MXPA01005174A

MXPA01005174A - Acetal benzylmaltosides as inhibitors of smooth muscle cell proliferation

Info

Publication number: MXPA01005174A
Application number: MXPA/A/2001/005174A
Authority: MX
Inventors: Paul Jeffrey Dollings
Original assignee: American Home Products Corporation
Priority date: 1998-11-24
Filing date: 2001-05-23
Publication date: 2001-12-04

Abstract

This invention provides smooth muscle cell proliferation inhibitors of formula (I), or pharmaceutically acceptable salts thereof.

Description

ACCIDAL BENZYLMALTOSIDES AS SMOOTH MUSCLE CELL PROLIFERATION INHIBITORS BACKGROUND OF THE INVENTION This invention relates to the use of substituted 4 ', 6'-acetal benzylaltosides as inhibitors of smooth muscle cell proliferation and as therapeutic compositions for treating diseases and conditions which are characterized by excessive proliferation of smooth muscle such as restenosis. . All forms of vascular reconstruction such as angioplasty and venous bypass procedures carry out a response to damage that ultimately leads to proliferation of smooth muscle cells (SMC) and subsequently, deposition of profuse amounts of extracellular matrix. (Clowes, A. W.: Reidy, M.A. J. Vasc. Surg- 1991, 13, 885). These phenomena are also central processes in the pathogenesis of atherosclerosis (Raines EW, Ross, R. Br, Heart J. 1993, 69 (supplement), S. 30) as well as transplant arteriosclerosis (Isik, FF, McDonald, TO, Ferguson , M., -Yamanaka, E., Gordon Am. J. Pathol, 1992, 141, 1139). In the case of restenosis after angioplasty, the solution is clinically important to control the proliferation of SMC Ref: 129140 through the pharmacological intervention have remained elusive until now (Herrman, J. P. R., Hermans, W. R. M., Vos, J., Serruys P., Drugs 1993, 4, 18 and 249). Any successful approach for the inhibition of selective SMC proliferation should not interfere with endothelial cell repair or the normal proliferation and function of other cells (eissberg, PL, Grainger, DJ, Shanahan CM, Metcalfe, JC, Cardiovascular Res. , 27, 1191). Glycosaminoglycans heparin and heparan sulfate are endogenous inhibitors of SMC proliferation, although they are able to promote the growth of endothelial cells (Castellot, JJ Jr., Wright, T.C. Karnovsky, MJ Seminars in Thromobosis and Hemostasis 1987 , 13, 489). However, the full clinical benefits of heparin, heparin fragments, chemically modified heparin, low molecular weight heparins, and other anionic polysaccharides that mimic heparin may be compromised due to other pharmacological abilities (excessive bleeding arising from the effects of anticoagulation in particular) coupled with heterogeneity of the various preparations (Bor an, S. Chemical and Engineering News 1993, June 29, 27). WO 96/14325 describes acylated benzyl glycosides as inhibitors of smooth muscle cell proliferation. The compounds of the present invention differ in that the substituents of the carbohydrate backbone are different. Zehavi, U., in Carbohyd. Res. 1986, 151, 371, describes 4-0-α-D-glucopyranosyl-β-D-glucopyranoside of 4-carboxy-2-nitrobenzyl which binds to a polymer for study as an acceptor in the glycogen synthase reaction. The compounds of the present invention differ in that the substituents on the benzyl groups are different and (c) the use (antiproliferation of smooth muscle) is different. United States Patents Numbers 5,489,775, W096 / 14324 and US 5,464,827 describe benzyl polyanionic glycosides or cyclodextrins as inhibitors of smooth muscle cell proliferation to treat diseases and conditions which are characterized by excessive proliferation of smooth muscle. Β-cyclodextrin tetradecasulfate has been described as an inhibitor of smooth muscle cell proliferation and is an effective inhibitor of restenosis (Reilly, CF; Fujita, T .; McFall, RC; Stabilito, II; Wai-se E .; Johnson, RG Drug Development Research 1993, 29, 137). US 5019562 discloses anionic derivatives of cyclodextrins for treating pathological conditions associated with undesirable cell or tissue growth. WO 93/09790 describes antiproliferative polyanionic derivatives of cyclodextrins having at least two anionic residues per carbohydrate residues. Meinetsberger (EP 312087 A2 and EP 312086 A2) describes antithrombotic and anticoagulant properties of bis-aldone sulphated acid amides. US 4431637 describes polysulphated phenolic glycosides as modulators of the complement system. The compounds of the present invention differ from all those of the prior art in that the compounds (a) are benzylaromosides of 4 ', 6 '-acetal which do not present structural similarity to heparin, sulphated cyclodextrins or dimers of sulphated lactobionic acid, (b) contain at most two contiguous sugar residues (disaccharides), (c) are of a defined structure, (d) and they are not sulfated.

