MXPA00009423A

MXPA00009423A - Macrolide lhrh antagonists

Info

Publication number: MXPA00009423A
Application number: MXPA/A/2000/009423A
Authority: MX
Inventors: Daryl R Sauer; Fortuna Haviv; John Randolph; Nicholas A Mort; Christopher R Dalton; Milan Bruncko; Michele A Kaminski; Bradley W Crawford; Lisa Marie Frey; Jonathon Greer
Original assignee: Abbott Laboratories
Priority date: 1998-03-27
Filing date: 2000-09-26
Publication date: 2001-07-31

Abstract

Disclosed are 3'-N-desmethyl-3'-N-susbstituted-6-O-methy l-11-deoxy-11, 12-cyclic carbamate erythromycin A derivatives which are antagonists of lutenizing hormone-releasing hormone (LHRH). Also disclosed are pharmaceutical compositions comprising the compounds, to methods of using the compounds and to the process of making the same.

Description

ANTAGONISTS OF LHRH, OF MACROL1DA TECHNICAL FIELD The present invention relates to a class of macrolide compounds which are antagonists of the lutenizing hormone-releasing hormone (LHRH); to pharmaceutical compositions comprising the compounds; to methods for using the compounds and the process to prepare them. More particularly, the present invention relates to erythromycin A derivatives, 3'-N-demethyl-3'-N-substituted-6-O-methyl-11-deoxy-11,12-cyclic carbamate, which are antagonists of LHRH.

BACKGROUND OF THE INVENTION Gonadotropins, follicle stimulating hormone (FSH), lutenizing hormone (LH) and chorionic gonadotropin (CG) are necessary for ovulation, spermatogenesis and sex steroid biosynthesis. A single hypothalamic hormone, gonadotropin-releasing hormone (GnRH), also known as LHRH, is responsible for regulating the secretion of both FSH and LH in mammals. LHRH is a decapeptide having the structure: pyro-Glu1-Hi2-Trp3-Ser4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH2 where the exponents designate the position of each aminoacyl residue in the decapeptide chain. LHRH is released from the hypothalamus and binds to a receptor in the pituitary gland, causing the release of LH and FSH that subsequently act on the gonads to stimulate the synthesis of steroidal sex hormones. The pulsatile release of LHRH and, thus, the release of LH and FSH, control the reproduction cycle in animals and in humans. Acute doses of LHRH agonists increase the levels of LH and steroidal sex hormones in both animals and humans. Paradoxically, chronic doses of LHRH agonists suppress the level of LH and steroidal sex hormones. Consequently, the effect of multiple doses of LHRH agonists is to suppress the formation of estrogen in females and the production of testosterone in males. The same effect is observed in both animals and humans, after administering acute or chronic doses of LHRH antagonists. In recent years considerable research effort has been devoted to finding LHRH antagonists. These efforts have produced many peptide antagonists of LHRH that suppress LH and reproductive hormones in mammals when administered in an acute or chronic manner. See, for example, M. J. Karten in Modes of Action of GnRH and GnRH anaiogs, edited by W. F. Crowley and P. M. Conn, p. 277 (1992). Literature has reported that LHRH antagonists are useful in the treatment of a variety of conditions in which the suppression of sex steroids plays a key role, including contraception, the delay of puberty, the treatment of benign prostatic hyperplasia, the palliative treatment or remission of hormone-dependent prostate ts, the treatment of cryptorachidism, hirsutism in women, gastric motility disorders, dysmenorrhea and endometriosis. Current LHRH antagonists are decapeptides which, due to their low oral bioavailability, are administered intravenously or subcutaneously. No heterocyclic non-peptide antagonist has been reported in the literature; see, for example, WO 95/29900, WO 97/22707 and WO 97/21704. LHRH antagonists that are not peptides have the potential advantage of improved oral bioavailability and are smaller molecules. However, it is not known from reports in the literature of macrolide compounds, as LHRH antagonists. The macrolide antibiotics and the prokinetic agents of macrolide are known. For example, antibiotics derived from erythromycin, which contain 11, 12-cyclic carbamate moieties are described in EP 248 279 A2. The 3'-N-substituted erythromycin derivatives, which are effective antibacterial agents, are described in EP 0 559 896 A1. The prokinetic agents of macrocyclic lactone (macrolide) are known. See J. S. Gidda and co-inventors, in European Patent Application No. 0349100, published on January 3, 1990, which describes 12 member macrolides for use as gastrointestinal motility enhancers. S. Omura and Z. Itoh, in U.S. Patent 4,677,097, issued June 30, 1987; European application No. 215,355, published on March 25, 1987 and European application No. 213,617, published on March 11, 1987, describe derivatives of erythromycins A, B, C and D, which are useful as stimulants of the movement of contraction in the digestive tract. Additionally, T. Sunazuka and co-authors, Chem.

Pharm. Bull., 37 (10): 2701-2709 (1989) describes quaternary derivatives of 6,9-semiacetal of 8,9-anhydroerythromycin A, and 6,9-epoxide of 9,9-dihydro-erythromycin, with motor stimulating activity gastrointestinal. None of these references disclose the erythromycin A, 3'-N-demethyl-3'-N-substituted-6-O-methyl-11-deoxy-11.12-cyclic derivatives of the present invention, which are effective as antagonists of LHRH.

BRIEF DESCRIPTION OF THE INVENTION In one aspect, the present invention relates to a compound having the formula: i. its salt q its ester, pharmaceutically acceptable; wherein: A is selected from the group consisting of: (a) -C, (b) -N; and (c) -O; X and Y, independently in each occurrence, are selected from the group consisting of: (a) hydrogen; (b) halide; (c) trifluoromethyl; (d) alkoxy; (e) alkyl; (f) aryl; and (g) substituted aryl; R is selected from the group consisting of: (a) alkyl, (b) cycloalkyl; (c) heterocyclic; (d) substituted heterocyclic, (e) alkylcycloalkyl, (f) substituted alkylcycloalkyl, (g) alkylaryl, (h) alkylheterocyclic, (i) alkenyl, (j) alkynyl, (k) -C (S) -NHR4, C ( NR4) -NHR4, where R4 is hydrogen, alkyl or aryl; and (I) - (CH2) n-C (CH2) m-R5, where m is 2, 3, 4 or 5; and R5 is alkyl, alkoxy, aryl or substituted aryl; R2 and R3, independently in each occurrence, are: (a) hydrogen; (b) methyl; or R2 and R3 together form a cyclic portion, when A is C; R3 is absent when A is N; and n = 1, 2 or 3. In another aspect, the present invention relates to a process for preparing the compound of formula I. The process comprises the steps of: (a) reacting a compound of the formula: with sodium hexamethyldisilazide and carbonyldiimidazole, to produce a compound of the formula: (b) reacting the compound obtained in step (a) with an amino compound of the formula: followed by deprotection of the 2 ', 4"-protected hydroxyl groups, to give a compound of the formula (c) demethylating the 3'-amino, treating the compound obtained in step (b), with iodine, in the presence of a base to produce a compound of the formula: and (d) alkylating the 3'-N-demethylated compound, obtained in step 8c), with an alkylating agent. The compounds of the invention exhibit little or no antibacterial activity, but bind to the LHRH receptors and are effective LHRH antagonists. In such a way, these compounds are effective in the treatment of prostate cancer, endometriosis, precocious puberty and other types of diseases that are related to sex hormones. Accordingly, in another aspect of the invention, the present invention relates to pharmaceutical compositions that are useful as LHRH antagonists and suppress LH, testosterone, estradiol and estrogen in mammals. In yet another aspect, the present invention relates to a method for suppressing levels of sex hormones in male or female mammals, comprising administering to a host in need of such treatment, a therapeutically effective amount of an LHRH antagonist compound in combination. with a therapeutically effective amount of an antiandrogen agent.

DETAILED DESCRIPTION OF THE INVENTION The terms "lower alkyl" or "alkyl", when used herein, refer to straight or branched chain alkyl radicals containing from 1 to 20 carbon atoms, sometimes represented as Cx-Cy-alkyl , where x and y, respectively, represent the minimum number and the maximum number of carbon atoms in the alkyl radical. Examples of lower alkyl include, but are not limited to: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, secondary butyl, tertiary butyl, n-pentyl, 1-methylbutyl, 2,2-dimethylbutyl, -methylpentyl, 2,2-dimethylpropyl, n-hexyl and the like. The term "alkoxy" or "lower alkoxy", when used herein, refers to lower alkyl groups as defined above., which are attached to an oxygen atom in an ether ligature. Examples of alkoxy include, but are not limited to: methoxy, ethoxy, isopropoxy, n-pentyloxy, terbutoxy, n-octyloxy and the like. This alkoxy radical may also contain a ring including, but not limited to, a ring of five or six atoms, composed of carbons, which may contain one or two heteroatoms, such as nitrogen, oxygen. The term "alkenyl", as used herein, refers to a branched or straight hydrocarbon chain, comprising two to twenty carbon atoms, preferably four to twelve carbon atoms, especially about eight to ten carbon atoms , which also comprises one or more double bonds of carbon to carbon, preferably around one to three double bonds.

The compounds of the present invention can have a known configuration, or they can exist as mixtures of isomers. The term "alkynyl", as used herein, refers to a straight or branched hydrocarbon chain, comprising two to twenty carbon atoms, preferably four to twelve carbon atoms, especially about eight to ten carbon atoms , which also comprises one or more triple carbon to carbon ligatures, preferably around a triple ligature. The compounds of the invention may have a known configuration or may exist as a mixture of isomers. The term "cycloalkyl", as used herein, refers to a monocyclic, saturated hydrocarbon group having from three to seven carbon atoms in the ring, including, but not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. , cycloheptyl and the like. The cyclic group may be optionally substituted, for example, with lower alkyl, hydroxy, halogen or an amino group. The term "alkylcycloalkyl", as used herein, refers to a cycloalkyl group as defined above, attached to a lower alkyl radical. The alkylcycloalkyl group is attached to the precursor portion by the alkyl radical, where the alkyl radical is from one to six carbon atoms. Examples include, but are not limited to: cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, and the like. The term "aryl", as used herein, refers to a monocyclic, fused bicyclic, or tricyclic fused carbocyclic ring system having one or more aromatic rings including, but not limited to: phenyl, naphthyl, tetrahydronaphthyl, phenanthrenyl, biphenylenyl , indanyl, indenyl and the like. The term "substituted aryl", as used herein, refers to an aryl group as defined herein, substituted by independent replacement of one, two or three of the hydrogen atoms, with Cl, Br, F, l, OH, cyano, mercapto, nitro, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkoxy of 1 to 6 carbon atoms, methoxymethoxy, amino, alkyl of 1 to 3 carbon-amino atoms, di (alk ui I of 1 to 3 carbon atoms) amino, formyl, carboxy, alkoxycarbonyl, alkyl of 1 to 3 carbon atoms-CO-O-, alkyl of 1 to 3 carbon atoms -CO-NH or carboxyamide; except that tetrafluorophenyl and pentafluorophenyl are also included within the definition of "substituted aryl". The term "arylalkyl", as used herein, refers to an aryl group as defined above, connected to an alkyl group as defined above. The arylalkyl group is attached to the precursor portion by means of an alkyl group, where the alkyl group is from one to six carbon atoms. The aryl group in the arylalkyl group may be substituted as defined above. Examples include, but are not limited to, [3- (4-hydroxy) phenyl] propyl, [3- (1-methyl) (4-hydroxy) phenyl] propyl, (4-hydroxybenzyl) methyl and the like. The terms "heterocyclic ring" or "heterocyclic" or "heterocycle", as used herein, refer to any 3 or 4 member ring containing a heteroatom selected from oxygen, nitrogen and sulfur; or a 5, 6 or 7 member ring containing one, two or three nitrogen atoms; a nitrogen atom and a sulfur atom, or a nitrogen atom and an oxygen atom. The 5-membered ring has 0 to 2 double bonds and the 6 and 7-membered ring has 0 to 3 double bonds. The nitrogen heteroatoms may optionally be quaternized. The term "heterocyclic" also includes bicyclic groups, wherein any of the above heterocyclic rings is fused to a benzene ring or a cyclohexane ring or other heterocyclic ring (e.g., indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, and the like) ). Heterocyclics include: azetidinyl, benzimidazolyl, 1,4-benzodioxanil, 1,3-benzodioxolyl, benzoxazolyl, benzothiazolyl, benzothienium, dihydroimidazolyl, dihydropyranyl, dihydrofuranyl, dioxanyl, dioxolanyl, furyl, homopiperidinyl, imidazolyl, imidazolinyl, imidazolidinyl, indole, indolyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isoxazolidinyl, isoxazolyl, morpholinyl, naphthyridinyl, oxazolidinyl, oxazolyl, piperazinyl, piperidinyl, pyrazinyl, pyrazolinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinolinyl, tetrahydrofuranyl, tetrahydropyranyl, thiazole, idinyl, thiazolyl and thienyl. Heterocyclics can be unsubstituted or monosubstituted or disubstituted with substituents independently selected from hydroxy, halo, oxo (= O), alkylimino (R * N =, where R * is a lower alkyl group), cycloalkyl, aryl, arylalkyl and lower alkyl . In addition, heterocycles containing nitrogen may be N-protected. The term "(heterocyclic) alkyl", as used herein, refers to a heterocyclic group as defined above, connected to a lower alkyl radical, as defined above. The (heterocyclic) alkyl group is attached to the precursor portion by means of an alkyl group, where the alkyl group is from 1 to 6 carbon atoms. Examples include, but are not limited to: 2-pyridylmethyl, 4-pyridyl, ethyl, 2-pyridylethyl, 3-piperidyl, propylamino, 2-pyridylpropyl, 4-pyridylpropyl, 2-furylmethyl, and Similar. The term "(heterocyclic) substituted alkyl", as used herein, refers to a heterocycloalkyl group, as defined above, in which the heterocyclic group or the alkyl group is substituted by independent replacement of one, two or three of the hydrogen atoms thereof, with Cl, Br, F, I, OH, cyano, mercapto, nitro, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, alkoxy of 1 to 6 carbon atoms , thioalkoxy of 1 to 6 carbon atoms, hydroxyalkyl, methoxymethoxy, amino, alkylamino of 1 to 3 carbon atoms, di (to I qui of 1 to 3 carbon atoms) amino, carboxyaldehyde, carboxy, alkoxycarbonyl, alkyl of 1 to 3 carbon atoms-CO-O-, alkyl of 1 to 3 carbon atoms-CO-NH- or carboxyamide. Examples include, but are not limited to, 3 - [(5-methyl) -2-pyridyl] propyl, 3 - [(6-methyl) -2-pyridyl] propyl, 4 - [(6-methyl) -2-pyrid. L] butyl, (5-nitro) -2-thienylmethyl, and the like. The term "heteroaryl", as used herein, refers to a cyclic aromatic radical having from five to ten ring atoms, of which one ring atom is selected from S, O and N; zero, one or two ring atoms are additional heteroatoms, selected from S, O and N; and the remaining ring atoms are carbon; the radical being attached to the rest of the molecule by any of the ring atoms; for example: pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thienyl, furanyl, quinolinyl, isoquinolinyl and the like. The term "substituted heteroaryl", as used herein, refers to a heteroaryl group as defined herein, substituted by independent replacement of one, two or three of the hydrogen atoms, with Cl, Br, F, I, OH, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 6 carbon atoms, methoxymethoxy, amino, or alkylamino of 1 to 3 carbon atoms; or it may also refer to a mono-oxo-substituted heteroaryl compound, such as, for example, 4-oxo-1 H-quinoline. The term "aprotic solvent", as used herein, refers to a solvent that is relatively inert in terms of proton activity, that is, it does not act as a proton donor. Examples include, but are not limited to: hydrocarbons, such as hexane and toluene; for example, halogenated hydrocarbons, such as, for example: methylene chloride, ethylene chloride, chloroform and the like; heterocyclic compounds, such as, for example, tetrahydrofuran and N-methylpyrrolidinone; ethers, such as diethyl ether and bis-methoxymethyl ether, as well as various other compounds, such as dimethylformamide, acetonitrile, acetone and ethyl acetate. Such compounds are well known to those skilled in the art and it will be obvious to those skilled in the art that individual solvents or mixtures thereof may be preferred for specific compounds and reaction conditions, depending on factors such as the solubility of the reagents, the reactivity of the reagents and preferred temperature scales, for example. Other discussions of aprotic solvents can be found in organic chemistry texts or specialized monographs, for example: Organic Solvents Physical Properties and Methods of Purification, 4a. edition, edited by John A. Riddick and others, volume II of the Techniques of Chemistry series, John Wiley & Sons, NY, 1986. As used herein, the term "pharmaceutically acceptable salt" refers to those salts which, within the scope of sound medical judgment, are suitable for use in contact with the tissues of human and lower animals, without toxicity. irritation, allergic response and the like, undue; and is consistent with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge and coauthors describe pharmaceutically acceptable salts, in detail, in J. Pharmaceutical Sciences, 66: 1-19 (1977), incorporated herein by this reference. The salts can be prepared in situ during the final isolation and purification of the compounds of the invention, or separately, by reacting the free base function with a suitable organic or inorganic acid. Examples of non-toxic pharmaceutically acceptable acid addition salts are salts of an amino group formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid, or with organic acids such as acetic acid, acid oxalic, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid; or by the use of other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include: the adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphor sulfonate, citrate, cyclopentane propionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, iodhydrate, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate , succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate and the like. Representative salts of alkali metal and alkaline earth metal include salts of sodium, lithium, potassium, calcium, magnesium and the like. Other pharmaceutically acceptable salts include, when appropriate, the non-toxic ammonium, quaternary ammonium and amine cation salts formed by the use of counter ions, such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkylsulfonate and Arylsulfonate.

As used herein, the term "pharmaceutically acceptable ester" refers to esters that are hydrolyzed in vivo and include those that are readily decomposed in the human body to leave the parent compound or its salt. Suitable ester groups include, for example, pharmaceutically acceptable aliphatic carboxylic acid derivatives, in particular alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, wherein each alkyl or alkenyl portion advantageously has no more than six carbon atoms. Examples of particular esters include formates, acetates, propionates, butyrates, acrylates and ethylsuccinates. There may be numerous asymmetric centers in the compounds of the present invention. Except when noted otherwise, the present invention contemplates the various stereoisomers and mixtures thereof. Consequently, whenever a ligature is represented by a wavy line, it is intended that a mixture of stereo orientations, or an individual isomer of assigned or unassigned orientation, may be present.

PREFERRED MODALITIES Preferred compounds of the invention comprise those in which R is alkyl, alkenyl, cycloalkyl, heterocyclic, (heterocyclic) alkyl or alkylcycloalkyl; X and Y are independently chloro, fluoro, dioxolane, hydrogen or alkoxy; A is -C or N; R2 and R3 are hydrogen or cyclopropyl and n is 1.

The representative compounds of the invention are selected from the group consisting of: 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3, 4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-0-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclohexyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isovaleryl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- / 3-methylthiopropyl) l-11-deoxy-11- [carboxy (3,4-dicyorophenethylamino)] - 6-O- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-methylthiopropyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl -erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-tetrahydrothienyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl -erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3,4-dimethylcyclopentyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O -methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichlorophenethylamino)] - 6-O -methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (, a-cyclopropyl-3,4-dichlorophenethyl-amino)] - 6- O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichlorophenethyl-amino)] - 6 -O-methyl-erythromycin A; 11, 2- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclohexyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichlorophenethyl-amino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-Nn-propyl-11-deoxy-11- [carboxy (3,4-dioxolanophenethylammon)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3,4-dioxolanophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-Nn-propyl-11-deoxy-11- [carboxy (4-chloro-3-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (4-chloro-3-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-chloro-3-fluorofenetylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutylmethyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutylmethyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethi-3'-N-ethyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (4-chlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 1, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl- erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopenty-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-pyridylmethyl) -11-deoxy-11- [carboxy (4-chlorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-butyl) -11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-pentyl) -11-deoxy-11- [carboxy (4-chlorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (cyclopropylmethyl) -11-deoxy-11- [carboxy (4-chlorophenethylamino)] - 6-0-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-cyclopropylethyl) -11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (4-methoxyphenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-methoxyphenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (3,4-dimethyl-phenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopethyl-11-deoxy-11- [carboxy (3-bromo-4-methoxyphenethylamino)] - 6-O-methyl- erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (3-bromo-4-methoxyphenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-furyl) methyl-11-deoxy-11 - [carboxy - (3-chloro-4-fluoro-fexylamino)] - 6-0-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2- (5-hydroxymethyl) furyl] methyl-11-deoxy-11- [carboxy (3-chloro-4- fluorofenetylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridyl) methyl-11-deoxy-11- [carboxy (3-cioro-4-fluorophenethylamino)] - 6- O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2- (6-methyl) pyridyl] methyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethyl amino)] - 6-0-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-hydroxyethoxybenzyl) -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethyl-amine)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-methylthio) butyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6- O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4,4,4-trifluorobutyl) -11-deoxy-11 - [carboxy- (3-cl or ro-4) -f luorof enetyl ami no)] - 6-O-methyl-epromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (4-chloro-3-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy [3,4- (1,4-dioxane) phenethylamino)]] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (methylsulfoxy) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6- O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-ethylthiourea-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2- (5-hydroxymethyl) furyl] methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethyl) amino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichloro-phenethylamino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11 - [carboxy (4-chloroanilinoethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-chloroanilinotylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-imidazole) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-0- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-pi r? Dil) m ethyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-0-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O- methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N - [(5-nitro) -2-thienyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [5- (4-chlorophenyl) -2-furyl] methyl-11-deoxy-11- [carboxy- (3,4- dichlorophenethyl amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [5-nitro-2-furyl] methyl-11-deoxy-11 - [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2,5-dimethoxy-3-tetrahydrofuryl] methyl-11-deoxy-11- [carboxy (3,4-dichloro-phenethylamino )] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [6-methyl-2-pyridyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4,4,4-trifluorobutyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (1-bromo-2-naphthyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-methyl-1-naphthyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-dimethylamino-1-naphthyl) methyl-11-deoxy-11 - [carboxy (3,4-dichlorophenethyl amino)] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-furyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O- methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (4-pyridyl) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3"-N-desmethyl-3'-N- [3- (2-pyridyl) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-desmethi-3'-N-3- [4- (4-pyridyl) butyl] -11-deoxy-11- [ carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (3-pyridyl) propyl ] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methylfithromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [(3- (3-pyridyl) propyl] -11-deoxy-1- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) 3'-N-demethyl-3'-N- [3- (4-pyridyl) propyl] -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (2-piperidyl) propyl] -11-deoxy-11 - [carboxy - (3-chloro- 4-f luorofenetylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [4- (4-pyridyl) butyl] -11- deoxi-11- [carb oxy- (3-chloro-4-fIuorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [4- (6-methyl-2-pyridyl) butyl] -11-deoxy-11 - [carboxy- (3-chloro- 4-f luorof eethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [1-methyl-3- (4-hydroxyphenyl) propyl] -11-deoxy-11 - [carboxy- (3,4 -dichlorophenethyl amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N - [(1-methyl) -3- (4-hydroxyphenyl) propyl] -11-deoxy-11- [carboxy (3- chloro-4-fluoro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (6-methyl-2-pyridyl) propyl] -11-deoxy-11- [carboxy- (3-chloro- 4-fluorophenethyl amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (5-methyl-2-pyridyl) propyl] -11-deoxy-11- [carboxy (3-chloro- 4-fluorophenethyl amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridylethyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl -erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridylethyl-11-deoxy-11 - [carboxy - (3-chloro-4-fluorophenethylamino)] - 6-0- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-hydroxybenzyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-pyridyl) methyl-11-deoxy-11- [carboxy (3,4 -dichlorphenethylamino)] - 6-O-methyl-erythromycin A; I 1, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N - [(3-methylthio) butyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (1-methylcyclopropyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethyl amino)] - 6-O -methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (1-methylcyclopropyl) methyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethyl amino)] - 6-O -methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-oxiranylmethyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-guanidino-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; and 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-2- (4,5-dihydroimidazole) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A. The most preferred compounds are selected from the group consisting of: II, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy- (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 1, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-Nn-propyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin TO; and 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropyl methyl I-11-deoxy-11- [carboxy- (3,4-difluorof eneti lami)] - 6-O-methyl-erythromycin A.

