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((5-nitro)-indol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 861.8 [M+l]
Compound No. 46: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo[4,5-c]pyridin-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 819.1 [M+l] Compound No. 47: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 818.9 [M+ 1]
Compound No. 48: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-πjll-foxycarbonyl-^-^S^-imidazo^jS-cJpyridin-S- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 819 [M+ 1]
Compound No. 49: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-phenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 855.8 [M+l]
Compound No. 50: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3- 0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 830.7 [M+l]
Compound No. 51 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-l 1 , 12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 830.9 [M+l]
Compound No. 52: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cycloρropyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(( lH)-imdazo [4,5-b]pyridin- 1 - yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 830.9 [M+l]
Compound No. 53: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-ll,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(indol- 1 -yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 828.9 [M+l]
Compound No. 54: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo-πjl l-foxycarbonyl-^-φenzotriazol-l-y^-buty^-imino)] erythromycin A; MS (+ ion mode): m/z 830.9 [M+l]
Compound No. 55: 2-α-Fluoro-5-O-(3t-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 829.9 [M+l]
Compound No. 56: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 830.9 [M+l]
Compound No. 57: 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-phenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 858.1 [M+l]
Compound No. 58: 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-ll,12-dideoxy-3-0- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 832.8 [M+l] Compound No. 59: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(indol- 1 -yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 830.9 [M+l]
Compound No. 60: 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isoρroρyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3H)-imidazo[4,5-b]pyridin-3- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 832.9 [M+l]
Compound No. 61 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((5-nitro)-indol- 1 -yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 875.38 [M+l]
Compound No. 62: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((5-nitro)-indol- 1 -yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 873.54 [M+l]
Compound No.63: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((5-fluoro)-indol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 834.57 [M+l]
Compound No. 64: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 818.9 [M+l]
Compound No. 65: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-methyl)-benzoimidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 831.57 [M+l]
Compound No. 66: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-ethyl)-benzoimidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 845.58 [M+l]
Compound No. 67: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 832.54 [M+l]
Compound No. 68: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-ethyl)-benzoimidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 857.56 [M+l]
Compound No.69: 2-α-Fluoro-5-O-(3!-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-3 -yl-imidazol)- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 856.64 [M+l]
Compound No. 70: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((2-methyl)-benzoimidazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 843.53 [M+l] Compound No. 71 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin- 1 -yl)- butyl)-imino)]erythromycin A; MS (+ ion mode): m/z 829.59 [M+l]
Compound No. 72: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-^l^-imidazo^^-bJpyridin-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 830.6 [M+l]
Compound No. 73: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l 1,12-dideoxy- S-O-decladinosyl-ό-O-methyl-S-oxo-^J l-foxycarbonyl-^-^^-imidazo^jS- b]pyridin-3-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 836.65 [M+l]
Compound No. 74: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroemyl)-l 1,12-dideoxy- 3 -O-decladinosyl-ό-O-methyl-S -oxo- 12,11- [oxycarbonyl-((4-((5-nitro)-indol- 1 -yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 879.5 [M+l]
Compound No. 75: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-pyridin-3-ylmethyl)- benzoimidazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 920.74 [M+l]
Compound No. 76: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((2-pyridin-3-ylmethyl)- benzoimidazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 908.71 [M+l]
Compound No. 77: 2-α-Fluoro-5-O-(3'-N-desmethyl-3I-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-phenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 855.6 [M+l]
Compound No. 78: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-((5-fluoro)-indol- 1 -yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 846.57 [M+l]
Compound No. 79: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((5,6-dimethyl)-benzoimidazol-l- yl)-butyl)-imino)]erythromycin A; MS (+ ion mode): m/z 857.89 [M+l]
Compound No. 80: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((5,6-dimethyl)-benzoimidazol-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 845.8 [M+l]
Compound No. 81 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-^^-imidazo^S-cJpyridin-S- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 831.7 [M+l]
Compound No. 82: 2-α-Fluoro-5-O-(3τ-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-methyl)- (3H)-imidazo[4,5- b]pyridin-3-yl)-butyl)-immo)]erythromycin A; MS (+ ion mode): m/z 844.67 [M+l] Compound No. 83: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((2-methyl)-(3H)-imidazo[4,5- b]pyridin-3-yl)-butyl)-imino)]erythromycin A; MS (+ ion mode): m/z 832.68 [M+ 1]
Compound No. 84: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo[4,5-c]pyridin-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 830.78 [M+l]
Compound No. 85: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-metb.yl-3-oxo-12,l l-[oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)- imino]erythromycin A; MS (+ ion mode): m/z 834.78 [M+l]
Compound No.86: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((2-phenyl)-imidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 843.8 [M+l]
Compound No. 87: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 - [oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)]erytliromycin A; MS (+ ion mode): m/z 831.82 [M+l]
Compound No. 88: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cycloρropyl methyl)-ll,12- dideoxy-S-O-decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-^^-imidazo^jS- b]pyridin-3-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 844.85 [M+l]
Compound No. 89: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)- 11,12- dideoxy-3 -O-decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 - yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 843.86 [M+l]
Compound No. 90: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cycloproρyl methyl)- 11,12- dideoxy-3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3- b]pyridin-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 843.8 [M+l]
Compound No.91 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-yl)- butyl)-immo)]erythromycin A; MS (+ ion mode): m/z 835.83 [M+l]
Compound No.92: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)- imino)] erythromycin A; MS (+ ion mode): m/z 836.74 [M+l]
Compound No. 93: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l 1,12-dideoxy- S-O-decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-butyl)- imino)]erythromycin A; MS (+ ion mode): m/z 835.77 [M+l]
Compound No. 94: 2-α-Fluoro-5-O-(3'-N-desmethyl-3t-N-2-fluoroethyl)-l 1,12-dideoxy- S-O-decladinosyl-δ-O-methyl-S-oxo-Ojl l-toxycarbonyl-^-^-pheny^-imidazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 861.8 [M+l] Compound No. 95: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((2-trifluoromethyl)- benzoimidazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 885.75 [M+l]
Compound No. 96: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4,5-diphenyl)-imidazol-l-yl)- butyl)-imino)]erythromycin A; MS (+ ion mode): m/z 919.15 [M+l]
Compound No.97: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4, 5-diphenyl)-imidazol- 1 -yl)- butyl)-imino)]erythromycin A; MS (+ ion mode): m/z 931.85 [M+l]
Compound No. 98: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 855.75 [M+l]
Compound No. 99: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cycloproρyl methyl)-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-phenyl)- imidazol-l-yl)-butyl)-imino)]erytliromycin A; MS (+ ion mode): m/z 869.85 [M+l]
Compound No. 100: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)- 11,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(benzotriazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 844.8 [M+l]
Compound No. 101 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cycloproρyl methyl)-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-pyridin-3-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 870.82 [M+l]
Compound No. 102: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 831.78 [M+l]
Compound No. 103: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-phenyl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 857.83 [M+l]
Compound No. 104: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((lH)-imidazo[4,5-b]pyridin-l- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 832.77 [M+l]
Compound No.lOS^-α-Fluoro-S-O-CS'-N-desmethyl-S'-N-acety^-llj^-dideoxy-S-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-((3H)-imidazo [4,5-b]pyridin-3- yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 832.77 [M+l]
Compound No. 106: 2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((3,5-diphenyl)-pyrazol-l-yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 931.85 [M+l] Compound No. 107: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l 1,12-dideoxy- 3-O-decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridn-3-yl)-imidazol- 1 - yl)-butyl)-imino)]erythromycin A; MS (+ ion mode): m/z 862.69 [M+ 1]
Compound No. 108: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-ll,12-dideoxy- 3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo[4,5- b]pyridin-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 834 [M+ 1]
Compound No. 109: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-((3,5-diphenyl)-pyrazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 919.85 [M+ 1]
Compound No. 110: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((lH)-imidazo[4,5- b]pyridin-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 844.8 [M+l]
Compound No. 111 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-3 -yl)-imidazo)- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 858.64 [M+l]
