Derivatives of erythromycin and method of production thereof

 

(57) Abstract:

The invention relates to new derivatives of erythromycin formula I where Z, X and Y are hydrogen; R is lower alkyl substituted by phenyl, which in turn may be substituted by one or more radicals selected from the group consisting of halogen, lower alkyl, hydroxyl, trifloromethyl, lower alkoxy, phenyl, phenoxy, with the possibility of substitution of the latter by one or more halogen; lower alkyl, substituted hydroxy, amino, halogen, phenoxy, cyclohexyl, (C8-C12)-alkylamino or triphenyl(lower)alkoxygroup; unsubstituted WITH8-C12alkyl, 3, 7, 11-trimethyl-2, 6, 10 - dodecadienal radical or (C3-6)-alkenyl, substituted phenyl, biphenyl or phenoxyphenyl; in all possible stereoisomeric forms. Compounds are used in medicine as antibiotics. A method of obtaining compounds of General formula I consists in the fact that the compound of formula II in any of the possible stereoisomeric forms or mixtures thereof, is exposed to the compound of the formula RCHO, where R has the values specified in paragraph 1 of the formula. The method is simple and convenient in operation. 3 S. and 12 C.p. f-crystals.

The present invention CLASS="ptx2">

The object of the present invention is the products of formula (I) in all possible stereoisomeric forms and mixtures thereof:

< / BR>
in which X and Y represent a hydrogen atom or together form the moiety:

< / BR>
R represents the radical:

< / BR>
in which m is an integer value from 0 to 20, n represents the number 0, 1, 2 or 3,

and or a and b, identical or different, represent a hydrogen atom or halogen atom, or an alkyl or aryl radical with up to 8 carbon atoms, and the geometry of the double bond is E or Z or a mixture of E + Z,

or A and B form a third bond between the carbon atoms to which they are linked,

and XAis:

linear or branched alkyl radical, saturated or unsaturated, comprising from 6 to 20 carbon atoms, with the possibility of interruption by one or more heteroatoms, and with a possible substitution by one or more halogen atoms,

cyclic alkyl radical comprising from 3 to 8 carbon atoms, with the possibility of substitution carbocyclic aryl radical,

halogen atom,

the radical CN,

radical OR3, COR4, CO2R5, SR6, , SO22CN, radicals such as alkyl, alkanniny and alkynylaryl, O-alkyl, O-alkanniny and O-alkynylaryl, S-alkyl, S-alkanniny and S-alkynylaryl, SO-alkyl, SO-alkanniny, SO-alkynylaryl, SO2-alkyl, SO2-alkanniny, SO2-alkynylaryl comprising up to 12 carbon atoms, with the possibility of substitution by one or more halogen atoms, radicals such as aryl, O-aryl, S-aryl, carbocyclic or heterocyclic, comprising up to 14 carbon atoms, radicals:

< / BR>
in which R'1and R'2identical or different, represent a hydrogen atom or an alkyl radical comprising up to 12 carbon atoms, with atomistically aryl radicals,

radical NR1R2where R1and R2identical or different, represent a hydrogen atom or a radical such as alkyl comprising up to 20 carbon atoms, -CO-alkyl or -- CO-alkyl comprising up to 8 carbon atoms, or a radical as aryl, -CO-aryl or-CO2-aryl, Uralkaliy, -CO-Aracely or-CO2-Aracely comprising up to 14 carbon atoms, and sledge aryl radicals can be substituted by one of the substituents listed above as substituents of aryl radicals; or R1and R2form together with the nitrogen atom to which they are linked, a cycle comprising from 3 to 8 atoms, optionally including another heteroatom, and with a possible substitution of one of the substituents listed above as substituents of aryl radicals,

carbocyclic aryl radical, with the possibility of substitution by one or more substituents listed above as substituents of aryl radicals,

heterocyclic aryl radical, containing one or more heteroatoms, with the possibility of substitution by one or more substituents listed above as Zam the capacity radical, with the ability to replace one or more substituents listed above as substituents of aryl radicals,

and Z represents a hydrogen atom or a residue of carboxylic acids comprising up to 18 carbon atoms, as well as additive salts with acids of compounds of formula (I).

The compounds of formula (I) can exist in any of their stereoisomeric forms, as well as in the form of mixtures.

The oxime in position 9 may be, for example, the geometry of E or Z, and the object of the present invention are oximes E, Z oximes and their blends E + z

As examples of the additive salts of these derivatives with inorganic or organic acids can be called salts formed with acids such as acetic, propionic, triperoxonane, maleic, tartaric, hydrochloric, sulfuric. Phosphate, stearic, methansulfonate, benzosulfimide, p toluensulfonate, hydrogen bromide and hydrogen iodide.

When X represents an alkyl radical comprising from 6 to 20 carbon atoms, we are talking primarily about such radical, as sexily, Gately, octillery, monilinia, decile, undecylenic, dodecylphenyl, Trida the deputies:

halogen is primarily fluorine or chlorine or bromine,

alkyl, alkenyl or alkynylaryl radical is, first of all, radical, such as methyl, ethyl, sawn, ISO-propyl, n-boutigny, isobutylene, tert-boutigny, decile or dodecylphenyl, vinyl, allyl, etinilnoy, prominently, propargyl,

cyclic alkyl radical is primarily cyclopropyl, cyclobutyl, cyclopentyl or tsiklogeksilnogo radical.

In the alkyl radical, with the possibility of interruption by one or more heteroatoms we are talking primarily about one or more oxygen atoms.

carbocyclic aryl radical is primarily a phenyl or nattily radical;

under the heterocyclic aryl radical understand or monocyclic heteroaryl radical with 5 or 6 atoms, containing one or more heteroatoms, or a condensed polycyclic system, each cycle of which contains 5 or 6 atoms and possibly one or more heteroatoms;

heterocyclic aryl radical comprises one or more heteroatoms, selected primarily from oxygen, sulfur and asny, pyrrolidinyl, diazolidinyl, oxazolidinyl, imidazolidinyl, thiadiazolidine, personilnya or isoxazolyl radical;

monocyclic heteroaryl radical with 6 atoms is primarily peredelnyj, pyrimidinyl, pyridazinyl or personilnya radical;

condensed polycyclic heteroaryl radical may be, for example, indaily, benzofuranyl, benzothiazolyl or finalininkiu radical or residue purine bases such as adenine;

alkyl, alkenyl or alkynylaryl radical is primarily radical, such as methyl, ethyl, through ISO-propyl n-boutigny, isobutylene, tert-boutigny, decile or dodecylphenyl, vinyl, allyl, etinilnoy, prominently, propargyl, cyclobutenyl, cyclopentenyl or tsiklogeksilnogo;

the remainder of the carboxylic acid is first and foremost acetyl, propylaniline, batilly, isobutyryloxy, n-valelly, isovaleryl, tert-weleily and picalilly the rest.

Among the preferred compounds of the present invention include compounds of formula (I) in which X and Y represent a hydrogen atom, and those where Z I is O, and XAis a linear or branched alkyl radical, saturated or unsaturated, comprising from 8 to 16 carbon atoms, with the possibility of substitution by one or more halogen atoms, or cyclic alkyl radicals comprising from 3 to 6 carbon atoms, for example those in which R represents undecylenic, dodecylphenyl, 3,7,11-trimethyl 2,6,10-dodecadienal or 3-cyclohexylpropionic radical, and their additive salts with acids.

You can also call the compounds of formula (I) in which R represents the radical:

< / BR>
in which Xarepresents a phenyl radical with the ability to replace one of the radicals t mentioned above as substituents of aryl radicals; m, n, A and B retain their previous values; among them, in particular, to call those in which m is 0 or 1, or those in which m is an integer value from 2 to 6, and those in which XArepresents a phenyl radical, with the possibility of substitution by one or more radicals selected from the group consisting of halogen atoms, methyl, triptorelin, hydroxyl, metaxylene, phenyl or phenoxyl radicals, with osmostat first connection, in which R represents the radical -(CH2)3Ar,-(CH2)4-Ar or-CH2-CH=CH-Ar, in which Ar is a phenyl radical, with the possibility of substitution, as well as their additive salts with acids.

Among the compounds that are the subject of the present invention can also include compounds of formula (I) in which XArepresents the radical:

-O-C(C6H5)3< / BR>
in which the phenyl radical (phenyl radicals may be substituted (can be substituted with one or more substituents from the above, as well as their additive salts with acids.

