MXPA96005208A - New derivatives of erythromycin, its procedure of preparation and its application as medicamen - Google Patents

Abstract

The present invention relates to the compounds of the formula (I) wherein: R represents a radical - (CH 2) n Ar, wherein n represents the number 3, 4 or 5, Ar represents a heterocyclic radical, optionally substituted, Z represents an atom of hydrogen or a residue acid. The compounds of the formula (I) have interesting antibiotic properties

Description

NEW DERIVATIVES OF ERYTHROMYCIN. YOUR PREPARATION PROCEDURE AND ITS APPLICATION AS MEDICINES The present invention relates to new erythromycin derivatives. to its preparation procedure and its application as medicines. The subject of the present invention is the compounds of the formula (I): wherein R represents a radical - (CH * _u) pAr. where n represents the numbers 3. 4 or 5 and Ar represents a heterocyclic radical. which eventually carries one or more substituents. which are selected from the group consisting of radicals: REF: 23346 / - K x or R represents a radical -; : H,; - -r ^ - * / 5 N / and Z represents a hydrogen atom or an acid residue, as well as its addition salts with acids. As examples of addition salts of the present derivatives with mineral or organic acids, mention may be made of the salts formed with acetic, propionic acids. trifluoroacetic, maleic. tartaric, methanesulfonic. Benzenesulfonic p-toluensul phonic, hydrochloric, hydrobromic, hydroiodic. sulfuric, phosphoric and especially the stearic, ethylsuccinic or lauryl sulfuric acids. The heterocyclic radical can be substituted with one or more radicals which are selected from the group consisting of free, salified, esterified and amidated carboxyl radicals. the hydroxyl radical. halogen atoms, radicals NO. ON, straight chain, branched or cyclic, straight chain or branched alkyl, alkenyl and alkynyl radicals, O-alkyl. O-alkenyl and 0-alkynyl. S-alkyl, S-alkenyl or S-alkynyl and N-alkyl, N-alkenyl and N-alkynyl. comprising up to 12 carbon atoms, optionally substituted with one or more halogen atoms, the radical N, R. and R, being identical or different, 0 representing a hydrogen atom or an alkyl radical containing up to 12 carbon atoms, aryl radicals. Carbocyclic 0-aryl or S-aryl, or aryl. Heterocyclic 0-aryl or S-aryl comprising one or more "" < heteroatoms. optionally substituted with one or more of the aforementioned substituents, and the radical 0 -C-R3. R3 representing an alkyl radical containing 0 to 12 carbon atoms or a carbocyclic or heterocyclic aryl radical, optionally substituted. When the heterocyclic radical comprises several cycles (joined together or condensed). the substituent (s) can be found in any of the heterocyclic or carbocyclic rings (or rings); thus, for example, if a heterocyclic ring is attached or condensed to an aryl radical, the heterocyclic ring and the aryl moiety can both carry one or more substituents. The aryl radical is preferably a phenyl or naphthyl radical. - the alkyl, alkenyl or alkynyl radical. preferably it is a methyl, ethyl radical. propyl, isopropyl, n-butyl. isobutyl, tert-butyl, decyl or dodecyl. vinyl, alilo. ethinyl. propinyl. propargyl cyclobutyl. cyclopentyl or cyclohexyl, the halogen is preferably a fluorine, chlorine or bromine atom, the alkyl radical substituted with a halogen atom, preferably is a radical CHCl ,, CHBr », CHF-. CC13. CBr3. CF3. CH2CF3. CH2CH2CC13. CH2CH2CF3. the sarboxylic acid residue is preferably an acetyl residue. propionyl. butyryl, isobutyryl. n-valeryl, isovaleryl, tert-valeryl and pivali lo. The present invention more particularly has as its object the compounds of the formula (I), wherein Z represents a hydrogen atom and the compounds of the formula (I) wherein n represents the number 4. The present invention especially has as its objective compounds of the formula (I) where Ar represents a radical: eventually replaced. as well as the compounds of Formula (I) wherein R represents the radical: optionally substituted, as well as the compounds of the formula (I) wherein Ar represents a radical: optionally substituted and more particularly the compounds of the formula (I) wherein Ar represents a radical eventually replaced. The present invention has as a particular objective, compounds of the formula (I) whose preparation is presented later in the experimental part. Among the preferred compounds of the present invention. The following compounds can be mentioned: 11, 12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl-1-a1 fa-L-ribohexopyranosi 1) -oxi) -6-o -methi 1-3-oxo-12.11- (oxycarbonyl - ((4- (4-phenyl-1H-imidazol-1-yl) -butyl) -imino)) -erythromycin, -12,12-dideoxy-3-des (( 2. d-dideoxy-SC-methyl-SO-methyl 1-al-L-riboh? Xopyranosi 1) -oxi) -6-o-methyl-1-3-oxo-12. ll- (oxycarbonyl- ((4- (3H-imidazo (4.5-b) pyridin-3-yl) -butyl-imino)) -erythromycin-11,12-dideoxy-3-des ((2,6-dideoxy) -3-C-methyl-3-0-methy1-a1fa-L-ribohexopyranosi 1) -oxy) -6-o-methyl 1-3-oxo-12- (oxycarbonyl- ((4- (4 -lH-imidazo (4.5-b) pyridin-li 1) -butyl) -imino)) -erythromycin-11, 12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0- meti 1-al-fa-L-riboh? xopyranosi 1) -oxi) -6-o-meti 1-3-oxo-12. ll- (oxycarbonyl- ((4- (4- (4-chlorophenyl) -lH- imidazol-li 1) -buti 1) -imino)) -erythromycin - 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl-1-alpha-L-riboh? xopiranosi 1) -oxi) -6-o-methyl 1-3-oxo-12, 11- (oxycarbon l- ((4- (4- (2-methoxyphenyl) -lH-imidazol-1-yl) -butyl) - imino)) -erythromycin - 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-O-methyl-1-alpha-L-ribohexopyranosyl) -oxy) -6-o-methyl-3 -oxo-12, ll- (oxycarbonyl- ((4- (4- (4-fluorophenyl) -lH-imidazol-li 1) -buti 1) -imino)) -erythromycin. - 11.12-dideoxy-3-des ((2,6-Dyssoxy-3-C-methyl-3-0-methyl 1-a1 fa-L-ribohexopyranosi 1) -oxi) -6-o-methyl 1-3-oxo- 12, 11- (oxycarbonyl- ((4- (7-methoxy-4-quinolinyl) -butyl) -imino)) -erythromycin. - 11.12-dideoxy-3-d? S ((2,6-dideoxy-3-C-methyl-3-0-methyl-1-alpha-L-riboh? Xopyranosi 1) -oxi) -6-o-methyl 1- 3-oxo-12. 11- (oxycarbonyl - ((4- (2- (2-pyridinyl) -4-thiazolyl) -buti 1) -imino)) -erythromycin, 11,12-dideoxy-3-des ((2'-6-dideoxy) 3-C-methyl-3-0-meti 1-alpha-L-riboh? Xopyranosi 1) -oxi) -6-o-methyl-3-oxo-12, ll- (oxycarbonyl- ((4- (3- (3-pyridinyl J-1H-1, 2,4-triazol-1-yl) -butyl) -imino)) -erythromycin, and especially in particular 11,1-dideoxy-3-des ((2, 6 dideoxy-3-C-methyl 1-3-O-methyl-lfa-L-ribohexopyranosi 1) -oxi) -6-o-methyl-3-oxo-12, 11- (oxycarbonyl- ((4- (4- (3-pyridinyl) -lH-imidazol-1-yl) -buti 1) -imino)) -erythromycin The products of the general formula (I) possess a very good antibiotic activity on gram-positive bacteria such as staphylococci, streptococci. and the pneumococci The compounds of the present invention, then, are used as medicaments in the treatment of infections by sensitive germs and mainly, in the case of staphylococci, such as staphylococcal septicemias, staphylococcal diseases of the face or skin. , pyodermitis, septic or ulcerative wounds or ulcers, boils, carbuncles, phlegmon, erysipelas and acne, staphylococcal diseases such as acute or post-acute acute tonsillitis, bronchopneumonias, pulmonary suppurations, streptococcal diseases such as acute tonsillitis, otitis. sinusitis, scarlet fever, pneumococcal diseases such as pneumonia, bronchitis; brucellosis diphtheria and gonorrhea. The products according to the present invention are also active against infections caused by germs such as Haemophi lua influßnzaß. Ricketsiais. Mycoplasma pneumoniae. Chlamydia Legionel la. Ureaplasma Toxoplasma or germs of the genus Mycobacterium. I would list, eningococci and Campylobacter. Likewise. The present invention has as its objective, as medicaments and mainly antibiotic medicaments, the products of the formula (I) such as those defined above, as well as their addition salts with pharmaceutically acceptable mineral or organic acids. More particularly, the present invention has as its objective, as medicaments and mainly antibiotic medicaments, the preferred products of the formula (I) defined above, namely, the products of Examples 1, 2. 3 and 29 to 35, as well as their pharmaceutically acceptable salts. The present invention also aims at pharmaceutical compositions containing as an active principle, at least one medicament as defined above. These compositions can be administered orally, rectally, parenterally or locally via topical application on the skin and mucous membranes, but the preferred route of administration is the oral route. These compositions can be solid or liquid and can be presented in the pharmaceutical forms commonly used in human medicine, for example. tablets, simple or coated, capsules, gres. suppositories. injectable preparations, ointments, creams, gels; These are prepared in accordance with the usual methods. The active ingredient (s) can be incorporated with the excipients usually employed in the pharmaceutical compositions, such as talc, gum arabic, lactose. starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fats of animal or vegetable origin, paraffinic derivatives, glycols. Derivatives of wetting agents, dispersants or emulsifiers, preservatives.