Compound No.l 12: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l 1,12-dideoxy- 3-O-decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-(2,4-difluoro)-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 897.6 [M+l]
Compound No.l 13: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(2,4-difluoro)-phenyl)- imidazol)-l-yl)-butyl)-imino)] erythromycin A; MS (+ ion mode): m/z 879.62 [M+l]
Compound No. 114: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(2,4-difluoro)-phenyl)- imidazol)-l-yl)-butyl)-imino)] erythromycin A; MS (+ionmode): m/z 891.65[M+1]
Compound No. 115: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladmosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-furan-3 -yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A; MS (+ionmode): m/z 833.56[M+1]
Compound No. 115a: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl— (4-((4-furan-3 -yl)-imidazol- 1 -yl)- butyl)-imino)] erythromycin A hydrochloride salt; M.Pt: 185-188 0C (decomposed)
Compound No. 116: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-phenyl-pyrazol-l -yl)-butyl)- imino))] erythromycin A; Mass: m/z 855.35 [M++l]
Compound No. 117: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-3-yl-lH-imidazol- 1 - yl)-pentyl)-imino)] erythromycin A; Mass: m/z 858.38 [M++l] Compound No. 118: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-pyridin-4-yl-lH-imidazol-l- yl)-butyl)-imino))] erythromycin A; Mass: m/z 844.41 [M++ 1]
Compound No. 119: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-alryl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-4-yl- 1 H-imidazol- 1 - yl)-butyl)-imino))] erythromycin A; Mass: m/z 856.39 [M++l]
Compound No. 120: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-((4-phenyl-pyrazol- 1 -yl)-butyl)- imino)) erythromycin A; Mass: m/z 843.55 [M++l]
Compound No. 121 : 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((indazol-2-yl)-butyl)- imino))] erythromycin A; Mass: m/z 817.54 [M++l]
Compound No. 122: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((indazol-2-yl)-butyl)-imino))] erythromycin; Mass: m/z 829.60 [M++l]
CompoundNo. 123: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-ll, 12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((3-pyridin-3-yl-pyrazol-l-yl)- butyl)-imino))] erythromycin A; Mass: m/z 844.54 [M++l]
Compound No. 124: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((indazol-l-yl)-butyl)- imino))] erythromycin A; Mass: m/z 817.52 [M++l]
Compound No. 125 : 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l 1 , 12-dideoxy-3-O- decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-((4-pyrazin-2-yl- 1 H-imidazol- 1 - yl)-butyl)-imino))] erythromycin A; Mass: m/z 845.56 [M++l]
Compound No. 126: 2-α-Fluoro-5-O-(3' -N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-thiophen-3 -yl- 1 H-imidazol- 1 - yl)-butyl)-imino))] erytliromycin A; Mass: m/z 849.45 [M++l]
Compound No. 127: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-thiophen-3 -yl- lH-imidazol- 1 - yl)-butyl)-imino))] erythromycin A; Mass: m/z 861.45 [M++l]
Compound No. 128: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-quinolin-3-yl-lH-imidazol-l- yl)-butyl)-imino))] erythromycin A; Mass: m/z 894.60 [M++l]
Compound No. 129: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(indazol-l -yl)-butyl)-imino))] erythromycin A; Mass: m/z 829.49 [M++l] Compound No. 130: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-pyrimidin-5-yl-lH-imidazol- l-yl)-butyl)-imino))] erythromycin A; Mass: m/z 845.46 [M++l]
Compound No. 131: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-pyrimidin-5-yl-lH-imidazol- l-yl)-butyl)-imino))] erythromycin A; Mass: m/z 857.48 [M++l]
Compound No. 132: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-((4-furan-2-yl- 1 H-imidazol- 1 -yl)- butyl)-imino))] erythromycin A; Mass: m/z 833.56 [M++l]
Compound No. 133: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-((4-thiophen-2-yl- lH-imidazol- 1 - yl)-butyl)-imino))] erythromycin A; Mass: m/z 849.57 [M++l]
Compound No. 134: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(4-chloro-phenyl)-lH- imidazol-l-yl)-butyl)-imino))] erythromycin A; Mass: m/z 877.40 [M++l]
Compound No. 135: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(4-chloro-phenyl)-lH- imidazol-l-yl)-butyl)-imino))] erythromycin A; Mass: m/z 889.40 [M++l]
Compound No. 136: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-pyridin-2-yl- 1 H-imidazol- 1 - yl)-butyl)-imino))] erythromycin A; Mass: m/z 844.46 [M++l]
Compound No. 137: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-pyridin-2-yl-lH-imidazol-l- yl)-butyl)-imino))] erythromycin A; Mass: m/z 856.44 [M++!]
Compound No. 138: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 - [oxycarbonyl-((9-(4-amino-butyl)-9H-purin-6-yl)- imino)] erythromycin A; Mass: m/z 846.45 [M++l]
Compound No. 139: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((3-pyridin-3-yl-lH-pyrazol-l- yl)-butyl)-imino))] erythromycin A; Mass: m/z 856.61[M++1]
Compound No. 140: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(4-chloro- phenyl)- 1 H-imidazol- l-yl)-butyl)-imino))] erythromycin A; Mass: m/z 895.49 [M++l]
Compound No. 141 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-pyridin-2-yl)- 1 H-imidazol- l-yl)-butyl)-imino))] erythromycin A; Mass: m/z 862.49 [M++!] Compound No. 142: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-Imidazo[4,5- b]pyridine-2-yl)-butyl)-imino)erythromycin A; Mass: m/z 818.95 [M++l]
Compound No. 143: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Tetrazol-l-yl- imidazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 835.44 [M++l]
Compound No. 144: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH- Benzoimidazol-2-yl)-butyl)-imino)erythromycin A; Mass: m/z 817.45 [M++!]
Compound No. 145 : 2-α-Fluoro-5 -O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12- dideoxy-S-O-decladinosyl-ό-O-methyl-S-oxo-^, 1 l-[oxycarbonyl-((4-[4-(6-Fluoro- pyridin-3-yl)-imidazol-l-yl]-butyl)-imino)erythromycin A; Mass: m/z 862.39 [M++l]
Compound No. 146: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-Imidazo[4,5- c]pyridine-2-yl)-butyl) iminoerytliromycin A; Mass: m/z 818.4 [M++!]
Compound No. 147: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12, 11 -[oxycarbonyl-((4-(4-[ 1 ,2,4]Trizol- 1 - yl-phenyl)-butyl)-imino)erytliromycin A; Mass: m/z 844.4 [M++l]
Compound No. 148: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-emyl)-desosaminyl-ll,12- dideoxy-3 -O-decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4-Imidazol- 1 -yl- phenyl)-butyl)-imino)erythromycin A; Mass: m/z 843.5 [M++l]
Compound No. 149: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-[4-(6-Chloro- pyridin-3-yl)-imidazol-l-yl]-butyl)-imino)erythromycin A; Mass: m/z 878.4 [M++l]
Compound No. 150: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(3-[l-(4-Amino-butyl)- lH-imidazol-4-yl]-phenyl)iminoerythromycin A; Mass: m/z 858.5 [M++l]
Compound No. 151 : 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Pyridin-3-yl- thiazol-2-yl)-butyl)-imino)erytlτromycin A; Mass: m/z 861.3 [M++l]
Compound No. 152: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(3-[2-(4-Amino-butyl)- thiazol-4-yl]-phenyl)iminoerythromycin A; Mass: m/z 875.4 [M++l]
CompoundNo. 153: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Pyrazol-l-yl- imidazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 833.4 [M++l] Compound No. 154: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-([l,4']-Bipyrazolyl- l'-yl)-butyl) iminoerythromycin A; Mass: m/z 833.4 [M++l]
Compound No. 155: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Iinidazol-l-yl- pyrazol-l-yl)-butyl)-immo)erythromycin A; Mass: m/z 833.4 [M++l]
Compound No. 156: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Pyrazol-l-yl- imidazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 833.4 [M++l]
Compound No. 157: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-S-O-decladinosyl-β-O-methyl-S-oxo-πjll-toxycarbonyl-^-fS^'JBithiophenyl- 5-yl-butyl)-imino)erythromycin A; Mass: m/z 865.3 [M++l]
Compound No. 158: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-S-O-decladinosyl-ό-O-methyl-S-oxo-πjl l-foxycarbonyl-^-P^^Bithiophenyl- 5'-yl-butyl)-imino)erythromycin A; Mass: m/z 865.3 [M++l]
Compound No. 159: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Furan-2-yl- thiaophen-2-yl)-butyl)-imino)erythromycin A; Mass: m/z 849.4 [M++l]
Compound No. 160: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Oxazol-5-yl- imidazol-l-yl)-butyl)-imino)erytliromycin A; Mass: m/z 834.4 [M++!]
Compound No. 161: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12- dideoxy-3 -O-decladinosyl-ό-O-methyl-S -oxo- 12,11 -[oxycarbonyl-((4-(3-Pyrrol- 1 -yl- [l,2,4]triazol-l-yl)-butyl) iminoerythromycin A; Mass: m/z 833.4 [M++l]
Compound No. 162: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-Thiophen-2-yl- tetrazol-2-yl)-butyl)-imino)erythromycin A; Mass: m/z 851.4 [M++l]
Compound No. 163 : 2-α-Fluoro-5 -O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12- dideoxy-3-O-decladinosyl-6-O-methyl-3--oxo- 12,11 -[oxycarbonyl-((4-(4-Thiophen-3-yl- pyrazol-l-yl)-butyl)-immo)erythromycin A; Mass: m/z 849.4 [M++l]
Compound No. 164: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-Furan-3-yl- pyrazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 833.4 [M++l]
Compound No. 165: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Furan-2-yl- pyrazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 833.4 [M++l] Compound No. 166: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-Phenyl-tetrazol- 2-yl)- butyl)-imino)erythromycin A; Mass: m/z 845.4 [M++l]
Compound No. 167: 2-α-Fluoro-5-O-(3'-N-desmemyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-raethyl-3-oxo-12,l l-[oxycarbonyl-((4-[5-(4-Meth.oxy- phenyl)-tetrazol-2-yl]-butyl)-imino)erythromycin A; Mass: m/z 875.3 [M++l]
Compound No. 168: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-Furan-3-yl- imidazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 833.5 [M++l]
Compound No. 169: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo- 12,11- [oxycarbonyl-((4-(6-Pyrazol- 1 -yl- pyridin-3-yl)-butyl)-imino)erythromycin A; Mass: m/z 844.4 [M++ 1]
Compound No. 170: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Pyridin-3-yl- pyrazol-l-yl)-butyl)-imino)erythromycin A; Mass: m/z 844.5 [M+H-I]
Compound No. 171 : 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-Thiophen-2-yl- pyridin-3-yl)-butyl)-imino)erythromycin A; Mass: m/z 860.3 [M++ 1]
Compound No. 172: 2-α-Fluoro-5-O-(3'-N-desmetliyl-3'-N-ethyl)-desosaminyl-l l,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-Phenyl-thiophen- 2-yl)-butyl)-imino)erytliromycin A; Mass: m/z 859.4 [M++l]
Compound No. 173: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(N-(4-Amino-butyl)-N- tliiazol-2-yl-nicotinimido)]erythromycin A; Mass: m/z 890.09 [M++l]
Compound No. 174 : 2-α-Fluoro-5 -O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(N-(4-Amino-butyl)-N- thiazol-2-yl-nicotinimido)]erythromycin A; Mass: m/z 904.4 [M++l]
Compound No. 175: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-[4-(6-Pyrrol-l-yl- pyridin-3-yl)-imidazol-l-yl]-butyl)-imino)erythromycin A; Mass: m/z 909.5 [M++!]