DESCRIPTION OF THE INVENTION This invention provides benzyl maltosides of 4 ', 6' acetal of formula I where W is S, SO, S02, NR; And it is O, S, NR or CH2; R is hydrogen or alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 and R7 are each independently alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms carbon, alkoxyalkyl of 2 to 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- - or trisubstituted with R8, pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms, algayl of 1 to 6 carbon atoms, perfluoroalguyl of 1 to 6 carbon atoms, benzyl , wherein the phenyl portion is mono-, di- or tri-substituted with R8, benzoyl wherein the phenyl portion is mono-, di- or trisubstituted with R8; R8 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN. -N02, halogen or -CF3; R9 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, -NHC02R13, -NHS02R13, -NR14R15, R 10, R 11 and R 12 are each independently hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, - CN, -N02, halogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms or benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R 13 is alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted by halogen; R14 and R15 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n = 0-3; or a pharmaceutically acceptable salt thereof.

The terms alkyl, alkoxy and acyl include both the straight chain as well as the branched portions optionally substituted with fluorine. Halogen means bromine, chlorine, fluorine and iodine. The pharmaceutically acceptable salts can be formed from organic and inorganic acids, for example acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric. , methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic and acceptable acids known in a similar manner. The salts can also be formed from organic and inorganic bases, preferably alkali metal salts, for example sodium, lithium or potassium. The acid addition salts can be prepared when Y is nitrogen or the compound of formula I contains a basic nitrogen and the acid addition salts can typically be prepared when the compound of formula I contains a hydroxyl group. The compounds of this invention may contain an asymmetric carbon atom or a sulfoxide moiety and some of the compounds of this invention may contain one or more asymmetric centers and therefore may generate optical isomers and diastereomers. Although shown without respect to any stereoguimics in formula I, the present invention includes such optical isomers and diastereomers; as well as the racemic and separated stereoisomers, enantiomerically pure R and S; as well as other mixtures of R and S stereoisomers and pharmaceutically acceptable salts thereof. Preferred compounds of this invention are 4 ', 6'-acetal benzylaromosides of the formula I where W is S, SO, S02, NR; And it is 0; R is hydrogen or alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 is alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms, alkoxyalkyl of 2 at 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- or trisubstituted with R8 , pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroacyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms or perfluoroalkyl of 2 to 7 carbon atoms; R7 is hydrogen, methyl or phenyl; R8 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen or -CF3; R9 is hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, -NHC02R13, -NHS02R13, -NR14R15, R10, R11 and R12 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, -CF3, acyl of 2 to 7 carbon atoms or benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R 13 is alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with halogen; R14 and R15 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n = 0-3; or a pharmaceutically acceptable salt thereof. The most preferred compounds of this invention are benzyl maltosides of formula I where W is S, SO, S02, NR; And it is 0; R is hydrogen or alkenyl of 1 to 6 carbon atoms; R1 is phenyl mono-, di- or trisubstituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen or acyl of 2 to 7 carbon atoms; R7 is hydrogen, methyl or phenyl; R8 is hydrogen, alkoyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl, -CN. -N02, halogen or -CF3; R9 is hydrogen, -N02, halogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, -NHC02R13, -NR14R15, R10, R11 and R12 are each independently hydrogen, alkoyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, -CF3, acyl of 2 to 7 carbon atoms , or benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R 13 is alkenyl of 1 to 6 carbon atoms; R 14 and R 15 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n = 0-3; or a pharmaceutically acceptable salt thereof. The specifically preferred compounds of this invention are: N-. { 5 - [(2,3,2 ', 3'-tetra-0-acetyl-6-deoxy-6-benzylsulfanyl-4', 6'-O-benzylidene-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl) -acetamide or a pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfanyl-ßD-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or a pharmaceutically acceptable salt thereof; N- (5- { [2,3,2 ', 3' -tetra-0-acetyl-6-deoxy-6- (2,4-dichloro-benzylsulfane) - ', 6' -O-benzylidene- ßD-maltosyl] -oxymethyl.