The compositions can also be in the form of a powder intended to be dissolved extemporaneously in a suitable vehicle, for example sterile pyrogen-free water. The dose administered varies according to. the disorder that is being treated, the subject that suffers it, the route of administration and the product considered. This can be, for example, between 50 and 300 mg per day orally, in adults for the product of Example 1 or Example 2. The present invention also aims at a process for the preparation of the compounds of the formula ( I), characterized in that a compound of the Formula (II) is subjected to: 0 Z 'wherein Z' represents an acid residue, to the action of a compound of the Formula (III): RNH, (III) wherein R is as previously defined, to obtain a compound of the formula (I-): 0 Z 'wherein R and Z' retain their preceding meaning, and the compound of Formula (I) is then subjected, if appropriate, to the action of an acid to form a salt. - the reaction of the compound of the formula (II) with the compound of the formula (III) is carried out in a solvent such as. for example. acetonitrile. dimethylformamide or even tetrahydrofuran. dimethoxyethane or dimethyl sulfoxide. - the hydrolysis of the ester function in the 2 'position. it is carried out with the help of methanol or aqueous hydrochloric acid. the salification is carried out by means of acids, in accordance with the classical procedures. The compounds of the formula (II) used as starting products are described and claimed in European Patent Application 0 596 802. The compounds of the formula RNH- are known products in general, although the precise compounds used for the preparation of the products of the Examples are novel and are themselves an object of the present invention, their preparation is presented below. The compounds of the formula (III): RNH, (III) for example, they can be prepared in accordance with the procedures described in J. Med.

Chem. (1982) vol. 25 p. 947 and in the following documents: Tetrahedron Lettßrs vol. 32, No. 14, p.p. 1699-1702 (1991); J. Org. Chem. 54 (18) 4298. 301 (1989); J. Org. Chem. 28 (101) 2589. 91 (1963) or in German Patent 3,406,416; J. Org. Chem. 6-895-901 (1941) or Synth.

Commun 17 (14) 1741-8 (1987). The subject of the present invention is in particular the amines of the formula (III) as defined above, the preparation of which is detailed below. The present invention is particularly aimed at the following compounds: 4-phenyl-1H-imidazole-1-butanamine, 3H-imidazo (4.5-b) -pyridin-3-butanamine, 1H-imidazo (4, 5-b) ) -pyridin-3-butanamine. - 2-phenyl-4-quinolinobutanamine. - lH-benzotriazole-1-butanamine. - 2H-benzotriazole-2-butanamine, l-methyl-lH-imidazo (4,5-c) -pyridin-2-butanami, 3-methyl-3H-imidazo (4.5-c) -pyridin-2-butanamine. - 5-chloro-lH-benzimidazole-l-butanamine, 7-methoxy-4-quinolinobutamine, lH-imidazo (4.5-c) -pyridin-1-butanamine. 9H-purin-9-butanamine, -l-methyl-lH-indol-4-butanamine. - 3-phenyl-lH-l.2.4-triazole-l-butamine (hydrochloride). 5-pheny1-lH-t-trazol-l-butanamine (hydrochloride), -2-benzothiazobutolamine, -4- (thieno (2,3-b) -pyridin-4-yl-butanamine. - 5,6-dimeti 1-lH-benzimidazol-l-butanamine. - 3-quinolinebutanomine. - 2-quinolinebutanomine. 5H-imidazo [4.5-c] pyridin-5-butanamine. - l-methyl-lH-benzimidazole-2-butanamine. 6-Chloro-lH-benzimidazole-2-butanamine, -2-methyl-lH-benzimidazole-2-butanamine. 4- (4-chloropheni-1) -lH-imidazole-l-butanamine, 2- (3-pyridinyl) -thiazole-5-butanamine, -7-methoxy-quinoline-4-butanamine. 4- (4-fluoropheni 1) -lH-imidazol-1-butanamine, 4- (2-methoxy-phenyl) -lH-imidazol-1-butanamine. 3- (3-pyridinyl) -lH-1,2,4-triazole-l-butanamine, 4- (3-pyridinyl) -lH-imidazole-l-butanamine, 2- (2-pyridin-1) -thiazole-4- butanamine, 2-phenylisothiazole-4-butanamine, 4- (4-methoxyphenyl) -lH-imidazole-l-butanamine, isoquinolysin-4-butanamine, - quinasolin-4-butanamine. 4,4-dipheni-lH-imidazol-l-butanamine, 4- (3-methoxy-phenyl) -lH-imidazol-l-butanamine. 4- (4- (trifluoromethoxy) -phenyl) -lH-imidazol-1-butanamine. 1,2,3,6-tetrahydro-l, 3-dimeti 1-2,6-dioxo-7H-purin-7-butanamine, 2- (4-pyridinium-1) -thiazole-4-butanamine, - lH-indole 1-Butanamine 2- (3-pyridinyl) -thiazole-4-butanamine as well as its addition salts with acids. The following examples illustrate the present invention. EXAMPLE 1: 11.12-Dysssoxy-3-dßβ ((2,6-Dyssoxy-3-C-methy1-3-0-methy1-a1 fa-L-ribohsxopyranosy1) -oxy) -6-o-m-ethyl-3- oxo-12.11- (oxycarbonyl- ((4- (4-phenyl-1 H-imidazol-1-yl) -butyl) -imino)) -β-rhyronicine. A mixture of 0.705 g of the 2'-deoxy-10-acetate compound is heated to 63 * C. ll-didehydro-3-des (2,6-dideoxy-3-C-methyl 1-3-0-methyl-1-alpha-L-ribohexopyranosyl) -oxi) -12-0- ((lH-imidazol-1-) i 1) -carbonyl 1) -6-0-methyl-3-oxo-erythromycin, prepared as indicated in Example 1C of European Patent Application EP 0 596 802, in 3 ml of asetonitrile at 10 * of water and 1.08 g of 4- (4-phenyl-lH-imidazol-1-yl) -butanamine. The reaction mixture is maintained at this temperature for 5 hours. The reaction mixture is allowed to return to room temperature, poured into a sodium hydrogen phosphate solution, extracted with ethyl acetate. The organic phases are washed with water, dried, filtered and concentrated. 1.5 g of a product are obtained to which 210 ml of methanol are added. It is kept under stirring for 16 hours, under a nitrogen atmosphere at room temperature. ST concentrates and 1.4 g of the product are obtained, which is purified by chromatography on silica gel and with CH2Cl2 / MeOH / NH40H (93: 7: 0.4). It is concentrated and 0.305 g of the desired crude product is obtained. which is recrystallized from isopropyl ether. it is washed and dried at 50 * C under reduced pressure. In this way, 0.267 g of the desired product are obtained, having a melting point of 222-231 * C. NMR CDC13. ppm aD - +18 '(c - 0.9 CHC13) 0.84 (t): CH3 - CH2; 1.01 (d) -1.17 (d) -1.24 (d): CH3-CH; 1.30 (d) -1.38 (d). 1.34 to 1.47: 6 and 12-Me; 2.27 (s): N (Me) 2; 2.45 (-): H'3; 2.61 (m): Hg; 2.63 (s): 6-OM ?; 3.04 (-): H4; 3.13 (q): H1Q; 3.18 (dd): H'2; 3.53 (-): H'5; 3.56 (s): H ^; 3.67 (-), 3.75 (-): the -C-NCH2; 3.87 (q): H2; 3.99 (t): CH2NC; 4.23 (d): Hg; 4. 27 (d): H ^; 4.94 (dd): H ^; 7.26 (s): H "5; 7.5 (s): H"; 7.20: H in para; 7.35: H in goal; 7.76: H in ortho. PREPARATION 1: 4- (4-phene 1-lH-imidazole-li 1) butanomine Stage A: 2- (4- (4-phenyl-1-lH-imidazol-1-yl) -butyl-1H-isoindol-1 » 3- (2H) -dione A 3-solution of 5.05 g of 4-phenyl-1H-imidazole in 25 cm d 3-dimethylformamide is added dropwise over a period of 1:30 h to a mixture of 7 cm. dimethylformamide and 2.02 g of sodium hydride, followed by 10.86 g of N-4-bromobutylphthalimide dissolved in 3 25 cm of dimethylformamide. The solution obtained is brought to 70 ° C for about 1:30 hours, it is allowed to return to room temperature, the obtained solution is concentrated, it is collected with water and subjected to extraction with ethyl acetate. The water is dried, filtered and concentrated to obtain 15 g of the product, which is recrystallized from ethyl acetate, the product obtained is drained, washed with ethyl acetate and dried under reduced pressure at 50 ° C. 5.5 g of the desired product are obtained, which has a melting point of about 130-132 * C. NMR CDC13 ppm 1.75 (m) (2H) -1.86 (m) (2H): CH2 central; 3. 74 (t): 2H; 4.03: 2H; 7.22 (t): 2HH4; 7.26 (m): 1H H'3; 7.36 (t): 2H Hg and Hg; 7.56 (d): H'5; - 7.73 (m): 4H; -7.86 (m): H2 and Hß: Stage B: 4- (4-phenyl-1H-imidazol-1-yl) -butamine.

A mixture of 3.45 g of the product obtained in stage A, 100 ml of ethanol and 0.97 ml of hydrazine hydrate is refluxed for 8 hours. The mix d? The reaction is concentrated, about 50 ml of 2N sodium hydroxide are added. it is extracted with ethyl acetate. The organic phases are washed with 2N sodium hydroxide. then with sodium chloride. Dry, filter and concentrate. 2.21 g of the desired product are obtained. NMR CDC13 ppm 1.47 (m) -1.87 (m): CH2 central; 2.73 (t). 3. 97: -CH2-NH2; 7.20 (d): H'3; 7.50 (d): H'g; 7.37 (ti) 2H: H3 H5; 7.24 (it) 1H: H4; 7.77 (m) 2H: H2 and Hß. EXAMPLE 2: 11.12-di-ßsoxy-3-dßβ ((2,6-didesoxy-3-C-methyl 1-3-O-mßti 1-alpha-L-ribohßxopyranosi 1) -oxi) -6-o-methyl- 3-oxo-12. 11- (oxycarbonyl- ((4- (3H-imidazo (4.5-b) pyridin-3-yl) -butyl) -imino)) -β-tricomycin. 708.2 mg of the 2 '-acetate of 11-deoxy-10 is dissolved. ll-didehydro-3- (2,6-diissoxy-3-C-meti 1-3-0-mßti 1-alpha-L-ribohexopyranosi 1) -oxi) -12-0- ((lH-imidazol-1-yl) -carbonyl) -6-0-methyl-3-oxo-erythromycin prepared in the manner indicated in Example 1C of the Application European Patent EP 0.596,802 and 958 mg d? (3H-imidazo (4.5- 3 b) -pyridin-3-butanamine in 2.82 cm of acetonitrile and 0.28 3 cm of water. The reaction mixture is brought to TO'C. Allow to return to room temperature and pour into a sodium acid phosphate solution. The mixture is extracted with methylene chloride and washed with water. The aqueous phases are combined and extracted again. The extract is dried, filtered, rinsed and 826 mg of the product are obtained. The product obtained is dissolved in 16.5 3 cm methanol. The reaction solution is maintained under stirring at room temperature for 20 hours. 789 mg of the crude desired product are obtained, which is purified by chromatography eluting with a mixture of methylene chloride / methanol / ammonia (94: 16: 0.4). 327 mg of the desired product are obtained, which has a melting point of 200 * C. an - +13 'c = 1% CHC13 NMR CDC13 400 MHz ppm 0.85 (t): CH3-CH2; 1.01 (d) -1.16 (d) -1.25 (d): CH3-CH; 1.30 (d) -1.26 (d). 1.35 and 1.47: 6 and 12 Me; -1.63 y - 1.98: the central CHs of the chain; 2.27 (s): N (CH3) 2; 2.46 (m): H'3; -2.59 (m): HQ; 2.61 (s): 6-OM ?; 3.07 (ra): H4; 3.12 (ql): H1Q; 3.18 (dd): H'2; 3.54 (m): H'5; 3.57 (s): Hn¡ 3.6 to 3.8: CH2NC; 3.85 (q): H2; OR 4.24 (d): H_; 4.29 (d): H '; - 4.35 (m): CH "NC; 4.93 II (dd): H13; 7.21 (dd): Hg; 8.04 (dd): H? aromatics; 8.11 (s): H2; 8.38 (dd): Hg.