Among the compounds that are the subject of the present invention can also include compounds of formula (I) as described above, in which XArepresents a radical:

< / BR>
in which R1and R2the same or different, represent a hydrogen atom or an alkyl radical comprising up to 12 carbon atoms, in particular dodecyl-amine radical.

The object of the present invention, in particular, are compounds which are described below in the experimental part, in particular the compound of Example 1, the compound of Example 2, as well as connections Note the practical activity against gram-positive bacteria, such as staphylococci, streptococci, pneumococci.

Therefore, compounds that are the subject of the present invention can be used as medication in the treatment of infections with sensitive germs, in particular in the treatment of staphylococcal infections, such as staphylococcal septicemia; facial or skin malignant staphylococcal infections, pyoderma, septic or suppurative wounds, furuncles, carbuncles, cellulitis, erysipelas and acne, such staphylococcal infection as primary or post-acute flu-like illness, pneumonia, pulmonary suppuration, such streptococcal infection, acute tonsillitis, otitis, sinusitis, scarlet fever, such pneumococcal infections like pneumonia, bronchitis, brucellosis, diphtheria, gonococcal disease.

The products that are the subject of the present invention also have activity against infections caused by these microbes, as Haemophilus Influenzae, Rickettsies, Mycoplasma pneumoniae, Chlamydia, Legionella spp., Ureaplasma, Toxoplasma, Listena, Campylobacter and Meningocoque.

Thus, the object of the present invention on the medical level, in particular as antibiotic funds, are also the products of formula (I) as described above, and their salts with an adult present invention on the medical level, in particular as antibiotic funds are also above the preferred products of formula (I), namely the products of Examples 1, 2, 4, 5, 21, 25, 26, 33, 37, 38, 42, 48, 51, 54, 57, 64, 65 and 66, as well as their additive salts that are acceptable from a pharmaceutical point of view.

The object of the present invention are also pharmaceutical compositions comprising as an active beginning at least one of the above compounds.

These compositions can be applied orally, by rectal, parenteral or local application to the skin or on the mucous membranes, but it is preferable to apply inside.

These compositions can be solid or liquid and can be any pharmaceutical form which is widely used in the treatment of the person, as, for example, simple or dragevent tablets, capsules, granules, suppositories, injectable preparations, ointments, creams, gels; they are produced by conventional methods. Active principle (active start) is inserted into the base, usually used in the manufacture of pharmaceutical compositions, such as talc, Arabic gum, lactose, amidon, magnesium stearate, cocoa butter, aqueous or anhydrous binder, fats of animal or rastitelen, the preservatives.

These compositions can also be in the form of a powder intended to be dissolved before taking in the appropriate binder, such as sterile pyrogen-free water.

Commonly used doses depend on the disease to be treated, the characteristics of the patient, method of application and the product. In the case of the product of Example 1 or of the product of Example 2, they can be, for example, from 50 to 300 mg per day for adults by ingestion.

The object of the present invention is also a method of obtaining compounds of formula (I), characterized in that the compound of formula (II):

< / BR>
in all possible stereoisomeric forms and mixtures thereof, in which X, Y and Z retain their previous values, is exposed to the compounds of formula (III):

RCHO (III)

in which R retains its previous value, to obtain the corresponding compound of formula (I), which is optionally exposed to tarifitsiruemih funds hydroxyl functional group in position 2' or acid to obtain the salt.

In the preferred conditions of implementation of the method which is the subject of this izobretatelstvo hydrogen and a suitable catalyst, such as palladium on charcoal.

The possible formation of ester at the 2' position, is performed by conventional methods. Possible the salt formation is carried out using acids also conventional methods.

The compounds of formula (II) in all their possible stereoisomeric forms and mixtures thereof are known products described in the patent application UES O 487 411.

The compounds of formula (II), in which the oxime in position 9 has the geometry of E, can be obtained, for example, by chromatography of mixtures of diastereoisomers R + S on the level of carbon in position 3 of the piperidine, but can also be obtained using, as a starting product, chiral (S) - 3-hydroxypiperidine obtained by separation using chiral acid according to the method described in the patent application UES O 487 411 (see preparation Example 27).

Compounds of the formula (III) are known products which can be obtained according to reaction scheme:

RCO2H ---> RCH2OH ---> RCHO

using conventional methods.

The following examples illustrate the present invention, however, limiting it.

P a product called (R)(E) 9-O-(3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl-3-0-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl-3-exoerythrocytic.

Method of preparation 1.

In 4 ml of methanol or in 3 ml of methyl cyanide + 1 ml of methanol is dissolved 0.5 mm product A, 0.5 mm of aldehyde, and then add 0.1 ml of glacial acetic acid, shake for 5 to 10 min and added one reception 0.55 mm NaBH3CN.

Then shaken at room temperature for 15 to 60 minutes and concentrate the solution under reduced pressure, after which get absorbed in 10 ml of water and 30 ml of ethyl acetate, pH adjusted to approximately the values 8, using caustic soda, defend and extracted, the aqueous phase is washed with 10 ml of ethyl acetate, and then washed the organic phase with a saturated solution of sodium chloride. After that dried on magnesium sulfate. These products are purified by chromatography on silica (as eluant mixture type ethyl acetate: triethylamine, simple isopropyl ether - triethylamine - methanol, methylene chloride - methanol, methylene chloride - methanol - ammonia, trichloromethane - methanol - ammonia; ethyl acetate - methanol, ethyl acetate - methanol - triethylamine).

Cooking method 2.

In 10 ml of methanol was dissolved 0.4 mm product And 0.45 mm aldehyde, and then add 30 ál of ice UKS the 4 o'clock

Then the solution is filtered on clasele, rinsed with 20 ml of methanol and concentrated. Then cleans up by chromatography on silica (as eluant use mixtures listed for the method of preparation 1).

The method of preparation 3.

0.6 ml of methyl cyanide and 0.5 ml of secondary sodium phosphate was dissolved 0.2 mm product A, 0.3 mm of aldehyde, shake for 5 minutes, then add 30 mg (0.48 mm) NaBH3CN, pH adjusted approximately to a value of 4.5 by adding to it drop by drop a solution of hydrochloric acid. The reaction ends after 5-60 minutes Then add 5 ml of water, adjusted pH to a value of 8 using sodium hydroxide, and extracted twice with both times in 10 ml of trichloromethane. Then the organic phase is dried on magnesium sulfate.

Cleaning is performed by chromatography on silica (as eluant use mixtures listed for the method of preparation 1).

EXAMPLE 1: (R) (E) 9-O-(1-(3-phenylpropyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+= 804+< / BR>
2,; of 4.04 (m) NOCH; to 5.17 (dd) H13; from 7.1 to 7.3 aromatic.

EXAMPLE 2: (R) (E) 9-O-(1-dodecyl 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+= 854+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
1,26 - (CH2)n; from 2.15 to 2,4 - 2,7 - 2,98 (m) CH2N: and 2.26 (s) NCH3; 2,74 (s) 6-OCH3; 3,68 (m) H8; a 3.87 (q) H2; Android 4.04 (m) NOCH; to 5.17 (dd) H13.

EXAMPLE 3: (R) (E) 9-O-(1-octyl 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+= 798+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
Of 1.22 to 1.33 (CH2)nand 12CH3; and 2.26 (s) NCH3: 2,74 (s) 6-OCH3; 2,2 - 2,7 - 2,98 - CH2N; 3,68 (m) H8; 3,86 (q) H2; Android 4.04 (m) NOCH; to 5.17 (dd) H13< / BR>
EXAMPLE 4: (R) (E) 9-O-(1-(3-(3-methoxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+= 834+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3; 2,74 (s) 6-OCH3; from 2.3 to 2.6 - CH EXAMPLE 5: (R) (E) 9-O-(1-(4-triphenylmethane) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+= 1000+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3: from 2.1 to 2.4 - 2,97 - 2,72 - CH2N: 3,06 CH2O; 3,66 (m) H8; 3,86 (q) H2; to 5.17 (dd) H13; 7,17 to 7.30 - 7,44 (m) aromatic.

