SK75099A3 - Novel erythromycin derivatives, method for preparing them and their use as medicine - Google Patents

Abstract

The invention concerns compounds of formula (I) in which R represents an alkyl radical optionally substituted or (CH2)nAr, n representing a whole number ranging from 0 to 6 and Ar representing an aryl or heteroaryl radical optionally substituted, and Z represents a hydrogen atom or the radical of a carboxylic acid. The compounds of formula (I) have very interesting antibiotic properties.

Description

Technical field

The present invention relates to novel erythromycin derivatives, a process for their preparation and their use as medicaments.

SUMMARY OF THE INVENTION

The present invention provides compounds of formula I

where

R represents either linear, branched or cyclic alkyl, alkenyl or alkynyl containing up to 18 carbon atoms optionally substituted by at least one substituent which is halogen, linear branched or cyclic O-alkyl, o-alkenyl or Oalkynyl, S-alkyl, S- alkenyl or S-alkynyl containing up to 12 carbon atoms, an NO ₂ , ON group, as well as groups

wherein R ^a and R ^b _f identical or different represent a hydrogen atom, a linear or branched alkyl group containing up to 4 carbon atoms, the following groups wherein R ^c , R ^d and R ^f , identical or different, represent a linear branched or cyclic alkyl group containing up to 4 atoms alkyl, optionally substituted with at least one halogen atom, or (CH _{2) n} Ar radical in which n represents an integer ranging from 0 to 6 and Ar is aryl or heteroaryl, optionally substituted with one or more substituents described above, is H or an acyl a residue containing up to 12 carbon atoms as their acid addition salts.

The aryl group may be phenyl or naphthyl.

The aryl group may also be a heterocyclic group substituted or unsubstituted such as thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, pyrazolyl or isopyrazolyl, pyridyl, pyrimidyl, pyridazinyl or pyrazinyl or also indolyl, benzofuranyl, benzothiazyl or quinol.

These aryl groups may contain at least one group selected from the group consisting of hydroxyl, halogen atoms, NH ₂ , NO ₂ , CN, alkyl, alkenyl or alkynyl, O-alkyl, O-alkenyl or O-alkynyl, S-alkyl, S-alkenyl or

S-alkynyl, or N-alkyl, N-alkenyl or N-alkynyl containing up to 12 carbon atoms optionally substituted by at least one halogen atom, wherein R ^a and R ^{b are} identical or different, are hydrogen or alkyl of up to 12 carbon atoms .

R ^{and a} group

ABOUT

wherein R ³ represents alkyl of up to 12 carbon atoms or optionally substituted aryl or heteroaryl, carboxyl aryl, O-aryl or S-aryl, heterocyclic aryl, O-aryl or S-aryl of 5 or 6 members containing at least one heteroatom optionally substituted at least one of the following substituents.

As a preferred heterocycle, the following may be mentioned:

-O 1 tP % 37o 1 οα 00 οό 1 r · ⁰ / E ⁸ Ν - / 1 | to 1 Ν-- IN ά.

and heterocyclic groups disclosed in European Patent Application 487411, 596802, 676409 and 680967. These preferred heterocyclic groups are capable of being substituted with one or more functional groups.

Hal preferably represents a fluorine, chlorine or bromine atom.

Among the acid addition salts, mention may be made of the salts formed with the following acids: acetic, propionic, trifluoroacetic, malic, tartaric, methanesulfonic, benzenesulfonic, p-toluenesulfonic and in particular stearic, ethylsuccinic or laurylsulfonic acid.

In particular, the present invention provides compounds of formula I wherein Z is hydrogen, compounds of formula I wherein R is (CH ₂ ) _n Ar wherein n is an integer ranging from 1 to 4 and Ar is optionally substituted aryl or heteroaryl and especially those in which Ar is optionally substituted phenyl, as well as those in which R represents an optionally substituted group

the preparation of which is given below in the experimental part, and in particular the products of Examples 2 and 3.

The products of formula I have very good antibiotic activity on Gram positive bacteria such as staphylococci, streptococci and pneumococci.