EXAMPLE 3: 11.12-didßßoxi-3-dßs ((2.6-didßßoxi- 3-C-mßti 1-3-0-meti 1-alpha-L-ribohßxopiranoßi 1) -oxi) -6-o-methyl-3-oxo-12. 11- (Oxycarbonyl- ((4- (lH-imidazo (4,5-b) pyridin-1-yl) -butyl) -imino)) -erythromycin 708 mg of the 2"-acetate of 11-deoxy-10 are added. ll-didehydro-3-des (2,6-dideoxy-3-C-methyl-3-0-methyl-alpha-L-ribohexopyranosyl) -oxi) -12-0- ((lH-imidazol-1-yl. ) -carboni 1) -6-0-methyl 1-3-oxo-erythromycin prepared as indicated in Example 1C of European Patent Application EP 0 596 802 in a solution of 953 mg of (1H-3 imidazo ( 4,5-b) -pyridin-3-butanamine, 2.82 cm of 3-acetonitrile and 0.28 cm of water, the reaction mixture is brought to 55 ° C. It is kept at this temperature for 44 3 hours and 0.5 cm of water is added. acetonitrile The heating is continued at 55 * C for 20 hours The reaction mixture is allowed to return to room temperature and poured into a saturated solution of sodium acid phosphate.

The aqueous phase is extracted with methyl ester chloride and the chloromethylene phases are washed with water. Dry over sodium sulfate, filter and evaporate. 806 3 mg of the product are obtained, to which 16.1 cm d? methanol The reaction mixture is maintained at room temperature for 24 hours and evaporated to dryness. 656 mg of a product are obtained, which is subjected to chromatography on silica gel eluting with a mixture of CH2Cl2 / MeOH / NH3 (94: 6: 0.4). The crude desired product is obtained, which is purified by chromatography on silica gel eluting with a mixture of CHCl3 / MeOH / NH40H (94: 6: 0.4). After dissolving the residue in a mixture of ethyl acetate and isopropyl ether, it is filtered and evaporated to dryness, thereby obtaining the desired product. p.f. = 203 * C. aD - 17.6"c - 1 * of CHClg 0.81 (t): CH3 - CH2; 1.00 (d) -1.17 (d) -1.25 (d) -1.31 (d) -1.38 (d): CHg - CH; 1.35 (s) -1.47 (s): 6 and 12-CH3; 1.68 (m) and 1.93 (m): CH2 central chains.-2.27 (S): NICHl; 2.61 (s): 6-0CH3; 2.45 (m); H'3; -2.60 (m partly masked): HD; 3.07 (m): H; -3.15 (ql): H1Q; 3.18 (dd): H'2; 3.56 (s): H ^, 3.53 (m): CH2-NC-, 4.24 (d): Hg, 4.28 (d): H ^, 4.91 (dd): H13, 7.21 (dd J - 5 and 8): Hg.- 7.80 (dd.J - 8 and 1.5): H? aromatics; 8.56 (dd. J = 5 and 1.5); Hg; 8.15 (s): H2 + CH2C12- PREPARATION 2: Preparation of the amines used as starting compounds (or starting compounds) in examples 2 and 3: 3H-imidazo (4.5-b) pyridin-3-butanan-ina and 1H-imidazo (4.5-b) pyridine -l-butanamine Stage a: To a solution of 5.95 g of 4-azabenzimidazole and 3 15.5 g of N-4-bromobutylidene in 30 cm of dimethylformamide, add 10.3 g of potassium carbonate. The mixture is stirred for 20 hours at room temperature. The insoluble product is filtered, rinsed with methylene chloride. The organic phase is washed with water, then dried over magnesium sulfate and evaporated; The oily residue obtained is washed with petroleum ether and then with isopropyl ether. 16.3 g d? a crude product, which is purified by chromatography on silica gel eluting with a methylene chloride / acetone mixture, to obtain 4.9 g of the product (A), m.p. - 143'C. and 3.9 g of the product (B). p.f. - 172'C. Stage bl: 3H-imidazo (4.5-b) pyridin-3-butanamine (starting compound of Example 2) A mixture of reflux is refluxed for 19 hours. 32. 86 g of the product (A) prepared as indicated in the preceding step. 697 cm 3 of ßtanol and 20 cm3 of hydrazine.

Let it return to room temperature. It is filtered, ST rinsed and evaporated to dryness. Collect with methylene chloride. it is filtered, ST rinsed and evaporated to dryness. 18.87 g of the desired product are obtained. NMR CDC13-250 MHz 1.52 (m) -2.00 (m): 2 CH2 central; 1.63 (s 5 long): 2 H mobile; 2.76 (t): CH2 ~ CH2-NH2; 4.33 (t): = C-N-CH2-CH2 7.24 (dd J = 8 and 5): Hg; 8.08 (dd. J = 8 y C = 0 1.5): H ?; 8.40 (dd. J »5 and 1.5): Hg; 8.08 (s): H2. • "" > Stage b2: lH-imidazo (4.5-b) pyridin-1-butanamine (starting compound of Example 3) A mixture of 3 32 g of product (B) d is refluxed for 21 hours. the preparation 3. 640 cm of 3 ethanol and 24.8 cm of hydrazine. He lets himself return to the room temperature. It is filtered, rinsed with ethanol and evaporated under reduced pressure. Collect with methylene chloride, filter, ST rinse and evaporate to dryness. 19.5 g of the desired product are obtained. NMR CDC13 20 1.45 (m) -1.9d (m): 2 central CH2; 2.74 (t) CH2-NH2; - 1.45 (m): mobile; 4.23 (t): C-N-CH2 ~ CH2; 7.24 c (dd, J = 8 and 5): Hg; 7.75 (dd. J = 8 and 1.5): H ?; 8.58 25 (dd J-5 and 1.5): Hg; 8.13 (s): H2 + EtOH.

By proceeding as described above, using the appropriate amines, the following compounds were prepared: EXAMPLE 4: 11, 12-Dysssoxy-3-dßa ((2,6-Dissysoxy-3-C-methy1-3-0-methy1-a) fa-L-ribohexopyranosi 1) -oxi) -6-o-methyl-3-oxo-12.11- (oxycarbonyl- ((4- (thien (2,3-b) -pyridin-4-yl) -butyl) -imino) ) -ßrythromycin, mp = 176 - 178'C. aD - + 17 *. c-0.9 * in CHC13 EXAMPLE 5: 11.12-dideoxy-3-dßs ((2,6-didesoxy-3-C-mßti 1-3-Op.ßti 1-a1 fa-L-ribohßxopyranosi 1) -oxi) - 6-o-mßti l-3-oxo-12, 11- (oxycarbonyl- ((4- (3-pheny1H-1.2.4-triazol-1-yl) -butyl) -imino)) -β-trichromycin. p.f. - 208 - 210'C.