Compound No. 176: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(6-Pyrrol-l-yl- pyridin-3-yl)-butyl)-imino)erythromycin A; Mass: m/z 834.4 [M++l]
Compound No. 177: 2-oc-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-ll,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-Pyrrol-l-yl- thiazol-5-yl)-butyl)-imino)erythromycin A; Mass: m/z 849.3 [M++l] Compound No. 178: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(6-Imidazol-l-yl- pyridin-3-yl)-butyl)-imino)erythromycin A; Mass: m/z 844.4 [M++ 1]
Compound No. 179: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-[4-(Tetrahydro- furan-2-yl)-pyridin-3-yl]-butyl)-imino)erythromycin A; Mass: m/z 848.4 [M++!]
Compound No. 180: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-((4-p-tolyl-imidazol- 1 -yl)-butyl)- imino)] erythromycin A; Mass: m/z 857.08[M++!]
Compound No. 181: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-emyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-l 2, 11 -[oxycarbonyl-((4-(4-(4-aminophenyl)-imidazol- 1 - yl)-butyl)-imino)] erythromycin A; Mass: m/z 858.07[M++!]
Compound No. 182: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-methyl-3-aminophenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 872.1[M++1]
Compound No. 183: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-π,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-(3-imidazol- 1 yl)- phenyl)imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 909.12[M++l]
CompoundNo. 184: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3-(N,N-dicyclopropyl- amino)-phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 938.20[M++l]
Compound No. 185: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(3-(N,N-dimethyl- amino)phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 886.12[M++1]
Compound No. 186: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(3-(tetrazol-lyl)-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 91 1.09[M++!]
Compound No. 187: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-((4-(2-(pyrrol- 1 yl)-thiozol-5-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 915.04[M++!]
Compound No. 188: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(3-trifluoromethyl-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 857.08[M++!]
Compound No. 189: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((N-(thiazol-2-yl)-benzimido)- butyl)-imino)] erythromycin A; Mass: m/z 903.4[M++ 1] Compound No. 190: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(2-ammo-pyrimidin)-5-yl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 680.04 [M++!]
Compound No. 191 : 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(4-(pyrrol-lyl)-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 908.13 [M++!]
Compound No. 192: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-β-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-((4-(3 -(pyrrol- 1 yl)-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 908.13 [M++!]
Compound No. 193: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-ll,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11- [oxycarbonyl-((4-(4-(3 -(N-acetyl-amino)-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 900.11[M++!]
Compound No. 194: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(3 -(N-isopropyl-amino)- phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 900.15[M++l]
Compound No. 195: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((4-(3-nitrophenyl)-imidazol-l- yl)-butyl)-imino)] erythromycin A; Mass: m/z 888.05[M++l]
Compound No. 196: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N-benzoyl-amino)- phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 962.18[M++!]
Compound No. 197: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(3,4-dimethyl-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 871.11[M++!]
Compound No. 198: 5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl- 6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((4-(4-Pyridin-3-yl-thiazol-2-yl)-butyl)-imino)] erythromycin A; Mass: m/z 862.4 [M++l]
Compound No. 199: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-(4-fluorophenyl)-imidazol- 1 - yl)-butyl)-imino)] erythromycin A; Mass: m/z 861.05 [M++l]
Compound No. 200: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(4-methoxy-phenyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 873.08 [M++!]
Compound No. 201: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((N-(benzthiazol-2-yl)- benzimido)-butyl)-imino)] erythromycin A; Mass: m/z 953.19 [M++l] Compound No. 202: 2-α-Fluoro-5-O-(3'-N-desmemyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-((N-(thiazol-2-yl)-nicotinamido)- butyl)-imino)] erythromycin A; Mass: m/z 904.12 [M++l]
Compound No. 203: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N-methyl-amino)-plienyl)- imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 872.10 [M++l]
Compound No. 204: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-(2- aminopyridyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 8590.6 [M++l]
Compound No. 205: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l 1,12- dideoxy-3 -O-decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4-(5 -(2- aminopyridyl)- 2H-tetrazol-5-yl)-butyl)-imino)] erythromycin A; Mass: m/z 861.03 [M++l]
Compound No. 206: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3,4- difluorophenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 878.04 [M++l]
Compound No. 207: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-(2- chloropyridyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 878.49 [M++l]
Compound No. 208: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(6- aminopyridyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A; Mass: m/z 859.06 [M++l]
Compound No. 209: 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l 1,12- dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(2-Chloro- pyridin-4-yl)-tetrazol-2-yl)-butyl)-imino)] erythromycin A; Mass: m/z 880.46[M++l]
Example 6. Pharmacological activity
Compounds described herein displayed antibacterial activity in vitro especially against strains that are resistant to macrolides either due to efflux (mef strains) or ribosomal modification (erm) strains. These compounds are useful in treating community acquired pneumonia, upper and lower respiratory tract infections, skin and soft tissue infections, hospital acquired lung infections, bone and joint infections, and other bacterial infections, for example, mastitis, catether infection, foreign body, prosthesis infections or peptic ulcer disease. - I ll -
Minimum inhibitory concentration (MIC) has been an indicator of in vitro antibacterial activity widely used in the art.
Procedure:
Medium
a) Cation adjusted Mueller Hinton Agar (MHA-Difco)
b) Trypticase Soya Agar (TSA)
Inoculum preparation
Cultures were streaked on TSA for aerobic cultures and MHA with 5 % sheep blood for fastidious cultures. Aerobic cultures were incubated at 37 0C for about 18-24 hours. Fastidious cultures were incubated CO2 incubation (5% CO2) at 37 0C for about 18-24 hours. Three to four well-isolated colonies were 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 obtain inoculum sizes of approximately 1-2 x 107 organisms/mL.
Preparation of drug concentration
1 mg/mL concentration of stock solution of drugs was prepared in dimethylsulfoxide/distilled water/solvent given in National Committee for Clinical Laboratory Standards (NCCLS) manual. Serial two-fold dilutions of the compounds and standard drugs were prepared as per NCCLS manual.
The stock solution was changed according to the need of the experiment.
Preparation of Agar Plates
Two rnL of respective drug concentration was added to 18 mL of Molten Mueller Hinton agar to achieve the required range, for example 0.015 μg/mL - 16 μg/mL. For fastidious cultures 1 mL of sheep blood was added in Molten Mueller Hinton agar. MHA and MHA with 5% sheep blood plates without antibiotic for each set were prepared for controls. One MHA and MHA with 5% sheep blood plate without antibiotic for determining quality check for media was prepared.
Preparation of Teflon template
1 μL of each culture on each plate was replicated with the help of a replicator (i. e. ,
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 0C in a 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 for purity.
Media Control: NCCLS disc diffusion assay using 10 μg 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.
References:
o National Committee for Clinical Laboratory Standards (NCCLS), Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically -
Fifth Edition; Approved Standard. M7-A5, Vol.20. No. 2 (January 2000).
o National Committee for Clinical Laboratory Standards, Performance Standards for Antimicrobial Susceptibility Testing - Twelfth informational supplement, M 100- 12, Vol. 22 No. 1 (January 2002).
Results:
a) The compounds described herein exhibited MIC values against
Staphylococcus aureus in the range of between about 0.03 μg/mL to about 8 μg/mL, for example between about 0.03 μg/mL to about 1 μg/mL.
b) The compounds described herein exhibited MIC values against sensitive Streptococcus pneumoniae in the range of between about 0.008 μg/mL to about
16 μg/mL, for example between about 0.008 μg/mL to about 0.5 μg/mL.
c) The compounds described herein exhibited MIC values against erythromycin resistant Streptococcus pneumoniae in the range of between about 0.06 μg/mL to about 16 μg/mL, for example between about 0.06 μg/mL to about 4 μg/mL.
d) The compounds described herein exhibited MIC values against Haemophilus influenzae in the range of between about 0.03 μg/mL to about 32 μg/mL, for example between about 0.03 μg/mL to about 16 μg/mL.
e) The compounds described herein exhibited MIC values against Moraxella species in the range of between about 0.004 μg/mL to about 4 μg/mL, for example between about 0.004 μg/mL to about 1 μg/mL. f) The compounds described herein exhibited MIC values against telithromycin resistant Streptococcus pneumoniae in the range of between about 0.5 μg/mL to about 16 μg/mL, for example between about 0.5 μg/mL to about 16 μg/mL.
g) The compounds described herein exhibited MIC values against sensitive Streptococcus pyogenes in the range of between about 0.008 μg/mL to about 1 μg/mL, for example between about 0.008 μg/mL to about 0.15 μg/mL.
h) The compounds described herein exhibited MIC values against erythromycin resistant Streptococcus pyogenes in the range of between about 0.015 μg/mL to about 16 μg/mL, for example between about 0.015 μg/mL to about 16 μg/mL.
i) The compounds described herein exhibited MIC values against methicillin resistant Staphylococcus aureus to about 16 μg/mL.
j) The compounds described herein exhibited MIC values against sensitive
Enterococci species in the range of between about 0.03 μg/mL to about 1 μg/mL, for example between about 0.03 μg/mL to about 0.5 μg/mL.
k) The compounds described herein exhibited MIC values against resistant
Enterococci species in the range of between about 1 μg/mL to about 16 μg/mL, for example between about 1 μg/mL to about 16 μg/mL.