EXAMPLE 6: (R) (E) 9-O-(1-(4-hydroxybutyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl-3-0-methyl-alpha-L-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Mass spectrum: MH+= 758+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3; 2,38 (sl) NCH2; 2,74 (s) 6-OCH3; 3,56 (sl) CH2OH; 3,70 (m) H8; 3,86 (q) H2; 4,08 (m) NOCH.

EXAMPLE 7: (R) (E) 9-0-(1-(2-amino-ethyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl-3-0-methyl-alpha-1-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Mass spectrum: MH+= 729+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3,: 2,4 (m) was 2.76 (m) - CH2N; 3,68 (m) H8; 3,86 (q) H2; Android 4.04 (m) NOCH; to 5.17 (dd) H13.

EXAMPLE 8: (R) (E) 9-O-(1-(3-((3-trifluoromethyl) phenyl) oxy) phenyl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MHB>3)2; 3,40 (d,J = 14) -3,459 (d,J = 14) N-CH2-F.

EXAMPLE 9: (R) (E) 9-O-(1-(2-phenylethyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+= 790+< / BR>
An NMR spectrum: CDCl3million-1< / BR>
2,74 6-OMe; 3,86 H2; 3,70 (E) H8from to 7.15 to 7.35 f -; from 2.5 to 2.7 - 2,77 - 3.04 from N-CH2-CH2-F and CH2N

EXAMPLE 10: (R) (E) 9-O-(1-(4-(4-methoxyphenyl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=848+< / BR>
Range Yarm: CDCl3million-1< / BR>
2.26 AND N(CH3)2; 2,74 (s) 6-OMe; 3,68 H8; 3,79 f-OMe; from 2.25 to 2.75 - 2,96 CH2N and CH2F.; A 3.87 H2.

EXAMPLE 11: (R) (E) 9-O-(1-(3-(1-(phenylmethyl) 1H-indole 4-yl) propyl 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl-3-0-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=933+< / BR>
Range Yarm: CDCl3million-1< / BR>
2.26 AND N(CH3)2; 2,74 6-OMe; 2.91 in CH2-F: 3,68 H8; 3,86 H2; 4,06 of axial. N-O-CH: 5,32 NCH2O; 6,58 - 6,92 from 7,05 to 7.30 arene is LLF-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of cooking

Mass spectrum: MH+=794+< / BR>
Range Yarm: CDCl3million-1< / BR>
of 2.26 N(Me)2; 2,74 6-OMe; 3,18 H2; 3,68 H8; 3,89 H2; 4,00 CH2-N-C=; 4,05 N-O-CH; 7,46 - 6,92 - 7.05 imidazole.

EXAMPLE 13: (R) (E) 9-O-(1-(4-phenylbutyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-1.-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=818+< / BR>
Range Yarm: CDCl3million-1< / BR>
of 2.26 N(Me)2; 2,62 CH2-F.; 2,73 6-OMe; 3,19 H2; 3,68 H8; 3,89 H2; 4,03 N-O-CH; 7,18 - 7,21 aromatic.

EXAMPLE 14: (R) (E) 9-O-(1-(((1,1 biphenyl) 4-yl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=852+< / BR>
Range Yarm: CDCl3million-12,73 (s) 6-OMe; 3,69 (m) H8; 3,86 (q) H2; 3,47 to 3,63 (d) N-CH2-F.; 4.09 to (m) NO-CH axial.

EXAMPLE 15: (R) (E) 9-O-(1-((pentafluorophenyl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl-3-0-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=866+< / BR>
Range Yarm: CDCl3million-1
The method of preparation 3

Mass spectrum: MH+= 800+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,68 (s) 6-OMe; 3,6 H8; a 3.87 (q) H2;,; 3,43 (d) of 3.60 N-CH207 (m) NO-CH axial.

EXAMPLE 17: (R) (E) 9-O-(1-((1H-imidazol-2-yl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=848+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,66 (s) 6-OMe; from 3.5 to 3.7 H8; a 3.87(q) H2; 4.09 to (m) NO-CH.

EXAMPLE 18: (R) (E) 9-O-(1-((3-methyl 2-thienyl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=796+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,70 (s) 6-OMe; from 3.5 to 3.75 H8; 3,86 (q) H2; 4,06 (m) NO-CH axial. ; 6,77 (d) 7,11 (d) thiophene H4H5.

EXAMPLE 19: (R) (E) 9-O-(1-((3,3-dimethylbutyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-1-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=770+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,74 (s) 6-OMe; 3,69 (m) H8; 3,86 (q) H2; Android 4.04 (m) is f-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=774+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,74 (s) 6-OMe; 3,67 (m) H8; 3,86 (q) H2; Android 4.04 (m) NO-CH axial.

EXAMPLE 21: TRANS (R) (E) 9-O-(1-(3-phenyl 2-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1 M

Mass spectrum: MH+=802+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,74 (s) 6-OMe; 3,68 (m) Kg; 3,86 (q) H2; 4,07 (m) NO-CH axial.; 6,24 (dt, J = 15.5 and 7) of 6.49 (d, J = 15,5 atilano. E.

EXAMPLE 22: (R) (E) 9-O-(1-((2-methoxyphenyl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=806+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,68 (s) 6-OMe; from 3.5 to 3.75 H8; 3,86 (q) H2; 4,07 (m) NO-CH axial.

EXAMPLE 23: (R) (E) 9-O-(1-decyl 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=826+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,74 (s) 6-OMe; 3,68 (m) H8; 3,86 (q) H2; Android 4.04 (m) NO-CH axial.

Prenosil) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=870+< / BR>
Range Yarm: CDCl3million-1< / BR>
2,74 (s) 6-OMe; 3,68 (m) H8; 3,86 (q) H2; 4,03 (m) NO-CH axial.

EXAMPLE 25: (R) (S) 9-0-(1-(3-(4-(trifluoromethyl) phenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=872+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3; 2,67 CH2F; 2,74 (s) 6-OCH3; 3,67 (m) H8; a 3.87 (q) H2; Android 4.04 (m) NO-CH; 5,17 (dd) H13; 7,30 - 7,53 aromatic.

EXAMPLE 26: (R) (E) 9-O-(1-(3-(3,4-differenl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Cooking method 2

Mass spectrum: MH+=848+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s) 12CH3; 2,28 (s) NH3; 2,58 SNF; 2,74 (s) 6-OCH3; 3,68 (m) H8; a 3.87 (q) H2; Android 4.04 (m) NO-CH; 5,17 (dd) H13; 6,95 - 7,10 aromatic.

EXAMPLE 27: (R) (E) 9-O-(1-(2-phenoxyethyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+H8; 3,86 (q) H2Android 4.04 (m) NO-CH; 4,08 (t) CH2OF; to 5.17 (dd) H13; 6,85 - 7,25 aromatic.

EXAMPLE 28: (R) (E) 9-O-(1-(2-((phenylmethyl) amino) ethyl) - 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=819+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3, ; 2,73 (s) 6-OCH3; 3,66 (m) 3,80 (s) NCH2F; 4,01 (m) NO-CH; 5,17 (dd) H13; 7,27-7,32 (m) aromatic.

EXAMPLE 29 (E) (R) 9-0-(1-(2-(methyl (phenylmethyl) amino) ethyl) - 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=833+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s) 12CH3; 2,22 (s) NCH3,; and 2.26 (s) NCH3desosamine; was 2.76 (s) 6-OCH3; 3,51 (s) NCH2F; 3,68 (m) H8; a 3.87 (q) H2; 4,03 (m) NO-CH; 7.20 to 7.40 aromatic.

EXAMPLE 30: (R) (E) 9-O-(1-(3-(4-methoxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Method of preparation 1

Mass spectrum: MH+=834+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s) 12CH3; and 2.26 (s) NCH3; 2,55 (m) CH2F: 2,74 (s) 6-OCH3; 3,67 (m) Hanimetal) ((phenylmethoxy) carbonyl) amino) ethyl) - 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=953+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s) 12Me; and 2.26 (s) NCH3; 2,71 (s) 6-OCH3; 2,92 - 3,30 - 3,37 (m) NCH2; 3,68 (m) H8; a 3.87 (q) H2; 3,98 (m) NOCH; 4,55 NCH2-F; from 7.2 to 7.40 aromatic.

EXAMPLE 32 (E) (R) 9-O-(1-((2-benzofuran) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=816+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22: 12Me; 1,35: 6Me; 2,27: N-(Me)2; 2,56: H10; 2,74: 6-OMe; 3,19 : H2'; 3,65: H8; A 3.87: H2; 4,11: NO-CH; 6,56: benzofuran H3.