EXAMPLE 6: 11.12-Dyssissoxy-3-dßs ((2,6-dideoxy-3-C-mßti 1-3-0-met 1-al-fa-L-ri ohexopyranosi 1) -oxi) -6-o-methyl -3-oxo-12.11- (oxycarbonyl- ((4- (l-methyl-lH-imidazo (4r5-c) -pyridin-2-yl) -butyl) -imino)) -β-trichromycin. or_ - + 19 *. c - 1 * in CHC13 EXAMPLE 7: 11.12-Dyssoxy-3-dßβ ((2,6-Dyssoxy-3-C-mßti 1-3-0-mßti 1-alpha-L-ribohßxopyranoßi 1) -oxi) -6-o -mßt il-3-oxo-12.ll- (oxycarbonyl- ((4- (3-mßti 1-3 H-imidazo (4.5-c) -pyridin-2-yl) -butyl) -imino)) -β-brromycin. aD - + 16 *. CHC13 - 1 * EXAMPLE 8: 11.12-Dysssoxy-3-dßβ ((2,6-dideoxy-3-C-mßti 1-3-O-mßti-1-lf-L-ri ohexopi anoßi 1) -oxi) -6-0 -methi 1-3-OXO-12.11- (oxycarboni l- ((4- (7-Mβtoxinquinóleinil) -butil) -imino)) -erythromycin. aD - + 15.8 *, c - 1 * in CHC13 EXAMPLE 9: 11.12-didesoxy-3-dßs ((2,6-Dissysoxy-3-C-methyl 1-3-0-methyl-1-alpha-L-ribohexopyranosyl) -oxi) -6-0-methyl 1-3-OXO -12. 11- (oxycarbonyl- ((4- (5-phenyl-lH-tetrazol-1-yl) -butyl) -imino)) -β-trichromycin. p.f. - 132 - 134'C. an - +25 ', c - 1 * in CHC EXAMPLE 10: 11.12-Dyssissoxy-3-dßß ((2,6-Dyssysoxy-3-C-mßti 1-3-0-mßti 1-alf-L-ribohßxopyranoß 1) - oxy) -6-o-mßti 1-3-OXO-12.11- (oxycarbonyl- ((4- (2-b-isothiazolyl) -butyl) -imino)) -β-trichromycin. p.f. - 179 - 181'C. aD - + 18 *. c - 1 * in CHC13 EXAMPLE 11: 11.12-Dyssiaoxi-3-dßs ((2,6-Dyssysoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohßxopyranoßi 1) -oxi) -6-0 -mßti 1-3-OXO-12.11- (oxycarbonyl- ((4- (2- (3-pyridinyl) -4-thiazolyl) -butyl) -imino)) -β-trichromycin, p.f. = 150 - 152'C. aD - + 17 *. c - 0.9 * in CHC13 EXAMPLE 12: 11.12-Dysßoxo-3-dßs ((2,6-Dyssysoxy-3-C-mßti 1-3-O-mßti 1 -alpha -L-ribosixopyranosyl 1) -oxi) -6- o -methyl-3-oxo-12, 11- (oxycarbonyl) - ((4- (2- (3-pyridinyl) -5-thiazolyl) -butyl) -imino)) -bromide, p. = 155 - 159'C. ctjj - +12". c» 1 * in CHC13 EXAMPLE 13: 11.12-Dysssoxy-3-dßs ((2,6-Dysßoxo-3-C-mßt 1-3-0-mßti 1 -alpha -L-ibohßxopyranoßi 1) -oxi) -6-o-m-ethyl-3-oxo-12.11- (oxycarbonyl - ((4- (9H-purin-9-yl) -butyl) -imino)) -bromi-bromide. EXAMPLE 14: 11.12-didßsoxi-3 -dßs ((2,6-diesßoxi-3-C-mßti 1-3-0-mßti 1-a1 fa-L-ribohßxopiranoßi 1) -oxi) -6-o-mßti 1-3-OX0-12.11- (oxycarboni) - ((4- (1H-imidazo (4,5-c) -pyridin-1-yl) -butyl) -imino)) -bromiomethyl. Rf-0.42 in CHC 3 + 8 * of MeOH with 8 * of NH 4. OH EXAMPLE 15: 11.12-Dyssissoxy-3-dßβ ((2,6-Dysßosoxy-3-C-mßti 1-3-0-mßti-1-l-L-ribos-β-pyranosyl) -oxi) -6-o-m-ethyl-3 -oxo-12.11- (oxycarboni l- ((5- (lH-bßnzimidazol-1-yl) -phenyl) -imino)) -β itromiciña Prepared from 2- (4-bromopentyl) -lH-isoindo1- 1, 3 (2H) -dione EXAMPLE 16: 11.12-Dysssoxy-3-dßβ ((2,6-Dyssysoxy-3-C-mßti 1-3-0-meti 1-alpha-L-ribohsxopyranosi 1) -oxi) - 6-O-Methyl-3-oxo-12.11- (oxycarbonyl- ((5-chloro-lH-bßnzimidazol-1-yl) -butyl) -imino)) - ßritromiciña. p.f. = 145 - 148'C. EXAMPLE 17: 11,12-Dyssßoxi-3-dßß ((2,6-Dysßosoxy-3-C-mßti 1-3-O-mßti 1-a1 fa-L-ribohßxopyranoßi 1) -oxi) -6-o-mßtil- 12.11- (oxycarbonyl - ((4- (lH-indol-l-yl) -butyl) -imino)) -erithromycin. EXAMPLE 18: 11.12-Dyssissoxy-3-dea ((2,6-Dyssiaoxi-3-C-mßti 1-3-0-mßti1-lfa-L-ribohsxopyranoayl) -oxy) -6-o-methyl-3-oxo-12.11 - (oxycarbonyl - ((4- (l-Methyl-lH-indol-4-yl) -butyl) -imino)) -β itomycin. aD - 20%. c - 1 * in CHC13 EXAMPLE 19: 11.12-Dysßoxo-3-dßa ((2,6-Dyssysoxy-3-C-mßti 1-3-0-mßti 1-alpha-L-ribohßxopyranoai D-oxy) -6-o- Methyl-3-oxo-12.11- (oxycarbonyl - ((4- (2-phenyl-4-quinolysinyl) -butyl) -imino)) -bromiomethyl., pf-195-197'C. EXAMPLE 20: 11.12-didesoxy-3 -dßß ((2,6-Dyssiaoxi-3-C-mßti 1-3-0-mßti 1 -alpha-L-ribohßxopyranoßi 1) -oxi) -6-o-methyl-3-oxo-12.11- (oxycarbonyl- ( (4- (1 H-bβ-tnotriazol-1-yl) -buti 1) -imino)) -bromiomycin .pf - 200 - 202'C EXAMPLE 21: 11.12-Dyssiaoxi-3-dßβ ((2,6-Dyssiaoxi-3-C) -mßti 1-3-O-mßti 1- lfa-L-ribohsxopyranosi1) -oxi) -6-o-mßti 1-3-oxo-l2.11- (oxycarboni l- ((4- (2H-bßnzotriazol-2 -il) -butil) -imino)) -βritromiciña .pf - 164 - 166 # C.

EXAMPLE 22: 11.12-Dyssiaoxi-3-dßß ((2,6-Dyssiaoxi-3-C-mßti 1-3-O-mßti 1- 1fa-L-ibohßxopyranoßi 1) -oxy) -6-o-methyl-3-oxo -12.11- (oxycarbonyl - ((4- (5,6-dimethyl-lH-benzimidazol-1-y1) -buti 1) -imino)) -β-romyme. p.f. = 174 - 176 * C. EXAMPLE 23: 11.12-Dysssoxy-3-dßß ((2,6-Dyssiaoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohásxopiranoßil) -oxi) -6-o-mßti l-3-oxo -12, 11- (oxycarbonyl l- ((4- (3-quinolysinyl) -butyl) -imino)) -β-romycin. p.f. - 195 - 197 * C. EXAMPLE 24: 11.12-Dyssiaoxi-3-dßß ((2,6-Dyssiaoxi-3-C-Mßti 1-3-0-Mßti 1-alpha-L-ribohßxopyranoßi 1) -oxi) -6-o-mßtil-3 -oxo-12, 11- (oxycarbon l- ((4- (2-quinolßin-l) -butyl) -imino)) -β-romycin. p.f. = 179 - 181'C. EXAMPLE 25: 11.12-Dysssoxy-3-dea ((2,6-Dyssiaoxi-3-C-Methyl-3-0-Methyl-alpha-L-ribosixopyranoßi 1) -oxi) -6-o-methyl-3-oxo-12.11 - (oxycarbonyl- ((4- (2-methyl-lH-benzimidazol-1-yl) -butyl) -imino)) -β-romyme. p.f. - 128 - 132"C EXAMPLE 26: 11.12-Dyssßoxi-3-dßß ((2,6-Dyssiaoxi-3-C-mßti 1-3-O-mßti 1-a1fa-L-ribohßxopiranoai 1) -oxi) - 6-O-Methyl-3-oxo-12,11- (oxycarbonyl- ((4- (6-chloro-lH-benzimidazol-1-yl) -butyl) -imino)) -bromide., Pf-192-194 ' C.