Claims

We Claim:
1. Compounds having the structure of Formula I,
Figure imgf000116_0001
pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers or polymorphs thereof, wherein:
R1 is hydrogen or a hydroxyl protecting group;
R2 and R3 are independently alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 is hydrogen, alkyl or aralkyl, with the proviso that R2 and R3 are not simultaneously methyl;
W is alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein
q is an integer of from 2 to 6;
G is no atom, -CO, -CS or -SO2;
R9 and R10 are independently hydrogen or alkyl; and
J is no atom, -CR9R10 or N(R12)(CH2)m, wherein m is an integer of from 0 to 6; R9 and R10 are the same as defined earlier; and R12 is hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 is alkyl, aryl or heterocycle;
R is aryl or heterocycle;
R4 is alkyl, alkenyl or alkynyl; R1 is alkyl or -(CH2)r-U, wherein r is an integer of from 1 to 4 and. U is alkenyl or alkynyl; and
Y is halogen, cyano or alkyl; Z is oxygen, sulfur or NOR11, wherein R11 is the same as defined earlier.
2. Compounds of claim 1, wherein R is heterocycle; R2 is methyl; R3 is alkyl (except methyl), alkenyl, cycloalkyl or COR11; W is -G(CH2)qJ- or CR9R10, wherein G, q, J, R9, R10 and R11 are the same as defined in claim 1.
3. Compounds of claim 1, wherein R1 is hydrogen or a hydroxy protecting group (wherein the hydroxy protecting is benzoyl, tetrahydropyranyl or a trialkylsilylether); R2 is CH3; R3 is C2H5, -CH2-CH=CH2 or -CH2CH2F; W is -(CH2)4-J- wherein J is CH2 or (CH2)0-1-N(CO)-Ra; and
R is
_Λ^
Figure imgf000117_0001
wherein
X1-X3 are independently CH or N; X4-X8 are independently CH, CR4 or N; X9 is O, S, N, NH or CH; X10 is NH or S; R3 is thienyl, furyl, pyrazolyl, oxazolyl, tetrazolyl, imidazolyl, pyridinyl, fluoropyridinyl, chloropyridinyl, aminopyridinyl, pyrazinyl, pyrimidinyl, aminopyrimidinyl, quinolinyl, pyrrolo-pyridyl, pyrrolo-thiazolyl or optionally substituted phenyl; R'a is hydrogen or furyl; Rb is hydrogen or amino; R0 is hydrogen, thienyl, furyl, pyrazolyl, pyrazinyl, pyridinyl, aminopyridinyl, pyrimidinyl, pyrrolyl, imidazolyl or optionally substituted phenyl; and Rd is thienyl, pyrazolyl, imidazolyl, triazolyl, pyrrolyl or tetrahydrofuryl. 4. A compound selected from: 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-(imidazol-l-yl)-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-b]- pyridin- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-b]- pyridin- l-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-o-O-methyl-3-oxo- 12,11 - [oxycarbonyl-((4-(benzoimidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosammyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo- 12,11- [oxycarbonyl-((4-(imidazol- 1 -yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosammyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((3-(imidazol- 1 -yl)- propyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-(imidazol-l-yl)-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-propyl)-desosaminyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((3-(imidazol-l-yl)-propyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ρropyl)-desosammyl- 11,12-dideoxy-3 -O- decladinosyl-β-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyty-desosaminyl- 11 , 12-dideoxy-3 - O-decladinosyl-ό-O-methyl-S-oxo-^, 11 -[oxycarbonyl-((4-(pyrrolo-[2,3- b]pyridin- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-desosammyl-l l,12-dideoxy-3-0- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo-[2,3-b]pyridin-l- yl)-butyl)-imino)] erythromycin A, 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-isopropyl)-desosatninyl-l l,12-dideoxy-3-O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-ό-O-methyl-S-oxo-^ll-foxycarbonyl-^-φenzoimidazol-l-yl)- butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-n-propyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(imidazol-l-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo- 12,1 l-[oxycarbonyl-((4-(pyrrolo-[2,3-b]pyridin- 1 - yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-b]- pyridin- 1 -yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(purin-9-yl)-butyl)- imino)] erythromycin A,
2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl)-desosaminyl-l l,12-dideoxy-3- O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-b]- pyridin-3-yl)-butyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyridin-3 -yl)- imidazol- 1 -yl)-butyl)-imino)] erythromycin A,
2α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-(((N'-methyl-N'-quinolm-4- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-ό-O-methyl-S-oxo-πjl l-foxycarbonyl-ζ^'-methyl-N'-pyridine-S- ylmethyl)-2-aminoethyl)-imino)] erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3-O- decladmosyl-6-O-methyl-3-oxo-125l l-[oxycarbonyl-(((N'-methyl-N-pyridine-4- ylmethyl)-2-aminoethyl)-imino)]erythromycin A,
2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-(((N'-methyl-N'-pyridine-2- ylmethyl)-2-aminoethyl)-imino)] erythromycin A, 94 2-α-Fluoro-5-O-(3l-N-desmethyl-3l-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
95 decladmosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-(((N'-methyl-Nl-pyridine-2-
96 ylmethyl)-2-aminoethyl)-imino)] erythromycin A, 97
98 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O-
99 decladinosyl-o-O-methyl-S-oxo-^jl l-foxycarbonyl-^^N'-methyl-N'-pyridine-S- 100 ylmethyl)-2-aminoethyl)-imino)]erytliromycin A,
101
102 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O-
103 decladinosyl-6-O-methyl-3 -oxo- 12,11- [oxycarbonyl-(((N'-methyl-N'-pyridine-4-
104 ylmethyl)-2-aminoethyl)-imino)] erythromycin A, 105
106 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O-
107 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-(((N'-methyl-N'-quinoline-4-
108 ylmethyl)-2-aminoethyl)-immo)] erythromycin A, 109
110 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
111 decladinosyl-6-O-methyl-3 -oxo- 12,1 l-[oxycarbonyl-(((N'-pyridine-3-ylmethyl)-2-
112 aminoethyl)-imino)] erythromycin A, 113
114 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
115 decladinosyl-6-O-methyl-3 -oxo- 12,1 l-[oxycarbonyl-(((N'-acetyl-N'-pyridine-3-
116 ylmethyl)-2-aminoethyl)-imino)] erythromycin A, 117
118 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
119 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((N'-ρyridine-3-ylmethyl)-2-
120 aminoethyl)-imino)] erythromycin A, 121
122 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
123 decladmosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(((N'-acetyl-N'-pyridine-3-
124 ylmethyl)-2-aminoethyl)-imino)]erythromycin A, 125
126 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O-
127 decladinosyl-β-O-methyl-S-oxo-πjll-foxycarbonyl-C^'jN'-di-pyridine-S-yl-
128 methyl)-2-aminoethyl)-imino)]erythromycin A, 129
130 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1,12-dideoxy-3-O-
131 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-(((N',N'-di-pyridine-3 -yl-
132 methyl)-2-aminoethyl)-imino)] erythromycin A, 133
134 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
135 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(quinolin-3-yl)-butyl)- 136 imino)] erythromycin A,
137
138 2-α-Fluoro-5-O- (S'-N-desmethyl-S'-N-ethy^-desosaminyl-l l,12-dideoxy-3-O-
139 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(quinolin-8-yl)-butyl)-
140 imino)] erythromycin A, 141 142 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-etliyl)-desosaniinyl-l l,12-dideoxy-3-O-
143 decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(pyridin-2-yl)-butyl)-
144 imino)] erythromycin A, 145
146 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
147 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(pyridin-3-yl)-butyl)-
148 imino)] erythromycin A, 149
150 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-ethyl)- desosaminyl-1 l,12-dideoxy-3-O-
151 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-φyridin-4-yl)-butyl)-
152 imino)] erythromycin A, 153
154 2-α-Fluoro-5-O- (3'-N-desmemyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
155 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-2-yl)-butyl)- 156 imino)] erythromycin A,
157
158 2-α-Fluoro-5-O- (3'-N-desmethyl-3'-N-allyl)-desosammyl-l l,12-dideoxy-3-O-
159 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(pyridin-4-yl)-butyl)-
160 imino)] erythromycin A, 161
162 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
163 decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyridin-3-yl)-pentyl)-
164 imino)] erythromycin A, 165
166 2-α-Fluoro-5-O- (3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
167 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(pyridin-3 -yl)-butyl)-
168 imino)] erythromycin A, 169
170 2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-ethyl)-desosaininyl-l l,12-dideoxy-3-O-
171 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(indol-l-yl)-butyl)-
172 imino)] erythromycin A, 173
174 2-α-Fluoro-5-O-(3'-N-desmethyl-3t-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
175 decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(4-phenylimidazol- 1 -yl)-
176 butyl)-imino)] erythromycin A, 177
178 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
179 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-butyl)-
180 imino)] erythromycin A, 181
182 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
183 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-
184 c]pyridin- 1 -yl)-butyl)-imino)] erythromycin A, 185
186 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
187 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)- 188 imino)] erythromycin A,
189 190 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O- 191 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-
192 c]pyridin-3-yl)-butyl)-imino)]erythromycin A3 193
194 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyty-desosaminyl- 11,12-dideoxy-3-
195 O-decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-phenylimidazol- 1 -
196 yl)-butyl)-imino)] erythromycin A, 197
198 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)-desosaminyl- 11,12-dideoxy-3-
199 O-decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(benzotriazol- 1 -yl)-
200 butyl)-imino)] erythromycin A, 201
202 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)-desosaminyl- 11,12-dideoxy-3 -
203 O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-2-yl)-
204 butyl)-imino)] erythromycin A, 205
206 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)-desosaminyl- 11,12-dideoxy-3-