EXAMPLE 33 (E) (R) 9-O-(1-(4-(4-were) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=832+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,37: 6Me; 2.26 and: N-(Me)2; 2.57 M: H10and CH2F; 2,73: 6-OMe; 3,19: H2'; 3,68: H2; 3,86: H2; 4,03: NO-CH; 7,07:

EXAMPLE 34 (E) (R) 9-O-(1-hexadecyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-1-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=910+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,7 - 1,33: 12Me; 1,38:6Me; 2.26 and:N-(Me)2; 2 is about) ethyl) - 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Range Yarm: CDCl3million-1< / BR>
1,32 (s): 6Me; 2,17 (t): CH2-CO; and 2.26 (s):N(Me)2; 3,32 (m):CH2NCO; 3,67 (m):H8; 3,86 (q):H2; was 4.02 (m):NO-CH; 5,17 (dd):H13.

EXAMPLE 36: TRANS (E) (R) 9-O-(1-((2-phenyl 1-cyclopropyl) methyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=816+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s): 12Me; 1,35 (s):6Me; 2.26 and (s):N-(Me)2; 3,67:H8; 3,86 (q):H2; 4,05:NO-CH; 5,17 (dd):H13;? 7.04 baby mortality-of 7.23: aromatic.

EXAMPLE 37 (E) (R) 9-O-(1-(3-cyclohexylprop) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=810+< / BR>
1,23: 12Me; 1,37: 6Me; 2,28: N-(Me)2; 2.57 M:H10; 2,73: 6-OMe; 3,20:H2'; 3,68:H8; 3,86:H2; 4,13:N-OCH.

EXAMPLE 38 (E) (R) 9-O-(1-(3-(4-hydroxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Range Yarm: CDCl3million-1< / BR>
1,23:12Me; 1,34:6Me; 2,28:N-(Me)2; 2,75:H10; CH2F:from 2.25 up to 2.65; 2,66: 6-OMe; 3,19:H2'; 3,65:H8; 3,88:H2; 4,07: NO-CH; 6,75 - 6,79:-F-O; 3,33-4,37: OH.

EXAMPLE 39 (E) (R) 9-O-(1-(3-(((phenylmethoxy iranoil) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=967,9+< / BR>
1,22 (s):12Me; 1,37(s):6Me; 2.26 and(s):N-(Me)2; 2,72 (s): 6-OMe; 3,66 (m): H8; 3,85 (q):H2; 4,5:NCH2Ar; 5,16:OCH2Ar; 7,14 to 7.4: aromatic.

EXAMPLE 40 (E) (R) 9-O-(1-(3,3-diphenyl 2-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=877+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s): 12Me; 1,36 (s):6Me; 2.26 and (s):N-(Me)2; 2,70 (s): 6-OCH3; 3,66 (m):H8; 3,85 (q): H2; Android 4.04 (m):NO-CH; 6,17(t)=CH; 7,10 to 7.4: aromatic.

EXAMPLE 41 (E) (R) 9-O-(1-(3-(4-chlorophenyl) 2 (E)-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=836+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s): 12Me; 1,38 (s): 6Me; 2.26 and (s): N-(Me)2; 2,74 (s): 6-OMe; 3,68 (m): H8; 4,06 (m): NO-CH; 5,14 (dd):H13; 6,2 (dt) and to 6.43 (d): atilano.; 7,2 - 7,3: aromatic.

EXAMPLE 42 (E) (R) 9-O-(1-undecyl 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=840+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,26 (m): CH2n and me; 1,38 (s): 6Me; 2.26 and (s): N-(Me)2; 2,56:H10; 2,74 (s): 6 oil) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Range Yarm: CDCl3million-1< / BR>
1,23 (s): 12Me; 1,37 (s):6Me; 2.26 and (s):N-(Me)2; 2,73 (s): 6-OMe; 3,67 (m): H8; 3,79 (AB):NCH2Ar; 3,86 (q):H2; 3,99 (m): NO-CH; 7,24 - 7,32:aromatic.

EXAMPLE 44 (E) (R) 9-O-(1-(8-phenylethyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=874+< / BR>
1,25: 12Me; 1,38: 6Me; 2.26 and: N-(Me)2; 2,56:H10; 2,60:CH2F:2,74:6-OMe; 3,18:H2'; 3,68:H8; 3,85:H24,03:N-OCH; 7,16 - 7,26:aromatic.

EXAMPLE 45 (E) (R) 9-O-(1-(3-(4-nitrophenyl) 2 (E)-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=847+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22: 12Me; 1,37: 6Me; 2.26 and: N-(Me)2; 2,56:H10; 2,73:6-OMe; of 3.05 to 3.20: H2', H4; 3,67: H8; 3,86: H2; 4,06:N-OCH; 7,5 - 8,17:-F-NO2.

EXAMPLE 46 (E) (R) 9-O-(1-(3-(methylacrylamide) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=869+< / BR>
Range Yarm: CDCl3million-1< / BR>
1.27mm (s): 12Me; 1,38 (s): 6Me; 2,22 (s): N-Me; and 2.26 (s):N-(Me)2; 3,68 (m):H8; 3,86 (q):H2; 4,03 (m): NO-CH; 5,17 (dd):H
Mass spectrum: MH+=979+< / BR>
Range Yarm: CDCl3million-1< / BR>
of 2.26 (s): N-(Me)2; 3,68 (m): H8; 3,98 (m): NO-CH; 4,48 - 4,6 (AB): NCH2Ar; 5,16 (dd): H13; 7,05-7,4:aromatic.

EXAMPLE 48 (E) (R) 9-O-(1-(3-(1,1-- biphenyl-4-yl) 2 (E)-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=878+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s): 12Me; 1,38 (s): 6Me; 2,25 (s): N-Me2; was 2.76 (s): 6-OMe; 3,69 (m): H8; 3,86 (q): H2; 5,16 (dd): H13; 6,29 - 6,53: atilano.; of 7.3 and 7.6 : aromatic.

EXAMPLE 49 (E) (R) 9-O-(1-(3-(methyl (phenylmethyl) amino) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=847+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,25 (s): 12Me; 1,38 (s): 6Me; 2,18 (s): NMe; 2,25 (s): N-(Me)2; 2,74 (s): 6-OMe; 3,47 (s):CH2Ar; 3,68 (m):H8; 3,86 (q): H2; 5,17:H13; 7,24 - 7,3: aromatic.

EXAMPLE 50 (E) (R) 9-O-(1-(3-(4-phenyl 1H-imidazol-1-yl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Mass spectrum: MH+=870+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,236 - 7,76: aromatic.

EXAMPLE 51 (E) (R) 9-O-(1-(3-(4-phenoxyphenyl) propyl) 2 (E)-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=895+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s): 12Me; 1,38 (s): 6Me; 2,27 (s): N-(Me)2; 2,74 (s): 6-OMe; 3,69 (m):H8; 3,86 (q):H2; was 4.02 (m): NO-CH; 5,15 (dd):H13; 6,15 and 6,46 (J=16 Hz):= CH; from 6.9 to 7.4: aromatic.

EXAMPLE 52 (E) (R) 9-0-(1-(3-(4-butoxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-0-methyl-3-exoerythrocytic

Mass spectrum: MH+=876,6+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,37: 6Me; 2.26 and: N-(Me)2; 2,30 - 2,60:H10; 2,74: 6-OMe; 3,70: H2'; 3,68: H8; A 3.87: H2; 4,05: NO-CH; 3,95: -F-O-CH2; 6,85-7,08:-f-.

EXAMPLE 53 (E) (R) 9-0-(1-(3-((((1,1'-biphenyl-4-yl) methyl) amino) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=909+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s): 12Me; 1,38 (s): 6Me; 2.26 and (s): N-(Me)2; 2,74 (s): 6-OMe; 3,45 (m): H8; 3,83 (s): CH2Ar; 3,86:H2; was 4.02 (m): NO-CH; 5,17 (dd):H13; of 7.3 and 7.6:aromatic.

EXAMPLE 54: (yl) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=911+< / BR>
Range Yarm: CDCl3million-1< / BR>
0,96 - 1,14: CH3-(CH)n; 1,37 (s): 6Me; 2,3 (s): N-(Me)2; was 2.76 (s): 6-OMe; 3,68 (m): H8; 3,86 (q): H2; to 5.17 (dd): H13.