EXAMPLE 27: 11.12-Dyssysoxy-3-dßβ ((2,6-Dyssiaoxi-3-C-mßti 1-3-0-Mßti 1-alpha-L-ribohásxopiranoßil) -oxy) -6-o-methyl-3-oxo- 12.11- (Oxycarbonyl - ((4- (l-Methyl-lH-bßnzimidazol-2-yl) -butyl) -imino)) -bromiomycin. EXAMPLE 28: 11.12-Dyssßoxi-3-dßa ((2,6-Dyssysoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohßxopyranoai 1) -oxi) -6-o-methyl-3-oxo -12. 11- (oxycarbonyl- ((4- (5H-imidazo (4.5-c) pyridin-5-y1) -buti 1) -imino)) -β-romyme. aQ = 12.2. c »1 * in CHC13 EXAMPLE 29: 11, 12-dideoxy-3-deß ((2,6-diissoxy-3-C-mßti 1-3-0-mßti 1 -alpha-L-ibohßxopyranoßi 1) -oxi) - 6-o-mßti 1-3-OXO-12.11- (oxycarboni 1- ((4- (4- (4-chlorophenol-1) -1H-imidazol-1-yl) -butyl) -imino)) -β-chromatin. It is heated for 7 hours at 75 * C. 1 g of 2'-l-deoxy-10 acetate. ll-didehydro-3-dßs (2,6-dideoxy-3-C-methyl 1-3-0-methyl-1-alpha-L-ribohsoxopyranosyl) -oxi) -12-0- ((1H-imidazol-1-yl) ) -carboni 1) -6-0-methyl-3-oxo-erythromycin prepared as indicated in example 1C of European patent application 3 EP 0 596 802 in 4 cm of acetonitrile with 10 * of water, with 1.4 g of 4- (4- (4-chlorophenyl) -lH-imidazole) -butanamine. Allow to return to room temperature, dilute with water, extract with acetate d? ethyl, dried, the solvent evaporated and 2.3 g of the acetylated product were obtained in the 2 'position. 60 ml of methanol are added and the mixture is stirred for 16 hours. the solvent is evaporated, the residue is chromatographed on silica gel (eluting with CH2Cl2 / MeOH / NH40H, 95: 5: 0.4). it is concentrated and the residue is crystallized from ether. The crystallized product is dried under reduced pressure at 80 * C and ST recover 381 mg of the expected product, m.p. - 192 - 194'C. NMR CDC13 ppm 0.83 (t): CH-CH; 1.00 (d) -1.16 (d) -1.24 (d) - 1.30 (d) -1.38 (d): CH3-CH; 1.33 (s): 6 and 12 Me; 2.26 (S): N (Me) 2; 2.44 (m): H'3; 2.61 (s): 6-OMß; 2.60 (m): HQ; 3.00 to 3.21: H4. H1Q and H'2; 3.55 (m): H'g.- 3.56 (s): Hn; 3.60 to 3.80 2H-3.99 (t) 2H: CH2NC; 3.87 (q): H2; 4. 23 (d): Hg; 4.28 (d): H ^; 4.93 (dd): H13; 7.26 (d): H "3-imidazole; 7.50 (d) H_2 imidazole; 7.32-7.70: aromatics; 3.51: OH. Preparation of the 4- (4-chloro-phenyl) -lH-imidazole-1-butanamine used as the starting compound of Example 29. Stage A: 4- (4-chlorophenyl) -lH-imidazole. 23.34 g of "-bromo-4-chloroacetophenone in 150 ml of formamide are refluxed for 1 hour; it is allowed to cool, is inized with a sodium hydroxide solution, extracted with dichloromethane, washed with water, dry ST, the solvent is evaporated, the residue is chromatographed on silica gel (eluting with CH2Cl2 MeOH / NH4OH, : 2: 0.04) and 13.4 g of the expected product are obtained. p.f. 146 - 148 * C. Stage B: 2- (4- (4- (4-chloropheni-1) -lH-imidazol-1-yl) -lH-isoindol-1.3- (2H) -dione, proceed as in state A of the preparation of the Example 1, using 12.2 g of the product obtained in state A. 4.96 g of sodium hydride and 23.83 g of N-4-bromobutylphthalimide 9.7 g of the expected product are obtained Stage C: 4- (4-chlorophenyl) -lH -imidazole-1-butanamine: Proceed as in stage B of the preparation of example 1, using 14.2 g of the product obtained as stage B above and 3.6 ml of hydrazine hydrate in 200 ml of ethanol. crude product, which is subjected to chromatography on silica gel (ß, with CH2Cl2 / MeOH / NH4OH, 8: 2: 0.04) and the product obtained is used as obtained for the synthesis, NMR (CDC13) ppm 1.22 (if ): 2H mobile, 1.47 (m) .1.88 (m): 2 CH2 ctrls .; 2.74 (m): CH2-CH2-N; 3.98 (m): -C-N-CH2-CH2; OR. 7. 19 (d.J.-1.5J-7.50 (d.J-1.5): H2 and Hg; 7.33 and 7.70: aromatics EXAMPLE 30: 11.12-Dyssxosi-3-Dßß ((2.6-Dyssiaoxi-3-C-Mßti 1 -3-0-mßti 1-alpha-L-ri ohßxopiranoßi 1) -oxi) -6-0-methyl-3-oxo-12. Ll- (oxycarbonyl- ((4- (4- (2-ratoxhoxyphenyl) - 1H-imidazol-1-yl) -butyl) -imino)) -rithromycin. 706 mg of the starting compound of Example 29 (obtained as indicated in Example 1C of the application for European Patent EP 0 596 802) in 3 ml of acetonitrile and 908 mg of 4- (4- (2-methoxyphenyl) -lH-imidazol-1-yl) -butamine, allowed to return to room temperature, poured over a sodium hydrogen phosphate solution (0.5 M), extracted with ethyl acetate, washed with water, dried, the solvent is evaporated, 1.6 g of the acetylated product are obtained in the 2 'position 50 ml of methanol are added. The mixture is stirred for 16 hours, the solvent is evaporated, the residue is subjected to chromatography on silica gel (eluting with 4 * AcOEt-TEA) and crystallize from ether, 194 mg of the expected product are obtained, m.p. - 143 - 145 * C. NMR CDC13 ppm 0.85 (t): CH3-CH2; 1.011 (d) -1.16 (d) -1.24 (d) -1.30 (d) -1.37 (d): CHg-CH; 1.34 (s): 6 and 12 Me; 2.26 (S): N (Mß) 2; 2.44 (m): H ^; 2.60 (m): Hg.- 2.64 (s): 6-OMe; 3.08 (m): H4; 3.12 (ql): H1Q; 3.17 (dd): H'2; 3.54 (m) H '5' 3.57 (s) H '11 3.66 (m) - 3.74 (m) CH2NC; or 3. 85 (q): H2; 3.95 (s): f-OM ?; 3.99 (ql): CH2-N-C "; 4.24 (d): Hg; 4.27 (d): H ^; 4.93 (dd): H13; 6.97 (di): Hg; 7.51 (s): the H imidazole; 7.02: Hg phenyl; 7.19 (ddd) H4 and Hg phenyl; 8.19 (dd): H2 > Preparation of 4- (2-M-methoxyphenyl) -lH-imidazole-1-butanamine used as the starting compound of Example 30. Stage A: 4- (2-M -toxhoxyphenyl) -lH-imidazole. 9.36 g of 2-bromo-2'-methoxyacetophenone are heated to reflux in 50 ml of formamide, allowed to return to room temperature, washed with a 2N hydrochloric acid solution. it is filtered, it is alkalized to a pH of 8-9 with the help of 2N soda. It is extracted with d loromethane. it is washed with water, dried, the solvent is evaporated, the residue is chromatographed on silica gel (eluting with CH 2 Cl 2 / MeOH NH 4 OH 95: 5: 0.4) and 6.15 g of the expected product are obtained. Stage B: 2- (4- (4- (2-methoxy-phenyl) -lH-imidazol-1-yl) -buty 1-lH-isoindol-l .3- (2H) -dione. as in stage A of the preparation of example 1 using 6 g of the product obtained as stage A. 1.99 g of sodium hydride and 9.93 g of N-4-bromobutylphthalimide. 6.15 g of the expected product are obtained. Stage C: 4- (2-methoxypheni 1) -lH-imidazole-l-butanamine (fumarate). The procedure is as in stage B of the preparation of example 1. using 5.65 g of the product obtained as stage B above and 1.45 ml of hydrazine hydrate in 75 ml of ethanol. 3.8 g of the crude product are obtained, which is dissolved in 4 ml of tetrahydrofuran and then 1.87 g of fumaric acid dissolved in 20 ml of methanol are added. 10 ml of ether are added, the crystals formed are drained, dried at 80 ° C. under reduced pressure and 3.77 g of fumarate are recovered from the expected product, m.p. * 160 - 162 * C. NMR (CDC13) ppra 1.48 (m) 2H-1.87 (m) 2H: the central CH; 3.46: NH2; 2.73 (t): CH2N; 3.94 (s): f-OMß; 3.97 (t): CH "N-C; 6.94 (dd): H ,; 7.04 (dt) -7.21 (ddd): H_ and H "; A or 3 4 7.51: H'2 and H'g; 8.19 (dd): H2. EXAMPLE 31: 11,12-Dyssßoxi-3-dßß ((2,6-Dyssoxy-3-C-Raßti 1-3-O-mßti 1-al-Fa-L-ribohßxopyranoßi 1) -oxi) -6-o-mßti l -3-oxo-12.ll- (oxycarboni l- ((4- (4- (4-fluorofissyl) -lH-imidazol-1-yl) -butyl) -imino)) -β-romycin.

ST heated to 60 * C for 4.5 hours 2.11 g of the starting compound of Example 29 (obtained as indicated in Example 1C of European Patent Application EP 0 596 802) in 9 mL of acetonitrile and 2.8 g of 4- ( 4- (4-fluorophenyl) -lH-imidazol-1-yl) -butanamine. The room temperature is allowed to recover, poured into water, extracted with ethyl acetate, washed with water, dried, the solvent is evaporated, 5.2 g of the acetylated product are obtained in the 2 'position. 20 ml of methanol are added. The mixture is stirred for 3 1/2 hours, the solvent is evaporated, the residue is chromatographed on silica gel (eluyentß: CH 2 Cl 2 / MeOH / NH 4 H 95: 5: 0.3) and crystallized from ether. 1.34 g of the expected product are obtained. p.f. - 190 - 192'C. NMR CDC13 ppm 1.33 (s) -1.47 (s): 6 and 12 Me; 2.27 (s) N (me) 2; 2.61 (s): 6-OMß; 3.0 to 3.18: H4 and H1Q; 3.56 (s) : H '; 3.59 to 3.81:; approx. 7.05 - approx. 7.73: fluorofeni 1; 7.21 (d): Hg imidazole; 7.49 (d): H2 imidazole. Preparation of the 4- (4-fluoro-phenyl-1H-imidazole-l-butanamine used as the starting compound of example 31. Stage A: 4- (4-fluorophen-1) -lH-imidazole.

S? heat for 2 hours at reflux, 10.85 g of 4-fluorofenaci bromide in 60 ml of formamide, let it return to room temperature, acidify to a pH of 2 with the help of hydrochloric acid N. it is filtered, neutralized adding ammonia, it is extracted with dichloromethane, washed with water. it dries, the solvent evaporates. the residue is chromatographed on silica gel (ßluyßntβ: CH 2 Cl 2 / MeOH / NH 4 OH 95: 5: 0.4) and 5.8 g of the expected product are obtained, m.p. - 130 - 132 * C. Stage B: 2- (4- (4- (4-fluoropheni 1) -lH-imidazo1-1-i 1) -buty 1-lH-isoindol-1,3- (2H) -dione. Stage A of the preparation of Example 1, using 10 g of the product obtained in stage A. 1.95 g of sodium hydride and 11.80 g of N-4-bromobutyl-1-phthalamide.ST obtain 7.53 g of the expected product. 140 * C Stage C: 4- (4-fluoropheni 1) -lH-imidazol-1-butanamine The procedure is as in stage B of the preparation of the example, using 3.64 g of the product obtained as stage B above and 1 ml. of hydrazine hydrate in 80 ml of ethanol, 2.4 g of the crude product are obtained, which is subjected to chromatography on silica gel (eluent: CH 2 Cl 2 MeOH NH 4 OH 8: 2: 0.03) and the product is obtained, which used as obtained for the synthesis NMR (CDC13) ppm 1.48 (m) -1.82 (m): the central CH2, 2.74 (t): N-CH3, 3.98 (t):> N-CH.2- CH2; 7.06 (t): > CH-F; 7.22 (m) : > CH-C "-; 7.49 (s): Hn imidazole; 7.15 (s): H * 3 imidazole. R EXAMPLE 32: 11.12-Dyssiaoxi-3-DIAA ((2,6-Dyssysoxy-3-C-Mßti 1-3-0-Mßti 1-alpha-L-riboh? Xopyranosi 1) -oxi) -6-o-m? Ti 1-3-OXO-12.11- (oxycarboni 1- ((4- (7-M-methoxy- (4-quinolysinyl) -butyl) -imino)) -bromiomycin.They are heated at 54 ° C for 53 hours, 706 mg of the compound Starting from example 29 (obtained as indicated in example 1C of European patent application EP 0 596 802) in 4 ml of acetonitrile and 1.43 g of 4-Í4.7-methoxy-4-quinoline-indobutane. ST allowed to recover to room temperature, ST poured into a sodium acid phosphate solution (0.5 M), extracted with dichloromethane, washed with water, dried, the solvent was evaporated, 1.09 g of the acetylated product were obtained in position 2 '. ST add 10 ml of methanol, ST stir for 16 hours, the solvent is evaporated, the residue is chromatographed on silica gel (eluent: CH2Cl_ / MeOH, 95: 5) and crystallized from ether. 295 mg of the expected product are obtained, mp about 110 ° C.