207 O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH)-imdazo[4,5-
208 bjpyridin- 1 -yl)-butyl)-imino)] erythromycin A, 209
210 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl)-desosaminyl- 11,12-dideoxy-3 -
211 0-decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(mdol-l-yl)-butyl)-
212 imino)] erythromycin A, 213
214 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O-
215 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(benzotriazol- 1 -yl)-butyl)-
216 imino)] erythromycin A, 217
218 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy:3-O-
219 decladinosyl-6-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-
220 butyl)-imino)] erythromycin A, 221
222 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
223 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-
224 b]pyridin-3-yl)-butyl)-imino)] erythromycin A, 225
226 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl-l 1,12-dideoxy-3-O-
227 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-phenylimidazol-l-yl)-
228 butyl)-imino)] erythromycin A, 229
230 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11,12-dideoxy-3 -O-
231 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(benzotriazol-2-yl)-butyl)-
232 imino)] erythromycin A, 233
234 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-isopropyl)-desosaminyl-l l,12-dideoxy-3-0-
235 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(indol-l-yl)-butyl)-
236 imino)] erytliromycin A,
237
Figure imgf000123_0001
240 b]pyridin-3-yl)-butyl)-imino)]erythromycin A, 241
242 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11 , 12-dideoxy-3-O-
243 decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-butyl)-
244 imino)] erythromycin A, 245
246 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyty-desosaminyl- 11,12-dideoxy-3-
247 O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-nitroindol-l-yl)-
248 butyl)-imino)] erythromycin A, 249
250 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
251 decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(5-fluoroindol- 1 -yl)-
252 butyl)-imino)] erythromycin A, 253
254 2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
255 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(benzotriazol-l-yl)-butyl)-
256 imino)] erythromycin A, 257
258 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
259 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-methylbenzoimidazol-
260 l-yl)-butyl)-imino)] erythromycin A, 261
262 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0-
263 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-ethylbenzoimidazol-l-
264 yl)-butyl)-imino)] erythromycin A, 265
266 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-isopropyl)-desosaminyl- 11,12-dideoxy-3 -O-
267 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarboiiyl-((4-(benzotriazol-l-yl)-butyl)-
268 imino)] erythromycin A, 269
270 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
271 decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(2-ethylbenzoimidazol- 1 -
272 yl)-butyl)-imino)] erythromycin A, 273
274 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3-O-
275 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-((4-(pyridin-3-yl)-
276 imidazol- 1 -yl)-butyl)-imino)] erythromycin A, 277
278 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
279 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(2-methylbenzoimidazol-
280 l-yl)-butyl)-imino)] erythromycin A, 281
282 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O-
283 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-
284 yl)-butyl)-imino)] erythromycin A, 285 286 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11 , 12-dideoxy-3 -O-
287 decladinosyl-ό-O-methyl-S-oxo-πjl-toxycarbonyl-^-ClH-imidazo^^-
288 b]pyridin-l-yl)-butyl)-imino)]erythromycin A, 289
290 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
291 3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-
292 b]pyridin-3-yl)-butyl)-imino)]erythromycin A, 293
294 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
295 S-O-decladinosyl-β-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(5-nitroindol- 1 -yl)-
296 butyl)-imino)]erytliromycin A, 297
298 2-α-Fluoro-5-O-(3l-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
299 decladinosyl-6-O-niethyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-(pyridin-3-ylmetb.yl)-
300 benzoimidazol-l-yl)-butyl)-imino)]erytlτromycin A, 301
302 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
303 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(2-(pyridin-3-yl-methyl)-
304 benzoimidazol-l-yl)-butyl)-imino)] erythromycin A, 305
306 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1,12-dideoxy-3-O-
307 decladinosyl-6-O-methyl-3-oxo- 12, 11 - [oxycarbonyl-((4-(2-phenylimidazol- 1 -yl)-
308 butyl)-imino)] erythromycin A, 309
310 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
311 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-fluoroindol-l-yl)-
312 butyl)-imino)] erythromycin A, 313
314 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-l l,12-dideoxy-3-O-decladinosyl-6-O-
315 methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(5 ,6-dimethyl-benzoimidazol- 1 -yl)-butyl)-
316 imino)] erythromycin A, 317
318 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O-
319 decladinosyl-o-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(5,6-
320 dimethylbenzoimidazol- 1 -yl)-butyl)-imino)] erythromycin A, 321
322 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-0-
323 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-
324 c]pyridin-3-yl)-butyl)-imino)]erythromycin A, 325
326 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-allyl)-desosaminyl-l 1,12-dideoxy-3-O-
327 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-methyl-3H-
328 imidazo[4,5-b]pyridin-3-yl)-butyl)-imino)]erythromycin A, 329
330 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
331 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(2-methyl-3H-
332 imidazo[4,5-b]pyridin-3-yl)-butyl)-imino)]erythromycin A, 333 334 2-α-Fluoro-5-O-(3'-N-desmethyl-3l-N-allyl)-desosaininyl-l l,12-dideoxy-3-O-
335 decladinosyl-6-O-metliyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-
336 c]pyridin-l-yl)-butyl)-imino)] erythromycin A, 337
338 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
339 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(6-amino-9H-purin-9-yl)-
340 butyl)-imino)] erythromycin A, 341
342 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
343 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(2-phenylimidazol-l-yl)-
344 butyl)-imino)] erythromycin A, 345
346 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-desosaminyl-l l,12-dideoxy-3-O-
347 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(benzoimidazol- 1 -yl)-
348 butyl)-imino)] erythromycin A, 349
350 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l 1,12-
351 dideoxy-3 -O-decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(3H-
352 imidazo[4,5-b]pyridin-3-yl)-butyl)-imino)]erythromycin A, 353
354 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l 1,12-
355 dideoxy-3-0-decladmosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-
356 (benzoimidazol-l-yl)-butyl)-imino)] erythromycin A, 357
358 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l 1,12-
359 dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12,114oxycarbonyl-((4-
360 (pyrrolo[2,3-b]pyridin-l-yl)-butyl)-immo)]erythromycin A, 361
362 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-ll,12-dideoxy-
Figure imgf000125_0001
364 b]pyridin- 1 -yl)-butyl)-imino)] erythromycin A,
365
366 2-α-Fluoro-5-O-(3 '-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl- 11 , 12-dideoxy-
367 S-O-decladinosyl-ό-O-methyl-S-oxo-^jl l-foxycarbonyl-^-φenzotriazol-l-yl)-
368 butyl)-imino)] erythromycin A, 369
370 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
371 S-O-decladinosyl-ό-O-methyl-S-oxo-π^ l-foxycarbonyl-^-φenzoimidazol-l-
372 yl)-butyl)-imino)] erythromycin A, 373
374 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-l l,12-dideoxy-
375 3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-phenyl-imidazol-
376 l-yl)-butyl)-imino)] erythromycin A, 377
378 2-α-Fluoro-5-O-(3 !-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
379 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(2-trifluoromethyl-
380 benzoimidazol-l-yl)-butyl)-imino)] erythromycin A, 381 382 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
383 decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4,5 -diphenyl-imidazol- 1 -
384 yl)-butyl)-imino)] erythromycin A, 385
386 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
387 decladinosyl-ό-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(4,5-diphenyl-imidazol- 1 -
388 yl)-butyl)-imino)] erythromycin A, 389
390 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-l l,12-dideoxy-3-O-
391 decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-phenyl-imidazol-l-yl)-
392 butyl)-imino)] erythromycin A, 393
394 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l 1,12-
395 dideoxy-S-O-decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4-phenyl-
396 imidazol-l-yl)-butyl)-imino)]erytliromycin A, 397
398 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-cyclopropyl methyl)-desosaminyl-l 1,12-
399 dideoxy-3-0-decladinosyl-6-0-memyl-3-oxo-12,l l-[oxycarbonyl-((4-
400 (benzotriazol-l-yl)-butyl)-imino)]erythromycin A, 401
402 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl methyl)-desosaminyl- 11,12-
403 dideoxy-3-O-decladinosyl-6-O-methyl-3-oxo-12, 11 -[oxycarbonyl-((4-(4-(pyridin-
404 3-yl)-imidazol-l-yl)-butyl)-imino)]erythromycin A, 405
406 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)-desosaminyl- 11,12-dideoxy-3 -O-
407 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(pyrrolo[2,3-b]pyridin-l-
408 yl)-butyl)-imino)]erythromycin A, 409
410 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-acetyl)-desosaminyl- 11,12-dideoxy-3-O-
411 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-phenyl-imidazol-l-yl)-
412 butyl)-imino)] erythromycin A, 413
414 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-acetyl)-desosaminyl-ll,12-dideoxy-3-0-
415 decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(lH-imidazo[4,5-
416 b]pyridin- 1 -yl)-butyl)-imino)] erythromycin A, 417
418 2-α-Fluoro-5-O-(3l-N-desmethyl-3'-N-acetyl)-desosaminyl-l l,12-dideoxy-3-O-
419 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(3H-imidazo[4,5-