EFFECT AND UTILITIES OF LHRH AGONISTS AND ANTAGONISTS The LHRH agonist and antagonist compounds of the present invention are useful for the treatment of precocious puberty, prostate cancer, benign prostatic hyperplasia (BPH), endometriosis, uterine fibroids, breast cancer, acne, premenstrual syndrome, polycystic ovarian syndrome and diseases that are the result of excesses or deficiencies in the production of gonadai hormones, in any of the sexes of humans and animals. The LHRH antagonists of the present invention are also useful for controlling reproduction in both females and males. The compounds of the invention are useful for suppressing levels of testosterone and dihydroxytestosterone (DHT) in males, and estrogen and estradiol in females. In the practice of the method of this invention, an effective amount of a compound of the invention or a pharmaceutical composition containing it is administered to the human or animal that needs or desires said treatment. Those compounds or compositions can be administered by a variety of routes, depending on the specific end use; and include routes of oral administration, parenteral (including subcutaneous, intramuscular and intravenous administration), vaginal (in particular for contraception), rectal, oral (including sublingual), transdermal or intranasal. The most appropriate route, in any given case, will depend on the use, the particular active ingredient, the subject involved and the judgment of the medical practitioner. The compound or composition can also be administered by means of slow-release, depot or implant formulations, as described more fully below. In general, to modulate sex hormone levels in male or female mammals, for the uses described hereinabove, it is expedient to administer the active ingredient in amounts between about 1 and 200 mg / kg of body weight per day, preferably between 1 and 30 mg / kg of body weight per day. This administration can be achieved through a single daily administration, by distribution in several applications, or by slow release, in order to obtain the most effective results. The exact dose and exact regimen for administration of these compounds and compositions will necessarily depend on the needs of the individual subject being treated, the type of treatment, the degree of distress or need, and the judgment of the medical practitioner. In general, parenteral administration requires less dosage than other methods of administration, which depend more on absorption. Another additional aspect of the present invention relates to pharmaceutical compositions containing as active ingredient a compound of the present invention, compositions comprising said compound in admixture with a non-toxic, pharmaceutically acceptable carrier. As mentioned above those compositions can be prepared for use in parenteral administration (subcutaneous, intramuscular or intravenous), particularly in the form of liquid solutions or suspensions; for use in vaginal or rectal administration, particularly in semi-solid forms, such as creams and suppositories; for oral or buccal administration, particularly in the form of tablets or capsules, or intranasally, in particular in the form of powders, nasal drops or aerosols. The compositions can be conveniently administered in unit dosage form and can be prepared by any of the methods well known in the pharmaceutical art, for example, as described in Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA, USA, 1970 The formulations for parenteral administration may contain as common excipients, sterile water or saline; polyalkylene glycols, such as polyethylene glycol, oils of vegetable origin, hydrogenated naphthalenes and the like. Formulations for administration by inhalation can be solid and contain as excipients, for example, lactose, or they can be aqueous or oily solutions for administration in the form of nasal drops. For buccal administration, typical excipients include, sugars, calcium stearate, magnesium stearate, pregeiatinized starch and the like. It is particularly convenient to deliver the compounds of the present invention to the subject, for extended periods of time, for example, for periods of one week to one year of an individual administration. Various forms of slow-release, depot or implant doses can be used. For example, a dosage form may contain a non-toxic, pharmaceutically acceptable salt of a compound of the invention that has a slow degree of solubility in body fluids.; for example: (a) an acid addition salt with a polybasic acid, such as phosphoric acid, sulfuric acid, citric acid, tartaric acid, tannic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalene-monosulfonic or disulfonic acids; polygalacturonic acid, and the like; (b) a salt with a polyvalent metal cation, such as zinc, calcium, bismuth, barium, magnesium, aluminum, copper, cobalt, nickel, cadmium and the like; or with an organic cation formed, for example, from N, N-debenzylethylenediamine or ethylenediamine; or (c) combinations of (a) and (b), for example, a zinc tannate salt. Additionally, the compounds of the present invention, or preferably a relatively insoluble salt, such as those just described, can be formulated in a gel; for example, an aluminum monostearate gel, for example, with sesame oil, suitable for injection. Particularly preferred salts are zinc salts, zinc tannate salts, pamoate salts and the like. Another type of slow release depot formulation for injection would contain the compound or salt dispersed or encapsulated in a non-antigenic, nontoxic, slowly degrading polymer, such as a polylactic acid / polyglycolic acid polymer, for example, as described in US Patent No. 3,773,919. The compounds of the invention or, preferably, the relatively insoluble salts, as described above, can be formulated in cholesterol matrix pellets, in particular for use in animals. Other slow release, depot or implant formulations, for example, liposomes, are well known in the literature. See, for example, Sustained and Controlled Relay Drug Delivery Systems, J. R. Robinson ed., Marcel Dekker, Inc., New York, 1978. Reference can be found with respect to compounds of the LHRH type; for example, in United States Patent 4,010,125.

The LHRH ANTAGONIST ACTIVITY Representative compounds of the present invention were evaluated in in vitro tests for rat pituitary LHRH receptor binding (pK1) and for inhibition of LH from rat pituitary cells for antagonistic potency (pA2). The tests employed the methods detailed in F. Haviv and co-authors, J. Med. Chem., 32: 2340-2344 (1989). The receptor binding affinity (pK |) is the negative logarithm of the equilibrium dissociation constants. The results of the pK | for the representative compounds of the present invention are presented in table 1.

TABLE I The pA2 value is the negative logarithm of the antagonist concentration that bypasses the response curve produced by the leuprolide agonist at a concentration twice as high. Leuprolide is the LHRH agonist which has the structure pyro-Glu1-His2-Trp3-Ser4-Tyr5-D-Leu6-Leu7-Arg8-Pro9-NHEt and is described and claimed in US Patent 4,005,063. Typically pA2 values of 7.0 or greater are indicative of good LHRH antagonist potency. The pA2 values for representative compounds are indicated in Table 2 below.

TABLE 2 METHODS OF SYNTHESIS The compounds and processes of the present invention will be better understood in connection with the synthesis schemes 1 and 2 which follow, which illustrate the methods by which the compounds of the invention can be prepared. The compounds are prepared using commercially available or synthesized reagents.

ABBREVIATIONS The abbreviations that have been used in the descriptions of the scheme and the examples that come later are: Ac by acetyl; APCI by chemical ionization at atmospheric pressure; CDI by carbonyldiimidazide; CH3CN by acetonitrile; Cl or DCI by chemical ionization by desorption; DMF by dimethylformamide; ESI by ionization by electrospray; EtOAc for ethyl acetate; FAB by bombardment with fast atoms; FTIR by infrared Fourier transformation spectroscopy; HPLC by high performance liquid chromatography; IR by infrared spectroscopy; MeOH by methanol; MHz per megahertz; MIC by microscope; MS by mass spectra; NaHMDS by sodium hexamethyldisilazide; NMR by nuclear magnetic resonance; Rf by retention factor; Rt by retention time; TBAF by tetrabutylammonium fluoride; THF by tetrahydrofuran; TLC by thin layer chromatography; TMS by trimethylsilyl; TMS Cl for tri-methyl chloride and silicate and DCM for dichloromethane. The starting material 1, 6-O-methyl-erythromycin A (clarithromycin, commercially available as BIAXIN® from Abbott Laboratories) is protected at the 2 'and 4"positions by reaction with a suitable hydroxy protecting reagent, such as those described by TW Greene and PGM Wuts in Protective Groups in Organic Synthesis, 2nd edition, John Wiley &Son, Inc., 1991. Protective hydroxy reagents include, for example: acetic anhydride, benzoic anhydride, benzyl chloroformate, hexamethyldisilazane or chloride of trialkylsilyl, in an aprotic solvent.

SCHEME 1 As shown in scheme 1, protection of the 2'-hydroxyl and 4"-hydroxy groups of 6-O-methyleptromycin A (1) can be achieved, sequentially or simultaneously to give the compound (2) where Rp is a hydroxy protecting group A preferred protecting Rp group is trimethi is ii il or acetyl Examples of aprotic solvents are dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methylpyrrolidinone, dimethyl sulfoxide, diethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, hexamethylphosphoric triamide, a mixture thereof or a mixture of one of these solvents with ether, tetrahydrofuran, 1,2-dimethoxyethane, acetonitrile, ethyl acetate, acetone and the like. The aprotic solvents do not adversely affect the reaction and are preferably: dichloromethane, chloroform, DMF, tetrahydrofuran (THF), N-methylpyrrolidinone or a mixture thereof. The compound (2) protected with sodium hexamethyldisilazide or sodium hydride in an aprotic solvent at 0-25 ° C, and carbonyldiimidazole, is treated to produce the compound (3). The treatment of the compound (3) with an amino compound of the formula without solvent or in acetonitrile at 25-80 ° C, followed by deprotection, results in the formation of N-substituted cyclic carbamate, represented by compound (4). The deprotection of the protecting groups of 2'-hydroxy and 4"-hydroxy to obtain the compound (4) is carried out by the methods described by TW Greene and PGM Wuts in Protective Groups in Organic Synthesis, 2nd edition, John Wiley &Son, Inc., 1991. The demethylation of the 3'-N-dimethyl group is obtained by treating the compound (4) with iodine, in the presence of a suitable base, such as sodium acetate, and a light or thermal source after which it is inactivated with sodium thiosulfate and treated to produce the compound (5). N-dealkylation can also be carried out using chloroformate reagents, such as benzyl chloroformate, allyl chloroformate, vinyl chloroformate and the like. The alkylation of the 3'-N-demethyl compound (5) is obtained by reaction with an appropriate aldehyde or ketone, in the presence of a metal hydride, such as sodium cyanoborohydride or sodium triacetoxyborohydride, or in the presence of a sodium catalyst. Pd / C, in a protic or non-protic solvent, under a hydrogen atmosphere. The aldehydes and ketones that can be used in the preparation of compound (5) include, for example: cyclopropylcarboxaldehyde, acetone, n-propanal, cyclohexanone, cyclopentanone, isovaleraldehyde, cyclobutanone, isopropyl aldehyde, 2'-pyridinecarboxyaldehyde, -thiazole-carboxyaldehyde. The alkylation of the 3'-N-demethyl compound (5) can also be obtained by reaction with an appropriate alkylating agent, in the presence of a base, by methods known in the art, to give the compound (6). Alkylating agents that can be used in the preparation of compound (5) include lower alkyl halides, such as ethyl bromide, lower alkyl halides substituted with halogen, lower alkyl halides substituted with cyano, lower alkyl halides substituted with hydroxy , other lower alkenyl halides, such as methylalumyl chloride, lower alkynyl halides, such as propargyl bromide, lower cycloalkyl halides, lower cycloalkylmethyl halides, such as cyclopropylmethyl halides and cyclopropylbenzyl. Scheme 2 illustrates a specific embodiment of Example 1, comprising the treatment of 2'-acetyl-6-O-methyl-erythromycin A (7) with trimethylsilyl chloride, to give the compound (8). Compound (8) is treated with sodium hexamethyldisilazide and carbonyldiimidazole, to give the 12-O-acylimidazole derivative, which is subsequently reacted with 3,4-dichlorophenethylamine to form the cyclic 11, 12-carbamate derivative. The cyclic 11,12-carbamate thus obtained is treated with methanol to give the compound (9). Deprotection of the 4"-protected hydroxy group is achieved by methods well known in the art, to produce the compound (10) .The treatment of the compound (10) with iodine, in the presence of sodium acetate, followed by inactivation of the mixture. reaction reaction with sodium bisulfite, produces the compound (11). The alkylation of the 3'-nitrogen is obtained by reaction with cyclopentanone, in the presence of sodium cyanoborohydride in methanol, and a few drops of acetic acid, to give the final product , the compound (12).

SCHEME 2 Jl 12 The above can be better understood by reference to the following examples, which are presented for illustration, and not to limit the scope of the concept of the invention.

EXAMPLES EXAMPLE 1 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CYCLE-PENTIL-11-DESOXY-11-rCARBOXY-3,4-DICHLOROPHENYL AMINO) 1-6-O-METHYL- ERYTHROMYCIN A (COMPOSITE 12. SCHEME 2) 6-O-methyl-erythromycin (commercially available from Abbott Laboratories as BIAXIN®, in the 2 'position, was protected with the acetyl protecting group, by methods described in the literature.

Step 1: 2'-0-acetyl-4"-0-trimethylsilyl-6-0-methyl-erythromycin A (Compound 8, scheme 2) 45 g (57 mmol) of 2'-O-acetyl-6-O-methyl-erythromycin A was dissolved in 450 ml of CH 2 Cl 2 and cooled to 0 ° C in an ice / water bath . 13.8 ml (171 mmol) of pyridine was added in one portion, followed by the dropwise addition of 14.5 ml (114 mmol) of TMS-CI over a period of 15 minutes. The reaction was stirred for one hour, under the protection of a drying tube, after which TLC (CH2Cl2: MeOH, 9: 1) indicated complete conversion to a new, less polar material. The reaction was then quenched with 500 ml of 0.5 M NaH2PO, the organic layer was separated and washed with 300 ml of water, 300 ml of saturated sodium bicarbonate, 300 ml of water and 100 ml of brine, before drying on sodium sulfate, filter and concentrate. p.f. 235-237 ° C (CH 3 CN); Rf = 0.5 (CH2Cl2: MeOH, 9: 1); MS ESI (M + H) + at m / z 862. NMR with 13 C (75 MHz, CDCl 3) d 221.0, 175.6, 169.9, 100.0, 96.0, 80.5, 80.3, 78.3, 77.8, 76.4, 74.1, 73.2, 72.0, 69.0 , 67.1, 65.2, 62.7, 50.3, 49.4, 45.1, 44.9, 40.5, 38.7, 38.6, 37.1, 35.6, 30.9, 22.1, 21.5, 21.4, 20.9, 19.7, 19.2, 19.2, 19.8, 17.8, 15.9, 15.8, 12.1, 10.4, 8.9 , 0.8.

Step 2: 11, 12- (cyclic carbamate) of 4"-O-trimethylsilyl-11-deoxyl-11-rcarboxy- (3,4-dichlorophenethylamino) 1-β-Q-methyl-erythromycin A- (Compound 9, scheme 2 20.4 g (24.2 mmol) of compound (8) was dissolved from step 1, in 20 ml of anhydrous THF, then diluted with 200 ml of DMF. The resulting solution was cooled in an ice / water bath and treated with 19.6 g (120.9 mmol) of 1,1 '-carbonyldiimidazole in one portion, followed by the portionwise addition of 1.45 g (36 mmol) of NaH (slurry). to 60% in oil). The reaction was allowed to warm to room temperature and stirred under nitrogen for one hour, after which the TLC [EtOAc: MeOH, 95: 5, visualization with Ce (IV)] indicated complete conversion to a more polar material. The reaction was carefully quenched with water and then partitioned between 400 mL of EtOAc and 300 mL of water. The organic phase was collected and washed with 300 ml of 1N NaOH, 2 x 300 ml of water and 200 ml of brine, before drying over sodium sulfate and concentrating. A sample of the resulting colorless foam was subjected to MS analysis, which showed (M + H) + at m / z 938 for the desired acylimidosol intermediate. The material was dissolved in 25 ml of acetonitrile, treated with 7.0 g (36 mmol) of 3,4-dichlorophenethylamine and stirred under nitrogen at 55 ° C. After 48 hours, TLC [EtOAc: MeOH, 95: 5, visualization with Ce (IV)] indicated the complete conversion of the starting compound to a less polar material, which precipitated on cooling to room temperature. The resulting precipitate was recrystallized from acetonitrile to give 16.1 g of the 2 ', 4"-protected cyclic carbamate, as colorless needles, 16.1 g (15.2 mmol) of this protected cyclic carbamate was suspended in 250 ml of methanol and the suspension was heated to 100 ml. 55 ° C under the protection of a drying tube After 24 hours the TLC [Methylene Chloride: MeOH, 9: 1, visualization with Ce (IV)] indicated the complete conversion of the starting acyl-imidosol intermediate, to a new more polar material, which precipitated on cooling at room temperature The resulting solid was crystallized from MeOH / water to give 13 g of compound (9), mp 112-114 ° C, Rf = 0.65 (methylene chloride: MeOH, 9). : 1), MS (ESI) (M + H) + at m / z 1017. HRMS m / z (M + H) + calculated 999.5116, observed, 999.5110. RMN with 1H (300 MHz, CDCl3) d 7.46 (d, J = 2 Hz, Ar H), 7.35 (d, J = 8 Hz, Ar H), 7.19 (dd, J = 8, 2 Hz, Ar H), 4.91 (d, J = 4.4 Hz, 1H), 4.56 (d, J = 7 Hz, 1H, C-1 'CH), 3.75 (d, J = 10 Hz, 1H, C-3 CH), 3.70 (s, 1H, C-11 CH), 3.67 (d, J = 8 Hz, 1H, C-1 'CH), 3.75 (d, J = 10 Hz, 1H, C-3 CH), 3.70 (s, 1H, C-11 CH), 3.67 (d, J = 8 Hz, 1H, C-5 CH), 3.31 (s, 3H, C-6 OCH3), 3.07 (s, 3H, C-6 OCH3), 2.38 (d, J = 15 Hz, 1H, C-2"CH), 2.28 (s, 6H, C-2 'N (CH3) 2, 1.43 (s, 3H, C-6 CH3), 1.40 (s, 3H , C-12, CH3), 1.07 (d, J = 23 Hz, 3H, C-10 CH3), 0.82 (t, J = 7 Hz, 3H, C-15 CH3), 0.16 (s, 9H, C- 4"OSi (CH3) 3. NMR with 13 C (75 MHz, CDCl 3) d 216.1, 176.5, 157.2, 139.3, 132.1, 131.0, 130.2, 130.0, 128.4, 102.4, 96.6, 82.8, 80.6, 79.9, 79.0, 78.0, 76.1, 73.1, 71.1, 68.0, 65.2, 64.7, 60.3, 50.6, 49.6, 45.5, 45.3, 44.8, 40.0 (2C), 39.1, 38.9, 35.6, 32.6, 28.6, 22.1, 21.8, 21.7, 20.1, 19.2, 18.8.16.0, 14.1, 14.0, 10.2 , 9.0, 0.8.

Step 3.- 11, 12- (cyclic carbamate) of 11 -deoxy-11-rcarboxy- (3,4-dichlorophenethylamino) 1-6-O-methyl-erythromycin A.- (compound 10, scheme 2). 2.51 g (2.46 mmol) of the compound (2) from the previous step was dissolved in 20 ml of THF, treated with 2.6 ml of TBAF (1M / THF, 2.6 mmol) and stirred at room temperature. After two hours the TLC [CHCl3: MeOH: NH4OH, 90: 8: 1, visualization with Ce (IV)] indicated the complete conversion of the starting material to a new more polar material. The reaction mixture was partitioned between 300 ml of ethyl acetate and 300 ml of water. The organic phase was washed with 200 ml of saturated sodium bicarbonate, with 200 ml of water and with 200 ml of brine, before drying in sodium sulfate and concentrating. The resulting residue crystallized from acetonitrile to give 1.5 g of product (64%). p.f. 240-243 ° C; Rf = 0.45 (CHCl3): MeOH: NH4OH, 90: 8: 1); MS (FAB) (M + H) + at m / z 945. 1 H NMR (300 MHz, CDCl 3) delta 7.45 (d, J = 2 Hz, 1H, Ar H), 7.35 (d, J = 8 Hz, 1H , Ar H), 7.19 (dd, J = 8.2 Hz, 1H, Ar H), 4.44 (d, J = 7 Hz, 1H, C-1 'CH), 3.75 (d, J = 10 Hz, 1H, C -3, CH), 3.69 (s, 1H, C-11 CH), 3.33 (s, 3H, C-3"OCH03), 3.07 (s, 3H, C-6 OCH3), 2.29 (s, 6H, C -3 'N (CH3) 2), 2.19 (d, J = 10 Hz, 1H, C-4"OH), 1.44 (s, 3H, C-7 CH3), 1.40 (s, 3H, C-12 CH3) ), 1.31 (d, J = 6H, 3H, C-6"CH3), 1.26 (s, 3H, C-3" CH3), 1.15 (d, J = 7 Hz, 3H, C-8 CH3), 1.12 (d, J = 8 Hz, 3H, C-4 CH3), 1.02 (d, J = 7 Hz, 3H, C-10 CH3), 0.83 (t, J = 8 Hz, 3H, C-15 CH3). NMR with 13 C (75 MHz, CDCl 3), delta 216.2, 176.4, 157.2, 139. 3, 132.1, 131.0, 130.2, 130.1, 128.4, 102.9, 96.2, 82.8, 80.1, 78.9, 77.9, 77.8, 76.2, 72.6, 70.9, 68.9, 65.8, 65.6, 60.3, 50.6, 49.5, 45.5, 45.3, 44.8, 40.2 (2C), 39.0, 38.9, 34.8, 32.6, 28.5, 21.9, 21.5, (2C), 20.2, 18.9, 18.7, 16.0, 14.2, 14.1, 10.2, 9.0. IR (KBr) a 3430, 2970, 2940, 1760, 1735, 1710, 1460, 1420, 1380, 1235, 1170, 1070, 1055, 1010, 1000 crrT1. Analysis calculated for C 7H74N2O13.0.5 H2O: C, 59.11; H, 7.91; N, 2.93; Found: C, 59.13; H, 8.12; N, 2.89.