NMR CDC13 ppm 3.06 (m): - (CH2) 2-CH <; 3.70 (m): -N-CH2-; 3.95 (s): -OCH3; 7.12 (d) -7.19 (dd) -7.42 (d) -7.94 (d) -8.70 (d): pyridine. Preparation of the 7-M-methoxyquinolines-4-butanamine used as the starting compound of example 32. Stage A: N-phenyl phosphonium phosphonium salt of N- (3-bromopropyl) -phthalimide. 44.4 g of N-bromopropyl phthalimide and 13.15 g of triphenylphosphine in suspension in 75 ml of xylene are heated at reflux for 44 hours. Let it return to room temperatureThe precipitate is drained, washed with ethyl ether and dried under reduced pressure at 60 ° C. 24.88 g of the expected product are obtained. p.f. "220 -22'C Stage B: Z- (2- (4- (7-methoxyquinoline-1) -3-buteni 1-lH-isoindo1-1.3- (2H) -dione 4 gd? 7-methoxy are added 4-quinoleinylcarboxaldehyde to a suspension of 12.47 g of triphenyl phosphonium salt of 3-bromopropylphthalide imide in 200 ml of tetrahydrofuran, cooled to -50 * C, 2.72 gd of potassium tert.butyrate is added, the temperature is slowly allowed to return to The filtrate is concentrated, the residue is taken up in ethyl acetate, washed with water, dried, the solvent is evaporated and 9.26 g of the crude product are obtained, which is subjected to silica gel (eluent: CHCl3-AcOEt 80:20, then 70:30) to obtain 3,500 g of the expected product Stage C: 2- (4- (7-methoxy-4-quinolenyl) -butyl) -lH- isoindol-1.3- (2H) -dione, ST dissolve 3.50 g of the product obtained in stage B in 50 ml of methanol, add 0.36 g of palladium in activated carbon and hydrogenate for 3 hours at 600 mbar. solvent evaporates and becomes They have 3.48 g of the expected product. Stage D: 7-methoxy-quinoline-4-butanamine. 3.46 g of the product obtained in stage C are dissolved in 70 ml of ß-ethanol with heating. 1.86 ml of hydrazine hydrate are added, the reaction mixture is refluxed for 17 hours, the precipitate is removed by filtration, the solvent is evaporated, the residue is taken up in 70 ml of dichloromethane. it is filtered, the solvent is evaporated and 2.19 g of the expected product are obtained. NMR (CDC13) ppm 1.6 (m) -1.79 (m): CH2 central; 2.75 (t): > -CH * 2- (CH2) 3; 3.05 (t): CH2-NH2; 3.95 (s): 0-CHg.- 7.10 (d, J-4.5) -7.21 (dd) -7.92 (d) -8.71 (d.J-4.5): quinoline.

EXAMPLE 33: 11, 12-dideoxai-3-dßβ ((2,6-Dissysoxy-3-C-mßti 1-3-O-mßti 1-al-fa-L-ribohßxopyranoßi 1) -oxi) -6-o-mßtil- 3-oxo-12. 11- (oxycarbonyl- ((4- (2- (2-pyridinyl) -4-thiazo1 i 1) -buti 1) -imino)) -bryromycin. 60 mg of the starting compound of example 29 (obtained as indicated in example 1C of European patent application EP 0 596 802) in 3 ml of acetonitrile and 0.705 g of 4- 4 hours are heated at 60 ° C for 5 hours. (2- (2-pyridinyl-4-thiazolyl) -butamine) The reaction mixture is allowed to return to room temperature, poured into water, extracted with ethyl acetate, washed with water, dried. The solvent is evaporated, yielding 1.8 g of the acetylated product in the 2 'position, 15 ml of methanol are added, the mixture is refluxed for 2 hours, the solvent is evaporated, the residue is chromatographed on silica gel (eluant: CH2Cl2). MeOH / NH 4 OH 95: 5: 0.3, then with AcOEt-TEA, 9: 1) and crystallized from ether.ST obtain 194 mg of the expected product, mp = 157-159 * C NMR (CDC13) ppm 1.33 and 1.47 : 6 and 12 Me; 2.26 (s): N (CH3) 2; 2.86 (t): CH2-C; 3.12 (ql): H1Q; 3.60 (s): Hn; 3.66 7. 03 (s): H5_ thiazole; 7.27 (ddd): H5_ pyridine; 7.77 (dt): H4 pyridine; 8.18 (dd) H3 pyridine; 8.53 (ddd): Hg pyridine. Preparation of the 2- (2-pyridinyl) -thiazole-4-butanamine used as the starting compound of Example 33. Stage A: 2-aminocarbonyl-pyridine. 50 ml of a solution of diazomethane (0.4 M / l) in a solution comprising 2 g d is added dropwise. picol acid only. 20 ml of dichloromethane and 5 ml of methanol. After stirring for 30 minutes at room temperature, the solvent is evaporated under reduced pressure, the residue is subjected to chromatography on silica gel (eluting with petroleum ether (60:80) -AcOEt. 5: 5) and 1.48 g of methyl ester are obtained. Heat 1.42 g of the ester in 5 ml of ammonia at 50 * C for 4 hours, the mixture is allowed to return to room temperature, is extracted with ether, washed with water and dried. the solvent is evaporated and 1.5 g of the expected product are obtained. p.f. "105" C. Stage B: 2-pyridinecarbotioamide. 43 g of phosphorus pentasulfide are added slowly to 46.8 g of the amide obtained in stage A in 700 ml of tetrahydrofuran. It is stirred for 4 hours at room temperature, poured into water, subjected to extraction with ether, dry ST and the solvent is evaporated under reduced pressure. After chromatography on silica gel (ßlulu: CH2Cl2-AcOEt, 8: 2). ST obtain 10 g of the expected product, mp = 137 ° C. Stage C: Ethyl 2- (2-pyridinyl) -4-thiazolecarboxylate: 16.3 ml of ethyl bromopyruvate are added dropwise to 15.9 g of the product prepared as stage B 250 ml of ethanol and reflux for 5 hours.The solvent is evaporated under reduced pressure, the residue is chromatographed on silica gel (eluent: hexane / AcOEt.:1: 1) and 10.2 g of the product are obtained. Expected, mp 69. 1 'C. Stage D: 2- (2-pyridinyl) -4- thiazolemethanol.There are slowly added 40 ml of methanol to a mixture of 9.3 g of the aster prepared as stage C and 4.1 g of Sodium borohydride in 100 ml of tetrahydrofuran and heated for 2 hours at reflux.The reaction mixture is allowed to recover to room temperature, poured into water, neutralized with the aid of hydrochloric acid N, extracted with dichloromethane, the organic phase is dried and the solvent is evaporated under reduced pressure, the residue and chromatography on silica gel (eluent: AcOEt / CH2Cl2, 11: 1) and 5.8 g of the expected product are obtained, m.p. = 100'C.

Stage E: 2- (2-pyridinyl) -4-thiazole-carboxaldehyde. 5.8 g of the product obtained as stage D in 60 ml of toluene are heated at reflux for 2 hours, in the presence of 13 g of manganese oxide, the solvent is filtered and evaporated under reduced pressure. 5 g of the expected product are obtained, m.p. - 131 * C. Stage F: (Z) -2- (4- (2- (2-pyridinyl) -4-thiazolyl) -3-butenyl) -lH-isoindol-1.3- (2H) -dione. The procedure is as in stage A of the preparation of example 32. using 5.70 g of the aldehyde prepared as stage E above and 15.9 g of triphenylphosphonium salt of 3-bromopropy1 phosphonium and 3.70 g of potassium terbutylate. 8.73 g of the expected product are obtained. p.f. = 139 - 141 'C. Stage G: (-2 (4- (2- (2-pyridinium-1) -4-thiazole 1) -butyl) -lH-isoindol-1.3- (2H) -dione, proceed as in stage B of the preparation of example 32. using as starting material 7.22 g of the product prepared as stage F above, and 1.5 g of palladium on activated carbon, is hydrogenated for 2 hours at 1,800 mbarßs. 6.33 g of the expected product are obtained, m.p. - 119 - 121 'C. Stage H: 2- (2-pyridinyl) -thiazole-4-butanamine.