420 b]pyridin-3-yl)-butyl)-imino)]erythromycin A, 421
422 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O-
423 decladinosyl-β-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(3,5 -diphenyl)-pyrazol- 1 -
424 yl)-butyl)-imino)] erythromycin A, 425
426 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
427 3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(pyridn-3-yl)-
428 imidazol- 1 -yl)-butyl)-imino)] erythromycin A, 429 430 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-fluoroethyl)-desosaminyl-l l,12-dideoxy-
431 3-0-decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-imidazo[4,5-
432 b]pyridin- 1 -yl)-butyl)-imino)] erythromycin A, 433
434 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
435 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3,5-diphenyl)-pyrazol-l-
436 yl)-butyl)-imino)] erythromycin A, 437
438 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-cyclopropyl methyl)-desosaminyl- 11,12-
439 dideoxy-3-0-decladmosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-
440 imidazo[4,5-b] pyridin-l-yl)-butyl)-imino)] erythromycin A, 441
442 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-acetyl)-desosaminyl-l l,12-dideoxy-3-O-
443 decladinosyl-ό-O-methyl-S-oxo-^J l-foxycarbonyl-^-^-φyridin-S-y^-imidazo-
444 l-yl)-butyl)-imino)] erythromycin A, 445
446 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
447 3-O-decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(2,4-difluoro-
448 phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A, 449
450 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-2-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
451 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2,4-difluorophenyl)-
452 imidazol-l-yl)-butyl)-imino)] erythromycin A, 453
454 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-allyl)-desosaminyl- 11,12-dideoxy-3-O-
455 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(2,4-difluoro-phenyl)-
456 imidazol-l-yl)-butyl)-imino)] erythromycin A, 457
458 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
459 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-3-yl)-imidazol-
460 l-yl)-butyl)-imino)] erythromycin A, 461
462 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1,12-dideoxy-3-O-
463 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-3-yl)-imidazol-
464 l-yl)-butyl)-imino)] erythromycin A hydrochloride salt, 465
466 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
467 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-((4-phenyl-2H-pyrazol- 1 -
468 yl)-butyl)-imino)] erythromycin A, 469
470 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
471 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridin-3-yl)- 1 H-
472 imidazol-l-yl)-pentyl)-imino)] erythromycin A, 473
474 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
475 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(pyridin-4-yl)- 1 H-
476 imidazol-l-yl)-butyl)-imino)] erythromycin A, 477 478 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
479 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-4-yl)-lH-
480 imidazol- 1 -yl)-butyl)-imino)] erythromycin A, 481
482 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
483 decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-phenyl-2H-pyrazol-l-
484 yl)-butyl)-imino) erythromycin A, 485
486 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
487 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(lH-indazol-2-yl)-butyl)-
488 imino)] erythromycin A, 489
490 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
491 decladinosyl-6-O-methyl-3 -oxo- 12,11- [oxycarbonyl-((4-( 1 H-indazol-2-yl)-butyl)-
492 imino)] erythromycin A, 493
494 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
495 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-3-yl)-2H-
496 pyrazol-l-yl)-butyl)-imino)] erythromycin A, 497
498 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
499 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-( 1 H-indazol- 1 -yl)-butyl)-
500 imino)] erythromycin A, 501
502 . 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
503 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyrazm-2-yl)-lH-
504 imidazol- l-yl)-butyl)-imino)] erythromycin A, 505
506 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
507 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(thiophen-3 -yl)- 1 H-
508 imidazol- l-yl)-butyl)-imino)] erythromycin A, 509
510 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
511 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(thiophen-3-yl)-lH-
512 imidazol- l-yl)-butyl)-imino)] erythromycin A, 513
514 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
515 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(quinolin-3-yl)- 1 H-
516 imidazol- l-yl)-butyl)-imino)] erythromycin A, 517
518 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3-O-
519 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(l H-indazol- 1 -yl)-butyl)-
520 imino)] erythromycin A, 521
522 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
523 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyrimin-5-yl)-lH-
524 imidazol- l-yl)-butyl)-imino)] erythromycin A, 525
526 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
527 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(pyrimin-5-yl)-lH-
528 imidazol- 1 -yl)-butyl)-imino)] erythromycin A, 529
530 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
531 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-2-yl)-lH-
532 imidazol- l-yl)-butyl)-imino)] erythromycin A, 533
534 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O-
535 decladinosyl-o-O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(thiophen-2-yl)- IH-
536 imidazol- l-yl)-butyl)-imino)] erythromycin A, 537
538 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
539 decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-chloro-phenyl)-lH-
540 imidazol- l-yl)-butyl)-imino)] erythromycin A, 541
542 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
543 decladinosyl-6-0-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(4-chloro-phenyl)-lH-
544 imidazol- l-yl)-butyl)-imino)] erythromycin A, 545
546 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
547 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-2-yl)-lH-
548 imidazol- l-yl)-butyl)-imino)] erythromycin A, 549
550 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-allyl)-desosaminyl- 11,12-dideoxy-3 -O-
551 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-2-yl)-lH-
552 imidazol- l-yl)-butyl)-imino)] erytliromycin A, 553
554 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-allyl)-desosaminyl-ll,12-dideoxy-3-O-
555 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((9-(4-amino-butyl)-9H-
556 purin-6-yl)-imino)] erythromycin A, 557
558 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-2-allyl)-desosaminyl-ll,12-dideoxy-3-0-
559 decladinosyl-ό-O-methyl-S-oxo- 12, 11 -[oxycarbonyl-((4-(4-(pyridin-3-yl)- IH-
560 pyrazol-l-yl)-butyl)-imino)] erythromycin A, 561
562 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
563 S-O-decladinosyl-β-O-methyl-S-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-chloro-phenyl)-
564 lH-imidazol-l-yl)-butyl)-imino)] erythromycin A, 565
566 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-2-fluoroethyl)-desosaminyl- 11,12-dideoxy-
567 3-O-decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-φyridin-2-yl)-lH-
568 imidazol- l-yl)-butyl)-imino)] erythromycin A, 569
570 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
571 decladinosyl-6-O-methyl-3-oxo-12, 1 l-[oxycarbonyl-((4-(3H-imidazo[4,5-
572 b]pyridine-2-yl)-butyl)-imino)] erythromycin A, 573
574 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
575 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(tetrazol- 1 -yl)-
576 imidazol-l-yl)-butyl)-imino)] erythromycin A, 577
578 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
579 decladinosyl-ό-O-metliyl-S-oxo-πjl l-foxycarbonyl-^-^lH-benzoimidazol^-yl)-
580 butyl)-imino)] erythromycin A, 581
582 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
583 decladinosyl-6-O-methyl-3-oxo-12,ll-[oxycarbonyl-((4-(4-(6-fluoro-pyridin-3-yl)-
584 imidazol-l-yl)-butyl)-imino)] erythromycin A, 585
586 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
587 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(3H-imidazo[4,5-
588 c]pyridine-2-yl)-butyl)-imino)] erythromycin A, 589
590 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11 , 12-dideoxy-3 -O-
591 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-([l,2,4]trizol-l-yl)-
592 phenyl)-butyl)-imino)] erythromycin A, 593
594 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O-
595 decladinosyl-6-O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(imidazol- 1 -yl)-
596 phenyl)-butyl)-imino)] erythromycin A, 597
598 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
599 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(6-chloro-pyridin-3-
600 yl)-imidazol-l-yl)-butyl)-imino)] erythromycin A, 601
602 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
603 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-(3 -(I -(4-aminobutyl)- IH-
604 imidazol-4-yl)-phenyl)imino] erythromycin A, 605
606 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
607 decladinosyl-ό-O-methyl-S-oxo-^J l-foxycarbonyl-^-^-φyridin-S-ylji-thiazol-
608 2-yl)-butyl)-imino)] erythromycin A, 609
610 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1 , 12-dideoxy-3-O-
611 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(3-(2-(4-aminobutyl)-thiazol-
612 4-yl)-phenyl)imino] erythromycin A, 613
614 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
615 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyrazol-l-yl)-
616 imidazol-l-yl)-butyl)-imino)] erythromycin A, 617
618 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)-desosaminyl-l 1, 12-dideoxy-3-O-
619 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-([l,4']-bipyrazolyl-l '-yl)-
620 butyl)-imino)] erythromycin A, 621
622 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
623 decladinosyl-ό-O-methyl-S-oxo-lZJ l-foxycarbonyl-^-^-^midazol-l-yl)-
624 pyrazol-l-yl)-butyl)-imino)] erythromycin A, 625
626 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosammyl-l l,12-dideoxy-3-O-
627 decladinosyl-ό-O-methyl-S-oxo-^J l-foxycarbonyl-^-^-φyrazol-l-yl)-
628 imidazol-l-yl)-butyl)-imino)] erythromycin A, 629
630 2-a-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
631 decladinosyl-ό-O-methyl-S-oxo-^J l-foxycarbonyl-^-^S^^bithiophenyl-S-yl)-