Step 4.- 11, 12- (cyclic carbamate) of 3'-N-demethyl-11-deoxy-11-carboxymethyl- (3,4-dichlorophenethylamino) 1-6-Q-methyl-erythromycin A (compound 11, scheme 2). 2.5 g (2.65 mmol) of the compound from step 3 was dissolved in 50 ml of methanol and treated with 1.80 g (13.25 mmol) of NaOAc.3H2O and 0.71 g (2.78 mmol) of 12. The solution was irradiated with a 500 W halogen work lamp and stirred at room temperature. After two hours, TLC indicated complete conversion of the starting compound to a new, more polar material. The excess of 12 was quenched by the dropwise addition of 1M Na 2 S 2 O 3. The reaction mixture was concentrated and the resulting residue was purified on a column of silica gel (elution with CHCl3: MeOH: NH4OH, 90: 8: 1) to give 1.75 g (71%) of compound 11, as an amorphous solid . p.f. 136-142 ° C (acetonitrile / water); Rf = 0.33 (CHCl 3: MeOH: NH 4 OH, 98: 8: 1); MS (FAB) (M + H) + at m / z 931. NMR with 1H (300 MHz, CDCl 3) delta 7.45 (d, J = 2 Hz, 1H, Ar H), 7.35 (d, J = 8 Hz, 1H , Ar H), 7.19 (dd, J = 8.2 Hz, 1H, Ar H), 4.42 (d, J = 7 Hz, 1H, C-1 'CH), 3.74 (d, J = 9 Hz, 1H, C -3 CH), 3.69 (s, 1H, C-11 CH), 3.32 (s, 3H, C-3"OCH3), 3.07 (s, 3H, C-6 OCH3), 2.42 (s, 3H, C- 3 'NCH3), 1.44 (s, 3H, C-6 CH3), 1.41 (s, 3H, C-12 CH3), 1.31 (d, J = 6 Hz, 3H, C-6"CH3), 1.26 (s) , 3H, C-3"CH3), 1.41 (s, 3 ?, C-12 CH3), 1.31 (d, J = 6 Hz, 3H, C-6" CH3), 1.26 (s, 3H, C-3"CH3), 1.16 (d, J = 7 Hz, 3H, C-8 CH3), 1.07 (d, J = 8 Hz, 3H, C-4 CH3), 1.03 (d, J = 7 Hz, 3H, C -10 CH3), 0.82 (t, J = 7 Hz, 3H, C-15 CH3). NMR with 13 C (75 MHz, CDCl 3) delta 216.2, 176.2, 157.1, 139.2, 132.2, 131.0, 130.3, 130.2, 128.4, 102.4, 96.2, 82.7, 80.5, 78.8, 77.8, 77.7, 76.3, 75.0, 72.7, 68.6, 65.7, 60.3, 50.7, 50.6, 49.5, 45.4, 45.3, 44.8, 39.0, 38.9, 38.8, 37.3, 34.8, 33.3, 32.6, 21.9, 21.5, 21.3, 20.1, 18.9, 18.7 16.0, 14.2, 14.1, 10.2, 9.6 IR (KBr) a 3420, 2970, 2940, 1760, 173 5, 1710, 1460, 1420, 1380, 1235, 1170, 1065, 1050, 1010, 1000 cm-1. Analysis calculated for C 6 H 72 Cl 2 N 2 13 13.0.75 H 2 O: C, 56.39; H, 7.44; N, 2.81. Found: C, 56.63; H, 7.36; N, 2.78.

Step 5. 11.12- (cyclic carbamate) 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11-rcarboxy- (3,4-dichlorophenethylamino) 1-6-O-methyl-erythro- mycin A (compound 12. scheme 2). 0.2 g (0.21 mmol) of the compound obtained in step 4 was dissolved in 3 ml of methanol and treated with 88 mg (1.05 mmol) of cyclopentanone, 20 mg (0.32 mmol) of sodium cyanoborohydride and one drop of acetic acid. and the mixture was stirred at room temperature. After 48 hours, the TLC [CH2Cl2: MeOH, 9: 1, visualization with Ce (IV)] indicated complete conversion to a new, less polar material. The reaction was partitioned between 300 ml of ethyl acetate and 300 ml of 50% saturated solution of sodium bicarbonate. The organic layer was washed with 2 x 200 ml of water and 200 ml of brine before drying in sodium sulfate, filtering and concentrating. The resulting residue was filtered through a plug of silica gel (CH2Cl2: MeOH, 9: 1) and the resulting product was crystallized from acetonitrile / water to give 153 mg (73%) of compound 12 as colorless needles. Rf 0.50 (CH2Cl2: MeOH, 9: 1), m.p. 145-147 ° C (CH3CN / H2O); MS (FAB) (M + H) + at m / z 999; HRMS m / z (M + H) + calculated 999.5116, observed 999.5110. NMR with 1H (300 MHz, CDCl 3) delta 7.44 (d, J = 2 Hz, 1H), 7.33 (d, J = 8 Hz, 1H), 7.18 (dd, J = 8.2 Hz, 1H), 4.91 (d, J = 4 Hz, 1H), 4.88 (dd, J = 11.2 Hz, 1H), 4.44 (d, J = 7 Hz, 1H), 4.03-3.98 (m, 1H), 3.88-3.76 (m, 2H), 3.73 (d, J = 10 Hz, 1H), 3.68 (s, 1H, 3.65 (d, J = 7 Hz, 1H), 3.49-3.46 (m, 1H), 3.32 (s, 3H), 3.17 (dd, J = 10, 7 Hz, 1H), 3.11 (c, J = 7 Hz, 1H), 3.05 (s, 3H), 3.02-2.95 (m, 2H), 2.93-2.83 (m, 3H), 2.64-2.60 (m, 2H), 2.36 (d, J = 15 Hz, 1H), 2.16 (s, 3H), 2.14 (d, J = 10 Hz, 1H), 1.93-1.75 (series of m, 7H), 1.70- 1.41 (series of m, 7H), 1.41 (s, 3H), 1.38 (s, 3H), 1.33-1.32 (m, 2H), 1.28 (d, J = 6 Hz, 3H), 1.28-1.24 (m, 1H), 1.24 (s, 3H), 1.20 (d, J = 6 Hz, 3H), 1.20 (d, J = 6 Hz, 3H), 1.13 (d, J = 7 Hz, 3H), 1.11 (d, J = 8 Hz, 3 H), 1.00 (d, J = 7 Hz, 3 H), 0.81 (t, J = 7 Hz, 3 H). NMR with 13 C (75 MHz, CDCl 3) delta 216.2, 176.3, 157.1, 139. 3, 132.1, 131.0, 130.2, 130.0, 128.3, 102.9, 96.0, 82.8, 80.1, 78.8, 77.9, 77.7, 76.1, 72.6, 70.2 68.9, 65.7, 63.5, 63.0, 60.3, 50.6, 49.4, 45.5, 45.2, 44.7 , 39.0, 38.9 (2C) 34.8, 33.1, 32.5, 31.5, 30.9, 30.1, 23.7, 23.6, 21.8, 21.4 (2C), 20.1, 18.8, 18.6, 15.9, 14.1, 14.0, 10.2, 8.9.

IR (KBr) a 3440, 2970, 1760, 1740, 1715, 1460, 1380, 1235, 1170, 1070, 1055, 1015, 1000 cm "1. Analysis calculated for C51H80Cl2N2O13: C, 61.24; H, 8.06; N, 2.80; Found: C, 61.07; H, 8.18; N, 2.54.

EXAMPLE 2 11.12- (CYCLIC CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOPROPIL-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYL AMINON-β-O-METHYL-ERYTHROMYCIN A The compound of the title according to the process described in example 1, replacing cyclopentanone with [(1-ethoxycyclopropyl) oxy] trimethylsilane Rf = 0.35 (CH2Cl2: MeOH, 95: 5); mp 258-260 ° C (CH3CN) : IR (KBr) a 3450, 2970, 2940, 1750, 1740, 1730, 1470, 1460, 1380, 1240, 1170, 1070, 1010, 1000 cm. "1 NMR with 1H (300 MHz, CDCI3) delta 7.46 (d. , J = 2 Hz, 1H), 7.36 (d, J = 8 Hz, 1H), 7.20 (dd, J = 8, 2 Hz, 1H), 4.93 (d, J = 4 Hz, 1H), 4.91 (dd) , J = 9, 2 Hz, 1H), 4.45 (d, J = 7 Hz, 1H), 4.08-3.98 (m, 1H), 3.95-3.76 (m, 2H), 3.75 (d, J = 9 Hz, 1H), 3.70 (s, 1H), 3.67 (d, J = 7 Hz, 1H), 3.58-3.48 (m, 1H), 3.34 (s, 3H), 3.20-311 (series of m, 2H), 3.08 (s, 3H), 3.04-2.82 (series of m, 4H), 2.65-2.55 (m, 2H), 2.39 (d, J = 15 Hz, 1H), 2.31 (s, 3H), 2.21 (d, J = 10 Hz, 1H), 1.99-1.81 (series of m, 3H), 1.78-1.75 (series of m, 3H), 1.65-1.50 (series of m, 3H), 1.44 (s, 3H), 1.42-1.38 (m, 1H), 1.40 (s, 3H), 1.32 (d, J = 6 Hz, 3H), 1.27 (s, 3H), 1.25 (d, J = 6 Hz, 3H), 1.23 (d, J = 6 Hz, 3H), 1.16 (d, J = 7 Hz, 3H), 1.11 (d, J = 7 Hz, 3H) , 1.03 (d, J = 7 Hz, 3H), 0.83 (t, J = 7 Hz, 3H), 0.62-0.45 (series of m, 3H), 0.36-0.28 (m, 1H). NMR with 13 C (75 MHz, CDCl 3) delta 216.3, 176.4, 157.2, 139.4, 132.2, 131.1, 130.3, 130.2, 128.4, 103.1, 96.2, 82.8, 80.4, 79.0, 78.0, 77.6, 76.3, 72.7, 70.5, 69.0, 65.8, 64.8 60.5, 50.7, 49.5, 45.6, 45.3, 44.8, 39.2, 39.1, 39.0, 37.0, 37.0, 36.6, 35.2, 32.7, 30.1, 22.0, 21.6, 21.5, 20.2, 18.9, 18.7, 16.1, 14.3, 14.2 , 10.3, 9.1, 7.9, 6.8. MS (APCI) (M + H) + 971; HRMS m / z (M + H) + calculated 971.4803, observed 971.4837. Analysis calculated for C 9H76Cl2N2O13: C, 60.55; H, 7.88; N, 2.88; Found: C, 60.62; H, 7.82; N, 2.88.

EXAMPLE 3 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETI L-3'-Nn-PROPI L-11-DESOXY-11-rCARBOXI - (3.4-DIC LORO FEN ETI LAMIN 0) 1-6-0 - METHYL-ERYTHROMYCIN A The title compound was prepared according to the process described in Example 1, except that cyclopentanone was replaced with propanal. Rf = 0.45 (CHCl3: MeOH: NH4OH, 90: 8: 1); IR (KBr) a 3440, 2970, 2930, 1760, 1735, 1710, 1460, 1380, 1235, 1170, 1065, 1055, 1010, 1000 cm. "1 NMR with 1H (300 MHz, CDCl 3) delta 7.46 (d, J = 2 Hz, 1H), 7.36 (d, J = 8 Hz, 1H), 7.20 (dd, J = 8.2 Hz, 1H), 4.93-4.88 (m, 2H), 4.45 (d, J = 7 Hz, 1H), 4.04-3.99 (m, 1H), 3.88-3.81 (m, 2H), 3.75 (d, J = 9 Hz, 1H), 3.70 (s, 1H), 3.68 (d, J = 8 Hz, 1H ), 3.49-3.48 (m, 1H), 3.34 (s, 3H), 3.22 (dd, J = 10, 7 Hz, 1H), 3.13 (c, J = 7 Hz, 1H), 3.058 (s, 3H) , 3.07-2.82 (series of m, 5H), 2.65-2.29 (series of m, 5H), 2.27 (s, 3H), 2.19 (d, J = 10 Hz, 1H), 1.94-1.48 (series of m, 9H), 1.44 (s, 3H), 1.40 (s, 3H), 1.31 (d, J = 7 Hz, 3H), 1.27 (s, 3H), 1.25-1.13 (m, 2H), 1.23 (d, J = 6 Hz, 3H), 1.22 (d, J = 7 Hz, 3H), 1.16 (d, J = 7 Hz, 3H), 1.12 (d, J = 7 Hz, 3H), 1.03 (d, J = 7 Hz, 3H), 0.91 (t, J = 7 Hz, 2H), 0.8 (t, J = 7 Hz, 3H). NMR with 13C (75 MHz, CDCI3) delta 216.3, 176.4, 157.2, 139.3, 132.2, 131.0 , 130.3, 130.2, 128.4, 102.9, 96.2, 82.8, 80.1, 78.9, 77.9, 77.8, 76.2, 72.6, 70.6, 68.9, 65.8 , 65.6, 60.3, 55.0, 50.7, 49.5, 45.5, 45.3, 44.8, 39.1, 39.2, 39.9, 38.9, 36.9, 34.8, 32.6, 29.5, 21.5, 21.5, 21.4, 21.3, 21.3, 20.2, 18.2, 18.7, 16.0, 14.2, 14.1 , 11.6, 10.2, 9.0. MS (APCI) (M + H) + m / z 972. Analysis calculated for C51H8oCI2N2O13.0.5 H2O: C, 59.86; H, 8.10; N, 2.84; Found: C, 59.93; H, 8.24; N, 2.88.

EXAMPLE 4 CHLORHYDRATE OF 11.12-ICARBA ATO) OF 3'-N-DESMETIL-3'-N-CYCLOBUTYL-11-DESOXY-11-rCARBOXI- (3,4-DICHLOROPHENEYL-AMINO) 1-6-O-METHYL-ERYTHROMYCIN 1 Step 1: The free base of the title compound was prepared according to the process described in Example 1, except cyclopentanone was replaced with cyclobutanone. Rf = 0.55 (CH2Cl2: MeOH, 9: 1); IR (KBr) a 3460, 2930, 1760, 1740, 1710, 1460, 1380, 1235, 1170, 1100, 1060, 1005, 995 cm "1. 1 H NMR (300 MHz, CDCl 3) delta 7.46 (d, J = 2 Hz, 1H), 7.35 (d, J = 8 Hz, 1H), 7.20 (dd, J = 8, 2 Hz, 1H), 4.94-4.88 (m, 2H), 4.45 (d, J = 7 Hz, 1H), 4.04-3.78 (m, 3H), 3.75 (d, J = 10 Hz, 1H), 3.70 (s, 1H), 3.67-3.64 (m, 1H), 3.66 (d, J = 8 Hz, 1H ), 3.64.3.45 (m, 1H), 3.33 (s, 3H), 3.28-3.12 (m, 3H), 3.05 (s, 3H), 3.06-2.82 (m, 4H), 2.65-2.60 (m, 1H) ), 2.49-2.29 (m, 2H), 2.13 (d, J = 10 Hz, 1H), 2.06 (s, 3H), 2.01-1.48 (series of m, 14H), 1.43 (s, 3H), 1.40 ( s, 3H), 1.31 (d, J = 6 Hz, 3H), 1.25 (s, 3H), 1.24 (d, J = 5.9 Hz, 3H), 1.22 (d, J = 5.9 Hz, 3H), 1.16 ( d, J = 8 Hz, 3H), 1.13 (d, J = 8 Hz, 3H), 1.03 (d, J = 7 Hz, 3H), 0.83 (t, J = 7 Hz, 3H). NMR with 13C ( 75 MHz, CDCI3) delta 216.2, 176.3, 157.1, 139.3, 132.2, 131.0, 130.2, 130.0, 128.4, 103.1, 96.1, 82.8, 80.4, 78.9, 77.9, 77.8, 76.3, 72.7, 70.1, 68.9, 65.8, 60.4, 60.1.56.8, 50.6, 49.4, 45.6, 45.3, 44.8, 39.1, 39.0, 34.9, 32.7, 31.0 , 29.7, 28.6, 28.2, 21.9, 21.5, 21.4, 20.2, 18.9, 18.7, 16.0, 14.2, 14.1, 14.0, 10.2, 9.0. MS (FAB) (M + H) + at m / z 985. HRMS m / z (M + H) + calculated, 985.49.59, observed 985.4949. Analysis calculated for C5? H 8Cl2N2? 13.0.75 H2O C, 60.55; H, 7.92; N, 2.76; Calculated: C, 60.56; H, 7.97; N, 3.02.

Step 2: Preparation of the HCl salt of 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11-rcarboxy. { (3,4-dichlorophenethylamino) 1-6-O-methyl-erythromycin A. 160 mg (0.16 mmol) of 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-N- was dissolved. Cyclobutyl-11-deoxy-11- [carboxy- (3,4-dicylo-phenethylamino)] - 6-O-methyl-erythromycin A in 5 ml of EtOAc and treated with 0.16 ml of 1 H of HCl / ether. The mixture was stirred for 0.5 hour at room temperature during which a white precipitate formed. The precipitate was filtered to give 125 mg of 11,12- (cyclic carbamate) hydrochloride of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy- (3,4- dichlorophenethylamino)] - 6-O-methyl-erythromycin A. MS (CI) (M) + at m / z 985. Analysis calculated for C5oH79Cl3N2O13.0.5 H2O: C, 58.21; H, 7.81; N, 2.71; Cl, 10.31; Found: C, 58.24; H, 7.90; N, 2.66; Cl, 10.06. RP-HPLC Rf = 22.0 min (45-90% CH3CN, 1% gradient min). EXAMPLE 5 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CYCLOHEXYL-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENEYL-AMINON-β-O-METHYL-ERYTHROMYCINE A Prepared the title compound according to the procedure described in Example 1, except that the cyclopentanone was replaced with cyclohexanone The crude product was purified on a column of silica gel (CH2Cl2: MeOH, 9: 1) to yield an amorphous solid Rf = 0.5 (CH2Cl2: MeOH, 9: 1). IR (KBr), a 3440, 2970, 2930, 1760, 1730, 1705, 1455, 1380, 1235, 1100, 1070, 1010, 1000 cm -1 NMR with 1H (300 MHz, CDCl 3) delta 7.46 (d, J = 2 Hz, 1H), 7.35 (d, J = 8 Hz, 1H), 7.20 (dd, J = 8.2 Hz, 1H), 4.93 (d, J = 5 Hz, 1H), 4.91 (dd, J = 11.2 Hz, 1H), 4.46 (d, J = 6 Hz, 1H), 4.08-3.98 (m, 1H), 3.88-3.80 (m, 2H), 3.76 (d, J = 10 Hz, 1H), 3.70 (s, 1H), 3.68 (d, J = 8 Hz, 1H), 3.50-3.46 (m, 1H), 3.34 (s, 3H), 3.17-3.11 (series of m, 2H), 3.08 (s, 3H), 3.04-2.82 (m, 5H), 2.61-2.32 (m, 2H), 21.39 (d, J = 15 Hz, 1H), 2.25 (s) , 3H), 2.19 (d, J = 10 Hz, 1H), 1.94-1.48 (series of m, 17H), 1.44 (s, 3H), 1.40 (s, 3H), 1.36-1.34 (m, 2H), 1.31 (d, J = 7 Hz, 3H), 1.27 (s, 3H), 1.23 (d, J = 6 Hz, 3H), 1.22 (d, J = 6 Hz, 3H), 1.16 (d, J = 7 Hz, 3H), 1.13 (d, J = 8 Hz, 3H), 1.03 (d, J = 7 Hz, 3H), 0.83 (t, J = 7 Hz, 3H). NMR with 13C (75 MHz, CDCI3) delta 216.2, 176.3, 157.1, 139.3, 132.1, 131.0, 130.2, 130.1, 128.4, 103.9, 96.2, 82.8, 80.1, 78.9, 77.9 (2C), 76.2, 72.6, 70.4, 68.9 , 65.8, 63.0, 61.2, 60.3, 50.7, 49.5, 45.5, 45.3, 45.3, 44.8, 39.2, 39.0, 38.9, 34.5, 33.5, 33.2, 32.6, 31.8, 31.7, 30.9, 26.0, 25.9, 21.9, 21.5, 20.1, 18.9, 18.7 , 16.0, 14.2, 14.1, 10.2, 8.9. MS (FAB) (M + H) + at m / z 1013; HRMS m / z (M + H) + calculated, 1013.5272, observed 1013.5242.

Analysis calculated for C52H82Cl2N2O13: C, 61.58; H, 8.15; N, 2.76; Found: C, 61.31; H, 8.16; N, 2.76.

EXAMPLE 6 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETLL-3'-N- ISOVALERIL-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENEYL-AMINO) 1-6-O-METHYL-ERYTHROMYCIN A Prepared the title compound according to the method described in Example 1, but replacing the cyclopentanone with isovaleraldehyde. The product was purified on a column of silica gel (CHCl3: MeOH: NH4OH, 90: 8: 1), to yield an amorphous solid. • Rf = 0.33 (CHCl3: MeOH, 94: 6); IR (KBr) a 3435, 2960, 2940, 1750, 1735, 1460, 1165, 1105, 1065, 1055, 1030, 1010 cm1. NMR with 1H (300 MHz, CDCl 3) delta 7.46 (d, J = 2 Hz, 1H), 7.34 (d, J = 8 Hz, 1H), 7.19 (dd, J = 8.2 Hz, 1H), 4.92-4.88 ( series of m, 2H), 4.44 (d, J = 7 Hz, 1H), 4.03-4.00 (m, 1H), 3.87-3.81 (m, 2H); 3.75 (d, J = 10 Hz, 1H), 3.69 (s, 1H), 3.67 (d, J = 8 Hz, 1H), 3.64 (broad singlet, 1H), 3.50-3.47 (m, 1H), 3.33 ( s, 3H), 3.21-3.17 (m, 1H), 3.14-3.11 (m, 1H), 3.07 (s, 3H), 3.05-2.97 (series of m, 2H), 2.94-2.86 (series of m 2H) , 2.64-2.62 (m, 1H), 2.57-2.52 (m, 1H), 2.38 (d, J = 14 Hz, 1H), 2.33-2.30 (m, 1H), 2.23 (s, 3H), 2.18 (d) , J = 10, 1H), 1.93-1.86 (series of m, 2H), 1.77-1.51 (series of m, 7H), 1.43 (s, 3H), 1.39 (s, 3H), 1.38-1.21 (series of m, 14H), 1.15 (d, J = 7 Hz, 3H), 1.12 (d, J = 8 Hz, 3H), 1.02 (d, J = 7 Hz, 3H), 0.90 (d, 6H), 0.82 ( t, J = 7 Hz, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.1, 176.4, 157.2, 139.3, 132.2, 131.0, 130.1, 128.4, 103.0, 96.1, 82.8, 80.2, 78.9, 77.9, 77.9, 76.22, 72.63, 70.6, 69.0, 65.8, 65.5, 60.3, 51.6, 50.6, 49.5.45.3, 44.8, 39.1, 39.0, 39.0, 39.5, 37.5, 36.8, 34.8, 32.6, 29.6, 29.4, 26.7, 22.7, 22.7, 22.7, 21.7, 21.4, 20.1, 18.9, 18.7, 16.0, 14.2, 14.1, 10.2, 9.0. MS (FAB) (M + H) + at m / z 1001. Analysis calculated for C5? H82Cl2N2O130.5 H2O: C, 60.58; H, 8.27; N, 2.77; Found: C, 60.46; H, 8.11; N, 2.78.