EXAMPLE 55 (E) (R) 9-O-(1-(4-(2,4,6-trimetilfenil) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=860+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22: 12Me; 1,37: 6Me; 2.26 and:N-(Me)2; 2,56:H10; 3,18:H'; 3,68:H8; 3,86: H2; 4,04: N-OCH; from 7.4 to 7.7:-f-.

EXAMPLE 56 (E) (R) 9-O-(1-(5-fenilpentil) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,38: 6Me; 2.26 and: N-(Me)2; 2,58: H10; 2,61: CH2F: 2,74 : 6-OMe; 3,18: H2'; 3,67: H8; 3,85: H2Android 4.04: N-OCH; to 7.15 to 7.35: aromatic.

EXAMPLE 57 (E) (R) 9-O-(1-(3,7,11-trimethyl 2 (E), 6 (E), 10-dodecatrien) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=890+< / BR>
1,22 (s): 12Me; 1,30 (s): 6Me; 1,6 - 1,62: CH3vinyls.; of 2.26 (s): N-(Me)2; 3,68 (m): H8; 3,86 (q): H2; 4,05 (m): NO-CH; of 5.05 - 5.25 to:H vinyl is-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=894+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,38: 6Me; 2.26 and: N-(Me)2; 2,39: H10; 2,74:6-OMe; 3,18:H2'; 3,68: H8; 3,8: H2; 4,05: NO-CH; 6,41: aromatic.

EXAMPLE 59 (E) (R) 9-O-(1-(5-((2-methoxyethoxy) methoxy) pentyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Range Yarm: CDCl3million-1< / BR>
1,38 (s):6Me; 2.26 and (s):N-(Me)2; was 2.76(s):6-Me; 3,52-3,71: OCH2CH2O; 3,82 (q):H2; 4.09 TO:NO-CH; 4,72:OCH2O:5,17(dd):H13.

EXAMPLE 60 (E) (R) 9-O-(1-(6-phenylhexa) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=846+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,38:6Me; 2.26 and: N-(Me)2; 2,60:CH2-F.; 2,74:6-OMe; 3,19: H2'; 3,69: H8; A 3.87: H2, Android 4.04:N-OCH; 7,10 to 7.30:aromatic.

EXAMPLE 61 (E) (R) 9-O-(1-(6-((4,6-dimethyl 2-pyrimidinyl) thio) hexyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-C-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=908+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23(s): 12Me; 1,38 (s):6Me; 2.26 and (s):N-(Me)2; 2,39 (s):CH3aromatic.; 2,7(s): 6-terpentin) sulfonyl) pentyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Range Yarm: CDCl3million-1< / BR>
1,23 (s): 12Me; 1,38 (s):6Me; 2.26 and (m):N-(Me)2; was 2.76 (s):6-OMe; 2,97-3,10:CH2SO2; 3,67 (m):H8; a 3.87 (q):H2as 4.02:NO-CH; 5,16 (dd):H13.

EXAMPLE 63 (E) (R) 9-O-(1-tetradecyl 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=848+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,25:12Me; 1,38:6Me; 2.26 and:N-(Me)2; 2,56:H10; 2,74:6-OMe; 3,19:H2'; 3,68: H8; 3,86:H2; 4,04:NO-CH.

EXAMPLE 64: (R) (E) 9-0-(1-(4-(1,1'-- biphenyl-4-yl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=894+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s): 12Me; 1,39 (s):6Me; 2,66 (t):CH2Ar; 3,68 (m): H8; 3,86 (q):H2of 4.05 (m):NO-CH; 5,17:H13; 7,25 - to 7.59: aromatic.

EXAMPLE 65: (R) (E) 9-O-(1-(3-(4-phenoxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=896+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22 (s): 12Me; 1,38 (s):6Me; 2.26 and (s):N-(Me)2; 2,6: CH2Ar; was 2.76 (s): 6-OMe; 3,86 (q):Hg; 4,05 (m): NO-CH; 5,17(dd): H13; 6,85-7,9:aromatic.

a-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=978+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s): 12Me; 1,38 (s): 6Me; 2.26 and (s): N-(Me)2; was 2.76 (s): 6-OMe; 3,67(m): H8; 3,86 (q): H2; 4,03 (m): NO-CH; is 5.18 (dd): H13; 6,85 (d)-7,05 (t)-6,82-7,29-7,03: aromatic.

EXAMPLE 67: (R) (E) 9-O-(1-(6-((4-were) thio) hexyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=892+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,22:12Me; 1,38: 6Me; 2.26 and: N-(Me)2; 2,31: CH3-F: 2,56: H10; 2,74:6-OMe; 2,87: S-CH2; 3,18: H2'; 3,69: H2; 3,86: H2; 4,03:N-OCH2; 7,09 and 7,24:-f-s

EXAMPLE 68 (E) (R) 9-O-(1-(4-(4-butylphenyl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=874,6+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,38: 6Me; 2.26 and: N-(Me)2; 2,58: H10and CH2F; 2,74:6-OMe; 3,19: H2'; 3,68: H8; a 3.87: Hg; 4,03:NO-CH; 7,08:-f-

EXAMPLE 69: (R) (E) 9-O-(1-(6-(4-chlorophenoxy) hexyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=896+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,24:1 70: (E) (R) 9-O-(1-(3-((4-were) thio) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=848+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,29 (s): 12Me; 1,37(s): 6Me; 2,28 (s):N-(Me)2; 2,32 (s):CH3Ar; 2,99: CH2-S; 3,67 (m):H8; 3,86(q): H2; to 5.17(dd):H13; 7,09-7,25:aromatic.

EXAMPLE 71 (E) (R) 9-O-(1-(4-(4-(1H-pyrrole 1-yl) phenyl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=883+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s):12Me; 1,39(s):6Me; 2.26 and(s):N-(Me)2; 2,64: CH2Ar; was 2.76(s):6-OMe; 3,68(m):H8; 3,86(q):H2; Android 4.04 (m):NO-CH; is 5.18(dd):H13; 6,33-7,07:pyrrole; 7,22 - 7,31:phenyl.

EXAMPLE 72 (E) (R) 9-O-(1-(4-(5-butyl 2-pyridinyl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=875+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23 (s): 12Me; 1,38 (s):6Me; 2.26 and (s):N-(Me)2; to 2.57 (t) and was 2.76 (t):CH2benilov. ; 3,68 (m):H8; 3,86 (q):H2, to 5.17 (dd):H13; 7,06 - 7,4 - 8,33: pyridine.

EXAMPLE 73 (E) (R) 9-O-(1-(3-(phenylmethoxy) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-Neil alpha-1-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=832+< / BR>
Range Yarm: CDCl>; 4,03: N-O-CH axial.; 4,5: O-CH2-F: of 7.25 to 7.40: aromatic.

EXAMPLE 74 (E) (R) 9-O-(1-(3-(4-phenyl cycle OGC forces) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=886+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,38: 6Me; 2.26 and: N-(Me)2; 2.57 M:H10; 3,18:H2; 3,68:H8; 3,86: H2'; 4,05: N-O-CH axial.; from 7,14 to 7.30: aromatic.

EXAMPLE 75 (E) (R) 9-O-(1-(4-(4-(4-pyridinyl) phenyl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=895+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,23: 12Me; 1,38: 6Me; 2,27: N-(Me)2; 2,58:H10; 2,69:CH2F; 2,75:6-OMe; 3,20: H2'; 3,67: H8; A 3.87: H2; 4,06:NOCH; 7,30 - EUR 7.57:phenyl; 7,51-8,64:pyridine.

EXAMPLE 76 (E) (R) 9-O-(1-(3-(4-were) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=158,818+< / BR>
2,31: CH3F; 2.57 M): CH2F; 3,67:H8; 4,04: NO-CH<; 7,08:phenyl.

EXAMPLE 77 (E) (R) 9-O-(1-(3-(3-hydroxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl and the Tr Yarm: CDCl3million-1< / BR>
From 2.3 to 2.7:CH2F; 3,65:H8; 4,06:NO-CH<; to 6.67 (3H)-7,11 (1H):phenyl.