632 butyl)-imino)] erythromycin A, 633
634 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
635 decladinosyl-o-O-methyl-S-oxo-n^ l-Coxycarbonyl-^-fe^'jbithiophenyl-S'-yl)-
636 butyl)-imino)] erythromycin A, 637
638 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
639 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-2-yl)-thiophen-
640 2-yl)-butyl)-imino)] erythromycin A, 641
642 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
643 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(oxazol-5-yl)-imidazol-
644 l-yl)-butyl)-imino)] erythromycin A, 645
646 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
647 decladinosyl-6-O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(3 -(pyrrol- 1 -yl)-
648 [ 1 ,2,4]triazol- 1 -yl)-butyl)-imino)] erythromycin A, 649
650 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
651 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(thiophen-2-yl)-
652 tetrazol-2-yl)-butyl)-imino)] erythromycin A, 653
654 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
655 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(thiophen-3-yl)-
656 pyrazol-l-yl)-butyl)-imino)] erythromycin A, 657
658 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
659 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(ruran-3-yl)-pyrazol-l-
660 yl)-butyl)-imino)] erythromycin A, 661
662 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11 , 12-dideoxy-3-O-
663 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(furan-2-yl)-pyrazol-l-
664 yl)-butyl)-imino)] erythromycin A, 665
666 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
667 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-phenyl-tetrazol-2-yl)-
668 butyl)-imino)] erythromycin A, 669 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
670 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(4-methoxy-plienyl)-
671 tetrazol-2-yl)-butyl)-imino)] erythromycin A, 672
673 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0-
674 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(5-(furan-3-yl)-imidazol-
675 l-yl)-butyl)-imino)] erythromycin A, 676
677 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
678 decladmosyl-6-O-methyl-3-oxo- 12, 11 - [oxycarbonyl-((4-(6-pyrazol- 1 -yl-pyridin-3-
679 yl)-butyl)-imino)] erythromycin A, 680
681 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3-O-
682 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(pyridin-3-yl)-pyrazol-
683 l-yl)-butyl)-imino)] erythromycin A, 684
685 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
686 decladinosyl-6-O-methyl-3-oxo-12, 1 l-[oxycarbonyl-((4-(5-thiophen-2-yl-pyridin-
687 3-yl)-butyl)-imino)] erythromycin A, 688
689 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
690 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-phenyl-thiophen-2-yl)-
691 butyl)-imino)] erythromycin A, 692
693 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
694 decladinosyl-β-O-methyl-S-oxo-^^ l-foxycarbonyl-^-^-amino-buty^-N-
695 thiazol-2-yl-nicotinimido)] erythromycin A, 696
697 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
698 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-(N-(4-amino-butyl)-N-
699 thiazol-2-yl-nicotinimido)] erythromycin A, 700
701 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
702 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(6-pyrrol-l-yl-pyridm-
703 3-yl)-imidazol-l-yl)-butyl)-imino)] erythromycin A, 704
705 2-α-Fluoro-5 -O-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
706 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(6-pyrrol-l-yl-pyridin-3-
707 yl)-butyl)-imino)] erythromycin A, 708
709 2-oc-Fluoro-5-0-(3 ' -N-desmethyl-3 ' -N-ethyl)-desosaminyl- 11,12-dideoxy-3 -O-
710 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(2 -pyrrol- 1 -yl-thiazol-5-
711 yl)-butyl)-imino)] erythromycin A, 712
713 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-O-
714 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(6-imidazol- 1 -yl-pyridin-
715 3-yl)-butyl)-imino)] erythromycin A, 716 717 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-desosaminyl-l l,12-dideoxy-3-0-
718 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(tetrahydro-furan-2-
719 yl)-pyridin-3 -yl] -butyl)imino] erythromycin A, 720
721 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
722 O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(4-tolyl-imidazol- 1 -yl)-butyl)-imino)]
723 erythromycin A, 724
725 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-
726 O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(4-aminophenyl)-imidazol- 1 -yl)-
727 butyl)-imino)] erythromycin A, 728
729 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
730 O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(4-methyl-3 -aminophenyl)-imidazol- 1 -
731 yl)-butyl)-imino)] erythromycin A, 732
733 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
734 O-methyl-3 -oxo-12,11- [oxycarbonyl-((4-(4-(3 -(imidazol- 1 yl)-phenyl)imidazol- 1 -
735 yl)-butyl)-imino)] erythromycin A, 736
737 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
738 0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N,N-dicyclopropyl-amino)-
739 phenyl)-imidazol-l-yl)-butyl)-imino)] erythromycin A, 740
741 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-
742 0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N,N-dimethyl-amino)phenyl)-
743 imidazol- l-yl)-butyl)-imino)] erythromycin A, 744
745 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
746 O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(3-(tetrazol- 1 yl)-phenyl)-imidazol- 1 -
747 yl)-butyl)-imino)] erythromycin A, 748
749 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
750 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2-(pyrrol-lyl)-thiozol-5-yl)-imidazol-
751 l-yl)-butyl)-imino)] erythromycin A, 752
753 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)- 11 ,12-dideoxy-3-O-decladinosyl-6-
754 O-methyl-3 -oxo-12,11- [oxycarbonyl-((4-(4-(3 -trifluoromethyl-phenyl)-imidazol- 1 -
755 yl)-butyl)-imino)] erythromycin A, 756
757 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
758 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(N-(thiazol-2-yl)-benzimido)-butyl)-
759 imino)] erythromycin A, 760
761 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-
762 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2-amino-pyrimidin-5-yl)-imidazol-l-
763 yl)-butyl)-imino)] erythromycin A, 764 765 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3 -O-decladinosyl-6-
766 O-methyl-3 -oxo- 12, 11 -[oxycarbonyl-((4-(4-(4-(pyrrol- 1 yl)-phenyl)-imidazol- 1 -
767 yl)-butyl)-imino)] erythromycin A, 768
769 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
770 0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(pyrrol-lyl)-phenyl)-imidazol-l-
771 yl)-butyl)-imino)] erythromycin A, 772
773 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-
774 0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N-acetyl-amino)-phenyl)-imidazol-
775 l-yl)-butyl)-imino)] erythromycin A, 776
777 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-
778 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N-isopropyl-amino)-phenyl)-
779 imidazol-l-yl)-butyl)-imino)] erythromycin A, 780
781 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
782 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-nitrophenyl)-imidazol-l-yl)-butyl)-
783 imino)] erythromycin A, 784
785 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0-decladinosyl-6-
786 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3-(N-benzoyl-amino)-phenyl)-
787 imidazol-l-yl)-butyl)-imino)] erythromycin A, 788
789 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
790 O-methyl-3 -oxo- 12,11- [oxycarbonyl-((4-(4-(3 ,4-dimethyl-phenyl)-imidazol- 1 -yl)-
791 butyl)-imino)] erythromycin A, 792
793 S-O-CS'-N-desmethyl-S'-N-ethy^-l ^^-dideoxy-S-O-decladinosyl-ό-O-methyl-S-
794 oxo- 12, 11 -[oxycarbonyl-((4-(4-Pyridin-3 -yl-thiazol-2-yl)-butyl)-imino)]
795 erythromycin A, 796
797 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11,12-dideoxy-3 -O-decladinosyl-6-
798 O-methyl-3 -oxo- 12,11 -[oxycarbonyl-((4-(4-(4-fluorophenyl)-imidazol- 1 -yl)-
799 butyl)-imino)] erythromycin A, 800
801 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)- 11 , 12-dideoxy-3-O-decladinosyl-6-
802 O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(4-methoxy-phenyl)-imidazol-l-yl)-
803 butyl)-imino)] erythromycin A, 804
805 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-0-decladinosyl-6-
806 O-methyl-3 -oxo- 12,11- [oxycarbonyl-((4-(N-(benzthiazol-2-yl)-benzimido)-butyl)-
807 imino)] erythromycin A, 808
809 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)-l l,12-dideoxy-3-O-decladinosyl-6-
810 O-methyl-3-oxo- 12,11- [oxycarbonyl-((4-(N-(thiazol-2-yl)-nicotinamido)-butyl)-
811 imino)] erythromycin A, 812 813 2-α-Fluoro-5-O-(3 '-N-desmethyl-3 '-N-ethyl)- 11,12-dideoxy-3-O-decladinosyl-6-
814 O-methyl-3-oxo- 12, 11 -[oxycarbonyl-((4-(4-(3-(N-methyl-amino)-phenyl)-
815 imidazol- 1 -yl)-butyl)-imino)] erythromycin A, 816
817 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosarαinyl-l l,12-dideoxy-3-O-
818 decladinosyl-ό-O-methyl-S-oxo-l 2, 11 -[oxycarbonyl-((4-(4-(2-aminopyridin-4-yi)-
819 imidazol- 1 -yl)-butyl)-imino)] erythromycin A, 820
821 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O-
822 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4-(2-aminopyridin-5-yl)-
823 2H-tetrazol-5-yl)-butyl)-imino)] erythromycin A, 824
825 2-α-Fluoro-5-O-(3 ' -N-desmethyl-3 ' -N-ethyl)desosaminyl- 11,12-dideoxy-3 -O-
826 decladinosyl-6-0-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(3,4-difluorophenyl)-
827 imidazol- l-yl)-butyl)-imino)] erythromycin A, 828
829 2-α-Fluoro-5-0-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l l,12-dideoxy-3-0-
830 decladinosyl-6-O-methyl-3-oxo-12,l l-[oxycarbonyl-((4-(4-(2-chloropyridin-4-yl)-
831 imidazol- l-yl)-butyl)-imino)] erythromycin A, 832
833 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosaminyl-l l,12-dideoxy-3-O-
834 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(4--(6-arninopvridin-3-
835 yl)-imidazol-l-yl)-butyl)-imino)] erythromycin A, or 836
837 2-α-Fluoro-5-O-(3'-N-desmethyl-3'-N-ethyl)desosatninyl-l l,12-dideoxy-3-O-
838 decladinosyl-6-O-methyl-3-oxo- 12,11 -[oxycarbonyl-((4-(5-(2-Chloro-pyridin-4-
839 yl)-tetrazol-2-yl])-butyl)-imino)] erythromycin A, 840
841 or pharmaceutically acceptable salts, pharmaceutically acceptable solvates,
842 enantiomers, diastereomers or polymorphs thereof.