The procedure is as in stage C of preparation 32. using 5.45 g of the product obtained as previous stage G and 1.6 ml of hydrazine hydrate and heating for 6 hours under reflux. The solvent is evaporated, the residue is taken up in ethyl acetate, washed with water, dried, the solvent is evaporated, the residue is chromatographed on silica gel (eluyentß: CH 2 Cl 2 (MeOH NH 4 OH 9: 1: 0.03 ) and 1.65 g of the expected product are obtained NMR (CDC13) ppm 1.50 (m) -1.82 (m): the central CH2, 2.76 (t) -2.85 (t): CH2-C = and CH2 ~ NH2; 7.85 ( s): Hg thiazole, 7.31 (m): H'g; 7.78 (dt): H'4; 8.18 (dt): H'3; 8.61 (ddd): EXAMPLE 34: 11.12-Dyssiaoxi-3-dßa ((2,6-Dyssysoxy-3-C-mßti 1-3-0-mßti 1-alpha-L-ribohßxopir noai 1) -oxy) -6-o-mßtil-3 oxo-12. 11- (oxycarbonyl- ((4- (4- (3-pyridinyl) -1H-imidazol-1-yl) -butyl) -imino)) -β-romyme. 20 g of the starting compound of example 29 (obtained as indicated in example 1C of European patent application EP 0 596 802) in 4 ml of acetonitrile and 936 mg of 4- 4 hours are heated at 70 * C for 20 hours. (4-3-pyridinium 1-lH-imidazol-li 1) -butamine. The ST reaction mixture allowed to recover to room temperature, poured into water, extracted with ethyl acetate, washed with water, dried, the solvent evaporated, obtaining 1.34 g of the acetylated product in the 2 'position. 40 ml of methanol are added. it is stirred for 2 hours, the solvent is evaporated, the residue is chromatographed on silica gel (eluyßnte: CH2Cl2 / Me0H / NH40H. 95: 5: 0.4) and crystallize from ether. 310 mg of the expected product are obtained. p.f. * 187 - 188 * C. NMR (CDC13) ppm 0.83 (t): CH3-CH2; 1.01 (d) -1.17 (d) -1.25 (d) - 1.31 (d) -1.38. (d): CH3-CH; 1.34 (s) -1.47 (s): 7 y 12 Me; 2.27 (s): N (Me) 2; 2.45 (m): H'3; 2.62 (s): 6- OMe; 2.60 (m): Hg; 2.85 to 3.25: H4 and H1Q. H'g; 3.56 (s): H ..; 3.60 to 3.85 (m): CH, NC; 4.23 (d): H_; 4.27 (d): l L A H ° H ^; 4.93 (dd): H13; 7.29 (ddd): Hg pyridine; 8.08 (dt): H 4. pyridine: 8.45 (dd): HO, pyridine; 8.97 (dd): H "pyridine; 7.35 (d) and 7.53 (d): H, and Hg imidazole. Preparation of the 4- (3-pyridinyl) -lH-imidazole-1-butanamine as the starting compound of Example 34. Sodium A: 2- (4- (3-pyridinyl) -lH-imidazole-li 1) - buil-lH-isoindol-1.3- (2H) -dione The procedure is as in step A of the preparation of Example 1. using 290 mg of 3-pyridinyl-1H-imidazole prepared as described in J. Chem. Soc. 753-5 (1938), 115 mg of sodium hydride and 633 mg of N-4-bromobutyl-imide. 377 mg of the expected product are obtained, m.p. - 150-152 'C Stage B: 4- (3-pyridinium 1) -lH-imidazol-1-butanamine. The procedure is as in step B of the preparation of Example 1, using 1.66 g of the product obtained as a-step A-acid and 046 ml of hydraine hydrate in 30 ml of ethanol. 936 mg of the product are obtained. which was found as obtained for the NMR synthesis (CDC13) ppm 1.49 (m) -1.89: the central CH2; 2.75 (t): CH2-CH2 ~ N; 7. 29 (d.JD-7.55 (d.Jl): H2 and Hg; 7.30 (partly masked): H'g; 8.09 (dt.J = 8 and 2): H'4; 8.47 (dd.J-5) and 2): H'g; 8.96 (d.J-2): H'2; 1.49 (if): approx 2H mobile.Example 35: 11.12-Dyssxoxi-3-DIAA ((2.6-Dysßoxo-3-c -methyl-3-o-mßti 1-alpha-L-ri-ohßxopyranoai 1) -oxi) -6-o-mßti1-3-oxo-12.11- (oxycarbonyl - ((4- (3- (3-pyridinyl) - lH-1.2.4-triazol-1-yl) -butyl) -imino)) -l brromide. 1 g of the starting compound of Example 29 (obtained as indicated in Example 1C) is heated at 75 * C for 8 hours. of European Patent Application EP 0 596 802) in 4 ml of acetonitrile and 1.21 g of 4- (3- (3-pyridinyl-lH-1,2,4-triazol-li 1) -butanamine. Return to room temperature, pour into water, extract with ethyl acetate, wash with water, dry, evaporate the solvent, obtaining 2 g of the product aceylated at the 2 'position. methanol, ST stirred for 16 h, the solvent evaporated. iduo is subjected to chromatography on silica gel (eluyßnte: CH2Cl2 / MeOH / NH4OH. 90: 10: 0.05) and crystallize from ether. 292 mg of the expected product are obtained. p.f. «190-192 * C. NMR (CDC13) ppm 0.84 (t): CH3-CH2; 1.01 (d): OMe; 1.16 (d): 8Me; 1.25 (d): 5Me; 1.30 (d): 4Me; 1.34 (d): 2Me; 1.33 (s) and 1.47 (s): 6 and 12 Me .- 1.67 (m) -1.99 (m): the basal CH2; 2.26 (s): N (Me) 2; 2.44 (m): H'3; 2.58 (m): Hg; 2 . 61 (s): 6-OMe; 3 . 06 (m): H4; 3 . 12 (q): H? O; 3 . 17 (dd): H '2; 3. 52 (m): H 'g; 3 . 56 (S): Hn; 3. 64 a 3. 85 (q): H2; -4.25: H ^. Hg and CH2NC; H 4.91 (dd): H13; 8.15 (s): H triazole; 7.35 (dd): Hg pyridine; 8.34 (dt): H4 pyridine; 8.62 (dd) Hg pyridine; 9.31 (di): H "pyridine. Preparation of the 3- (3-pyridinium 1) -lH-1, 2,4-triazol-1-butanamine used as the starting compound of Example 35. Stage A: 2- (4- (3- (3-pyridinyl J-1H-1.2.4-triazolol-1-yl) -butyl-lH-isoindol-1.3- (2H) -dione, proceed as in stage A of the preparation of Example 1. using 2.1 g of 3- pyridinyl-lH-1,2,4-triazole prepared as indicated in J. Org Chem. (44) No. 33, 4160-4164 (1979), 1.02 g of sodium hydride and 4.13 g of N-4-bromobutyl 1 ftal imide Obtained 2.4 g of the expected product, mp 150-152 * C Stage B: 3- (3-pyridinium 1) -lH-l.2.4-triazole-l-butanamine (fumarate). in stage B of the preparation of Example 1. Using 3.46 g of the product obtained as stage A above and 1 ml of hydraine hydrate in 50 ml of ethanol, 2.41 g of the crude product are obtained, which is transformed into ttal fumarate. as indicated in the preparation of Example 30. and 1.13 g of the fumarate of the expected product are obtained, mp about 190-192'C. (CDC13) ppm 1. 50 (m) - • 2. 01 (m): 1 OS 1 CH2 central; 2.76 (t): NH2- =; 4. 24:; 7.37 (ddd): Hg; 8.35 (dt): H ,; 8. .63 (dd): H6; .32 (dd): H2; 8.12 (s): -CH [triazole. Proceeding as described above, using the appropriate amines. The following products are prepared: EXAMPLE 36: 11.12-Dyssissoxy-3-dßs ((2,6-Dyssiaoxi-3-C-mßti 1-3-0-Mßti 1-alpha-L-ribohßxopyranoßi 1) -oxi) -6-O - mßti 1-3-oxo-12-yl- (oxycarboni l- ((4- (3-quinolysinyl) -buti 1) -imino)) - β-romromycin. p.f. - 190 - 192 C. EXAMPLE 37: 11.12-Dyssiaoxi-3-dßß ((2,6-Dyssysoxy-3-C-mßti 1-3-0-Mßti 1-alpha-L-ribohßxopyranoßi 1) -oxi) -6-O -mßti l-3-oxo-12.11- (oxycarboni 1- ((4- (4- (4-m-methoxy-phenyl-1) -1H-imidazol-1-yl) -butyl) -imino)) -β-romycin. p.f. - 152 - 154 * C. EXAMPLE 38: 11.12-Dyssissoxy-3-deß ((2,6-Dyssiaoxi-3-C-mßti 1-3-0-mßti 1-a1fa-L-ribohexopyranoai 1) -oxi) -6-o-mßti 1-3- oxo-12-yl- (oxycarboni l- ((4- (2-phenyl-4-thiazolyl) -butyl) -imino)) -β-romycin. p.f. - 141 - 143'C.

EXAMPLE 39: 11.12-Dyssiaoxi-3-dßβ ((2,6-Dyssiaoxi-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohßxopyranoai 1) -oxi) -6-o-methyl-3-oxo -12.11- (oxycarbonyl - ((4- (4- (3-m-methoxy-phenyl) -lH-imidazol-1-yl) -butyl) -imino)) -β-romyme. p.f. - 144 - 146'C EXAMPLE 40: 11.12-Dyssiaoxi-3-dßβ ((2,6-dideoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohexopyranoail) -oxi) -6-o- Methyl-3-oxo-12.11- (oxycarbonyl l- ((4- (4,5-diphenyl) -lH-imidazol-1-yl) -butyl) -imino)) -β-trichromycin. p.f. - 180 - 182 * C EXAMPLE 41: 11.12-Dyssßoxi-3-dßa ((2,6-Dyssissoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohßxopyranosi 1) -oxi) -6 -o-mßti 1-3-OXO-12.11- (oxycarboni l- ((4- (4-quinazolinyl) -butyl) -imino)) -β-romromycin. p.f. = 212 - 214'C EXAMPLE 42: 11.12-Dyssßoxi-3-dßß ((2,6-Dyssysoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohßxo iranoßi 1) -oxi) -6- o-Methyl-3-oxo-12.11- (oxycarboni l- ((4- (2- (4-pyridinyl) -4-thiazolyl) -butyl) -imino)) -β-romycin. p.f. - 192 - 194 * C. EXAMPLE 43: 11.12-Dyssissoxy-3-dßβ ((2,6-Dissßoxy-3-C-mßti 1-3-O-mßti 1-alpha-L-ribohexopyranosi 1) -oxi) -6-o-mßti l-3- oxo-12, 11- (oxycarbonyl- ((4- (1,2,3,6-tβ-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purin-7-yl) -butyl) -imino)) -bryromycin. p.f. = 251 - 253'C EXAMPLE 44: 11.12-dideoxy-3-des. { (2,6-Dyssoxy-3-C-methy1-3-0-methy1-alpha-L-riboh? Xopyranosy 1) -oxi) -6-o-methyl-3-oxo-12, 11- (oxycarbonyl) ((4- (4- (4-trifluoromethoxy) -phenyl) -lH-imidazol-4-yl) -butyl) -imino)) -erithromycin. p.f. - 168 - 170'C The amines used as starting materials are prepared according to the following methods: A - When the chain is attached to a carbon, for example it is possible to start from the corresponding aldehydes: ? l t t l? The amines used for the preparation of the products of Examples 4, 8, 11, 12, 18, 19, 23 and 24 are prepared in this manner. B - When the chain is attached to a nitrogen, the amines can be prepared as follows: He: jf - CH2), H, H H ", * KeG < cs» < 'NH, H The amines used for the preparation of the products of examples 1, 2, 3, 5. 9. 13. 14. 15. 16, 17. 20. 21. 22. 25. 26 and 28 are prepared in this manner. C - Certain amines are prepared in a particular way: the heterocyst is constructed and the chain is introduced at the same time (examples 6. 7. 10 and 27). EXAMPLES OF PHARMACEUTICAL COMPOSITIONS Pharmaceutical compositions are prepared which contain: Product of Example 1 150 mg Excipient c.b.p. 1 g Details of excipient: starch, talcum, magnesium stearate Product of example 2 150 mg Excipient c.b.p 1 g Details of excipient: starch, talcum, magnesium stearate Product of example 3 150 mg Excipient c.b. 1 g Details of the excipient: starch, talc, magnesium stearate. PHARMACOLOGICAL STUDY OF THE PRODUCTS OF THE PRESENT INVENTION Methods of dilution in liquid medium ST prepares a series of tubes in which the same quantity of sterile nutritive medium is distributed. Increasing amounts of the product to be studied are distributed in each tube, then each tube is inoculated with a bacterial strain. After incubating for 24 hours at 37'C. the inhibition of bacterial growth is observed by transillumination, which allows to determine the minimum inhibitory concentrations 3 (C.M.I.), which are expressed in micrograms / cm. The following results were obtained: Bactériana grampositive strains Gram-positive bacterial strains (continued) In addition, the products of Examples 1 and 3 showed an interesting activity on the following Gram-negative bacterial strains: Haßmophilus Influences 351HT3. 351CB12. 351CA1 and 351GR6. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as an antecedent, what is contained in the following is claimed as property.