EXAMPLE 78 (E) (R) 9-0-(1-(4-(4-hydroxyphenyl) butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl APHA-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=834,840+< / BR>
Range Yarm: CDCl3million-1< / BR>
3,63:H8; 4,00:NO-CH<; 6,80-7,00:phenyl.

EXAMPLE 79: 11,12-cyclic carbonate (E) (R) 9-0-(1-(3-(4-hydroxyphenyl) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Mass spectrum: MH+=846+< / BR>
Range Yarm: CDCl3million-1< / BR>
1,38 (s) - 1.55V (s): 6Me; 2.26 and (s): N-(Me)2; 2,62 (s): 6-OMe; 3,67 (m): H8(E isomer); 3,83 (q): H2; 4.09 to: NO-CH<; of 5.05 (dd): H13; 6,76-7,05: hydroxyphenyl.

EXAMPLE 80 (E) (R) 9-O-(1-(3-(4-chinoline) 2 (E)-propenyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

EXAMPLE 81 (E) (R) 9-O-(1-(3-(4-chinoline) propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-exoerythrocytic

Examples of pharmaceutical compounds

There were prepared tablets having the following fo the talc, magnesium stearate).

The product of example 2, 150 mg

The basis for the finished tablets - 1 g

(Detailing the basics of: starch, talc, magnesium stearate).

The product of example 4, 150 mg

The basis for the finished tablets - 1 g

(Detailing the basics of: starch, talc, magnesium stearate).

Pharmacological study of the products of the invention.

a) Activity "in vitro"

Method of cultivation in liquid medium.

Prepare a series of tubes, which is allocated the same amount of sterile nutrient medium. Then in each tube pour in increasing the number of the investigated product, after which each tube is sown bacterial strain.

After incubation in an oven for 24 h at a temperature of +37oWith the growth inhibition was evaluated by x-ray that gives the possibility to determine the minimum inhibitory concentration (M. I. K.), expressed in micrograms per cm3.

Thus were obtained the following results (the reading of the results was performed after 24 h):

The product of Example 1

Staphylococcus aureus 011 UC4 - 0,3

Staphylococcus aureus 011 HT17 - 0,3

Staphylococcus aureus 011G0251 - 1,2

Staphylococcus epidermidis 012G011C - 0,3
Streptococcus faecalis - Group D 02D2UC1 - 0,08

Streptococcus faecium Group D 02D3HT1 - 0,08

Streptococcus sp - Group G 02COCR5 - 0.04

Streptococcus mitis - 02mitCB1 - 0.02

Streptococcus agalactiae Group B 02B1SJ1 - 0,3

Streptococcus sp - Group C 02GOGB1 - 0,15

Streptococcus faecalis - Group D 02D2Gr8 - 1,2

Streptococcus pneumoniae 032UC1 - 0,08

Streptococcus pneumoniae 030SJ1 - 1,2

Streptococcus pneumoniae 030SJ5 - 0,3

Haemophilus influenzae 351 HT3 - 5

Haemophilus influenzae 351CB12 - 0,6

Haemophilus influenzae 351 CA1 - 2,5

The product of Example 2

Staphylococcus aureus 011 UC4 - 1,2

Staphylococcus aureus 011HT17 - 1,2

Staphylococcus aureus 011 D18C - 5

Staphylococcus aureus 011GR12C - 5

Staphylococcus aureus 011G0251 - 2,5

Staphylococcus epidermidis 012G011 C - 1,2

Staphylococcus aureus 011 CB20 - 2,5

Staphylococcus epidermidis 012G040 - 2,5

Streptococcus pyogenes - Group A 02A1 UCl - 0,3

Streptococcus agalactiae Group B 02B1 HT1 - 1,2

Streptococcus sp - Group C 02COCB3 - 1,2

Streptococcus faecalis - Group D 02D2UCl - 0,3

Streptococcus faecium Group D 02D3HT1 - 0,3

Streptococcus sp - Group Q 02GOGR5 - 1,2

Streptococcus mitis - 02mitCB1 - 1,2

Streptococcus pyogenes - Group A 02A1SJ1 - 1,2

Streptococcus agalactiae Group B 02B1SJ1 - 1,2

Streptococcus sp - Group C 02COCB1 - 0,6

Streptococcus faecalis - Group D 02D2Gr8 - 2,5

Streptococcus faecalis - Group D 02D2DU15 - 2,5

Streptococcus sp - Group G 02GOGR4 - 1,2

Streptococcus sanguis 02sgGR10 - 2,5

Streptococcus mitis - 02mitGR16 - 1,2

Streptococcus pneumoniae 032UC1 - 1,2

Streptococcus pneumoniae 030SJ1 - 1,2

Streptococcus pneumoniae 030SJ5 - 2,5

Haemophilus influe epidermidis 012G011 i - 1,2

Streptococcus pyogenes - Group A 02A1 UC1 - 0,08

Streptococcus agalactiae Group B 02B1 HT1 - 0.02

Streptococcus faecalis 02D2UC1 - 0,08

Streptococcus faecium Group D 02D3HT1 - 0,08

Streptococcus Group G 02GOGr5 - 0,08

Streptococcus mitis 02mitCB1 - 0.02

Streptococcus agalactiae 02B1SJ1c - 0,3

Streptococcus sanguis 02sgGR10i - 0,08

Streptococcus mitis 02mitGR16i - 0,08

Streptococcus pneumoniae 032UC1 - 0,3

Streptococcus pneumoniae 030GR20 - 0,6

Streptococcus pneumoniae 030SJ51 - 0,15

Streptococcus pneumoniae 030R01 - 0,3

Streptococcus pneumoniae 030SJ1c - 2,5

The product of Example 5

Staphylococcus aureus 011 UC4 - 2,5

Staphylococcus aureus 011 G025i - 5

Staphylococcus aureus 011CB20c - 5

Staphylococcus epidermidis 012G040c - 5

Streptococcus pyogenes - Group A 02A1 UC1 - 0,3

Streptococcus agalactiae Group B 02B 1 HT1 - 0,08

Streptococcus faecalis 02D2UC1 - 0,3

Streptococcus faecium Group D 02D3HT1 - 0,3

Streptococcus Group G 02GOGr5 - 0,6

Streptococcus mitis - 02mitCB1 - 0,15

Streptococcus pyogenes 02A1SJ1 c - 2,5

Streptococcus agalactiae 02B1SJ1 c - 2,5

Streptococcus faecalis - Group D 02D2DU15c - 2,5

Streptococcus sanguis 02sgGR10i - 0,3

Streptococcus mitis - 02mitGR16i - 0,6

Streptococcus pneumoniae 032UC1 - 0,3

Streptococcus pneumoniae 030GR20 - 0,3

Streptococcus pneumoniae 030SJ5i - 1,2

Streptococcus pneumoniae 030cr18 - 2,5

Streptococcus pneumoniae 030PW23 - 2,5

Streptococcus pneumoniae 030R01 - 1,2

The product of Example 21

Staphylococcus aureus 011 UC4 - 0,3

Staphylococcus aureus011UC4 + serum - 0,15

Staphylococcus aureus 011G025i - 1,2

Staphylococcus epidermis 012G011 i - 0,3

Streptococcus pyogeneD 02D3HT1 - 0,15

Streptococcus Group G 02GOGr5 - 0,15

Streptococcus agalactiae 02B1SJ1c - 0,6

Streptococcus sanguis 02sgGR10i - 0,8

Streptococcus mitis 02mitGR16i - 0,15

Streptococcus pneumoniae 032UC1 - 0.04

Streptococcus pneumoniae 030GR20 - 0,08

Streptococcus pneumoniae 030SJ5i - 0,3

Streptococcus pneumoniae 030cr18 - 0,6

Streptococcus pneumoniae 030PW23 - 2,5

Streptococcus pneumoniae 030R01 - 0,3

Haemophilus influenzae 351 HT3 - 5

Haemophilus influenzae 351CB12 - 0,6

Haemophilus influenzae 351 CA1 - 2,5

The product of Example 26

Staphylococcus aureus 011 UC4 - 0,3

Staphylococcus aureus 011 UC4 + serum - 0,6

Staphylococcus aureus 011G025i - 2,5

Staphylococcus epidermidis 012G011 i - 0,06

Streptococcus pyogenes - Group A 02A1 UC1 - 0,008

Streptococcus agalactiae Group B 02B1 HT1 - 0.02

Streptococcus faecalis 02D2UC1 - 0,08

Streptococcus faecium Group D 02D3HT1 - 0,08

Streptococcus Group G 02GOGr5 - 0,08

Streptococcus mitis 02mitCB1 - 0,4

Streptococcus agalactiae 02B1SJ1c - 0,6

Streptococcus sanguis 02sgGR10i - 0,3

Streptococcus pneumoniae 032UC1 - 0,03

Streptococcus pneumoniae 030GR20 - 0.04

Streptococcus pneumoniae 030SJ5i - 0,6

Haemophilus influenzae 351CB12 - 5u

1. Derivatives of erythromycin a General formula I

< / BR>
where X and Y are hydrogen;