1 5. A pharmaceutical composition comprising therapeutically effective amounts of one
2 or more compounds of claim 1 together with one or more pharmaceutically
3 acceptable carriers, excipients, or diluents.
1 6. A method for treating or preventing a condition caused by or contributed to by
2 bacterial infection comprising administering to a mammal in need thereof
3 therapeutically effective amounts of one or more compounds of claim 1.
1 7. The method of claim 6, wherein the condition is selected from community acquired
2 pneumonia, upper or lower respiratory tract infections, skin or soft tissue
3 infections, hospital acquired lung infections, hospital acquired bone or joint infections, mastitis, catetlier infection, foreign body, prosthesis infections or peptic ulcer disease.
8. The method of claim 6, wherein the bacterial infection is caused by Gram-positive, Gram-negative or anaerobic bacteria.
9. The method of claim 8, wherein the Gram-positive, Gram-negative or anaerobic bacteria is selected from Staphylococci, Streptococci, Enterococci, Haemophilus, Moraxalla spp., Chlamydia spp., Mycoplasm, Legionella spp., Mycobacterium, Helicobacter, Clostridium, Bacteroides, Corynebacterium, Bacillus or Enterobactericeae.
10. The method of claim 9, wherein the bacterium is cocci.
11. The method of claim 10, wherein the cocci is drug resistant.
12. A process for preparing a compound of Formula XIII,
Figure imgf000136_0001
Forrrula XIII
(Formula I wherein, R1 = H1 R= R2 = CH3, Z = O, R4 = C2H5, Y= F)
or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers or polymorphs, wherein
R3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 is hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl;
W is alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein q is an integer of from 2 to 6;
G is no atom, -CO, -CS or -SO2;
R9 and R10 are independently hydrogen or alkyl; and
J is no atom, -CR9R10 or N(R12)(CH2)m, wherein m is an integer of from 0 to 6; R9 and R10 are the same as defined earlier; and R12 is hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 is alkyl, aryl or heterocycle; and
R is aryl or heterocycle;
which comprises the steps of:
(a) hydrolyzing clarithromycin of Formula II,
Figure imgf000137_0001
Formula II
to form a compound of Formula III,
Figure imgf000137_0002
Formula HI (b) protecting the compound of Formula III by reacting with one or more reagents of Formula RX 2O or R1X (wherein X is halogen) to form a compound of Formula IV,
Figure imgf000138_0001
Formula IV
(c) desmethylating the compound of Formula IV at the 3'-N-dimethyl group to form a compound of Formula V,
Figure imgf000138_0002
Formula V
(d) alkylating the compound of Formula V with one or more reagents of Formula R3CHO, R2 3CO or R3X (wherein X is halogen) to form a compound of Formula VI (wherein R3 is the same as defined earlier),
Figure imgf000138_0003
Formula YI (e) converting the compound of Formula VI with one or more suitable reagents to form a compound of Formula VII,
Figure imgf000139_0001
Formula VII
(f) reacting the compound of Formula VII with one or more organic bases to form a compound of Formula VIII,
Figure imgf000139_0002
Formula VHI
(g) oxidizing the compound of Formula VIII to form a compound of Formula IX,
Figure imgf000139_0003
Formula IX (h) reacting the compound of Formula IX with N,N'-carbonyldimidazole to form a compound of Formula X,
Figure imgf000140_0001
Formula X
(i) reacting the compound of Formula X with a compound of Formula R-W- NH2 to form a compound of Formula XI (wherein W and R are the same as defined earlier),
Figure imgf000140_0002
Formula XI
G) fluorinating the compound of Formula XI to form a compound of Formula XII, and
Figure imgf000140_0003
Formula Xn (k) deprotecting the compound of Formula XII to form a compound of Formula XIII.
13. A process for preparing a compound of Formula XIII,
Figure imgf000141_0001
Formula Xm
(Formula I wherein, R1 = H, R2 = CH3, Z = O, R4 ^ QH5, Y= F)
or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs,stereoisomers or polymorphs, wherein
R3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 is hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl;
W is alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein
q is an integer of from 2 to 6;
G is no atom, -CO, -CS or -SO2;
R9 and R10 are independently hydrogen or alkyl; and
J is no atom, -CR9R10 or N(R12)(CH2)m, wherein m is an integer of from 0 to 6; R9 and R10 are the same as defined earlier; and R12 is hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 is alkyl, aryl or heterocycle; and
R is aryl or heterocycle;
which comprises the steps of: (a) reacting a compound of Formula IV with a suitable reagent,
Figure imgf000142_0001
Formula IV
to form a compound of Formula XIV,
Figure imgf000142_0002
Formula XIV
(b) reacting the compound of Formula XIV with one or more organic bases to form a compound of Formula XV,
Figure imgf000142_0003
Formula XV
(c) oxidizing the compound of Formula XV to form a compound of Formula XVI,
Figure imgf000143_0001
Formula XVI
(d) desmethylating the compound of Formula XVI at the 3'-N-dimethyl group to form a compound of Formula XVII,
Figure imgf000143_0002
FotmulaXVπ
(e) alkylating the compound of Formula XVII with one or more reagents of Formula R3CHO, R3 2 CO or R3X (wherein X is halogen) to form a compound of Formula IX,
Figure imgf000143_0003
Formula IX
CD fluorinating the compound of Formula IX to form a compound of Formula XVIII,
Figure imgf000144_0001
(g) reacting the compound of Formula XVIII with N,N'-carbonyldiimidazol to form a compound of Formula XIX,
Figure imgf000144_0002
Formula XK
(h) reacting the compound of Formula XIX with a compound of Formula R-W- NH2 to form a compound of Formula XII, and
Figure imgf000144_0003
(i) deprotecting the compound of Formula XII to form a compound of Formula XIII.
14. A process for preparing a compound of Formula XIII,
Figure imgf000145_0001
Formula Xm (Formula I, wherein, R'=R2=CH3; R4 ^C2H5; R1=H,Z=O,Y=F)
or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs or polymorphs, wherein
R3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 is hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl;
W is alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein
q is an integer of from 2 to 6;
G is no atom, -CO, -CS or -SO2;
R9 and R10 are independently hydrogen or alkyl; and
J is no atom, -CR9R10 or N(R12)(CH2)m, wherein m is an integer of from 0 to 6; R9 and R10 are the same as defined earlier; and R12 is hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 is alkyl, aryl or heterocycle; and
R is aryl or heterocycle;
which comprises the steps of:
(a) fluorinating the compound of Formula XVI,
Figure imgf000146_0001
Formula XVI
to form a compound of Formula XX,
Figure imgf000146_0002
(b) reacting the compound of Formula XX with N,N'- carbanoyldiimidazole to form a compound of Formula XXI,
Figure imgf000146_0003
(c) reacting the compound of Formula XXI with a compound of Formula R-W- NH2 to give a compound of Formula XXII,
Figure imgf000147_0001
(d) deprotecting the compound of Formula XXII to form a compound of Formula XXIII,
Figure imgf000147_0002
(e) desmethylating the compound of Formula XXIII at the 3'-N-dimethyl group to form a compound of Formula XXIV, and
Figure imgf000147_0003
(f) alkylating the compound of Formula XXIV with one or more reagents of Formula R3CHO, R3 2CO or R3X (wherein X is halogen) to form a compound of Formula XIII.
15. A process for preparing a compound of Formula XIII,
Figure imgf000148_0001
Formula XIII
(Formula I wherein, R1 = H, R2 = R' = CH3, Z = O1 R^ = C2H55 Y= F)
or its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, stereoisomers, prodrugs or polymorphs, wherein
R3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, aralkyl, (heterocycle)alkyl or COR11, wherein R11 is hydrogen, alkyl or aralkyl, with the proviso that R3 is not methyl;
W is alkenyl, -G(CH2)qJ-, -CR9R10, -NR9- or -SO2, wherein
q is an integer of from 2 to 6;
G is no atom, -CO, -CS or -SO2;
R9 and R10 are independently hydrogen or alkyl; and
J is no atom, -CR9R10 or N(R12)(CH2)m, wherein m is an integer of from 0 to 6; R9 and R10 are the same as defined earlier; and R12 is hydrogen, alkyl, alkylene, alkynyl, COR8 or -(CH2)m-R8, wherein R8 is alkyl, aryl or heterocycle; and
R is aryl or heterocycle;
which comprises the steps of: (a) deprotecting the compound of Formula XX (wherein R1 is COPh),
Figure imgf000149_0001
Formula XX to form a compound of Formula XXV,
Figure imgf000149_0002
Formula XXV
(b) desmethylating the compound of Formula XXV at 3 -N' -dimethyl group to form a compound of Formula XXVI,
Figure imgf000149_0003
Formula XXVl (C) alkylating the compound of Formula XXVI with one or more reagents of Formula R3CHO, R3 2CHO or R3X (wherein X is halogen) to form a compound of Formula XXVII,
Figure imgf000150_0001
Formula XXVH
(d) protecting the compound of Formula XXVII with one or more reagents of Formula R*2O or R1X (wherein X is halogen) to form a compound of Formula XVIII (wherein R1 is COCH3),
Figure imgf000150_0002
Formula XVTII
(e) reacting the compound of Formula XVII with N,N'-carbonyldiimidazole to form a compound of Formula XIX,
Figure imgf000151_0001
Formula XK
(f) reacting the compound of Formula XIX with a compound of Formula R-W- NH2 to form a compound of Formula XII, and
Figure imgf000151_0002
(h) deprotecting the compound of Formula XII to form a compound of Formula XIII.
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