EXAMPLE 7 11,12-CYCLIC FCARBAMATE) OF 3'-N-DESMETIL-3'-N- (3-METHYLTHOPROPYL) -11-DESOXY-11-rCARBOXY- (3,4- DICHLOROFENETILAMI O) 1-6-O-METHYL- ERYTHROMYCIN A The compound was prepared according to the method described in Example 1, but replacing the cyclopentanone with 3-methylthiopropionaldehyde. The crude product was purified on a column of silica gel (CHCl3: MeOH: NH4OH, 90: 8: 1) to yield an amorphous solid. IR (KBr) a 3460, 2970, 2930, 1750, 1460, 1235, 1165, 1125, 1100, 1065, 1050, 1010, 995 crn. "1 NMR with 1H (300 MHz, CDCl 3) delta 7.44 (d, 1H) , 7.34 (d, 1H), 7.19 (dd, 1H), 4.91-4.87 (series of m, 2H), 4.43 (d, 1H), 4.02- 3.99 (m, 1H), 3.86-3.81 (m, 2H) , 3.74 (d, 1H), 3.69 (s, 1H), 3.66 (d, 1H), 3.50-3.47 (m, 2H9, 3.32 (s, 3H), 3.22-3.19 (m, 1H), 3.13-3.10 ( m, 1H), 3.06 (s, 3H), 3.04-2.99 (series of m, 2H), 2.91-2.87 (series of m, 2H), 2.64-2.62 (series of m, 2H), 2.54-2.43 (series of m, 4H), 2.37 (d, 1H), 2.24 (s, 3H), 2.20 (d, 1H), 2.09 (s, 2H), 1.99 (d, 1H), 1.90-186 (series of m, 2H), 1.78-1.73 (series of m, 4H), 1.65 (d, 1H) , 1.60-1.50 (series of m, 2H), 1.42 (s, 3H), 1.39 (s, 3H), 1.29 (d, 3H), 1.25-1.20 (series of m, 10H), 1.14 (d, 3H) , 1.11 (d, 3H), 1.02 (d, 3H), 0.82 (t, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.3, 176.4, 157.1, 139.3, 132.1, 131.0, 130.2, 130.1, 128.4, 102.9, 96.1, 82.8, 80.1, 78.9, 77.8, 76.2, 72.6, 70.7, 68.8, 65.7, 65.7, 60.3, 52.2, 50.6, 49.5, 45.5, 45.3, 44.8, 39.1, 39.2, 38.9, 36.7, 34.8, 32.6, 32.0, 29.5, 27.5, 21.9, 21.4, 21.4, 20.1, 18.8, 18.6, 16.0, 15.6, 14.2, 14.1, 10.2, 8.9. MS (FAB) (M + H) + at m / z 1019. Analysis calculated for C5oH8oCl2N2O13S: C, 58.87; H, 7.90; N, 2.75. Found: C, 58.81; H, 7.75; N, 2.96.

EXAMPLE 8 11.12- (CHLORIC CARBAMATE) OF 3'-N-DESMETI L-3'-N- (3-TETRAHYDROTIENIL) -11-DESOXY-11-rCARBOXY- (3,4- DICLOROFENETILAMIN? N-6-O-METIL-ERYTHROMYCIN) A The title compound was prepared according to the method described in Example 1, but replacing the cyclopentanone with 1,1,14,4-tetrahydrothiophen-3-one The product was purified on a column of silica gel 8CHCI3: MeOH: NH 4 OH, 90: 8: 1) to produce an amorphous solid. Rf = 0.45 (CHCl3: MeOH, 94: 6); (KBr) a 3440, 2965, 2930, 1760, 1735, 1460, 1165, 1130, 1100, 1065, 1050, 1030, 1010, 1000 cm -1 NMR with 1H (300 MHz, CDCl 3) delta 7.45 (d, J = 2 Hz, 1H), 7.34 (d, J = 8 Hz, 1H), 7.19 (dd, J = 8, 2 Hz, 1H), 4.92- 4.88 (series of m, 2H), 4.46 (d, J = 7 Hz, 1H), 4.02-3.99 (m, 1H), 3.89-3.77 (m, 2H), 3.74 (d, J = 10 Hz, 1H) , 3.69 (s, 1H), 3.52-3.49 (m, 1 H) 3.32 (d, J = 3 Hz, 3H), 3.30-3.26 (m, 1H), 3.21 (dd, J = 10, 7 Hz 1H) , 3.12 (c, J = 7 Hz, 1H), 3.06 (s, 3H), 3.05-2.82 (series of m, 7H) 2.78-2.61 (series of m, 3H), 2.36 (d, J = 15 Hz, 1H), 2.28 (s, 3H) 2.19-2.14 (series of m, 2H), 1.93-1.49 (series of m, 9H), 1.42 (s, 3H) 1.39 (s, 3H), 1.38-1.21 (series of m, 13H), 1.15 (d, J = 7 Hz, 3H) 1. 10 (d, J = 8 Hz, 3H), 1.02 (d, J = 7 Hz, 3H), 0.82 (t, J = 7 Hz, 3H). NMR with 13C (75 MHz, CDCI3) delta 216.2, 176.3, 157.1 139. 2, 132.1, 131.0, 130.2, 130.1, 128.4, 102.8, 96.1, 96.1, 82.8 80. 3, 80.2, 78.9, 77.9, 77.8, 76.2, 72.7, 70.6, 70.5, 68.7, 68.7, 66.7 65.8, 65.8, 65.8, 63.9, 63.5, 63.5, 60.3, 50.6, 49.5, 49.5, 45.5, 45.2, 45.2, 44.8, 39.0, 39.0, 38.9, 34.8, 34.2, 33.4, 33.2, 33.0, 32.6, 32.4.31.8 31.3, 27.9, 27.9, 21.9, 21.4, 21.4, 20.1, 18.8, 18.6, 16.0, 14.2, 14.1 10.2, 9.0, 9.0 (more signs than real carbons, due to a mixture of diastereoisomers). MS (FAB) (M + H) + at m / z 1017.

Analysis calculated for C5H78CI2N2O13S: C, 58.99; H, 7.72; N, 2.75; Found: C, 58.85; H, 7.93; N, 2.67.

EXAMPLE 9 11.12- (Cyclic CARBAMATQ) OF 3'-N-DESMETIL-3'-N- (3,4-DI ETHYLCYCLOPENET) -11-DESOXY-11-rCARBOXY- (3,4-DICHLORQ-FENETHYLAMINE) 1-6-Q-METHYL -ERITHROMYCIN A The title compound was prepared according to the method described in Example 1, but replacing the cyclopentanone with 3,4-dimethylcyclopentan-1 -one. The product was purified on a column of silica gel (CHCl3: MeOH: NH4OH, 90: 8: 1) to yield an amorphous solid. IR (KBr) a 3450, 2970, 2950, 1750, 1735, 1460, 1170, 1110, 1070, 1045, 1015, 1000 cm. "1 NMR with 1H (300 MHz, CDCI3) delta 7.45 (d, J = 2 Hz , 1H), 7.34 (d, J = 8 Hz, 1H), 7.18 (dd, J = 8, 2 Hz, 1H), 4.93-4.92 (m, 1H), 4.89 (dd, J = 2, 10, 1H ), 4.45 (t, J = 7 Hz, 1H), 4.03 (4.00 (m, 1H), 3.88-3.77 (m, 2H), 3.74 (d, J = 10 Hz, 1H), 3.69 (s, 1H) , 3.66 (d, J = 7 Hz, 1H), 3.50-3.47 (m, 1H), 3.33 (s, 3H), 3.19-3.10 (series of m, 2H), 3.066 (d, J = 7 Hz, 1H ), 3.50-3.47 (m, 1H), 3.33 (s, 3H), 3.19-3.10 (series of m, 2H), 3.06 (s, 3H), 3.04-2.94 (series of m, 3H), 2.92-2.84 (series of m, 2H), 2.65.2.55 (series of m, 2H), 2.36 (d, J = 15 Hz, 1H), 2.17-2.14 (series of m, 4H), 1.94-1.74 (series of m, 6H), 1.63-1.44 (series of m, 4H), 1.42 (s, 3H), 1.39 (s, 3H), 1.30 (d, J = 6 Hz, 3H), 1.27-1.17 (series of m, 10H) , 1.14 (d, J = 7 Hz, 3H), 1.12 (d, J = 8 Hz, 3H), 1.02 (d, J = 7 Hz, 3H), 0.98 (d, J = 6 Hz, 3H), 0.96 -0.94 (m, 3H), 0.82 (t, J = 7 Hz, 3H) MS (APCI) (M + H) + at m / z 1027. Analysis calculated p for C5? H82CI2N2013: C, 61.91; H, 8.23; N, 2.72. Found: C, 61.63; H, 8.22; N, 2.69.

EXAMPLE 10 11.12- (Cyclic CARBAMATQ) 3'-N-DESMETIL-3'-N-ISOPROPIL-11-DESOXY-11-rCARBOXY- (aa-CICLOPROPYL-3,4-DICHLOROPHENEYL-AMIN? N-6-O-METHYL -ERITRQMICIN A Step 1: Preparation of aa-cyclopropyl-3,4-dichlorophenethylamine 25 g (134 mmol) of 3,4-dichlorophenylacetonitrile in 50 ml of anhydrous ether was added dropwise to a suspension of . 5 g (268 mmol) of NaNH2 in 200 ml of ether. Upon completion of the addition, the reaction mixture was heated to reflux temperature for four hours, then cooled to 0 ° C. A solution of 11 ml (134 mmol) of 1-bromo-2-chloroethane in 25 ml of ether, at 0 ° C, was added dropwise to the reaction mixture.; after which it was heated to reflux temperature for another 18 hours. The reaction mixture was then cooled and carefully quenched with water, before dividing between 200 ml of EtOAc and 200 ml of water. The organic layer was washed with 100 ml of brine, before drying over sodium sulfate, filtering and concentrating. The desired product was obtained by distillation in a rotary oven (165 ° C, | 10 torr), as a colorless oil, which solidified upon standing. The solid was crystallized from MeOH / water to give 11.75 g (44%) of α, α-cyclopropyl-3,4-dichlorophenyl acetonitrile, MS (Cl) (M) + at m / z 211. Analysis calculated for C 10 H 7 Cl 2 N: C, 56.63; H, 3.21; N, 6.60; Found: C, 56.48; H, 3.27; N, 6.55. 12.3 g (57.8 mmol) of α, α-cyclopropyl-3,4-dichlorophenylacetonitrile was added dropwise to a suspension of 2.2 g (58.0 mmol) of lithium aluminum hydride in 50 ml of THF at such a rate that maintain a moderate reflux. Upon completion of the addition, the reaction was stirred at room temperature for four hours, under nitrogen. After this period of time the reaction is quenched by the sequential addition, dropwise, of 2 ml of water, 2 ml of 15% aqueous NaOH and 6 ml of water. The reaction mixture was filtered and the insoluble solid was washed with more ether. The combined filtrates were dried in sodium sulfate, filtered and concentrated to give a, α-cyclopropyl-3,4-dichlorophenethylamine as a colorless oil. MS Cl (M + H) + at m / z 216; RP-HPLC Rf = 4.8 min (40-70%) of CH3CN0, 1% gradient min). 1 H NMR (300 MHz, CDCl 3, delta 7.42 (d, J = 2 Hz, 1H), 7.37 (d, J = 8 Hz, 1H), 7.37 (d, J = 8 Hz, 1H), 7.17 (dd, J = 8, 2 Hz, 1H), 2.78 (s, 2H), 1.17 (s, 2H), 0.81-0.77 (m, 4H).

Step 2. 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-iso-ropil-11-deoxy-11-rcarboxy- (aa-cyclopropyl-3,4-dichlorophenethylamine) l- 6-Q-methyl-erythromycin A. The compound was prepared according to the method described in Example 1, but replacing 3,4-dichlorophenethylamine with a, -cyclopropyl-3,4-dichlorophenethylamine from step 1 above, and the cyclopentanone by acetone. The crude product was crystallized from acetonitrile / water; p.f. 210-212 ° C (CH3CN / H2O); Rf = 0.95 (CHCl3: MeOH: NH4OH, 90: 8: 1); HPLC Rt = 19.7 min (C-18) column 50-80% CH3CN, gradient 1% min; IR (KBr) a 3440, 2960, 2930, 2880, 1760, 1730, 1710, 1460, 1440, 1380, 1230, 1165, 1100, 1060, 1010, 1000 cm "1. 1 H NMR (300 MHz, CDCl 3) delta 7.64 (d, J = 2 Hz, 1H), 7.44 (dd, J = 8, 2 Hz, 1H), 7.33 (d, J = 8 Hz, 1H), 4.98 (d, J = 4 Hz, 1H); 4.68 (dd, J = 11.3 Hz, 1H), 4.47 (d, J = 7 Hz, 1H), 4.35 (d, J = 15 Hz, 1H), 4.07-4.01 (m, 1H), 3.77-3.67 (m , 2H), 3.77 (s, 1H), 3.73 (d, J = 7 Hz, 1H), 3.68 (d, J = 7 Hz, 1H), 3.53-3.48 (m, 1H), 3.34 (s, 3H) , 3.32-3.13 (m, 2H), 3.19 (s, 3H), 3.06 (c, J = 8 Hz, 1H), 2.95-2.87 (m, 2H), 2.60-2.56 (m, 2H), 2.40 (d , J = 15 Hz, 1H), 2.20 (s, 3H), 2.18 (d, J = 10 Hz, 1H), 1.90 (t, J = 7 Hz, 1H), 1.77-1.56 (series of m, 7H) , 1.42-1.21 (m, 2H), 1.42 (s, 3H), 1.33 (d, J = 6 Hz, 3H), 1.32 (s, 3H), 1.27 (s, 3H), 1.24 (d, J = 6 Hz, 3H), 1.22 (d, J = 6 Hz, 3H), 1.14-1.04 (series of d, 12H), 0.99-0.94 (m, 1H), 0.91 (d, J = 7 Hz, 3H), 0.69 (t, J = 7 Hz, 3H), 0.63-0.58 (m, 1H). NMR with 13C (75 MHz, CDCI3) delta 216.8, 175.3, 157.5, 139.3, 132.1, 131.5, 130.2 , 130.0, 129.5, 102.9, 96.2, 82.4, 80.2, 78.8, 78.1, 78.0, 76.6, 72.7, 70.5, 68.9, 65.8, 62.9, 61.9, 52.6, 51.3, 50.3, 49.5, 45.6, 45.0, 39.4, 39.3, 38.7 , 34.9, 33.1, 30.8, 24.1, 21.9, 21.5, 21.1, 20.5, 20.2, 19.5, 18.7, 16.1, 15.2, 14.5, 12.0, 10.9, 9.7, 9.1. MS (FAB) (M + H) + at m / z 999. Analysis calculated for C51H8oCI2N2O13: C, 61.24; H, 8.06; N, 2.80; Found: C, 61.12; H, 8.28; N. 2.74 EXAMPLE 11 11.12- (CYCLIC CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOBUTIL-11-DESOXY-11-rCARBOXI- (aa-CICLOPROPIL-3,4- DICHLOROFENETILAMIN? N-6-O-METHYL-ERYTHROMYCIN A) The title compound was prepared according to the method described in Example 10, but replacing the acetone with cyclobutanone The crude product was crystallized from acetonitrile / water, mp 148-150 ° C (CH 3 CN / HzO); Rf = 0.6 ( CHCl3: MeOH: NH4OH, 90: 8: 1); HPLC Rt = (C-18) 19.7 min 50-80% CH3CN, 1% / min gradient-IR (KBr) a 3440, 2970, 2930, 1760 , 1735, 1710, 1460, 1380, 1230, 1170, 1100, 1060, 1010, 1000 cm. "1 NMR with 1H (300 MHz, CDCl 3) delta 7.64 (d, J = 2 Hz, 1H), 7.44 (dd, J = 8.2 Hz, 1H), 7.33 (d, J = 8 Hz, 1H), 4.99 (d, J = 5 Hz, 1H), 4.69 (dd, J = 11, 3 Hz, 1H9, 4.47 (d, J = 8 Hz, 1H), 4.35 (d, J = 15 Hz, 1H), 4.06-4.01 (m, 1H), 3.77 (s, 1H), 3.74-3.72 (m, 2H); 3. 69 (d, J = 4 Hz, 1H), 3.63-3.60 (s, broad, 1H), 3.52-3.46 (m, 1H), 3.34 (s, 3H), 3.22-3.12 (m, 3H), 3.19 ( s, 3H), 3.04 (t, J = 10 Hz, 1H), 2.96-2.90 (m, 1H), 2.65-2.55 (m, 1H), 2.50-2.40 (m, 1H), 2.40 (d, J = 15 Hz, 1H), 2.13 (d, J = 10 Hz, 1H), 2.06 (s, 3H), 1.95-1.53 (series of m, 12H), 1.45-1.32 (m, 1H), 1.43 (s, 3H ), 1.33 (s, 3H), 1.33 (d, J = 6 Hz, 3H), 1.27 (s, 3H), 1.22 (d, J = 6 Hz, 6H), 1.14 (d, J = 7 Hz, 3H ), 1.12 (d, J = 7 Hz, 3H), 1.07 (d, J = 8 Hz, 3H), 1.00-0.96 (m, 1H), 0.91 (d, J = 7 Hz, 3H), 0.69 (t ', J = 7 Hz, 3H), 0.64-0.58 (m, 1H). NMR with 13 C (75 MHz, CDCl 3) delta 216.8, 175.3, 157.4, 143.5, 131.7, 131.5, 130.2, 129.9, 129.4, 102.9, 96.1, 82.4, 80.3, 78.6, 77.9, 76.7, 72.7, 70.1, 68.9, 65.7, 61.8, 60.1, 56.8, 51.3, 50.3, 49.5, 45.6, 45.0, 39.3, 39.2, 38.6, 34.9, 31.0, 29.9, 28.5, 28.1, 24.0, 21.5, 21.5, 20.2, 19.5, 18.7, 16.0, 15.2, 14.5, 14.1, 12.0, 10.9, 9.7, 9.1. MS (APCI) (M + H) + at m / z 1011 with 2-Cl. Analysis calculated for C52H8oCI2N2013: C, 61.70; H, 7.96; N, 2.76; Found: C, 61.67; H, 7.89; N, 2.46.

EXAMPLE 12 11.12- (CYCLE CARBAMATE OF 3'-N-DESMETLL-3'-N-CICLOPENTIL-11-DESOXY-11-rCARBOXI- (aa-CICLOPROPIL-3,4-DICHLOROFENETILAMIN? N-6-O-ERYTHROMYCIN A) prepared the compound according to the method described in Example 10, replacing the acetone with cyclopentanone The crude product was crystallized from acetonitrile / water, mp 175-178 ° C (CH3CN / H2O); Rf = 0.65 (CHCl3: MeOH: NH4OH, 90: 8: 1). IR (MIC) a 3480, 2960, 2880, 1755, 1740, 1715, 1460, 1380, 1230, 1170, 1070, 1060, 1015, 1000 cm1. 'NMR with H (300 MHz, CDCl 3) delta 7.64 (d, J = 2 Hz, 1H), 7.45 (dd, J 0 9, 2 Hz, 1H), 7.33 (d, J = 9 Hz, 1H), 4.99 (d, J = 5 Hz, 1H); 4.69 (dd, J = 11.3 Hz, 1H), 4.48 (d, J = 7 Hz, 1H), 4.35 (d, J = 15 Hz, 1H), 4.07-4.02 (m, 1H), 3.78 (s, 1H) ), 3.75-3.68 (m, 4H), 3.55-3.45 (m, 1H), 3.35 (s, 3H), 3.22-3.10 (m, 2H), 3.19 (s, 3H), 3.05 (t, J = 10 Hz, 1H), 2.96-2.88 (m, 2H), 2.70-2.58 (m, 2H), 2.40 (d, J = 15 Hz, 1H), 2.18 (s, 3H), 2.15 (d, J = 10 Hz , 1H), 1.94-1.58 (series of m, 14H), 1.43 (s, 3H), 1.34 (d, J = 5 Hz, 3H), 1.33 (s, 3H), 1.28 (s, 3H), 1.25 ( d, J = 5 Hz, 3H), 1.23 (d, J = 4 Hz, 3H), 1.15 (d, J = 3 Hz, 3H), 1.12 (d, J = 4 Hz, 3H), 1.08-1.06 ( m, 3H), 1.00-0.96 (m, 2H), 0.91 (d, J = 7 Hz, 3H), 0.70 (t, J = 7 Hz, 3H), 0.64-0.59 (m, 2H). NMR with 13 C (75 MHz, CDCl 3) delta 216.8, 175.3, 157.1, 143.5, 131.7, 131.5, 130.1, 129.9, 129.4, 102.9, 96.1, 82.4, 80.2, 78.7, 77.9, 76.7, 72.6, 70.3, 68.9.65.7, 63.0, 61.8, 51.4, 50.3, 49.5, 45.7, 45.0, 39.3, 39.2, 38.6, 34.5, 33.2, 31.2, 31.7, 31.5, 23.5, 23.5, 23.7, 23.7, 21.2, 21.5, 20.2, 19.5, 19.5, 19.5, 19.2, 19.2, 16.0, 15.1, 14.5, 12.0, 10.9, 9.7, 9.0. MS (FAB) (M + H) + at m / z 1025 Analysis calculated for C53H82Cl2N2O13: C, 62.03; H, 8.05; N, 2.72; Found: C, 61.86; H, 7.86; N, 2.52.