The compounds of the invention can therefore be used as medicaments in infections caused by susceptible germs and in particular in staphylococcal diseases such as staphylococcal septicemia, malignant staphylococcus of the kidney or skin, pyodermatitis, septic or septic wounds, ulcers, anthrax, phlegmones and erphalomas, acute primary or influenza angina, bronchopneumonia, pulmonary supuration, streptococia such as acute angina, otitis, sinusitis, scarlet fever, pneumococia such as pneumonia, bronchitis, brucellosis, diphtheria and gonococcal infection.

The products of the present invention are also effective against infections caused by germs such as Haemophillus influenzae, Rickettsie, Nycoplasna pneuiaoniae, Chlamytia, Leglonella, Ureaplasna, Toxoplasaa or Mycobacterium germs.

Accordingly, the present invention also provides, as medicaments and in particular antibiotic medicaments, the products of formula I as defined above, as well as their addition salts with pharmaceutically acceptable mineral or organic acids.

A particular object of the invention are, as medicaments and in particular antibiotic medicaments, the products of Examples 2 or 3 and pharmaceutically acceptable salts thereof.

The present invention also provides pharmaceutical compositions comprising at least one of the drugs defined above as an active ingredient.

These compositions may be administered by the buccal, rectal, parenteral, or topical route such as topical application to the skin and mucous membranes, but the preferred route of administration is the buccal route.

The compositions may be solid or liquid and may be presented in pharmaceutical forms commonly used in human medicine, such as plain or sugar-coated tablets, capsules, granules, suppositories, injectables, ointments, creams, gels. They can be prepared by conventional methods.

The active ingredient (s) may be incorporated with excipients commonly used in these pharmaceutical compositions such as talk, acacia, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, animal or vegetable fatty substances, paraffin derivatives, glycols, various wetting, dispersing or emulsifying agents and preservatives.

The compositions may also be presented in the form of a powder to be dissolved at the time of need, in a suitable vehicle, for example pyrogen-free, sterile water.

The agent to be administered is variable according to the patient's disease to be treated, the mode of administration and the product contemplated. For example, it may be included between 50 mg and 300 mg per day in an adult oral route for the product of Example 2.

The invention also provides a process for the preparation of compounds of formula I, characterized in that the compound of formula II

ABOUT

δζ ¹ (II) where Z * represents a carboxylic acid residue containing up to 12 carbon atoms, is treated with a ketone protecting group at the 3-position in the form of an enol ether or an enol ester.

to obtain a compound of formula III

(III) wherein E represents a residue of an enol ether or an enol ester and Z * is as previously defined.

is treated with a compound of formula IV

Hal - CH ₂ OR (IV) wherein Hal represents a halogen atom to obtain the corresponding compound of formula VO

OZ '(W) which is subjected, if appropriate, the action of an agent which releases the ketone function in position 3 and / or the action of an agent which releases the hydroxy1 in the ^2-1 to provide the corresponding compound of formula I,

(I) where R and Z retain their earlier meaning.

OZ

The products of formula II used as starting products are known products which can be prepared as described in EP 487411 or WO 9321199.

In particular the chloromethyl ether, such as MEM-chloride or 2-methoxyethoxy chloride or also SEM-chloride or 2- (trimethylsily) ethoxymethyl chloride, may also be used as the protecting agent of the ketone group at the 3-position in the form of enol ether, the halomethyl ether used benzyloxymethyl ether (BOM), wherein Hal preferably represents a chlorine atom. Z * is preferably an acetyl radical or a means to release the ketone group at position 3, the release of the hydroxyl in position 2 is carried out by methanolysis ^1.

The compounds of formulas III and V used in the preparation process are novel and are themselves subject to the present invention.

Examples of elaboration of wn & c

Example 1

11,12-dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-0-methyl-.alpha.-ribohexopyranosyl) oxy] -6-0-methyl-3-oxo-12, ll- [oxycarbonyl [[(2-methoxyethoxy) methyl] imino]] erythromycin

Grade A

2 ₁ 3-Didehydro-11,12-dideoxy-3-O-de [(2,6-di-deoxy-3-C-methyl-

3-O-methyl-alpha-L-ribohexopyranosyl) -6-O-methyl-11,12- (iminocarbonyloxy) -3-O - [[(2-trimethylsilyl) ethoxy] methyl] erythromycin-2'-acetate

Solution containing 6 ml DMF, 0.654 g 11,12-dideoxy-

3-de [(2,6-dideoxy-3-C-methyl-alpha-L-ribohexopyranosyl) oxy] -60-methyl-3-oxo-11,12- (iminocarbonyloxy) erythromycin-2'-acetate and 0, 57 g of sodium hydride at 50% concentration in oil are stirred for 10 minutes. The reaction mixture was heated to 40 ° C. After cooling to -5 DEG C., 0.177 microliter of CISEM in 5 ml of DMF is introduced dropwise. Stirring is performed at 0C for 30 minutes (pH 9).