R is lower alkyl substituted by phenyl, which in turn may be substituted by one or more radicals selected from the group consisting of halogen, lower alkyl, hydroxyl, trifloromethyl, lower alkoxy, phenyl, phenoxy, with the possibility of replacing the, what yclohexanol, C8- C12-alkylamino or triphenyl (lower) alkoxygroup; unsubstituted C8- C12-alkyl, 3,7,11 - trimethyl-2,6,10-dodecadienal radical or a C3- C6alkenyl, substituted phenyl, biphenyl or phenoxyphenyl;

Z is hydrogen,

in all possible stereoisomeric forms.

2. Derivatives of erythromycin General formula I under item 1, in which R is an unsubstituted C8- C12-alkyl.

3. Derivatives of erythromycin General formula I under item 1, in which R means undecylenic, dodecylphenyl, 3,7,11 - trimethyl-2,6,10-dodecadienal radical.

4. Derivatives of erythromycin General formula I under item 1, in which R is C3- C6alkenyl, substituted phenyl, biphenyl or phenoxyphenyl.

5. Derivatives of erythromycin General formula I under item 1, in which R signifies lower alkyl, substituted phenyl radical, possibly substituted by one or more radicals selected from the group consisting of halogen, methyl, triptorelin, hydroxyl, metaxylene, phenyl or phenoxyl radicals, with the ability to replace the last one or more Halogens, or C3- C6alkenyl, replaced penile - 4-alkyl or C3alkenyl, substituted phenyl radical, with the possibility of substitution.

7. Derivatives of erythromycin General formula I under item 1, in which R signifies lower alkyl, substituted triphenyl (lower) alkoxygroup.

8. Derivatives of erythromycin General formula I under item 1, in which R signifies lower alkyl, substituted amino or C8- C12-alkylaminocarbonyl.

9. Derivatives of erythromycin General formula I on p. 8, in which R signifies lower alkyl, substituted dodecylamino.

10. Derivatives of erythromycin General formula I under item 1, which is (R)(E) 9-O-(1-(3-phenylpropyl)-3-piperidinyl)oxime of 3-de((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic.

11. Derivatives of erythromycin General formula I under item 1, which is: (R)(E) 9-O-(1-dodecyl-3-piperidinyl)oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic.

12. Derivatives of erythromycin General formula I under item 1, which are:

(R)(E) 9-O-(1-(3-(3-methoxyphenyl)propyl)3-piperidinyl)oxime of 3-de((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl-3-okaerinasaimase)oxy) 6-O-methyl-3-exoerythrocytic,

(R)(E) 9-O-(1-(3-(4-trifluoromethyl)phenyl)propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(R)(E) 9-O-(1-(3-(3,4-differenl)propyl) 3-piperidinyl)oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic.

13. Derivatives of erythromycin General formula I on p. 1, representing the following connections:

(E)(R) 9-O-(1-(4-(4-were)butyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(E)(R) 9-O-(1-(2-cyclohexylprop) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl-3-exoerythrocytic,

(E)(R) 9-O-(1-(3-(4-hydroxyphenyl)propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip) oxy) 6-O-methyl 3-oxo)erythromycin,

(E)(R) 9-O-(1-undecyl 3-piperidinyl)oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(E)(R) 9-O-(1-(3-(1,1-- biphenyl-4-yl) 2(E)-propenyl)3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(R)(E) 9-O-(1-(3-(4-phenoxyphenyl) 2-(E)-propecia.

(E)(R) 9-O-(1-(3-(dodecylamino)propyl) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(E)(R) 9-O-(1-(3,7,11-trimethyl) 2(E), 6(E), 10-dodecatrien) 3-piperidinyl) oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl-3-exoerythrocytic,

(R)(E) 9-O-(1-(4-(1,1'-biphenyl-4-yl)butyl) 3-piperidinyl)oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(R)(E) 9-O-(1-(3-(4-phenoxyphenyl)propyl) 3-piperidinyl)oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic,

(R)(E) 9-O-(1-(4-(3-(3,5-dichlorophenoxy(phenyl)butyl 3-piperidinyl)oxime of 3-de ((2,6-dideoxy-3-C-methyl 3-O-methyl-alpha-L-abovecaptionskip)oxy) 6-O-methyl 3-exoerythrocytic.

14. Connection PP.1 - 13, has antibiotic activity.

15. The method of obtaining erythromycin derivatives of General formula I as defined in paragraph 1, characterized in that the compound of formula II

< / BR>
in any of the possible stereoisomeric forms or mixtures thereof, in which X, Y and Z have the values listed in paragraph 1, is exposed to a compound of formula III

RCHO,

in which R has a value,

 

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The invention relates to biotechnology

The invention relates to the field of biotechnology and related to tylosin is a macrolide antibiotic of broad-spectrum, used in agriculture

The invention relates to new N-substituted [2R, 3R (2'R, 3'R), 6R, 7S, 8S, 9R, 10R]-3-(2',3'-dihydroxyphenyl-2'-yl)-7-[(2,6-dideoxy-3-C-methyl-3-O--L-RIBO-hexopyranosyl)-oxy] -9-[(3,4,6-trideoxy-3-amino-B-D-Xylo-hexopyranosyl)-oxy] -2,6,8,10,12-pentamethyl-4,13-dioxabicyclo [8,2,1] -tridec-12-EN-5-he-connections with metalinguistically properties, to their salts, the acid products of accession, as well as to pharmaceutical remedies containing these compounds and methods and intermediate products for their production

FIELD: organic chemistry, chemical technology, antibiotics.

SUBSTANCE: invention relates to a method for preparing fumarate salt of compound of the formula (II) wherein R1 represents hydrogen atom or lower alkyl group; R2 represents lower alkyl group. Method involves interaction of compound of the formula (I) wherein R1 represents hydrogen atom or lower alkyl group with chloroformate. Then all carbamate groups are removed followed by alkylation of nitrogen atom at 3'-position of desosamine ring to obtain compound of the formula (II) and conversion of this compound to fumarate salt. Interaction of compound of the formula (I) with chloroformate is carried out in the presence of cyclic ether or carboxylic acid ester. Carbamate groups are removed in the presence of sodium hydrocarbonate. Crystallization and re-crystallization of compound of the formula (II) fumarate salt is carried out from alcohol-containing solvent, in particular, from isopropyl alcohol. Method provides increasing yield and enhancing purity of the end product.

EFFECT: improved preparing and purifying method.

28 cl, 11 ex

FIELD: production of macrolide road-spectrum antibiotic tylosine.

SUBSTANCE: claimed method includes tylosine deposition from organic tylosine base concentrate with organic solvent (hexane). Deposition is carried out by addition of organic tylosine base concentrate to hexane at velocity of 3-5 ml/min per 50 ml of concentrate.

EFFECT: method for production of tylosine base in granulated form with homogeneous composition.

2 cl, 6 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to new acid-additive nitrate salts of compounds taken among salbutamol, cetirizine, loratidine, terfenadine, emedastine, ketotifen, nedocromil, ambroxol, dextrometorphan, dextrorphan, isoniazide, erythromycin and pyrazinamide. Indicated salts can be used for treatment of pathology of respiratory system and elicit an anti-allergic, anti-asthmatic effect and can be used in ophthalmology also. Indicated salts have less adverse effect on cardiovascular and/or gastroenteric systems as compared with their non-salt analogues. Also, invention proposes pharmaceutical compositions for preparing medicinal agents for treatment of pathology of respiratory system and comprising above indicated salts or nitrate salts of metronidazol or aciclovir.

EFFECT: improved and valuable properties of compounds.

6 cl, 5 tbl, 19 ex

FIELD: antibiotics, chemical technology.