EXAMPLE 13 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETI L-3'-N-CYCLOHEXYL-11-DESOXY-11-rCARBOXY-aa-CICLOPROPYL-3,4-DICHLOROFENETILAMINO) 1-6-O-METHYL -ERITHROMYCIN The compound was prepared according to the method described in Example 10, but replacing the acetone with cyclohexanone. The crude product was crystallized from hexane; p.f. 210-212 ° C; Rf = 0.80 (CHCl3: MeOH: NH4OH, 90: 8: 1); IR (KBr) a 3440, 2965, 1770, 1760, 1735, 1710, 1460, 1380, 1230, 1165, 1100, 1055, 1010, 1000 cm NMR with 1H (300 MHz, CDCl3) delta 7.63 (d, J = 2 Hz, 1H), 71.45 (dd, J = 9, 2 Hz, 1H), 7.33 (d, J = 9 Hz, 1H), 4.98 (d, J = 5 Hz, 1H), 4.68 (dd, J = 11 , 3 Hz, 1H), 4.47 (d, J = 7 Hz, 1H), 4.35 (d, "J = 5 Hz, 1H), 4.07-4.02 (m, 1H), 3.77-3.67 (m, 2H), 3.77 (s, 1H), 3.73 (d, J = 7 Hz, 1H), 3.69 (d, J = 7 Hz, 1H), 3.53-3.48 (m, 1H), 3.35 (s, 3H), 3.32-3.11 (m, 2H), 3.19 (s, 3H), 3.05 (t, J = 10 Hz, 1H), 2.95-2.90 (m, 2H), 2.60-2.52 (m, 2H), 2.43-2.38 (m, 2H) ), 2.36 (d, J = 15 Hz, 1H), 2.25 (s, 3H), 2.20 (d, J = 10 Hz, 1H), 1.93-1.56 (series of m, 12H), 1.43-1.28 (series of m, 4H), 1.43 (s, 3H), 1.34 (d, J = 5 Hz, 3H), 1.32 (s, 3H), 1.28 (s, 3H), 1.24 (d, J = 5 Hz, 3H), 1.22 (d, J = 4 Hz, 3H), 1.15-1.05 (series of m, 3H), 1.14 (d, J = 3 Hz, 3H), 1.11 (d, J = 4 Hz, 3H), 1.08-0.96 (m, 1H), 0.91 (d, J = 7 Hz, 3H), 0.69 (t, J = 7 Hz, 3H), 0.64-0, .57 (m, 1H). NMR with 13C (75 MHz, CDCl3 ) delta 216.8, 175.3, 157.1, 143.6, 131.7, 131.5, 130.1, 129.4, 102.9, 96.3, 82.4, 80.2, 78.8, 78.1, 78.0, 77.2, 76.8, 72.6, 70.5, 68.9, 65.8, 63.0, 61.9, 61.2, 51.3, 50.3, 49.5, 45.6, 45.1, 39.4, 38.7, 34.9, 33.6, 31.9, 31.8, 30.9, 25.9, 24.0, 21.9, 21.5, 21.4, 20.3, 19.5, 18.7, 16.1, 15.2, 14.5, 12.0, 10.9, 9.7, 9.1. MS (ESI) (M + H) + at m / z 1039. Analysis calculated for C54H84Cl2O13: C, 62.35; H, 8.14; N, 2.69. Found: C, 62.45; H, 8.16; N, 2.67- EXAMPLE 14 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-NN-PROPYL-11-DESOXY-11-rCARBOXY- (3,4-DIOXOLANOFENETILAMINO) 1-6-O-METHYL- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 3, but replacing 3,4-dichlorophenethylamine with 3,4-dioxolanophenethylamine. The desired product crystallized from CH3CN / water, Rf = 0.31 (8% MeOH / DCM + 1% NH4OH); IR (KBr) a 3440, 2960, 2940, 2870, 18745, 1725, 1710, 1500, 1485, 1455, 1440, 1420, 1375, 1320, 1280, 1230, 1165, 1120, 1100, 1070, 1050, 1010, 995 cm "1. NMR with 'H (300 MHz, CDCl 3) delta 6.86-6.71 (series of m, 3H), 5.91 (s, 2H), 4.97 (dd, J = 10.8, 2.0 Hz, 1H), 4.91 (d. , J = 4.8 Hz, 1H), 4.06-3.96 (m, 1H), 3.86-3.73 (series of m, 3H), 3.70 (s, 1H), 3.66 (d, J = 7.5 Hz, 1H), 3.53-3.43 (m, 1H), 3.33 (s, 3H), 3.24-3.10 (m, 2H), 3.08 (s, 3H), 3.08-2.74 (series of m, 5H), 2.69-2.58 (m, 1H), 2.55-2.40 ( m, 2H), 2.38 (d, J = 15.3 Hz, 1H), 2.34-2.25 (m, 1H), 2.23 (s, 3H), 2.19 (d, J = 10.5 Hz, 1H), 2.00-1.85 (m , 2H), 1.80-1.74 (m, 2H), 1.71-1.44 (series of m, 7H), 1.43 (s, 3H), 1.40 (s, 3H), 1.30 (d, J = 6.4 Hz, 3H), 1.26 (s, 3H), 1.24-1.20 (m, 6H), 1.15 (d, J = 7.1 Hz, 3H), 1.12 (d, J = 7.5 Hz, 3H), 1.02 (d, J = 7.1 Hz, 3H ), 0.90 (t, J = 7.5 Hz, 3H), 0.84 (t, J = 7.1 Hz, 3H). NMR with 3C (75 MHz, CDCl 3) delta 216.1, 176.3, 157.2, 147. 5, 145.9, 132.8, 121.9, 109.5, 108.2, 103.0, 100.6, 96.2, 82.7, 80.2, 78.9, 78.0, 77.9, 76.3, 72.7, 70.7, 69.0, 65.8, 65.6, 60.5, 55.1, 50. 7, 49.5, 45.5 (2C), 45.3, 39.2 (2C), 39.1.36.9 34.9, 33.2, 29.5, 22. 0, 21.5, 21.4, 20.2, 18.9, 18.7, 16.0, 14.3, 14.1, 11.6, 10.3, 9.0: MS (FAB) (M + H) + at m / z 949. Analysis calculated for C5oH8oN2O? 5: C, 63.27; H, 8.49; N, 2.95; Found: C, 63.07; H, 8.65; N, 2.84.

EXAMPLE 15 11.12- (Cyclic CARBAMATE OF 3'-N-DESMETIL-3'-N-CICLOPENTIL-11-DESOXY-rCARBOXI- (3,4-DIOXOLANOFENEYL-AMINO) 16-O-METHYL-ERYTHROMYCIN A The title compound of according to the method described in Example 1, but replacing 3,4-dichlorophenethylamine with 3,4-dioxolanophenethylamine MS (FAB) (M + H) + at m / z 975.

EXAMPLE 16 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-NN-PROPYL-11-DESOXY-11-rCARBOXY- (4-CHLORO-3-FOUOROFENETILAMINO) 1-6-O-METHYL- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 3, but replacing 3,4-dichlorophenethylamine with 4-chloro-3-fluorophenethylamine. The desired product crystallized from CH3CN / water, m.p. 217-19 ° C (CH 3 CN / water). IR (KBr) a 3440, 2965, 2940, 2880, 2830, 1755, 1730, 1710, 1580, 1490, 1460, 1425, 1380, 1360, 1325, 1285, 1235, 1170, 1130, 110, 1070, 1055, 1015 , 1000 cm "1. NMR with 1H (300 MHz, CDCl 3) delta 732-7.26 (m, 1H), 7.16 (dd, J = 10.2, 2.1 Hz, 1H), 7.07 (dd, J = 8.1, 1.3 Hz, 1H), 4.93-4.88 (m, 2H), 4.45 (d, J = 7.2 Hz, 1H), 4.06-3.96 (m, 1H), 3.92-3.77 (m, 2H), 3.74 (d, J = 9.2 Hz , 1JH), 3.69 (s, 1H), 3.67 (d, J = 7.4 Hz, 1H), 3.54-3.44 (m, 1H), 3.33 (s, 3H), 3.27-3.08 (series of m, 2H), 3.07 (s, 3H), 3.06-2.82 (series of m, 5H), 2.68-2.41 (series of m, 3H), 2.37 (d, J = 15.3, Hz, 1H), 2.37-2.27 (m, 1H9, 2.27 (s, 3H), 2.18 (d, J = 9.8 Hz, 1H), 1.98-1.83 (m, 2H), 1.80-1.46 (series of m, 8H), 1.43 (s, 3H), 1.40 (s, 3H), 1.30 (d, J = 6.1 Hz, 3H), 1.26 (s, 3H), 1.23 (d, J = 7.1 Hz, 3H), 1.21 (d, J = 7.4 Hz, 3H), 1.15 (d, J = 7.1 Hz, 3H), 1.12 (d, J = 7.4 Hz, 3H), 1.02 (d, J = 7.2 Hz, 3H), 0.91 (t, J = 7.3 Hz, 3H), 0.82 (t, J = 7.3 Hz, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.3, 176.4, 158.8, 1 57.2, 140.0, 139.9, 130.3, 125.4 (2C), 118.8, 117.3, 117.0, 102.9, 96.2, 82.8, 80.1, 78.9, 77.9 (2C), 76.2, 72.6, 70.6, 68.8, 29.5, 21.9, 21.5 21.4, 20.2 , 18.9, 18.7, 16.0, 14.2, 14.1, 11.6, 10.2, 9.9. MS (FAB) (M + H) + at m / z 957. Analysis calculated for C 9H78CIFN2O13 C, 61.46; H, 8.21; N, 2.93; Found: C, 61.45; H, 8.17; N, 3.10.

EXAMPLE 17 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-ISOPROPIL-11-DESOXY-11-rCARBOXI- (4-C LORO-3-F LUORO FEN ETI LAMÍ NO) 1-6- O-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 10, but replacing a, a-cyclopropyl-3,4-dichloro phenethylamine with 4-chloro-3-fluoro phenethylamine. MS (FAB) (M + H) + at m / z 957.

EXAMPLE 18 11.12- (CYCLE CARBAMATE OF 3'-N-DESM ETI L-3'-N-CICLOPENTIL-11-DESOXI-11-rCARBOXI- (4-CHLORO-3- FLUOROFENETILAMINO) 1-6-O-METHYL-ERYTHROMYCIN A The compound was prepared according to the method described in Example 1, but substituting 3,4-dichlorophenethylamine with 4-chloro-3-fluorophenethylamine; MS (FAB) (M + H) + at m / z 983.

EXAMPLE 19 11.12- (CYCLE CARBAMATE OF 3'-N-DESMETI L-3'-N- CYCLOBUTILMETIL-11-DESOXY-11-rCARBOXY- (4-CHLOROPHENEYL-AMINO) 1-6-Q-METHYL-ERYTHROMYCIN A It was prepared the title compound according to the method of Example 1, but replacing 3,4-dichlorophenethylamine with 4-chlorophenethylamine and cyclopentanone with cyclobutylcarboxaldehyde MS (FAB) (M + H) + at m / z 965.

EXAMPLE 20 11.12-CYCLICAL Icarbamate) 3'-N-DESMETIL-3'-N-CICLOBUTILMETIL-11-DESOXY-11-rCARBOXY- (4- CHLOROPHENETHYLAMINE) 1-6-0-METHYL-ERYTHROMYCIN A The compound was prepared of the titer in accordance with the method described in example 1, but replacing 3,4-dichlorophenethylamine with 4-chlorophenethylamine and cyclopentanone with cyclobutylcarboxaldehyde. The desired product crystallized in CH3CN / water: Rf = 0.46 (8.5% MeOH / DCM + 0.1% NH4OH). IR (KBr) a 3440, 2970, 1760, 1740, 1715, 1490, 1455, 1420, 1375, 1345, 1320, 1280, 1165, 1100, 1090, 1060, 1005, 990 cm. "1 NMR with 1H (300 MHz , CDCI3) delta 7.26-7.25 (series of m, 4H), 4.96-4.92 (series of m, 2H), 4.45 (d, J = 67.5 Hz, 1H), 4.04- 3.98 (m, 1H), 3.87-3.54 (series of m, 6H), 3.50-3.43 (m, 1H), 3.33 (s, 3H), 3.19-3.11 (m, 2H), 3.07 (s, 3H), 3.05-2.84 (series of m, 5H) , 2.64-2.61 (m, 1H), 2.50-2.42 (m, 1H), 2.37 (d, J = 15.3 Hz, 1H), 2.12 (d, J = 10.5 Hz, 1H), 2.06 (s, 3H), 2.00 (s, 1H), 1.98-1.48 (series of m, 12H), 1.42 (s, 3H), 1.40 (s, 3H), 1.29 (d, J = 6.4 Hz, 3H), 1.25 (s, 3H) , 1.25-1.24 (m, 1H), 1.23-1.20 (m, 6H), 1.15 (d, J = 7.5 Hz, 3H), 1.12 (d, J = 57.4 Hz, 3H), 1.02 (d, J = 6.8 Hz), 3H), 0.83 (t, J = 7.5 Hz, 3H). NMR with 13C (75 MHz, CDCl3) delta 216.2, 176.3, 157.2, 137.4, 131.8, 130.3, 128.4, 103.0, 96.0, 82.7, 80.3, 78.8, 77.9, 77.7, 76.2, 72.6, 70.0, 68.9, 65.7, 60.3, 60.1, 56.8, 50.6, 49.4, 45.5, 45.2, 45.2, 45.0, 39.0, 34.8, 50.2, 49.8, 32.8, 31.0, 29.6, 28.5, 28.1, 21.9, 21. 4, 20.1, 18.8, 18.6, 15.9, 14.2, 14.1, 14.0, 10.2, 9.0. MS (FAB) (M + H) + at m / z 951. Analysis calculated for C5oH79CIN2O13.0.6 H2O: C, 62.40; H, 8.40; N, 2.91 Found: C, 62.22; H, 8.33; N, 3.28.

EXAMPLE 21 11,12-CYCLICAL FCARBAMATE) OF 3'-N-DESMETIL-3'-N-ETHYL-11-DESOXY-11-rCARBOXY- (4-C LOROF IN ETI-LAMI O)] -7-O-METHYL- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 20, but replacing the cyclobutylcarboxaldehyde with acetaldehyde. MS (FAB) (M + H) + at m / z 925.

EXAMPLE 22 11.12- (CYCLICAL CARBAMATE) OF S'-N-DESMETIL-S'-N-ISOPROPIL-11-DESOXY-11-rCARBOXY- (4-CHLOROPHENETHYLAMINE) 1-6-O-METHYL-ERYTHROMYCIN A The compound was prepared of the title according to the method described in example 20, but replacing the cyclobutylcarboxaldehyde with acetone. MS (FAB) (M + H) + at m / z 939.

EXAMPLE 23 11,12- (CYCLICAL CARBANATE) OF 3'-N-DESM ETI L-3'-N-CICLOPE TIL-11-DESOXY-11-rCARBOXY- (4- CHLOROPHENETHYLAMINE) 1-6-O-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 20, but replacing the cyclobutylcarboxaldehyde with cyclopentanone. MS (FAB) (M + H) + at m / z 965. EXAMPLE 24 11.12- (CYCLE CARBAMATE OF 3'-N-DESMETIL-3'-N-CICLOPE TIL-11-DESOXY-11-rCARBOXY- (3- CHLOROPHENETHYLAMINE) 1-6-O-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 1, but replacing the, 4-dichlorophenethylamine with 3-chlorophenethylamine. The desired product crystallized from CH3CN / water: Rf = 0.55 (8% MeOH / DCM + 0.1% NH4OH). IR (KBr) a 3440, 2965, 2940, 2870, 1750, 1730, 1710, 1595, 1570, 1455, 1420, 1375, 1360, 1310, 1280, 1235, 1165, 1125, 1100, 1075, 1050, 1010, 995 cm "1. NMR with 1H (300 MHz, CDCl 3) delta 7.34 (s, 1H), 7.23- 7.15 (series of m, 3H), 4.97-4.90 (series of m, 2H), 4.46 (d, J = 7.1 Hz, 1H), 4.08-3.96 (m, 1H), 3.92-3.78 (m, 2H), 3.77-3.70 (m, 2H), 3.66 (d, J = 7.5 Hz, 1H), 3.54-3.42 (m, 1H), 3.33 (s, 3H), 3.17-3.11 (m, 2H), 3.09 (s, 3H), 3.07-2.82 (series of m, 5H), 2.70-2.56 (m, 2H), 2.38 (d, J = 15.6 Hz, 1H), 2.18 (s, 3H), 2.14 (d, J = 10.5 Hz, 1H), 2.02-1.48 (series of m, 14H), 1.47-1.22 (series of m, 3H), 1.43 (s, 3H), 1.40 (s, 3H), 1.30 (d, J = 6.1 Hz, 3H), 1.26 (s, 3H), 1.22 (d, J = 6.1 Hz), 3H), 1.22 (d, J) = 6.1 Hz, 3H), 1.15 (d, J = 7.4 Hz, 3H), 1.12 (d, J = 7.8 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.84 (t, J = 7.1 Hz, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.2, 176.3, 157.2, 141. 1, 134.1, 129.6, 129.2, 127.1, 126.4, 103.1, 96.1, 82.8, 80.3, 78.9, 78.0, 76.3, 72.7, 70.4, 69.0, 65.8, 63.6, 63.1, 60.4, 50.7, 49.5, 45.5, 45.3, 45.0, 39.1, 39.0, 34.9, 33.2, 33.1, 31.6, 31.0, 30.2, 23.8, 22.0, 21.5, 20.2, 18.9, 18.7, 16.0, 14.2, 14.1, 10.3, 9.0. MS (FAB) (M + H) + at m / z 965. Analysis calculated for C51H81CIN2O13.0.4 H2O: C, 62.96; H, 8.47; N, 2.88. Found: C, 62.97; H, 8.57; N, 2.68.

EXAMPLE 25 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-NN-PROPYL-11-DESOXY-11-rCARBOXY- (3-CHLOROPHENETHYLAMINE) 1-6-0-METHYL-ERYTHROMYCIN A The compound was prepared of the title according to the method described in example 3, but replacing 3,4-dichlorophenethylamine with 3-chlorophenethylamine. MS (FAB) (M + H) + at m / z 939.

EXAMPLE 26 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOPENTIL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4- FLUOROFENETILAMI O) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 1, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine. The crude product was purified on a column of silica gel (MeOH: CHCl3, 5:95) and crystallized from acetonitrile / water: Rf = 0.32 (MEOH: CHCl3, 5:95). NMR with 1H (300 MHz, CDCl 3) delta 7.39 (dd, J = 2.7 Hz, 1H), 7.22-7.19 (m, 1H), 7.04 (dd, J = 9 Hz, 1H), 4.93-4.89 (series of m) , 2H), 3.74 (d, J = 10 Hz, 1H), 3.70 (s, 1H), 3.67 (d, J = 7 Hz, 1H), 3.49-3.47 (m, 1H), 3.33 (s, 2H) , 3.19 (dd, J = 3.7 Hz, 1H), 3.13 (m, 1H), 3.07 (s, 3H), 3.04-2.86 (series of m, 5H), 2.66-2.61 (m, 2H), 2.37 (d , J = 15 Hz, 1H), 2.18 (s, 3H), 2.15 (d, J = 10 Hz, 1H), 1.93-1.51 (series of m, 13H), 1.43 (s, 3H), 1.40 (s, 3H), 1.38-1.35 (m, 2H), 1.30 (d, J = 6, 3H), 1.25 (s, 3H); 1.22 (s, 3H), 1.21 (s, 3H), 1.15 (d, J = 7 Hz, 3H), 1.12 (d, J = 7 Hz, 3H), 1.02 (d, J = 7 Hz, 3H), 0.83 (t, J = 7 Hz, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.3, 176.4, 157.7, 157.2, 155.8, 136.0, 136.0, 131.0, 128.6, 128.5, 116.4, 116.2, 103.0, 96.1, 82.8, 80.2, 78.9, 77.9, 77.8, 76.2, 72.6, 70.3, 69.0, 65.7, 63.5, 63. 0, 60.3, 50.6, 49.4, 45.5, 45.2, 45.0, 39.1, 39.0, 34.8, 33.1, 32.5, 31.6, 31.0, 30.1, 23.7, 23.7, 23.7, 21.9, 21.5, 20.1, 18.8, 18.6, 16.0, 14.2, 14. 1, 10.2, 8.9. MS (APCI) (M + H) + at m / z 983. Analysis calculated for C51 H80CIFN2O 3: C, 62.27; H, 8.20; N, 2.85; Found: C, 62.03; H, 8.34; N, 2.76.

EXAMPLE 27 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETI L-3'-N-CICLOBUTIL-11-DESOXY-11-rCARBOXI- (3-CHLORO-4- FLUOROFENETILAMINO) 1-6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 4, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine. The crude product was purified on a column of silica gel (MeOH: CHCl3, 5:95) and crystallized from acetonitrile / water: Rf = 0.30 (CHCl3: MeOH, 92: 8); HPLC Rt = (C-18) 19.6 min, 45.55% CH3CN, 1% gradient min; MS (APCI) (M + H) + at m / z 9.69.

EXAMPLE 28 11.12-CYCLIC ICARBAMATE) OF 3'-N-DESMETIL-3'-N-ISOPROPI L-11-D ESOXI-11-rCARBOXI- (3-CHLORO-4-F LUOROF IN ETL LAMINO)] -6- OR -METIL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 1, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine (y) with acetone cyclopentanone. The crude product was purified on a column of silica gel (MeOH: CHCl3, 5:95) and crystallized from acetonitrile / water. NMR with H (300 MHz, CDCl 3) delta 7.40 (dd, J = 2.7 Hz, 1H), 7.22-7.19 (m, 1H), 7.05 (dd, J = 9 Hz, 1H), 4.93-4.90 (series of m, 2H), 4.46 (d, J = 7 Hz, 1H), 4.04-4.01 (m, 1H), 3.87, 3.79 (series of m, 2H), 3.75 (d, J = 10 Hz, 1H), 3.70 (s, 1H), 3.67 (d, J = 7 Hz, 1H), 3.52- 3.49 (m, 1H), 3.34 (s, 3H), 3.16-3.11 (series of m, 2H), 3.08 (s, 3H), 3.05-2.86 (series of m, 5H), 2.65-2.63 (m, 1H) ), 2.58-2.56 (m, 1H), 2.37 (d, J = 15 Hz, 1H), 2.21 (s, 3H), 2.17 (d, J = 10 Hz, 1H), 1.94-1.86 (series of m, 2H), 1.78-1.75 (series of m, 2H), 1.66-1.52 (series of m, 3H), 1.44 (s, 3H), 1.40 (s, 3H), 1.31 (d, J = 6 Hz, 3H), 1.26 (s, 3H), 1.24-1.21 (series of m, 6H), 1.15 (d, J = 7 Hz, 3H), 1.13 (d, J = 7 Hz, 3H) , 1.09 (d, J = 6 Hz, 3H), 1.06 (d, J = 6 Hz, 3H), 1.03 (d, J = 7 Hz, 3H), 0.83 (t, J = 7 Hz), 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.3, 176.4, 157.7, 157.2, 155.8, 136.0, 136.0, 131.0, 128.6, 128.5, 116.4, 116.2, 102.9, 96.1, 82.8, 80.1, 78.9, 77.9, 76.2, 72.6, 70.4, 68.9, 65.7, 62.8, 60.3, 52.5, 50.6, 49.5, 45.5, 45.3, 45.0, 39.1, 39.0, 39.0, 39.0, 34.8, 32.5, 30.8, 21.9, 21.5, 20.1, 18.8, 18.6, 16.0, 14.2, 14.2, 10.2, 8.9. MS (ESI) (M + H) + at m / z 957. Analysis calculated for C49H78CIFN2O13: C, 61.46, H, 8.21, N, 2.93; Found: C, 61.69; H, 8.36; N, 3.07.

EXAMPLE 29 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOPROPYLMETHYL-11-DESOXY-11- (3-CHLORO-4- FLUOROFENETILAMINO) -6-Q-METHYL-ERYTHROMYCIN A prepared the title compound according to the method described in Example 1, but replacing the 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine and the cyclopentanone with cyclopropanecarboxaldehyde. The crude product was purified on a column of silica gel (MeOH: CHCl3, 5:95) and crystallized from acetonitrile / water. NMR with 1H (300 MHz, CDCl 3) delta 7.40 (d, J = 2.7 Hz, 1H), 7.23-7.20 (m, 1H), 7.05 (dd, J = 9 Hz, 1H), 4.93-4.91 (series of m, 2H), 4.47 (d, J = 7 Hz, 1H), 4.04-4.02 (m, 1H), 3.87-3.81 (series of m, 2H), 3.75 (d, J = 10 Hz, 1H), 3.71 (s, 1H), 3.67 (d, J = 7 Hz, 1H), 3.51-3.49 (m 1H), 3.34 (s, 3H), 3.22-3.19 (m, 1H), 3.13 (c, J = 7 Hz) , 1H), 3.08 (s, 3H), 3.04-2.84 (series of m, 5H), 2.64-2.61 (series of m, 2H), 2.44-2.42 (m, 1H), 2.39 (d, J = 15 Hz , 1H), 2.31 (s, 3H), 2.26-2.24 (m, 1H), 2.17 (d, J = 10 Hz, 1H), 1.94-1.85 (series of m, 2H), 1.78-1.76 (series of m , 2H), 1.64-1.57 (series of m, 5H), 1.44 (s, 3H), 1.41 (s, 3H), 1.31 (d, J = 6, 3H), 1.03 (d, J = 7 Hz, 3H ), 0.84 (t, J = 7 Hz, 3H), 0.55-0.51 (m, 2H), 0.11 (d, J = 4 Hz, 2H). NMR with 13 C (75 MHz, CDCl 3) delta 216.3, 176.4, 157.8, 157.2, 155.8, 136.0, 136.0, 131.0, 128.6, 128.5, 116.4, 116.2, 103.0, 96.1, 82.8, 80.2, 78.9, 77.9, 76.3, 72.6, 70.6, 68.9, 65.8, 60.4, 58.6, 50.7. 49, .5, 45.5, 45.3, 45.0, 39.1, 39.1, 39.1, 39.0, 36.9, 34.9, 32.5, 29.5, 21.5, 21.5, 20.2, 18.2, 18.7, 16.0, 14.2, 14.1, 10.2, 10.0, 9.0, 4.4, 3.4 . MS (ESI) (M + H) + at m / z 868. Analysis calculated for C4oH78CIFN2O13.0.25 (CH3CN): C, 61.90; H, 8.10; N, 3.21; Found: C, 61.96; H, 8.27; N, 3.44.