Pour the medium onto ice, then extract with ethyl acetate, wash with water, dry, filter and concentrate. 0.785 g of product is obtained, which is dissolved in isopropyl ether.

Crystallization is initiated, followed by separation, washing and drying at 70 ° C. The desired product is obtained by melting at 100 ° C.

NMR CDClg ppm possible

0.07 (S): Si (Me) ₃ ; 0.87 (t): CH ₃ -CH ₂ ; ~ l 03 CH ₂ Si; 1.10 (d) -1.12 (d) -1.14 (d) -1.24 (d) CH ₃ ; 1.24 (s) -1.43 (s): 6 a. 12 CH ₃ ; 1.95 (s): 2-Me; 2.08 (s): OAc; 2.27 (s): N (Me) 2; 2.47 (m) H .: _8; 2.68 (m): H- ₃ ; 2.82 (s): 6-OMe; 3.04 (q): _H10; 3.31 * (dqj: ₄ H; 3.48 (m): H ' _5, 3.73 (d, J - 2.5): _H5; 3.80 -3.92: _OCH2; 3.89 (S): _Η χι; 4.69 (d): _Η χ, 4.78 (dd): _H2; 4.99 (d) 5.04, (C ) OCH ₂ O, 5.29 (dd): H _13th

Grade B

12,11-dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha and L-ribohexapyranosyl) oxy-6-O-methyl-3-oxo-11,12- (oxycarbonyl 1 [[(methoxymethyl)] imino] erythromycin

0.150 g of a mixture containing 0.150 g of the product of step 11 is dissolved in 1.5 ml of DMF.

The reaction mixture was cooled to +10 < 0 > C and 14 mg of sodium hydride at 50 * concentration in oil was added. The reaction mixture was cooled to 0 ° C and 26 µL of MEM-chloride in solution in 0.5 mL of DMF was introduced. Stirring is performed for 25 minutes at 0 ° C, followed by pouring the mixtures on ice, concentrating, collecting in ethyl acetate, washing with water, extracting with ethyl acetate, drying, filtering and concentrating. The product is diluted with 4 ml of methanol.

The solution is refluxed for 2 hours, then returned to ambient temperature. Add 1 ml of a 6.5 H solution of hydrochloric acid in methanol. The methanol was evaporated, followed by collection in ethyl acetate, washing with ammonium hydroxide, dilution, extraction with ethyl acetate, drying, filtration and concentration. 0.11 g of product is obtained, which crystallizes. After purification, the crude desired product is obtained. MP: = 238-240 * 0.

NMR CDCl ₃ ppm

0.88 (t): CH ₃ -CH ₂ ; 1.03 (d) 10-Me; 1.16 (d): 8 Me; 1.25 (d): 5'Me; 1.32 (d): 4 Me; 1.38 (d): 2 Me; 1.34. And 1.51: 0 · 12 Me; "1,57 and 1,38 CH ₂ in position · <> -Aj ⁶⁰ and 1,84:

_CH2 at position 7; ~ 1.67 and 1.25: 0¾ in position 4 '; 2.27 (s): N (Me) ₂ ; 2.44 (m): H- ₃ ; 2,62 (m): θ; 2.67 (s): 6-OMe;

3.09 (ql): _H10; 3.12 (m): H ₄ ; 3.18 (dd): H * ₂ ; 3.36 (s): OMe; _3j47: OH · 3.86 (q): _H2; 3.87 (s): Η _11? 4.24 (d) s Η · _χ ; 4.93 J 5,27 (d): NCH ₂ O; 5.05 (dd): H ₁₃ .