SUBSTANCE: invention relates to a method for preparing erythromycin oxime in homogenous conditions by oximylation of erythromycin A with hydroxylamine hydrochloride in dry methanol using triethylamine as a base. Method provides enhancing yield and quality of product.

EFFECT: improved method for preparing.

3 ex

FIELD: organic chemistry, antibiotics, chemical technology.

SUBSTANCE: invention relates to a novel crystalline form E of erythromycin derivative fumarate salt represented by the formula (I)

and to a method for its preparing. Indicated crystalline form E shows strong roentgen diffraction peaks at diffraction angles (2θ) 5.6° and 10.4° that was established by roentgen diffractometry with Cu-Kα-radiation. Also, invention proposes crystalline form D of erythromycin derivative fumarate salt represented by the formula (I) showing average particles size 90 mcm or above and/or the content of residual solvent 1500 ppm or less. Method for preparing indicated crystalline form D involve suspending indicated crystalline form E in mixture ethyl acetate and water in the ratio = (99:1)-(97:3) at temperature from -20°C to 20°C. Invention provides reducing the content of residual solvent and elimination of difficulties in making tablets.

EFFECT: improved preparing methods.

14 cl, 1 tbl, 5 dwg, 6 ex

FIELD: organic chemistry, antibiotics, pharmacy.

SUBSTANCE: invention describes crystalline forms A, C and D of erythromycin derivative of the formula (VII): . Crystalline forms are prepared by recrystallization of crude fumarate crystal from an alcoholic solvent (form A) and, additionally, from ethyl acetate (form C) or, additionally, from an aqueous ethyl acetate (form D). Also, invention relates to methods for preparing intermediate compounds. Prepared crystalline forms possess the better quality, in particular, high stability that is important in preparing pharmaceutical preparations.

EFFECT: improved preparing methods.

16 cl, 8 dwg, 13 ex

FIELD: antibiotics.

SUBSTANCE: invention relates to azithromycin as a stable monohydrate comprising from 4.0% to 6.5% of water and to a method for its preparing. Invention provides preparing the stable form of azithromycin monohydrate.

EFFECT: improved preparing method.

3 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention concerns macrolide compounds of the formula I , where R is hydrogen or methyl; R1 is hydrogen, N,N-di(C1-C3)alkylamino, N,N-di(C1-C3)alkylamino-N-oxide, N-(C1-C3)alkyl-N-benzylamino, N-(C1-C4)acyl-N-(C1-C3)alkylamino, N-[N,N-dimethylamino-(C1-C4)alkylamino]acetyl-N-(C1-C3)alkylamino or a chain of the formula: , where A is hydrogen, phenyl or thiazolyl; X is O or NR6 where R6 is hydrogen; Y is thiazolyl, pyrinidyl or NR6 where R6 is hydrogen; r is a whole number of 1 to 3; m is a whole number of 1 to 6; n is a whole number of 0 to 2; R2 is hydrogen; or R1 and R2 together form a link; R3 is a hydroxygroup or forms a =N-O-R5 group together with R4, where R5 is hydrogen, alkyl or a chain of the formula -(CH2)r-X-(CH2)m-Y-(CH2)n-A where r, m, n are the whole number as defined above; A is hydrogen, thiazolyl, furanyl or thiophenyl; X is NR6 where R6 is hydrogen; Y is a phenylene group or NR6 where R6 is hydrogen; R4 is hydrogen or forms =N-O-R5 group together with R3, with the same R5 as defined above; and its pharmaceutically acceptable salts, on the condition that R1 is not a dimethylamino group when R3 is a hydroxy group, and both R2 and R4 are hydrogen; R1 is not a dimethylamino group when in the =N-O-R5 substitute in 9 position R5 is hydrogen, linear or branched (C1-C5)alkyl; R1 is not a methylamino group when in the =N-O-R5 substitute in 9 position R5 is hydrogen, linear or branched (C1-C5)alkyl. The invention also concerns a method of obtaining the claimed compounds by elimination of L-cladinose residuum in the 3 position in compounds of the general formula II , where R, R1, R2, R3 and R4 are the same as defined above. Besides, the invention also concerns compounds of the general formula II, where R is hydrogen or methyl; R1 is hydrogen, N,N-di(C1-C3)alkylamino, N,N-di(C1-C3)alkylamino-N-oxide, N-(C1- C3)alkyl-N-benzylamino, N-(C1-C4)acyl-N-(C1-C3)alkylamino, N-[N,N-dimethylamino(C1-C4)alkylamino]acetyl-N-(C1-C3)alkylamino or a chain of the formula: where A is hydrogen, phenyl or thiazolyl; X is O or NR6 where R6 is hydrogen or C1-C3alkoxycarbonyl; Y is thiazolyl, pyrinidyl or NR6 where R6 is hydrogen or C1- C3alkoxycarbonyl; r is a whole number of 1 to 3; m is a whole number of 1 to 6; n is a whole number of 0 to 2; R2 is hydrogen; or R1 forms a link together with R2; R3 is a hydroxy group; R4 is hydrogen; and their pharmaceutically acceptable salts; on the condition that (i) R1 is not N,N-dimethylamino or (ii) R1 is not N,N-dimethylamino-N-oxide when R is hydrogen. The invention also concerns pharmaceutical composition based on the compound of the formula I, exhibiting anti-inflammatory effect.

EFFECT: obtaining of compounds with anti-inflammatory effect.

29 cl, 78 ex

FIELD: chemistry.

SUBSTANCE: invention concerns avermectin B1 and avermectin B1 monosaccharide derivatives of the general formula I , where n is 0 or 1; A- B is -CH=CH- or -CH2-CH2-; R1 is C1-C8-alkyl, C3-C8-cycloalkyl or C2-C8-alkenyl; R2 is C1-C8-alkyl or C2-C8-alkenyl, optionally substituted by a subsitutde selected out of the group of -OH, - N3, -NO2, C1-C8-alkoxy-, C1-C6-alkoxy-C1-C6-alkoxy, C1-C8-alkylthio, C1-C8-alkylsulfinyl, C1-C8-alkylsulfonyl, -NR4R6, -X- C(=Y)-R4, -X-C(=Y)-Z-R4, or phenyl substituted optionally by halogen; R3 is H or C1-C8-alkyl substituted by halogen; or R2 and R3 together are a 3-7-membered alkylene bridge substituted optionally by C1-C4-alkyl, or form together a -CH2-CH2-O-CH2- or -CH2-CH2-C(=O)-CH2- group; X is -O- or NR5; Y is -O-; Z is -O-; R4 is hydrogen or C1-C8-alkyl substituted optionally by C1-C6-alkoxy; R5 is hydrogen or C1-C8-alkyl; R6 is hydrogen or C1-8-alkyl if the compound is not a avermectin B1a or B1b derivative where n is 1, R3 is H and R2 is -CH2-CH2-OCH3 or -CH2-CH2-O-phenyl; and is not a B1a or B1b derivative where n is 1, and R2 and R3 form together an unsubstituted -CH2-CH2-CH2- group; while their E/Z isomers, mixes of E/Z isomers and/or tautomers, in a free or salt form in each case.

EFFECT: production of insecticide composition and method of cultivated plant pest eradication.

7 cl, 5 tbl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention concerns (a) new compounds of the formula I: , where M is a macrolipid subunit (macrolipid group) obtained from a macrolipid inclined to accumulation in inflamed cells, S is a steroid subunit (steroid group) obtained from a steroid medicine with anti-inflammatory effect, and L is a linker molecule connecting M and S; (b) their pharmacologically acceptable salts, prodrugs and solvates; (c) methods and mediators for their obtaining; and (d) methods of their application in treatment of human and animal inflammation diseases and conditions. The claimed compounds are inhibiting many cytokines and immune mediators participating in immune reactions that cause inflammation, allergy or alloimmunity, including IL (interleukin)-1, 2, 4, 5, 6, 10, 12, GMCSF (Granulocyte Macrophage Colony Stimulating Factor), ICAM (Intercellular Adhesion Molecule) and TNF (tumour necrosis factor) - α without limitation. At that, antiinflammation steroids have immediate anti-inflammatory effect due to the link to glycocorticosteroid receptor.

EFFECT: application in treatment of human and animal inflammation diseases and conditions.

30 cl, 40 ex, 4 dwg

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