EXAMPLE 30 11.12 (CYCLE CARBAMATE OF 3'-N-DESMETIL-3'-N-CICLOBUTIL-11-DESOXY-11-rCARBOXI- (3,4-DIFLUOROFENETILAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 4, but replacing 3,4-dichlorophenethylamine with 3,4-difluorophenethylamine The desired product was crystallized from CH 3 CN / water, mp 222-224 ° C (CH 3 CN / water). FTIR / MIC) a 3494, 2969, 2943, 2879, 2832, 1746, 1735, 1712, 1608, 1519, 1457, 1449, 1429, 1378, 1327, 1278, 1234, 1167, 1111, 1104, 1071, 1059, 1012 1002 cm "1 NMR with 1H (300 MHz, CDCI3) delta 7.23-7.03 (series of m, 3H), 4.95-4.90 (series of m, 2H), 4.45 (d, J = 7.1 Hz, 1H), 4.06-3.96 (m, 1H), 3.92-3.76 (m, 2H), 3.74 (d, J = 8.8 Hz, 1H), 3.70 (s, 1H), 3.67-3.62 (m, 1H), 3.66 (d, J = 7.4 Hz, 1H), 3.53-3.42 (m, 1H), 3.33 (s, 3H), 3.19-3.07 (m, 2H), 3.07 (s, 3H), 3.06-2.80 (series of m, 5H) , 2.68-2.57 (m, 2H), 2.50-2.42 (m, 1H), 2.37 (d, J = 14.9 Hz, 1H), 2.13 (d, J = 10.2 Hz, 1H), 2.05 (s, 3H) ), 2.05-1.47 (series of m, 14H), 1.43 (s, 3H), 1.40 (s, 3H), 1.30 (d, J = 6.1 Hz, 3H), 1.25 (s, 3H), 1.22 (d, J = 8.5 Hz, 3H), 1.21 (d, J = 6.1 Hz, 3H), 1.15 (d, J = 7.4 Hz, 3H), 1.12 (d, J = 7.5 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.83 (t, J = 7.5 Hz, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.28, 176.39, 157.19, 152.5-146.5 (m, 2C), 136.5-135.5 (m, 1C), 125.0-124.7 (m, 1C), 117.9-116.8 (m, 2C) ), 103.08, 96.07, 82.78, 80.34, 78.93, 77.096, 77.86, 76.29, m 72.68, 70.14, 68.99, 65.76, 60.42, 60.20, 56.84, 50.66, 49.46, 45.58, 45.30, 45.01, 39.10, 39.02 (2C), 34.88, 32.71, 31.04, 29.74, 28.56, 28.16, 21.97, 21.50, 21.47, 20.14, 18.88, 18.65, 16.00, 14.23, 14.12 (2C), 10.23, 9.00. MS (FAB) (M + H) + at m / z 953. Analysis calculated for C50H78F2N2O? 3.0.2 H2O: C, 62.77; H, 8.26; N, 2.93; Found: C, 62.75; H, 8.36; N, 2.91.

EXAMPLE 31 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N CICLOPENTIL-11-DESOXY-11-rCARBOXY- (3,4-DIFLUOROFENETILAMIN? N-6-O-METTIL-ERYTHROMYCIN A) prepared the title compound according to the method described in Example 1, but replacing 3,4-dichlorophenethylamine with 3,4-difluorophenethylamine The desired product crystallized from CH 3 CN / H 2 O, mp 166-168 ° C (CH 3 CN / H 2 O. IR (FTIR / MIC) a 3451, 2968, 2943, 2880, 2831, 1763,1747, 1709, 1520, 1453, 1432, 1378, 1327, 1283, 1234, 1168, 1128, 1106, 1069, 1055, 1012, 1000 cm. "1 NMR with 1H (300 MHz, CDCI3) delta 7.22-7.03 (series of m, 3H), 4.95-3.75 (m, 2H), 3.74 (d, J = 9.5 Hz, 1H), 3.70 (s, 1H), 3.66 (d, J = 7.5 Hz, 1H), 3.55-3.43 (m, 1H) ), 3.33 (s, 3H), 3.24-3.11 (m, 2H), 3.11, 2.80 (series of m, 5H), 3.07) s, 3H), 2.69-2.58 (m, 2H), 2.37 (d, J) = 15.2 Hz, 1H), 2.18 (s, 3H), 2.14 (d, J = 10.2 Hz, 1H), 1.98-1.48 (series of m, 14H), 1.43 (s, 3H), 1.40 (s, 3H) , 1.35-1.131 (m, 2H), 1.30 (d, J = 6.1 Hz, 3H), 1.18-1.21 (m, 1H), 1.26 (s, 3H), 1.22 (d, J = 6.1 Hz, 3H), 1.22 (d, J = 6.1 Hz, 3H), 1115 (d, J = 7.1 Hz, 3H), 1.12 (d, J = 7.8 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.83 ( t, J = 7.3 Hz, 3H). NMR with 13 C (75 MHz, CDCl 3) delta 216.35, 176.42, 157.20, 152.5-146.5 (m, 2C), 136.4-135.5 (m, 1C), 125.0-124.7 (m, 1C), 117.9-116.8 (m, 2C), 103.04 (96.07, 82.77, 80.23, 78.91, 77.94, 77.81, 76.24, 72.65, 70.29, 69.01, 65.74, 63.53, 63.06, 60.34, 50.67, 49.49, 45.58, 45.27, 44.99, 39 .07, 38.99 (2C), 34.85, 33.15, 32.69, 31.67, 31.00, 30.10, 23.74, 23.71, 21.95, 21.51, 20.17, 18.87, 18.66, 16.03, 14.23, 14.15, 10.25, 8.99.

MS (FAB) (M + H) + at m / z 967. Analysis calculated for C5? H8oF2N2O13.0.4 CH3CN.0.4 H2O C, 62.79; H, 8.34; N, 3.39; Found: C, 62.78; H, 8.45; N, 3.46.

EXAMPLE 32 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-Nn-PROPIL-11-DESOXY-11-rCARBOXI- (3,4-DI FLUORO FEN ETI LAMIN 0) 1-6-0- METHYL -ERITHROMYCIN A The title compound was prepared according to the method described in Example 3, but replacing 3,4-dichlorophenethylamine with 3,4-difluorophenethylamine. The desired product was crystallized from CH 3 CN / H 2 O; p.f. 228-229 ° C (CH3CN / H2O). IR (FTIR / MIC) a 3484, 2970, 2941, 2883, 1754, 1734, 1711, 1519, 1459, 1436, 1423, 1379, 1351, 1326, 1282, 1236, 1167, 1127, 1110, 1075, 1055, 1044 , 1014, 997 crtT1. NMR with 1H (CDCI3) delta 7.22-7.03 (series of m), 3H), 4.95-4.89 (series of m, 2H), 4.44 (d, J = 7.2 Hz, 1H), 4.06-3.96 (m, 1H) , 3.92-3.75 (m, 2H), 3.75 (d, J = 9.2 Hz, 1H), 3.69 (s, 1H), 3.67 (d, J = 7.8 Hz, 1H); 3.54-3.43 (m, 1H), 3.33 (s, 3H), 3.23-3.11 (m, 2H), 3.10-2.80 (series of m, 5H), 3.07 (s, 3H), 2.69-2.58 (m, 1H) ), 2.54-2.40 (m, 2H), 2.37 (d, J = 14.9 Hz, 1H), 2.33-2.24 (m, 1H), 2.23 (s, 3H), 2.17 (d, J = 10.2 Hz, 1H) , 1.98-1.82 (m, 2H), 1.79-1.75 (m, 2H), 1.71-1.44 (series of m, 6H) ~, 1.43 (s, 3H), 1.40 (s, 3H), 1.30 (d, J = 6.4 Hz. 3H), 1.12 (d, J = 7.4 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.90 (t, J = 7.5 Hz, 3H), 0.83 (t, J = 7.3 Hz, 3H). 13 C NMR NMR (CDCl 3) delta 216.36, 176.45, 157.19, 152.5-146.5 (m, 2C), 136.5, 135.5 (m, 1C), 125.0-124.7 (m, 1C), 117.9, 116.8 (m, 2C), 102.94 , 96.17, 82.76, 80.09.78.94, 77.91 (2C), 76.24, 72.62, 70.64, 68.99, 65.76, 65.60, 60.31, 54.96, 50.67, 49.47, 45.46, 45.28, 44.96, 39.09 (2C), 38.98, 36.87 (34.84 , 32.67, 29.39, 21.91, 21.48, 21.40, 20.17, 18.87, 18.68, 16.03, 14.22, 14.13, 11.58, 10.24, 8.96 MS (FAB) (M + H) + at m / z 941. Analysis calculated for C 9H78F2N2O13: C, 62.53; H, 8.35; N, 2.98; Found: C, 62.69; H, 8.34; N, 3.12; EXAMPLE 33 11.12- (CYCLICAL CARBAMATE) OF 3'-n-DESMETIL-3'-N-Cl CLOP ROPI LMETIL-11-DESOXY-11-rCARBOXI - (3,4-DI FLUORO FENETILAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 1, but replacing 3,4-dichlorophenethylamine with 3,4-difluorophenethylamine and with cyclopropancarboxyaldehyde the cyclopentanone. The desired product crystallized from CH3CN / H2O, m.p. 220-222 ° C (CH 3 CN / H 2 O); IR (KBr) a 3446, 2977, 2938, 2883, 1745, 1734, 1713, 1607, 1518, 1459, 1425, 1378, 1327, 1284, 1236, 1168, 1103, 1094, 1070, 1055, 1013, 1001 cm1.

NMR with 1H (300 MHz, CDCI3) delta 7-23-7.03 (series of m, 3H), 4.94-4.89 (series of m, 2H), 4.46 (d, J = 7.4 Hz, 1H), 4.07-3.97 ( m, 1H), 3.92-3.78 (series of m, 2H), 3.75 (d, J = 9.1 Hz, 1H), 3.70 < s, 1H), 3.67 (d, J = 7.8 Hz, 1H), 3.54-3.44 (m, 1H), 3.33 (s, 3H), 3.24-3.11 (m, 2H), 3.10-2.80 (series of m, 5H), 3.07 (s, 3H), 2.68-2.55 (m, 2H), 2.47-2.40 (m, 1H), 2.37 (s, J = 15.2 Hz, 1H), 2.31 (s, 3H), 2.31-2.19 (m, 1H), 2.15 (d, J = 10.1 Hz, 1H), 1.98-1.72 (series of m, 4H), 1.68-1.46 (series of m, 4H), 1.43 (s, 3H), 1.40 (s) , 3H), 1.30 (d, J = 6.1 Hz, 3H), 1.25 (s, 3H), 1.22 (d, J = 6.1 Hz, 3H), 1.22 (d, J = 6.1 Hz, 3H), 1.15 (d , J = 7.4 Hz, 3H), 1.25 (s, 3H), 1.22 (d, J = 6.1 Hz, 3H), 1.22 (d, J = 6.1 Hz, 3H), 1.15 (d, J = 7.4 Hz, 3H ), 1.13 (d, J = 7.5 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 0.89-0.78 (m, 1H), 0.83 (t, J = 7.3 Hz, 3H), 0.58-0.46 (m, 2H), 0.15-0.07 (m, 2H). NMR with 13 C (75 MHz, CDCl 3) delta 216.35, 176.43, 157.20, 152.5-146.5 (m, 2C), 136.5-135.5 (m, 1C), 125.0-124.7 (m, 1C), 117.9-116.8 (m, 2C) ), 103.02, 96.13, 82.77, 80.19, 78.94, 77.92, 77.89, 76.26, 72.63, 70.55, 68.96, 65.78, 64.61, 60.34, 58.59, 50.67, 49.49, 45.56, 45.30, 44.99, 39.09 (2C), 39.01, 36.91 , 34.85, 32.69, 29.42, 21.93, 21.49, 20.18, 18.89, 18.68, 16.03, 14.23, 14.13, 10.25, 10.04, 9.01, 4.41, 3.36. MS (FAB) (M + H) + at m / z 953. Analysis calculated for C50H78F2N2O13: C, 63.01; H, 8.25; N, 2.94. Found: C, 63.08; H, 8.28; N, 2.89.

EXAMPLE 34 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (4- PYRIDYLMETHYL) -11-DESOXY-11-rCARBOXY- (4- CHLOROPHENETHYLAMINE) 1-6-Q-MET-L- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 20, but replacing cyclobutanone with 4-pyridylcarboxaldehyde. MS (APCI) (M + H) + at m / z 988.

EXAMPLE 35 11.12- (CYCLICAL CARBAMATE) 3'-N-DESMETIL-3'-N- (2-BUTIL) -11-DESOXY-11-rCARBOXI- (4-C LO ROFENETI LAMI O)! -6-O-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 20, but replacing cyclobutanone with 2-butanone. MS (APCI) (M + H) + at m / z 953.

EXAMPLE 36 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (3-PENTIL) -11-DESOXY-11-rCARBOXY- (4-CHLOROPHENETHYLAMINE) 1-6-O-METHYL-ERYTHROMYCIN prepared the title compound according to the method described in Example 20, but replacing cyclobutanone with 3-pentanone: MS (APCI) (M + H) + at m / z 967.

EXAMPLE 37 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (CICLOPROPYLMETHYL) -11-DESOXY-11-rCARBOXY- (4- CHLOROPHENETHYLAMINE) 1-6-Q-METHYL-ERYTHROMICI AA The title compound was prepared according to the method described in Example 20, but replacing cyclobutanone with cyclopropancarboxaldehyde MS (APCI) (M + H) + at m / z 951.

EXAMPLE 38 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DEMETIL-3'-N-r2- (Cl CLOPROPÍ DETIL1 -11-DESOXI-11-rCARBOXI - (4- CHLOROFENETILAMINO) 1-6-Q-METHYL -ERITROMYCLE A The title compound was prepared according to the method described in Example 20, but replacing cyclobutanone with cyclopropylmethyl ketone MS (APCI) (M + H) + at m / z 965. MS (APCl) (M + H) + at m / z 965.

EXAMPLE 39 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-PROPYL-11-D ESOXY-11-rCARBOXY- (4-M ETOXY FEN ETI LAMIN Q) 1-6-Q-METHYL- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 20, but replacing 4-chlorophenethylamine with 4-methoxyphenethylamine and with propanal cyclobutanone. MS (APCI) (M + H) + in m / z 935.

EXAMPLE 40 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOPENTIL-11-DESOXY-11-rCARBOXY- (4-METOXYPHENETLLAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A It was prepared the title compound according to the method described in Example 20, but replacing 4-chlorophenethylamine with 4-methoxyphenethylamine and with cyclopentanone cyclobutanone. MS (APCI) (M + H) + at m / z 961.

EXAMPLE 41 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-PROPYL-11-DESOXY-11-rCARBOXY- (3,4-DIMETHYLPHENETILAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The compound was prepared of the title according to the method described in example 20, but replacing 4-chlorophenethylamine with 3,4-dimethylphenethylamine and with propanal cyclobutanone. MS (APCI) (M + H) + at m / z 933.

EXAMPLE 42 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOPENTIL-11-DESOXY-11-rCARBOXY- (3-BROMO-4-METOXY-FENETILAMINO) 1-6-Q-METHYL- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-bromo-4-methoxyphenethylamine and with cyclopentanone for cyclobutanone; MS (APCI) (M + H) + at m / z 1039.

EXAMPLE 43 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-PROPIL-11-DESOXY-11-rCARBOXY- (3-BROMO-4-METOXY FEN ETI LAMÍ NO) 1-6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-bromo-4-methoxyphenethylamine and with propanal cyclobutanone. MS (APCI) (M + H) + at m / z 1013.

EXAMPLE 44 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-PROPYL-11-D ESOXY-11-rCARBOXY- (3-CHLORO-4-FLUORO FE ETI-LAMINO)] -6-Q- METHYLERITROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and with propanal cyclobutanone, MS (APCI) (M + H) + am / z 957.

EXAMPLE 45 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-FURYL) METHYL-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4-FLUOROFE ETHYLAMINE)) - 6 -Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and with 2-furaldehyde cyclobutanone. MS (APCI) (M + H) + at m / z 995.

EXAMPLE 46 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r2- (5-HYDROXYMETHYL) FURYL1METIL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4-FLUOROFENETILAMI O) 1- 6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and cyclobutanone with 5-hydroxymethyl-2-furaldehyde . MS (APCI) (M + H) + at m / z 1025.

EXAMPLE 47 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-PYRIDYL) METHYL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4-FLUORO-FENETHYL) 1-6 -Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and cyclobutanone with 2-pyridylcarboxaldehyde. MS (APCI) (M + H) + at m / z 1006.

EXAMPLE 48 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r2- (6-METHYL) PYRIDYL-1-METHYL-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4-FLUORO-PHENYLAMINE) 1-6 -Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and 6-methyl-2-pyridylcarboxaldehyde cyclobutanone. MS (APCI) (M + H) + in m / z 1020.

EXAMPLE 49 11.12- (CYCLE CARBAMATE) 3'-N-DESMETIL-3'-N- (4-HYDROXYETOXYBE CIL) -11-DESOXY-11-rCARBOXY- (3-CHLORO-4- FLUOROFENETILAMINO) 1-6-Q- METHYL-ERYTHROMICI AA The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and cyclobutanone with 4-hydroxyethoxybenzaldehyde. MS (APCI) (M + H) + in m / z 1065.

EXAMPLE 50 11,12- (CHLORIC CARBAMATE) OF 3'-N-DESMETIL-3'-N- (3-METHYLTHYL) BUTIL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4- FLUOROF ENETI LAMÍ NO) 1-6-Q-METHYL-ERITROMI CIÑA A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and cyclobutanone with 3-methylthiobutyraldehyde. MS (APCI) (M + H) \ at m / z 1017.

EXAMPLE 51 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETI L-3'-N- (4.4.4- TRIFLUOROBUTIL) -11-DESOXY-11-rCARBOXI- (3-CHLORO-4- FLUOROFENETILAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3-chloro-4-fluorophenethylamine and cyclobutanone with 4,4,4 -trifluorobutyraldehyde. MS (APCI) (M + H) + at m / z 1025.

EXAMPLE 52 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOBUTIL-11-DESOXY-11-rCARBOXY- (4-CHLORO-3-FLUOROFENETILAMINO)) - 6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethiamine with 4-chloro-3-fluorophenethylamine. MS (APCI) (M + H) + at m / z 969.

EXAMPLE 53 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-ISOPROPIL- 11 -DESOXY-11 -TC ARBOXI - (3, 4-Dl FLU OROF ENETI LAMI O)] -6-0- MET1L-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3,4-difiuorophenethylamine and cyclobutanone with acetone. MS (APCI) (M + H) + at m / z 941.

EXAMPLE 54 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-PROPYL-11-DESOXY-11-rCARBOXI-r3,4- (1,4-DIOXANE) F IN ETI-LAMINO)] -6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in example 19, but replacing 4-chlorophenethylamine with 3,4- (1,4-dioxane) phenethylamine and cyclobutanone with propanal . MS (APCI) (M + H) + at m / z 963.

EXAMPLE 55 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-CICLOPROPYLMETHYL-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENETHYLAMINE) 1-6-Q-METHYL-ERYTHROMYCIN A Prepared the title compound according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3,4-dichlorophenethylamine and cyclobutanone with cyclopropanecarboxaldehyde. MS (APCI) (M + H) + at m / z 985.

EXAMPLE 56 11.12- (cyclic carbamate) 3'-DESMETI L-3'-N-T3- (methylsulfoxy) PROPIL1-11-deoxy-11-rCARBOXI- (3.4- dichloro-6-FENETILA Inoh O-METHYL-ERITROMlClNA A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3,4-dichlorophenethylamine and cyclobutanone with 3- (methylsulfoxy) propanal), and then oxidized to the sulfoxide. MS (APCI) (M + H) + at 1035.

EXAMPLE 57 11. 12-CYCLEIC ICARBAMATE) i DE 3 '-DESMETIL-3' -N-ETHYTIOUREA-11-DESOXY- 11-rCARBOXI- (3.4- DIC LOROF IN ETI LAMI O)! -6-O-METHYL-DRITROMICII JA A 0.36 g (0.39 mmol) of the 3-amino derivative (11) was dissolved in 10 ml of chloroform and treated with 0.39 mmol of the ethyl isothiocyanate derivative; and the reaction mixture was stirred at room temperature. After 24 hours the reaction was partitioned between 100 ml of ethyl acetate and the organic phase was washed with 3 x 100 ml of saturated sodium bicarbonate, 100 ml of brine and then dried over sodium sulfate and concentrated. The title compound was isolated by column silica gel purification. MS (APCI) (M + H) + at m / z 1018, EXAMPLE 58 11.12- (CARBAMATQ CYCLIC) of 3'-N-DESMETI L-3'-N-T2- (5- hydroxymethyl) FURIL1METIL-11-deoxy-11-rCARBOXI- (3,4- DICLOROFENETILAMI O) 1-6 -0-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3,4-dichlorophenethylamine and cyclobutanone with 5-hydroxymethyl-2-furaldehyde. MS (APCI) (M + H) + at m / z 1041.

EXAMPLE 59 11.12- (cyclic carbamate) 3'-N-desmethyl-3'-N-cyclopropylmethyl-11-deoxy-11-rCARBOXI- (aa-cyclopropyl- 3.4-DICLOROFENETILAMI O) 1-6-Q-METHYL-ERlTROMICINA A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with α, α-cyclopropyl-3,4-dichlorophenethylamine and cyclobutanone with cyclopropanecarboxaldehyde. MS (APCI) (M + H) + at m / z 1011.

EXAMPLE 60 11.12- (cyclic carbamate) 3'-N-desmethyl-3'-N-propyl-11-deoxy-11-GCARBOXI- (4-CLOROANILINOETILAMINO) 1-6-Q-methyl- erythromycin A Step 1: Preparation of 4-chloroanilino-ethylamine 6.2 g (38 mmol) of the hydrochloride salt of 4-chloroaniline and 3.29 g (38 mmol) of 2-oxazolidone were suspended in a minimum amount of diethylene glycol methyl ether, and heated the resulting suspension at 160 ° C. After four hours the evolution of CO2 ceased and the reaction mixture was cooled to room temperature. The resulting solid crystallized from EtOH / ether to give 4.6 g (58%) of 4-chloroanilinoethylamine, as its hydrochloride salt. MS (Cl) (M + H) + at m / z 171. The free amine was prepared by dividing the hydrochloride salt between methylene chloride and sodium bicarbonate (saturated), drying the organic layer in sodium sulfate, filtering and concentrating.

Step 2: 11.12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11-rcarboxy- (4-chloroanilinoethylamino) 1-6-Q-methyl-erythromycin A. Prepared the title compound according to the method described in example 19, but replacing 4-chlorophenethylamine with 4-chloroanilinoethylamine, obtained in step 1, and cyclobutanone with propanal. MS (APCl) (M + H) + at m / z 954.