Claims (16)

1. CLAIMS The compounds of the formula (I) wherein R represents a radical - (CH ") Ar. where n represents the number 3. 4 or 5 and Ar represents a hetβrocyclic radical. optionally containing one or more substituents that are selected from the group consisting of the following radicals:
2. H, C "\ o R represents a CH radical. and Z represents a hydrogen atom or an acid residue, as well as its addition salts with acids. 2. The compounds of the formula (I). according to claim 1. characterized in that Z represents a hydrogen atom.
3. 3. The compounds of the formula (I), according to any of claims 1 or 2. characterized in that n represents the number 4.
4. 4. The compounds of the formula (I), according to any of claims 1. 2 or 3. characterized because Ar represents a radical: eventually replaced
5. 5. The compounds of the formula (I). according to any of claims 1, 2 or 3, characterized in that R represents a radical: eventually replaced.
6. 6. The compounds of the formula (I). according to any of claims 1, 2 or 3. characterized in that Ar represents a radical: eventually replaced.
7. 7. The compounds of the formula (I). according to any of claims 1, 2 or 3. characterized in that Ar represents a radical: -i® evsually replaced.
8. 8. As novel chemical products. The compounds of the formula (I) according to claim 1. which are the following: - 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl-1-alpha- L-riboh? Xopyranosi 1) -oxi) -6-o-methyl 1-3-oxo-12.11- (oxycarbonyl) - ((4- (4-phenyl-1-lH-imidazol-1-yl) -butyl) - imino)) -erithromic. 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl-alpha-L-ribohexopyranosyl) -oxy) -6-o-methyl-3-oxo-12, 11- ( oxycarboni l- ((4- (3H-imidazo (4 »5-b) pyridin-3-yl) -buti 1) -imino)) -bromiomycin, - 11.12-diissoxy-3-des ((2,6-dideoxy-3 -C-methyl-3-0-methy1-al fa-L-riboh? Xopyranosi 1) -oxi) -6-o-methyl 1-3-oxo-12. 11- (oxycarbonyl- ((4- (4-lH-imidazo (4.5-b) pyridin-1-yl) -butyl) -imino)) -erithromycin. 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-O-methyl-1-alpha-L-ribohexopyranosi 1) -oxi) -6-o-methyl 1-3-oxo- 12, 11- (oxycarboni l- ((4- (4- (4-chlorophysi-1) -lH-imidazol-li 1) -buti 1) -imino)) -bromiomycin. 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-O-mßti 1-al fa-L-riboh? Xopyranosi 1) -oxi) -6-o-mßti 1-3-oxo -12. 11- (oxycarbonyl l- ((4- (4- (2-methoxy-phenyl-1) -lH-imidazol-1-yl) -butyl) -imino)) -β-romycin. - 11, 12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl 1-a1 fa-L-ribohexopyranosi 1) -oxi) -6-o-meti 1-3- oxo-12, 11- (oxycarbonyl- ((4- (4- (4-fluorophenyl) -lH-imidazol-li 1) -buti 1) -imino)) -erithromycin. - 11.12-dideoxy-3-dßs ((2,6-dideoxy-3-C-methyl-3-0-methyl-alpha-L-ribohexopyranosyl) -oxy) -6-o-methyl-3-oxo-12.11- ( oxycarboni l- ((4- (7-methoxy-4-quinolinyl) -butyl) -imino)) -erythromycin. - 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl-1-a1fa-L-ribohexopyranosi 1) -oxi) -6-o-methyl-3-oxo- 12.11- (oxycarboni l- ((4- (2- (2-pyridinyl) -4-thiazolyl) -butyl) -imino)) -erithromycin. - 11.12-dideoxy-3-des ((2,6-dideoxy-3-C-methyl-3-0-methyl-1-al fa-L-ribohexopyranosi 1) -oxi) -6-o-mßti 1-3-oxo- 12.11- (oxycarbonyl- ((4- (3- (3-pyridinyl) -lH-1, 2,4-triazol-1-yl) -butyl) -imino)) -β-romyme.
9. 9. As a novel chemical product, the compound of the formula (I) according to claim 1, which name is as follows: - 11.12-dideoxy-3-des- ((2,6-dideoxy-3-C- methyl-3-0-meti 1-a1 fa-L-ribohexopiranosi 1) -oxi) -6-0-eti 1-3-oxo-12.11- (oxycarboni l- ((4- (4- (3-pyridinyl) -lH-imidazol-1-yl) -butyl) -imino)) -erythromycin.
10. 10. As medicaments, the compounds of the formula (I) according to any of claims 1 to 7, as well as their addition salts with pharmaceutically acceptable acids.
11. 11. As medicines, the compounds defined in claim 8. as well as their addition salts with pharmaceutically acceptable acids.
12. 12. As a medicament, the compound defined in claim 9. as well as its addition salts with pharmaceutically acceptable acids.
13. 13. Pharmaceutical compositions containing as active ingredient at least one medicament according to any of claims 10 to 12.
14. 14. A process for preparing compounds of the formula (I) according to claim 1. characterized in that a compound is subjected to of the formula 02 'wherein Z' represents an acid residue, to the action of a compound of the formula (III): RNH, (III) wherein R is as defined in claim 1, to obtain a compound of the formula 0 Z ' wherein R and Z 'are as previously defined, then, if the case arises, the compound of the formula (I.) is subjected to the action of a hydroxyl function release agent at the 2' position and / or. if the case is reached, to the action of an acid to form a salt.
15. 15. The compounds of the formula (III) according to claim 14.
16. 16. The amines of the formula (III) according to claim 15. Whose names are the following: - 4-phene-1-lH-imidazole l-Butanamine. - 3H-imidazo (4.5-b) -pyridin-3-butanamine. - lH-imidazo (4.5-b) -pyridin-3-butanamine. - 2-fßni 1-4-quinolinobutanamine. - lH-benzotriazole-1-butanamine. 2H-benzotriazole-2-butanamine, l-methyl-lH-imidazo (4.5-c) -pyridin-2-butanamine, 3-methyl-3H-imidazo (4.5-c) -pyridin-2-butanamine. 5-Chloro-1 H-bissimidazole-l-butanamine, 7-methoxy-4-quinol-inbutamine, lH-imidazo (4.5-c) -pyridin-1-butanamine. - 9H-purin-9-butanamine. - l-methyl-lH-indole-4-butanamine. 3-Pheni 1-1H-1.2.4-triazole-l-butanamine (hydrochloride). 5-fßni 1-lH-tetrazol-l-butanamine (hydrochloride). - 2-benzothiazolebutanamine. - 4- (Thieno (2,3-b) -pyridin-4-yl-butanamine - 5,6-dimeti 1-lH-benzimidazole-l-butanamine - 3-quinolinebutanomine - 2-quinolinebutane - 5H-imidazo [4.5-c ] pyridine-5-butanamine. - l-methyl-lH-bßnzimidazole-2-butanamine. - 6-chloro-lH-benzimidazole-2-butanamine. 2-methyl-lH-benzimidazole-2-butanamine. 4- (4-chloropheni 1) -lH-imidazol-1-butanamine. 2- (3-pyridinyl) -thiazole-5-butanamine. 7-methoxyquin-1-yn-4-butanamine. 4- (4-f-luo-phosphyl) -lH-imidazol-1-butanamine, 4- (2-methoxyphenyl) -lH-imidazol-1-butanamine. 3- (3-pyridinyl) -lH-1, 2,4-triazole-l-butanamine, 4- (3-pyridinyl) -lH-imidazol-1-butanamine. 2- (2-pyridinyl) -thiazole-4-butanamine, 2-phenylthiazole-4-butanamine. 4- (4-methoxyphenyl) -lH-imidazole-l-butanamine. - isoquinoline-4-butanamine. - quinasolin-4-butanamine. - 4,5-diphenyl-lH-imidazol-l-butanamine. 4- (3-Raetoxyphenyl) -lH-imidazol-1-butanamine. 4- (4- (trifluoromethoxy) -pheni 1) -lH-imidazol-1-butanamine. 1,2,3,6-tetrahydro-1,3-dimethyl 1-2.6-dioxo-7H-purin-7-butanamine, 2- (4-pyridin-1) -thiazole-4-butanamine. - IH-indol-l-butanamine. - 2- (3-pyridinyl) -thiazole-4-butanamine as well as its acid addition salts