Example 2

11,12-dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexapyranosyl) oxy] -6-O-methyl-3-oxo-12,11 - [oxycarbonyl [[[2- [4- (3-pyridinyl) -1H-imidazol-1-yl] ethoxy] methyl] imino] Jerythromycin

Grade A

2,3-didehydro-11,12-dideoxy-3-O-de (2,6-dideoxy-3-C-methyl-3O-methyl-alpha and L-ribohexapyranosyl) -6-O-methyl-12,11- [oxycarbonyl [[(2-bromoethoxy) methyl] imino]] -3-O - [[2- (trimethylsilyl) ethoxy] methyl] erythromycline-2 * -acetate

0.278 g of sodium hydride at 50% concentration in oil was stirred in 2 ml of THF. The mixture was cooled to 0 ° C and 510 mg of the product of Step A of Example 1 in solution in 8 mL of THF was added. The reaction medium is returned to room temperature and introduced into 100 microliters of ClCH ₂ OCH ₂ CH ₂ Br in solution in 4 mL of THF. The reaction medium is returned to 0 ° C, poured onto ice, extracted with ethyl acetate, washed with brine, dried by filtration and concentrated. 0.709 g of the expected product is obtained.

Grade B

2,3-Didehydro-11,12-dideoxy-3-O-de (2,6-dideoxy-3-C-methyl-

3-O-methyl-alpha-L-ribohexopyranosyl) -6-O-methyl-12,11- [oxycarbonyl [[2- [4- (3-pyridinyl) -1H-imidazol-1-yl] ethoxy] methyl] imino ]] -3-O - [[2- (trimethylsilyl) ethoxy] methyl] erythromycin-2'-acetate

A solution of 3 mL of DMF and 0.377 g of de-4- (3-pyridinyl) -1H-imidazole is introduced into a solution containing 2 mL of DMF, and 0.162 g of sodium hydride at 50% concentration in oil. Stirring is carried out for 1/4 hour and 0.709 g of the product from Step A, Example 2 are introduced in solution in 8 ml of DMF. Stir 3 hours at ambient temperature and for 15 minutes at 60 ° C. The reaction medium is poured onto ice, extracted with ethyl acetate, washed with brine, then with water, dried, filtered and concentrated. 0.644 g of product is obtained.

Grade C

11,12-Dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl) oxy] -6-O-methyl-3-oxo-12,11- [oxycarbonyl [[[2- [4- (3-pyridinyl) -1H-imidazol-1-yl] ethoxy] methyl] imino]] erythromycin

A solution containing 0.644 g of the product of Step B and 8 ml of methanol is stirred for 48 hours at ambient temperature, then 0.565 g of the obtained product is diluted in 5 ml of ethyl acetate. The reaction medium is cooled to O'C and 2.5 ml of a 2.0N hydrochloric acid / methanol solution is introduced and the whole is returned to ambient temperature. Stirring is maintained at ambient temperature for 1 hour.

The solvents were evaporated, followed by dilution with water, pouring into saturated aqueous sodium carbonate solution, extraction with ethyl acetate, washing with water, drying, filtration and concentration. 0.508 g of an oil is obtained which is chromatographed on silica gel with CH ₂ Cl ₂ / MeOH (93-7), then CH ₂ Cl ₂ / MeOH / NH ₄ OH (93-7-0.5). The homogeneous fractions were concentrated by thin layer chromatography followed by collection in ethyl acetate, washing with ammonium hydroxide, dilution, extraction with ethyl acetate and water, drying, filtration and concentration. 66 mg of the expected product are obtained.

CDCl ₃ ppm

0.85 (t): _{CH3 --CH2;} 1.00 (d) - 1.15 (d) - 1.25 (d) 1.31 (d) -

1.40 (d): CH ₃ -CH; 1.34 and 1.51: 6 and 12 Me; 2.26 (s):

N (Me) 2; 2.44 (m): H * ₄ ; 2.60 (m): Ηθ; 2.68 (s): 6-OMe; 3.03 (m): H ₄ and H ₁₀ ; 3.18 (dd): H- ₂ ; 3.55 (m): H '_s; 3.76 (s) 3.92 (m) -4.38 (m): OCH ₂ CH ₂ N; 3.87 (s): _{χ χι} ; 3.83 (q): _H2; 4.24 (d): _H5; 4.31 (d): H1 _; 4.96 (dd): H ₁₃ ; 4.99 (d) - 5.37 (d): NCH ₂ 0. 7.36 (d) - 7.54 (d): H imidazoles; 7.30 (ddd): _H5; 8.08 (dt): H ₄ - 8.45 (dd): Hg - 8.95 (ddd): pyridine :.