EXAMPLE 61 11.12- (cyclic carbamate N-desmethyl-3'-3'-N-pentyl-11 - deoxy-11 rCARBOXI- (4-CLOROANILINOETILAMINO) 1-6-Q-methyl- erythromycin A Step 1: Preparation of 4-chloroanilino-ethylamine 6.2 g (38 mmol) of the hydrochloride salt of 4-chloroaniline and 3.29 g (38 mmol) of 2-oxazolidone were suspended in a minimum amount of diethylene glycol methyl ether and heated the resulting suspension to 160 ° C. After four hours the evolution of C02 ceased and the reaction mixture was cooled to room temperature. The resulting solid crystallized in EtOH / ether to yield 4.6 g (58%) of 4-chloroanilinoethylamine, as its hydrochloride salt. MS Cl (M + H) + at m / z 171. The amine was prepared by dividing the hydrochloride salt between methylene chloride and saturated sodium bicarbonate, drying the organic layer in sodium sulfate and filtering and concentrating.

Step 2: 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11-rcarboxy- (4-chloroanilinoethylamino) 1-6-0-methyl-erythromycin A. The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 4-chloroanilinoethylamine obtained in step 1, and cyclobutanone with propanal, MS (APCI) (M + H) + am / z 980.

EXAMPLE 62 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DES METHYL-3'-N-ISOPROPYL-11-DESOXY-11-GCARBOXY- (3,4-DIFLUOROFENET-1LAMI O) 1-6-Q-METHYL- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 19, but replacing 4-chlorophenethylamine with 3,4-difluorophenethylamine and with acetone cyclobutanone. MS (APCI) (M + H) + at m / z 941.

EXAMPLE 63 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-IMIDAZOLYL) METHYL-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENETILAMINO) T-6-Q-METHYL -ERITROMYCLE A The title compound was prepared according to the method described in Example 1, but replacing the cyclopentanone with imidazole-2-carboxyaldehyde. MS (APCI) (M + H) + at m / z 1013.

EXAMPLE 64 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (3-PIRIDYL) METHYL-11-DESOXY-11-rCARBOXY- (3,4- DICHLOROPHENETILAMIN? N-6-O-METHYL-ERYTHROMICI AA The title compound was prepared according to the method described in Example 1, but replacing the cyclopentanone with pyridyl-3-carboxyaldehyde MS (APCI) (M + H) + at m / z 1022.

EXAMPLE 65 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-PIRIDYL) METHYL-11-DESOXY-11-rCARBOXY- (3,4- DICHLOROPHENETIME-6-O-METHYL-ERYTHROMYCIN) A The title compound was prepared according to the method described in Example 1, but replacing the cyclopentanone with pyridyl-2-carboxyaldehyde MS (APCI) (M + H) + at m / z 1022.

EXAMPLE 66 11,12-CYCLEIC FCARBAMATE) OF 3'-N-DESMETLL-3'-Nr (5-NlTRO) -2-TIENYL-1-methyl-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYLAMINE) 1-6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 5-nitro-thiophene-2-carboxyaldehyde. MS (APCI) (M + H) + at m / z 1072.

EXAMPLE 67 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r5- (4- CHLOROFE IL) -2-FURYLMETIL1-11-DESOXY-11-rCARBOXl- (3,4-DICHLOROFENETILAMI O) 1-6-0-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 5- (4-chlorophenyl) -2-furaldehyde. MS (APCI) (M + H) + at m / z 1123.

EXAMPLE 68 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r5-NITRO-2- FURYLMETIL1-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYLAMINE) 1-6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing cyclopropanecarboxydehyde with 5-nitro-2-furaldehyde. MS (APCI) (M + H) + at m / z 1059.

EXAMPLE 69 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETI L-3'-N-r2.5- DIMETOXY-3-TETRAHYDROFURYLMETHYL1-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROFE ETHYLAMINE) 1-6 -Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 2,5-dimethoxy-3-tetrahydrofuraldehyde. MS (APCI) (M + H) + at m / z 1075.

EXAMPLE 70 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETHYL-3 '-N-T6-M ETI L-2- PIRIDYLMETIL1-11-DESOXY-11-rCARBOXI- (3.4- DICLOROFENETILA INO) 1-6- Q-METHYL-ERYTHROMYLCAN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 6-methyl-pyridyl-2-carboxyaldehyde. MS (APCI) (M + H) + at m / z 1036.

EXAMPLE 71 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETLL-3'-N- (4,4,4-TRIFLUOROBUTIL) -11-DESOXY-11-rCARBOXY- (3,4- DICLOROFENETILAMINO) 1-6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 4,4,4-trifluorobutyraldehyde. MS (APCI) (M + H) + at m / z 1041.

EXAMPLE 72 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (1-BROMO-2-NAFETYMETIL) -11-DESOXY-1-rCARBOXY- (3,4- DICHLOROFENETILAMI O) 1-6 -Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 1-bromo-2-naphthylcarboxyaldehyde. MS (APCI) (M + H) + at m / z 1149.

EXAMPLE 73 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (4-METHYL-1-NAFETYMETIL) -11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENETHYLAMIN-6) O-METHYL-ERLTROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 4-methyl-1-naphthylcarboxyaldehyde MS (APCI) (M + H) + at m / z 1085 .

EXAMPLE 74 11,12-CYCLEIC ICARBAMATE) OF 3'-N-DESMETI L-3'-N- (4-DIMETHYLAMINO-1-NAFETYMETIL) -11-DESOXY-11-rCARBOXI- (3,4- DICLOROFE ETILAMINO) 1-6 -Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxyaldehyde with 4-dimethylamino-1-naphthylcarboxyaldehyde. MS (APCI) (M + H) + at m / z 1114.

EXAMPLE 75 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-FURYL-METHYL) -11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYLAMINE) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxydehyde with 2-furaldehyde. MS (APCI) (M + H) + at m / z 1011 EXAMPLE 76 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETI L-3'-N-T3- (4- PYRIDIL) PROPIL1-11-DESOXY-11-rCARBOXI- (3,4- DICLOROFENETILAMINO) 1-6-Q METHYL-ERYTHROMYCAL A This material was prepared in a manner analogous to that used for the preparation of Example 1, but replacing the cyclopentanone with 4-pyridylpropanal. The crude product was purified on a column of silica gel (CHCl3 -> MeOH: CHCl3, 5:95) to produce a crystalline solid; p.f. 144-5 ° C; IR (film) a 3315, 2968, 2937, 1754, 1733, 1603, 1457, 1417, 1168, 1066, 1011, 1000 cm "1. NMR with 13 C (CDCI 3) delta 216.27, 176.37, 157.16, 150.72, 149.67, 146.79 , 139.25, 132.14, 130.99, 130.24, 130.10, 128.37, 102.76, 96.15, 82.77, 80.20, 78.88, 77.89, 77.83, 76.22, 72.67, 70.71, 68.77, 65.78, 65.58, 60.31, 52.69, 50.64, 49.46, 45.48, 45.24 , 44.77, 39.06, 39.01, 38.96, 36.76, 34.80, 32.59, 29.71, 28.63, 21.87, 21.44, 21.38, 20.14, 18.86, 18.66, 16.01, 14.18, 14.10, 10.22, 9.02 MS (APCI) (M + H) + a / z 1052. Analysis calculated for C5 H8? CI2N3O13: C, 61.70; H, 7.77; N, 4.00; Found: C, 61.56; H, 7.78; N. 4.03.

EXAMPLE 77 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r3- (2-PIRIDYL) PROPYLM1-DESOXY-11-rCARBOXY- (3,4-DICHLOROFENETHYLAMINE-6-O-METHYL -ERITHROMYCIN A This material was prepared in a manner analogous to that used for the preparation of Example 1, but replacing the cyclopentanone with 3- (2-pyridyl) propanal. The crude product was purified on a column of silica gel (CHCl 3 - > MeOH: CHCl3, 5:95) to produce an amorphous solid, IR (film) a 3446, 2970, 2937, 1756, 1458, 1167, 1052, 1011, 998 cm "1. 13 C NMR (CDCl 3) delta 216.29 , 176.44, 157.19, 149.14, 139.31, 136.42, 132.19, 131.04, 130.26, 130.15, 128.45, 128.40, 122.78, 121.05, 102.97, 96.22, 82.83, 80.17, 78.99, 78.00, 77.94, 76.27, 72.66, 70.67, 68.81, 65.83 , 65.68, 60.41, 53.38, 52.83, 50.66, 49.48, 45.53, 45.32, 44.83, 39.15, 39.02, 36.58, 35.57, 34.89, 32.64, 29.73, 28.15, 21.92, 21.47, 21.44, 20.18, 18.88, 18.70, 16.01, 14.22 , 14.12, 10.23, 9.02 MS (APCI) (M '+ H) + am / z 1052. Analysis calculated for C54H8? CI2N3O13: C, 61.70; H, 7.77; N, 4.00; Found: C, 61.69; H, 7.62; N, 3.87.

EXAMPLE 78 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r4- (4-PIRIDYL) BUTILM1-DESOXY-11-rCARBOXY- (3,4-DICHLOROFENETHYLAMINE) 1-6-Q-METHYL -ERITHROMYCIN A This material was prepared in a manner analogous to that used for the preparation of Example 1, but replacing the cyclopentanone with 4- (4-pyridyl) butanal. The crude product was purified on a column of silica gel (CHCl3 -> MeOH: CHCl3, 5:95) and crystallized from acetonitrile, p. F. 192-3 ° C. IR (film) a 3416, 2969, 2936, 1755, 1733, 1457, 1168, 1067, 1011, 1000 cm "1.

NMR with 13C (CDCI3) delta 216.27, 176.40, 157.15, 151.04, 149.65, 139.25, 132.13, 130.99, 130.24, 130.10, 128.37, 128.85, 102.76, 96.25, 82.77, 80.22, 78.91, 78.00, 77.87, 76.26, 72.68, 70.66 , 68.74, 65.79, 65.55, 60.31, 52.93, 50.64, 49.44, 45.48, 45.27, 44.78, 39.07, 38.96, 36.86, 35.01, 34.92, 34.84, 32.60, 32.12, 29.66, 27.62, 21.87, 21.44, 21.38, 20.15, 18.86 , 18.66, 16.03, 14.20, 14.10, 10.22, 9.02. MS (APCI) (M + H) + at m / z 1066. Analysis calculated for C55H83Cl2N3? 13: C, 62.02; H, 7.85; N, 3.94; Found: C, 62.31; H. 7.80; N, 3.77.

EXAMPLE 79 11.12-CYCLICAL ICARBAMATE) OF 3'-N-DESM ETI L-3'-N-T3- (3- PIRIDYL) PROPYL1-11-DESOXY-11-rCARBOXY- (3,4- DICHLOROFENETILAMI O) 1-6-Q -METIL-ERITROMICI AA This material was prepared in a manner analogous to that used for the preparation of Example 1, but replacing the cyclopentanone with 3- (3-pyridyl) propanal. The crude product was purified on a column of silica gel (CHCl3-MeOH: CHCl3, 2:98). IR (MIC) a 2971, 2936, 1759, 1735, 1457, 1423, 1167, 1128, 1067, 1053, 1013 cm. "1. NMR with 13 C (CDCl 3) delta 216.32, 176.43, 157.20, 149. 78, 147.38, 139.33, 137.14, 135.82, 132.16, 131.03, 130.27, 130.12, 128.42, 123.34, 102.90, 96.23, 82.83, 80.20, 78.95, 7797, 77.93, 76.23, 72.72, 70.77, 68.86, 65.82, 65.33, 60.35, 52.59, 50.67, 49.51, 45.53, 45.29, 44.81, 39.12, 39.07, 38.99, 36.77, 34.91, 32.63, 30.48, 29.66, 29.53, 21.91, 21.46, 21.43, 20.18, 18.89, 18.71, 16.04, 14.20, 14.13, 10.25, 9.04 MS (APCI) m / z 1038 (M + H) +. Analysis calculated for C53H79Cl2N3Oi3: C, 61.37; H, 7.69; N, 4.05; Found: C, 61.61; H, 7.81; N, 3.98.

EXAMPLE 80 11.12- (CYCLE CARBAMATE OF 3'-N-DESMETIL-3'-N-r3-y3-PYRIDYL) PROPYL1-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4- FLUOROFENETILAMIN? N-6- O-METHYL-ERYTHROMYCIN A This material was prepared in a manner analogous to that used for the preparation of Example 79, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine The crude product was purified on a silica gel (CHCI3 - > MeOH: CHCl3, 2:98). 13 C NMR (CDCl 3) delta 216.31, 176.42, 157.22, 149.83, 147.45, 135.80, 131.07, 128.53, 123.35, 102.95, 96.25, 82.81, 80.28, 78.96, 78.00, 76.30, 72.74, 70.80, 68.90, 65.86, 65.39, 60.39, 52.66, 50.69, 49.52, 45.56, 45.33, 45.04, 39.16, 39.11, 39.03, 36.80, 34.92, 32.54, 30.52, 29.71, 21.95, 21.48, 21.43, 20.20, 18.91, 18.71, 16.04, 14.25, 14.15, 10.28, 9.07. MS (APCI) m / z 1034 (M + H) +.

Analysis calculated for C54H81CIFN3O? 3: C, 62.68; H, 7.91; N, 4.06; Found: C, 62.76; H, 7.87; N, 3.92.

EXAMPLE 81 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r3- (4- PLRIDIL) PROPIL1-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4- FLUOROFENETILAMINO) 1-6 -0-METHYL-ERLTROMYCIN A This material was prepared in a manner analogous to that used for the preparation of example 76, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine. The crude product was purified on a column of silica gel (CHCl3 - > MeOH: CHCl3, 5:95) and crystallized from acetonitrile; p.f. 162-3 ° C. IR (film) a 3312, 2972, 29.36, 1752, 1459, 1168, 1063, 1010 cm "1. NMR with 13 C (CDCI 3) delta 216.22, 176.33, 157.10, 156.65 (d, J = 247 Hz), 150.82, 149.62 , 146.69, 135.94 (d, J = 3.7 Hz), 130.93, 128.47 (d, J = 6.7 Hz), 126.09, 123.69, 120.39 (d, J = 17.4 Hz), 116.22 (d, J = 20.4 Hz), 102.75 , 96.10, 82.70, 80.06, 78.83, 77.81, 77.79, 76.14, 72.59, 70.67, 68.75, 65.67, 65.50, 60.23, 52.50, 50.56, 49.39, 45.43, 45.18, 44.90, 39.00, 38.97, 38.89, 36.66, 34.76, 32.53 , 32.40, 29.53, 28.77, 21.81, 21.35, 21.33, 20.07, 18.79, 1861, 1592, 14.11, 14.02, 10.16, 8.92 MS (APCI) at m / z 1034 (M + H) + Analysis calculated for C54H81 CIFN3O13: C, 62.68; H, 7.89; N, 4.06; Found: C, 62.40; H, 7.53; N, 3.89.

EXAMPLE 82 11.12- (CYCLICAL CARBAMATE) OF 3'-N-PESMETIL-3'-N-r3- (2-PIRIDYL) PROPIL1-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4- FLUOROPHENEYLAMINE) 1-6 -Q-METHYL-ERYTHROMYCIN A This material was prepared in a manner analogous to that used for the preparation of Example 77, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine. The crude product was purified on a column of silica gel (CHCl3 - > MeOH: CHCl3, 5:95) and crystallized from acetonitrile; p. F. 167-9 ° C. IR (film) a 3266, 2971, 2937, 1754, 1459, 1167, 1064, 1010, cm "1. NMR with 13 C (CDCl 3) delta 216.22, 176.33, 157.10, 156.8, (d, J = 247 Hz), 149.15, 136.4, 136.03, 13.04, 128.56 (d, J = 10 Hz), 122.84, 121.08, 120.40 (d, J = 17 Hz), 116.34 (d, J = 28 Hz) , 102.84, 96.20, 82.79, 80.08, 78.96, 77.95, 77.92, 76.26, 72.65, 70.61, 68.80, 65.82, 65.68, 60.34, 52.56, 50.67, 49.49, 45.53, 45.30, 45.01, 39.11, 39.01, 36.62, 35.54, 34.87 , 32.52, 29.65, 28.54, 21.93, 21.49, 21.43, 20.18, 18.89, 18.71, 16.04, 14.25, 14.14, 10.27, 9.06. MS (APCI) at m / z 1034 (M + H) +. Analysis calculated for C5 H81CIFN3O? 3: C, 62.68; H, 7.89; N, 4.06; Found: C, 62.64; H. 7.81; N, 3.99.

EXAMPLE 83 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-r4- (4-PIRIDYL) BUTIL1-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4- FLUOROFENETHYLAMINE) 1-6 -Q-METHYL-ERYTHROMYCIN A This material was prepared in a manner analogous to that used for the preparation of Example 78, but replacing 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine. The crude product was purified on a column of silica gel (CHCl3 -> MeOH: CHCl3, 5:95) (and crystallized from acetonitrile, mp 118-120 ° C. IR (film) 3437, 2971, 2938, 1755, 1459, 1167, 1055, 1011 cm "1. NMR with 13 C (CDCl 3) delta 216.23, 176.40, 157.17, 156.78 (d, J = 247 Hz), 151.07, 149.71, 136.03 (d, J = 5 Hz), 131.02, 128.52 (d, J = 5 Hz), 123.82, 120.61 (d, J = 14 Hz), 116.31 (d, J = 28 Hz), 102.89, 96.28, 82.76, 80.24, 78.98, 78.09, 77.92, 76.30, 72.71, 70.75, 68.84, 65.80, 65.62, 60.39, 52.91, 50.64, 49.45, 45.50, 45.32, 45.01, 39.15, 39.12, 39.01, 36.85, 35.05, 34.89, 32.51, 29.66, 29.61, 27.656, 21.92, 21.45, 21.41, 20.16, 18.86, 18.67, 16.02, 14.22, 14.09, 10.24, 9.01 MS (APCI) m / z 1048 (M + H) + Analysis calculated for C54H81CIFN3O13: C, 62.99; H, 7.98; N, 4.01; Found: C, 63.14; H, 7.95; N, 3.80.

EXAMPLE 84 11.12- (CYCLE CARBAMATE OF 3'-N-DESMETIL-3'-N-r4- (6-METlL) -2-PIRIDYLBUTYL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4-FLUOROPHENEYLAMIN)} -6-Q-METHYL-ERITROMICI AA This material was prepared in a manner analogous to that used for the preparation of example 80, but replacing 3- (3-pyridyl) propanal with [4- (6-methyl) - 2-pyridyl] butanal The crude product was purified on a column of silica gel (CHCl3-MeOH: CHCl3, 2:98), which produces the crystalline product: mp 68.78 ° C (acetonitrile). 2971, 2938, 1758, 1734, 1457, 1168, 1105, 1054, 1013 cm. "1. NMR with 13 C (CDCl 3) delta 216.31, 176.45, 157.78, 157.20, 136.67, 136.54, 136.09 (d, J = 3.7 Hz), 131.07, 128.58 (d, J = 7.3 Hz), 120.53, 119.62 (d, J = 20.8 Hz), 116.35 (d, J = 20.8 Hz), 102.93, 96.21, 82.81, 80.15, 78.99, 77.95, 77.63, 77.22, 76.53, 76.49, 76.30, 72.69, 70.70, 68.92, 65.84, 65.78, 62.43, 60.40, 50.69, 49.51, 45.56, 45.33, 45.04, 39.16, 39.11, 39.03, 38.34, 37.48, 36.86, 34.90, 32.54, 32.15, 27. 70, 25.92, 24.54, 21.95, 21.50, 21.47, 20.19, 18.89, 18.71, 16.03, 14.23, 14.13, 10.26, 9.00. MS (APCI) m / z 1062 (M + H) +. Analysis calculated for C56H85C1FN3013.1.75 H20: C, 61.46; H, 8.15; N, 3.83. Found: C, 61.54; H, 7.86; N, 3.76.

EXAMPLE 85 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (1 -METID-r3- (4-HYDROXY) PHENYL1PROPIL-11-DESOXY-11-rCARBOXY- (3,4- DICHLOROPHENETILAMI O) 1 -6-0-METHYL-ERYTHROMYCIN A This material was prepared in a manner analogous to that used for the preparation of Example 1, but replacing the cyclopentanone with 4- (4-hydroxyphenyl) -2-butanone The crude product was purified by crystallization from acetonitrile, mp 133-4 ° C, IR (MIC) 3396, 2971, 2937, 1760, 1735, 1458, 1168, 1053, 1012, 997 cm "1 .. NMR with 13 C (CDCl 3) delta 216.49, 176.50, 176.45, 157.33, 154.19, 139.20, 133.81, 133.63, 132.14, 130.99, 130.30, 130.23, 130.10, 129.31, 129.21, 128.37, 115.27, 115.22, 102.89, 102.75, 96.23, 96.18, 82.94, 80.01, 78.98, 78.02, 77.94, 77.91, 76.21, 72.66, 72.658, 70.80, 70.44, 68.86, 68.71, 65.73, 64.97, 63.34, 60.41, 58.50, 55.95, 50.61, 49.45, 45.46, 45.28, 45.78, 39.12, 38.95.37.69, 37.30, 34.83, 34.78, 33.79, 33.73, 33.64, 32.58, 32.38, 32.28, 31.83, 27.93, 23.53, 21.88, 21.45, 21.41 , 20.16, 18.80, 18.64, 17.50, 16.00, 14.15, 14.06, 10.20, 8.94 (more signals than carbons due to a mixture of diastereomers). MS (APCI) (M + H) + at m / z 1079. Analysis calculated for C56H84Cl2N2O1: C, 62.27; H, 7.84; N, 2.59; Found: C, 62.29; H, 7.67; N, 2.53.

EXAMPLE 86 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESM ETHYL-3'-NM-ETI D-r3- (4-HYDROXY) FENIL1PROPIL-11-DESOXY-11-rCARBOXY- (3-CHLORINE- 4- F LUOROF IN ETI LAM IN 0) 1 -6-O-METHYL-ERITRO Ml CINA A This material was prepared in a manner analogous to that used for the preparation of example 79, but replacing 3,4-dichlorophenethylamine with 3-chloro -4-fluorophenethylamine. The crude product was purified by crystallization from acetonitrile; p. F. 131-2 ° C. IR (MIC) a 3373, 2971, 2937, 1733, 1457, 1168, 1055, 1012 cm "1. 1 C NMR (CDCl 3) delta 216.42, 176.47, 158.42, 157. 30, 155.15, 154.03, 136.01, 135.96, 134.1, 133.9, 131.04, 129. 41, 129.37, 129.31, 128.60, 128.50, 120.65, 120.40, 116.47, 116. 18, 115.30, 115.24, 102.95, 102.82, 96.28, 96.25, 82.88, 80.09, 79.01, 78.12, 78.07, 77.99, 77.94, 77.19, 76.27, 72.71, 72.61, 70.85, 70. 48, 68.89, 68.76, 65.80, 65.04, 63.53, 60.42, 58.45, 56.05, 50 * 64, 49. 48, 45.51, 45.35, 45.01, 39.17, 39.00, 37.68, 37.34, 34.88, 34.81, 33. 79, 33.66, 32.51, 32.40, 32.33, 31.70, 29.68, 27.96 (21.92, 21.54, 21. 50, 21.42, 20.19, 18.85, 18.67, 17.63, 17.55, 16.03, 14.20, 14.09, 1025, 8.99 (more signals than real carbons, due to a mixture of diastereomers); MS (APCI) (M + H) + at m / z 1063. Analysis calculated for C56H84CIFN2O14: C, 63.23; H, 7.96; N, 2.63; Found: C, 63.45; H, 7.93; N, 2.48.

EXAMPLE 87 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-n-r3- (6-METI L-2-PIRIDYL) PROPIL1-11-DESOXY-11-rCARBOXY- (3-CHLORINE-4-) FLUOROFENETILAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A Step 1: Preparation of 3- (6-methyl-2-pyridyl) propin-1-ol To a solution of 3.0 g (17.4 mmol) of 2-bromo-6-methylpyridine in 30 ml / 6 ml of triethylamine / water, 65 mg of LiCl, 65 mg of CuBr and 1.06 g (19 mmol) of propargyl alcohol were added. Argon was slowly bubbled through the reaction mixture for 15 minutes before adding 150 mg of Pd (PPh3) 4. The reaction mixture was heated to reflux for 3 hours, under argon. After cooling to room temperature, the solvents were evaporated in vacuo and the brown residue was treated with 2N NaOH. The aqueous layer was extracted three times with chloroform, the organic layer was dried over magnesium sulfate and concentrated in vacuo. The product was purified by column chromatography (silica gel, ethyl acetate), which yielded a yellow solid (78%) MS (DCI) (M '+ H) + at m / z 148.

Step 1b: 3- (6-methyl-2-pyridyl) propanol. 3- (6-Methyl-2-pyridyl) propin-1 -ol was dissolved in 100 ml of MeOH and 0.09 g of PtO2 was added. The reaction mixture was hydrogenated at 4 atmospheres for 30 minutes. The catalyst was filtered off and methanol was evaporated in vacuo. 2 g of the orange oily residue was purified by chromatography (silica gel, ethyl acetate) which produced a yellow oil (77%). MS (DCI) (M + H) + at m / z 152.

Step 1c: 3- (6-methyl-2-pyridyl) propanal A solution of 1.78 g (22.9 mmol) of DMSO in 4 ml of dichloromethane, for 3 minutes, to a solution of 11.3 mmol of oxalyl chloride in 6 ml of dichloromethane, cooled to -78 ° C, under nitrogen. The reaction mixture was stirred for 5 minutes when 1.57 g (10.4 mmol) of 3- (6-methyl-2-pyridyl) propanol in 20 ml of dichloromethane was added over 5 minutes. Stirring was continued for 20 minutes at -78 ° C and 8 ml of triethylamine was added, which resulted in a dark suspension. The cooling bath was removed and after three hours the reaction mixture was quenched with brine, followed by extraction three times with dichloromethane. After removing the solvent, the dark residue was purified by column chromatography (silica gel, ethyl acetate) which produced a yellow oil (77%). MS (DCI) M + H) + at m / z 150.

Step 2: 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-r3- (6-methyl-2-pyridyl) propin-11-deoxy-11-rcarboxy- (3-chloro- 4-fluorophenethylamine) 1-6-Q-methyl-erythromycin A. The title compound was prepared analogously to that used for the preparation of example 80, but replacing 3- (3-pyridyl) propanal with 3- (6-methyl-2-pyridyl) propanal. The crude product was purified on a column of silica gel (CHCl3 -> MeOH: CHCl3, 2:98), which produced the crystalline product; p. F. 165-173 ° C. IR (MIC) a 2970, 2936, 1756, 1731, 1501, 1458, 117Q, 1104, 1092, 1061, 1012, 996 'cm. "1 NMR with 13, (CDCI3) delta 215.02, 175.18, 159.96,156.43, 155.89, 155.45 (d, J = 247 Hz), 135.31, 134.73 (d, J = 3.8 Hz), 129.72, 127.26 (d, J = 6.8 Hz), 119.20, 119.19 (d, J = 17.4 Hz ), 118.24, 115.02 (d, J = 21.2 Hz), 101.67, 94.89, 81.49, 78.71, 77.67, 76.61, 74.91, 71.31, 69.26, 67.53, 64.49, 59.02, 50.88, 49.35, 48.17, 44.21, 43.98, 43.69, 37.86, 37.68, 35.42, 34.17, 33.55, 31.20, 28.31, 27.26, 23.07, 20.60, 20.15, 20.10, 18.87, 17.56, 17.40, 14.71, 12.90, 12.80, 8.94,7.69. MS (APCI) m / z 1048 (M + H) +. Analysis calculated for C55H83CIFN3? 13: C, 62.99 * H, 7.98; N, 4.01; Found: C, 62.83; H, 8.09; N, 4.16.

EXAMPLE 88 11, "12- (CYCLE CARBAMATE OF 3'-N-DESMETIL-3'-N-r3- (5-METHYL-2-PIRlDIL) PROPILM1-DESOXY-11-rCARBOXY- (3-CHLORINE-4-FLUORO) - FENETILAMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared analogously to that used for the preparation of Example 80, but replacing 3- (3-pyridyl) propanal with 3- (5-methyl) -2-pyridyl) propanal The crude product was purified on a column of silica gel (CHC13-MeOH: CHQ | 3, 2:98), which produced the crystalline product: pf196-202 ° C. 2972, 2938, 1756, 1732, 1501, 1458, 1169, 1128, 1105, 1068, 1060, 1012, 997 cm. "1 NMR with 13 C (CDCl 3) delta 216.35, 176.49, 158.73, 157.21, 156.77 (d, J = 247 Hz), 149.44, 137.02, 136.07, 136.06 (d, J = 3.8 Hz), 131.04, 130.22, 128.59 (d, J = 6.9 Hz), 122.21, 120.52 (d, J = 17.4 Hz), 116.34 (d , J = 21.2 Hz), 105.50, 103.01, 96.21, 82.82, 80.08, 79.00, 77.94, 76.23, 72.65, 70.67, 68.87, 65.78, 65.69, 60.35, 2.71, 50.68, 49.47, 45.55, 45.31, 45.31 , 45.01, 39.16, 39.14, 39.01, 36.56 , 35.11, 34.88, 32.52, 29.61, 28.47, 21.93, 21.47, 20.19, 18.90, 18.72, 18.04, 16.04, 14.22, 14.13, 10.28, 9.00. MS (APCI) m / z 1048 (M + H) + Analysis calculated for C55H83ClFN3O? 3: C, 62.99; H, 7.98; N, 4.01. Found: C, 62.40; H, 8.06; N, 4.13.

EXAMPLE 89 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-PIRIDYL) ETHYL-11-DESOXY-11-rCARBOXY- (3,4- DICHLOROPHENYLAMIN-6-O-METHYL -ERITROMICI AA A reflux solution was heated at reflux for four days. (11) (described in example 1 (0.150 g, 0.161 mmol), 0 085 g, (0.805 mmol) of 2-vini Ipi ridi na and 0.048 g (0.046 ml, 0.805 mmol) of acetic acid in 3 ml of methanol The residue was partitioned between chloroform and saturated sodium bicarbonate solution, the organic layer was dried over anhydrous magnesium sulfate and the solvents were evaporated in vacuo The crude product was purified on silica gel column (CHCl3 -> MeOH : CHCl3, 5:95), which produced the crystalline product, mp 125-6 ° C (acetonitrile IR (MIC) a 3452, 2972, 2938, 1760, 1735, 1459, 1168, 1055, 1012, 1000 cm " 1. MS (APCI) (M + H) + at m / z 1036. Analysis calculated for C53H79Cl2N3O13: C, 61.38; H, 7.68; N, 4.05; Found: C, 61.25; H, 7.57; N, 4.05.

EXAMPLE 90 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (2-PYRIDIL) ETHYL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4- FLUOROFENETILAMINO) 1-6-Q-METHYL-ERITRONICI AA The title compound was prepared analogously to that used for the preparation of Example 89, but replacing it 3,4-dichlorophenethylamine with 3-chloro-4-fluorophenethylamine. The crude product was purified on a column of silica gel (CHCl3-MeOH: CHCl3, 5:95), which produced the crystalline product; p. F. 200-202 ° C (acetonitrile). IR (MIC) a 3452, 2972, 2938, 1757, 1732, 1459, 1168, 1055, 1012, 1000 cm "1. MS (APCI) (M + H) + at m / z 1020.

EXAMPLE 91 11,12-CYCLICAL FCARBAMATE) OF 3'-N-DESMETIL-3'-N- (4-HYDROXYBENCIL) -11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYL AMINO) 1-6-0- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxaldehyde with 4-hydroxybenzaldehyde. MS (APCI) (M + H) + at m / z 1037.

EXAMPLE 92 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (4-PYRIDYLMETHYL) -11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYL AMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxaldehyde with 4-pyridylcarboxyaldehyde. MS (APCI) (M + H) + at m / z 1022.

EXAMPLE 93 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-Nr (3-METHYLTlO) BUTIL1-11-DESOXl-11-rCARBOXI- (3,4-DICHLOROPHENYL AMINO) 1-6-Q-METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 55, but replacing the cyclopropanecarboxaldehyde with 3- (methylthio) butyraldehyde. MS (APCI) (M + H) + at m / z 1033.

EXAMPLE 94 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N- (1-METHYLCYCLOPROPYL) METHYL-11-DESOXY-11-rCARBOXY- (3,4-DICHLOROPHENYLAMINE) 1-6-Q -METIL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 1, but replacing the cyclopropanecarboxaldehyde with 2-methylcyclopropanecarboxyaldehyde. MS (APCI) (M + H) + at m / z 999.

EXAMPLE 95 11.12- (CYCLICAL CARBAMATE) OF 3'-DESMETIL-3'-N- (1-METHYLCYCLOPROPIL) METHYL-11-DESOXY-11-rCARBOXY- (3-CHLORO-4- FLUOROPHENEYLAMINE) 1-6-0-METHYL -ERITHROMYCIN A The title compound was prepared according to the method described in Example 29, but replacing the cyclopropanecarboxaldehyde with 2-methylcyclopropanecarboxyaldehyde. MS (APCI) (M + H) + at m / z 983.

EXAMPLE 96 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-OXYRANYLMEETHYL-11-DESOXY-11-rCARBOXY- (4- CHLOROPHENETHYLAMINE) 1-6-Q-METHYL-ERYTHROMYCIN A The compound of the title according to the method described in Example 57, but replacing ethyl isothiocyanate with epibromohydrin and triethylamine, and 3,4-dichlorophenethylamine with 4-chlorophenethylamine. MS (APCl) (M + H) + at m / z 981.

EXAMPLE 97 11.12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-GUANLDINO- 11-DES OXY-11-rCARBOXI- (4-C LO ROF IN ETI LAMIN Q) 1-6-Q-METI L- ERYTHROMYCIN A The title compound was prepared according to the method described in Example 96, but replacing it with epibromohydrin with 3,5-dimethylpyrazolecarboxamidine. MS (APCl) (M + H) + at m / z 939.

EXAMPLE 98 11,12- (CYCLICAL CARBAMATE) OF 3'-N-DESMETIL-3'-N-2- (4,5-DIHYDROIMIDAZOLYL) -11-DESOXY-11-rCARBOXY- (3,4- DICHLOROPHENETILAMINO) 1-6-Q- METHYL-ERYTHROMYCIN A The title compound was prepared according to the method described in Example 97, but replacing it with epibromohydrin with 3,5-dimethylpyrazolyl-4,5-dihydroimidazole. MS (APCl) (M + H) + at m / z 965.

Claims

CLAIMS 1.- A compound characterized because it is represented by the formula: ?, or its pharmaceutically acceptable salt or ester, where: A is selected from the group consisting of: (a) -C, (b) -N; and (c) -O; X and Y, independently in each occurrence, are selected from the group consisting of: (a) hydrogen; (b) haiogenide; (c) trifluoromethyl; (d) alkoxy; (e) alkyl; (f) aryl; and (g) substituted aryl; R is selected from the group consisting of: (a) alkyl, (b) cycloalkyl; (c) heterocyclic; (d) substituted heterocyclic, (e) alkylcycloalkyl, (f) substituted alkylcycloalkyl, (g) alkylaryl, (h) alkyheterocyclic, (>) alkenyl, (j) alkynyl, (k) -C (S) -NHR4, C (NR4) -NHR4, where R4 is hydrogen, alkyl or aryl; and (I) - (CH2) n-C (CH2) m-R5, where m is 2, 3, 4 or 5; and R5 is alkyl, alkoxy, aryl or substituted aryl; R2 and R3, independently in each occurrence, are: (a) hydrogen; (b) methyl; or R2 and R3 together form a cyclic portion, when A is C; R3 is absent when A is N; and n = 1, 2 or 3.
The compound according to claim 1, further characterized in that R is alkyl, alkenyl, cycloalkyl, heterocyclic (heterocyclic) alkyl or alkylcycloalkyl; X and Y are independently, in each occurrence: chlorine, fluorine, dioxolane, hydrogen or alkoxy; A is -C or N; R2 and R3 are independently, in each occurrence, hydrogen; or together form the cyclopropyl moiety; and n is 1.
3. A compound according to claim 1, further characterized in that it is selected from the group consisting of: 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl- 11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-0-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclohexyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylammon) j-6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isovaleryl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-methylthiopropyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl -erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-methithiopropyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl -erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-tetrahydrothienyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamine)] - 6-O -methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3,4-dimethylcyclopentyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamine)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichlorophenethyl)] - 6- 0-methyl-eritrorr? Icine A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichlorophenethyl-amino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (a, a-cyclopropyl-3,4-dichlorophenethyl-amine)] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclohexyl-11-deoxy-11- [carboxy (a, -cyclyopropyl-3,4-dichlorophenethyl-amino)] - 6- O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-dioxolanophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3,4-dioxolanophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-Nn-propyl-11-deoxy-11- [carboxy (4-chloro-3-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (4-chloro-3-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11 - [carboxy - (4-chloro-3-f-luo-phenethylamino)] - 6-O-methyl- erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutylmethyl-11-deoxy-11 - [carboxy (4-chloro-e-nylamino)] - 6-O- met i I-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutylmethyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 1, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-ethyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (4-cioophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3-chlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3-chloro-phenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-0-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3,4-difluorophenethylammon)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3,4-difluorof eneti lami)] - 6-O-methyl -erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-pyridylmethyl) -11-deoxy-11- [carboxy (4-chlorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-butyl) -11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-N- (3-pentyl) -11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromy Na A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (cyclopropylmethyl) -11-deoxy-11- [carboxy (4-chlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-cyclopropylethyl) -11-deoxy-11- [carboxy (4-chloro-phenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (4-methoxyphenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-methoxyphenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (3,4-dimethyl-phenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethi-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3-bromo-4-methoxyphenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (3-bromo-4-methoxyphenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy- (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-furi!) Methyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-N- [2- (5-hydroxymethyl) furyl] methyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino )] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridyl) methyl-11-deoxy-11- [carboxy (3-chloro-4-fluoro-fexy-amino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2- (6-methyl) pyridyl] methyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethyl amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-hydroxyethoxybenzyl) -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethyl-amino)] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-methylthio) butyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamine)] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4,4,4-tri-fluoro-butyl) -11-deoxy-11- [carboxy (3-chloro-4-fluorofenetyl) i no)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (4-chloro-3-fluorophenethylamino)] - 6-O-methyl-erythromycin TO; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy [3,4- (1,4-dioxane) phenethylamino)]] - 6 -O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-0-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (methylsulfoxy) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino) j-6- O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N-ethylthiourea-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2- (5-hydroxymethyl) furyl] methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethyl) amino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (, a-cyclopropyl-3,4-dichloro-phenethylamino)] - 6- O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-propyl-11-deoxy-11- [carboxy (4-chloroanilinoethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (4-chloroanilinotylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-imidazole) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (3-pyridyl) methyI-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O- metfl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N - [(5-nitro) -2-thienyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino) ] -6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [5- (4-chlorophenyl) -2-furyl] methyl-11-deoxy-11- [carboxy (3, 4-dichlorophenethyl amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [5-nitro-2-furyl] methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [2,5-dimethoxy-3-tetrahydrofuryl] methyl-11-deoxy-11- [carboxy (3,4-dichloro-phenethylamino )] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-desmetM-3'-N- [6-methyl-2-pyridyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-0-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4,4,4-trifluorobutyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6 -0-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (1-bromo-2-naphthyl) methyl-11-deoxy-11- [carboxy- (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-methyl-1-naphthyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethylamino) j- 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-dimethylamino-1-naphthyl) methyl-11-deoxy-11- [carboxy (3,4-dichlorophenethyl) amino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-furii) methyl-11-deoxy-11 - [carboxy- (3,4-dichlorophenethylamino)] - 6-O- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (4-pyridyl) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (2-pyridyl) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-3- [4- (4-pyridyl) butyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino) ] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (3-pyridyl) propyl] -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N - [(3- (3-pyridyl) propyl] -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino )] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (4-pyridyl) propyl] -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamine)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-N- [3- (2- pyridyl) propyl] -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamine)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N- demethyl-3'-N- [4- (4-pyridyl) butyl] -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin A; - (cyclic carbamate) of 3'-N-demethyl-3'-N- [4- (6-methyl-2-pyridyl) butyl] -11-deoxy-11- [carboxy (3-chloro-4-fluorophenethyl) amino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [1-methyl-3- (4-hydroxyphenyl) propyl] -11 -deoxy-11- [carboxy (3,4-dichlorophenethyl amino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N - [( 1-methyl) - 3- (4-hydroxyphenyl) propyl] -11-deoxy-11- [carboxy (3-chloro-4-fluoro-phenethylamino)] - 6-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (6-methyl-2-pyridyl) propyl] -11-deoxy-11- [carboxy (3-chloro- 4-fluorophenethyl amino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- [3- (5-me ti l-2-pyridyl) propyl] -11-deoxy-11- [carboxy (3- chloro-4 -fluoro-faith, netil-amino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridylethyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl -erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (2-pyridylethyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O- methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-hydroxybenzyl) -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate) of 3'-N-demethyl-3'-N- (4-pyridyl) methyl-11-deoxy-11- [carboxy (3,4 -dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate of 3'-demethi-3'-N- (1-methylcyclopropyl) methyl-11-deoxy-11- [carboxy (3 , 4-dichlorophenethylamino)] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate of 3'-demethyl-3'-N- (1-methylcyclopropyl) m ethyl-11-deoxy-11- [ca rbox- (3-chloro-4-f Iorophenethyl-amino)] -6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate of 3'-demethyl-3'-N-oxiranylmethyl-11-deoxy- 11- [carboxy- (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11,12- (cyclic carbamate of 3'-demethyl-3'-guanidino-11-deoxy-11 - [carboxy] - (3, 4-di-chloro-fexylamino)] - 6-O-methyl-erythromycin A; 11, 12- (3'-demethyl-3'-N-2- (4,5-dihydroimidazolyl) -11-deoxy-11- [carboxy- (3,4-dichlorophenethylamino)] -6-O- cyclic carbamate methyl-erythromycin A;
4. A compound according to claim 3, further characterized in that it is selected from the group consisting of: 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopropyl -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-Nn-propyl -11-deoxy-11- [carboxy (3,4-dichlorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-isopropyl 11-deoxy-11 - [carboxy- (3-chloro-4-fluoro-e-cytamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3 ' -N-cyclopropylmethyl-11-deoxy-11- [carboxy (3-chloro-4-fluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclobutyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-cyclopentyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; 11, 12- (cyclic carbamate) of 3'-N-demethyl-3'-N-n-propyl-11-deoxy-11- [carboxy (3,4-difluorophenethylamino)] - 6-O-methyl-erythromycin A; and 11, 12- (cyclic carbamate) of 3'-N-desmethyl-3'-N-cyclopropylmethyl-11-deoxy-11- [carboxy (3,4-di-fluoro-phenethylamino)] - 6-O-methyl-erythromycin A
5. A pharmaceutical composition for inhibiting the release of LH, characterized in that it comprises a therapeutically effective amount of a compound according to claim 1, in combination with a pharmaceutically acceptable carrier.
6. A method for inhibiting the release of LH in a mammal in need of such treatment, characterized in that it comprises administering to the mammal a therapeutically effective amount of a compound, in accordance with claim 1.
7.- A process for preparing a compound represented by the formula: or its pharmaceutically acceptable salt or ester, wherein: A is selected from the group consisting of: (a) -C, (b) -N; and (c) -O; X and Y, independently in each occurrence, are selected from the group consisting of: (a) hydrogen; (b) halide; (c) trifluoromethyl; (d) alkoxy; (e) alkyl; (f) aryl; and (g) substituted aryl; R is selected from the group consisting of: (a) alkyl, (b) cycloalkyl; (c) heterocyclic; (d) substituted heterocyclic, (e) alkylcycloalkyl, (f) substituted alkylcycloalkyl, (g) alkylaryl, (h) alkylheterocyclic, (i) alkenyl, (j) alkynyl, (k) -C (S) -NHR4, C ( NR4) -NHR4, where R4 is hydrogen, alkyl or aryl; and (I) - (CH2) n-C (CH2) m-R5, where m is 2, 3, 4 or 5; and R5 is alkyl, alkoxy, aryl or substituted aryl; R2 and R3, independently in each occurrence, are: (a) hydrogen; (b) methyl; or R2 and R3 together form a cyclic portion, when A is C; R3 is absent when A is N; and n = 1, 2 or 3; characterized in that it comprises the steps of: (a) reacting a compound of the formula: with sodium hexamethyldisilazide and carbonyldiimidazole, to produce a compound of the formula: (b) reacting the compound obtained in step (a) with an amino compound of the formula: followed by deprotection of the 2 ', 4"-protected hydroxyl groups, to give a compound of the formula: (c) demethylating the 3'-amino, treating the compound obtained in step (b), to give a compound of the formula: (d) alkylating the 3'-N-demethylated compound obtained in step (c), with an alkylating agent.
8. The process according to claim 7, further characterized in that the reaction of step (a) is carried out in an aprotic solvent at 0-25 ° C.
9. The process according to claim 7, further characterized in that the reaction of step (b) is carried out without solvent or in acetonitrile at 25-80 ° C.
10. The process according to claim 7, further characterized in that demethylation is carried out by reaction of the compound obtained in step (b) with iodine, in the presence of a base and a source of light or heat.
11. The process according to claim 7, further characterized in that the demethylation is carried out by reaction of the compound obtained in step (b) with a chloroformate selected from the group consisting of benzyl chloroformate, allyl chloroformate and chloroformate. of vinyl.
12. The process according to claim 7, further characterized in that the alkylation of step (d) is obtained by reacting the compound obtained in step (c) with an aldehyde or ketone, in the presence of a metal hydride, or in the presence of Pd / C catalyst, in a protic or non-protic solvent, under nitrogen.
13. The process according to claim 7, further characterized in that the alkylation of step 8d) is obtained by reacting the compound obtained in step 8c) with an alkyl halide, in the presence of a base.
14. The process according to claim 7, further characterized in that R is alkyl, alkenyl, cycloalkyl, heterocyclic, (heterocyclic) alkyl or alkylcycloalkyl; X and Y are independently, in each occurrence, chloro, fluoro, dioxolane, hydrogen or alkoxy; A is -C; R2 and R3 are independently, in each occurrence, hydrogen; or together form the cyclopropyl moiety; and n is 1.
15. The process according to claim 7, further characterized in that the alkylating agent is cyclopentanone and alkylation is carried out in the presence of sodium cyanoborohydride in methanol.