Example 3

II, 12-dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexapyranosyl) oxy] -6-O-methyl-3-oxo-12,11 - [oxycarbonyl [[(2-phenylethoxy) methylimidino]] erythromycin

Grade A

2,3-Didehydro-11,12-dideoxy-3-O-de (2,6-dideoxy-3-C-methyl-3O-methyl-alpha-L-ribohexapyranosyl) -6-O-methyl-12,11 - [oxycarbonyl [[(2-phenylethoxy) methyl] imino]] - 3-O - [[2- (trimethylsilylethoxy) methyl] erythromycin-2'-acatate mg of sodium hydride at 50% oil concentration is added at 10 ° C to a solution containing 2 ml DMF and 203 mg of the product obtained in Step A _{f of} Example 1.

Stirring is carried out for 15 minutes, followed by cooling to -5 ° C and 46 microliters of chloromethylphenyl ether in solution in 0.5 ml of DMF is added.

The DMF was evaporated, followed by collection in ethyl acetate, washing with water, drying, filtration and concentration. 0.277 g of the expected product is obtained.

Grade B

11,12-Dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-Libibohexapyranosyl) oxy] -6-0-methyl-3-oxo-12,11- [oxycarbonyl [[(2-phenylethoxy) methyl] imino] Jerytromycín

0.227 g of the product obtained in Step A is introduced in one portion into 0.33 ml of a 0.19N hydrochloric acid in ethyl acetate solution cooled to + 5 ° C. The reaction medium is returned to ambient temperature and stirring is performed for 2 hours. After cooling to 0 ° C, water is added, the pH is adjusted to 9-10 with concentrated ammonium hydroxide solution, followed by extraction with ethyl acetate, washing with water, drying, filtration and concentration. 0.201 g of product is obtained, which is diluted in 2.5 ml of methanol. The whole is brought to reflux for 2 hours 30 minutes. The methanol was evaporated to give 0.88 mg of product which was chromatographed on silica gel eluting with methylene chloride-isopropanol-ammonium hydroxide (95-50.5). After concentration, the residue is taken up in methylene chloride, a drop of concentrated ammonium hydroxide is added, followed by stirring, drying, filtration and concentration. 55 mg of product are obtained, which product is separated and dried at 80 ° C. 36 mg of product are obtained. MP: - 210-212C.

NMR CDCl ₃ ppm

0.88 (t): CH ₃ -CH ₂ ; 1.02 (d) - 1.15 (d) - 1.25 (d) - 1.31 (d) - 1.39 (d): the _CH3 --CH; 1.33-1.51: 6 and 12 Me; 2.27 (s): N (MS) ₂ ; 2.45 (m): H- ₃ ; 2,62 (m): θ; 2.70 (s): 6-OMe; 2.91 (m): _CH2 '; 3.08 (ql): H ₁₀ · "3.15 (m): _H4; 3.18 (dd): H- ₂ ; 3.58 (m): H ₅ ; "3.58 and 3.77 :. OCH ₂ ; 3.87 (q); H ₂ ; 3.91 (s): _Ηχ ; 4.25 (d): _H5; 4.32 (d): _Hx ; 5.00 (d) - 5.33 (d): _NCH2 0; 5.05 (dd): H _ia ; 7.13 to 7.30: phenyl, ether ("0.3 mol :).

Working up as described above gave the following product.

Example 4

11,12-Dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl) oxy] -6-O-methyl-3-oxo-12,11 - [oxycarbonyl- [[(2- (trimethylsilyl) ethoxy] methyl] imino]] erythromycin

MP: = 141-143 * C, Rf = 0.38 (AcOEt-TEA 95-5).

An example of a pharmaceutical composition

A composition was prepared containing the product of Example 2 ........................ 150 mg, * excipient sqf ............ ................ 1 g excipient component: Starch, talk, magnesium stearate.

Pharmacological Study of the Products of the Invention

Method of dilution in liquid medium

A series of tubes are prepared in which an equal amount of sterile nutrient medium is distributed. Spread an increasing amount of the product to be studied in each tube, then inoculate each tube with a bacterial strain. After incubation for 24 hours in a thermostate at 37 ° C, growth inhibition is evaluated by transilumination, which allows the determination of the minimum inhibitory concentrations (MIC), expressed in micrograms / cm ³ .

The following results were obtained.

Gram-positive bacterial strains Products Exam.2 Prikl.3 Staphylococcus aureus 011UC4 0.08 0.04 Staphylococcus aureus 011G025I 0.08 0.15 Staphylococcus epideraidis 012G011I 0.08 0.08 Streptococcus pyogenes group A £ 0.02 £ 0.02 02A1UC1 Streptococcus agalactiae group B £ 0.02 £ 0.02 02B1HT1 Streptococcus faecalis group D £ 0.02 £ 0.04 02D2UC1 Streptococcus faeciua group D £ 0.02 £ 0.02 02D3HT1 Streptococcus sp. group G £ 0.02 £ 0.02 O2GOGR5 Streptococcus aitis 02mitCB1 £ 0.02 £ 0.02 Streptococcus aitis 02mitGR16I £ 0.02 £ 0.02 Streptococcus agalactiae group B 0.08 0.04 02B1SJ1 Streptococcus pneuaoniae 032UC1 0.02 £ 0.02

In addition, the product of Example 1 showed useful activity on the following gram-negative bacterial strains: Haeaophilus influenzae 351HT3, 351CB12, 351CA1 and 351GR6.

Claims (10)

PATENT CLAIMS Compounds of formula I R represents either linear, branched or cyclic alkyl, alkenyl or alkynyl containing up to 18 carbon atoms, optionally substituted with at least one substituent being halogen, linear branched or cyclic O-alkyl, O-alkenyl or Oalkynyl, S-alkyl, S- alkenyl or S-alkynyl containing up to 12 carbon atoms, an NO ₂ , ON group, further wherein R ^a and R ^b are identical or different to hydrogen, a linear or branched alkyl containing up to 4 carbon atoms, the following groups wherein R ^c , R ^d and ^Rf, identical or different, represent a line and we branched or cyclic alkyl having up to 4 carbon atoms, optionally substituor SPECIFIED at least one halogen atom, or (CH _{2) n} Ar radical in which n represents an integer ranging from 0 to 6 and Ar represents aryl or heteroaryl, optionally substituted with at least one of the substituents mentioned above, represents a hydrogen atom or an acyl radical containing 1 to 12 carbon atoms. as well as their acid addition salts. Compounds of formula I according to claim 1, wherein Z represents a hydrogen atom. Compounds of formula I according to claim 1 or 2, wherein R is (CH ₂ ) _n Ar wherein n is an integer ranging from 1 to 4 and Ar is optionally substituted aryl or heteroaryl. Compounds of formula I according to claim 3, wherein Ar is optionally substituted phenyl. Compounds of formula I according to claim 3, wherein R represents an optionally substituted group 6. Compounds of formula I which are 11,12-didexy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-1-hexohexopyranosyl) oxy] -6-O-methyl-3-oxo-12,11- [oxycarbonyl- [[(2- [4- (3-pyridinyl) -1H-imidazol-1-yl] ethoxy) methyl] imino]] erythromycin, 11,12-dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-1-hexohexopyranosyl) oxy] -6-O-methyl-3-oxo-12,11- [oxycarbonyl [[(2-phenylethoxy) methyl] imino]] erythromycin. Compounds of formula I as defined in any one of claims 1 to 6 as medicaments. Pharmaceutical compositions comprising at least one medicament according to claim 7 as an active ingredient. 9. A process for the preparation of compounds of formula I, wherein the compound of formula II (II) wherein Z &lt; ¹ &gt; is a carboxylic acid residue containing up to 12 carbon atoms, is treated with a ketone 3-protecting group in the form of an enol ether or enol ester. wherein E represents a residue of an enol ether or an enol ester and Z ¹ retains its meaning as previously defined. (III) is treated with a compound of formula IV Hal - CH ₂ OR (IV) wherein Hal represents a halogen atom to give the corresponding compound of formula V (V) which, if necessary, is treated with a composition which releases the ketone group at the 3-position and / or with a composition which releases hydroxy at the 2 'position to give the corresponding compound of formula I Trademarks where R and Z retain their meaning as previously defined. Compounds of formulas III and V as defined in claim 9 as novel chemical products.