} -2-chloro-phenyl) acetamide or a pharmaceutically acceptable salt thereof; N- (5- { [4 ', 6'-O-benzylidene-6-deoxy -6- (2,4-dichloro-benzylsulfane) -β-D-maltosyl] -oxi-methyl.} -2 -chloro-phenyl) -acetamide or a pharmaceutically acceptable salt thereof; N-. { 5- [(2, 3, 2 ', 3' -tetra-O-acetyl-4 ', 6' -O-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxy-methyl] - 2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-d-benzylsulfinyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfonyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(2,2 ', 3,3' -Tetra-O-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6-phenylsulfanyl-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-phenylsulfanyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(2,2 ', 3,3'-tetra-0-acetyl-4', 6'-O-benzylidene-6-deoxy-6-phenylsulfinyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-phenethylsulfanyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(2,2 ', 3,3'-tetra-0-acetyl-4', 6 '-0-benzylidene-6-deoxy-6-phenethylsulphane-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N- (5- [(4 ', 6' -0-benzylidene-6-deoxy-6- (phenyl-ethyl-sulfinyl) -β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof: N- (5- {[4 ', 6' -O-benzylidene-6-deoxy-6- (3-phenyl-propylsulfane) -β-D-maltosyl) -oxi-methyl.} -2-chloro-phenyl) -acetamide or a pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; N- (5- { [4 ', 6' -0-benzylidene-6-deoxy-6- (2-phenyl-1-oxo-ethyl-amino) -β-D-maltosyl] -oxi-methyl} -2-chloro-phenyl) -acetamide or an acceptable pharmaceutically acceptable salt thereof; N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-phenethyl-sulphane) -β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof; and methyl ester of N- acid. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfinyl) -β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -carbamic or an acceptable pharmaceutically acceptable salt thereof. The compounds of this invention are prepared according to the following scripts from commercially available starting materials or starting materials which can be prepared using literature procedures. This reaction template shows the preparation of representative compounds of this invention. Acetobromomaltose 1 is coupled with benzyl alcohol 2 in the presence of a catalyst such as mercuric bromide, mercuric cyanide, silver triflate or silver perfluoroate in an aprotic solvent such as acetonitrile, dichloromethane, ether, toluene or nitromethane at temperatures varying from - 40 ° C to reflux temperature to provide glycoside 3 (Reaction Scheme 1). These glycosidation can also be carried out using the coupling of Schmidt's trichloroacetimidate, with zinc bromide in a solvent such as dichloromethane. The reduction of the nitro group of 3 can be carried out with a reducing agent such as stannous chloride in a polar aprotic solvent such as ethyl acetate at room temperature to reflux to provide the anilino compound 4. The coupling of 4 with an acid chloride or a sulfonyl chloride can be completed in the presence of an amine base such as triethylamine or diisopropylethylamine or using a stronger base such as sodium hydride (for sterically hindered systems) in an aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures ranging from 0 ° C to room temperature to provide the target compound 5. The peracetylated compound 5 can be converted to the heptahydroxy compound 6 with catalytic sodium methoxide in methanol or aqueous sodium hydroxide in methanol at temperatures which vary from room temperature to reflux. As illustrated in Reaction Scheme 2, the 4 'and 6' groups of 6 can be reacted with an acetal in the presence of an acid catalyst such as camphorsulfonic acid or p-toluenesulfonic acid in a polar aprotic solvent such as N, N-dimethylformamide at temperatures ranging from 25 to 25%. ° C at reflux to provide the acetal derivative 7. The acetal 7 can be converted to the 6-tosylate 10 using tosyl chloride and pyridine in a solvent such as dichloromethane (Reaction Scheme 3); the resulting intermediate is then peracylated with an acid chloride or an acid anhydride in the presence of an amine base such as triethylamine or diisopropylethylamine in an aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures ranging from 0 ° C to room temperature to generate compound 11 In Reaction Scheme 4, the tosylate intermediate 11 can be converted to a thioether via direct displacement with a sulfide nucleophile generated from a base such as sodium hydride and a suitable thiol in a polar solvent such as N , N-dimethylformamide. This thioether intermediate can then be subjected to hydrolysis conditions as previously mentioned to provide 13 (W = S). Alternatively, the thioether intermediate can be oxidized with one or two equivalents of m-chloroperoxybenzoic acid followed by hydrolysis to generate 13 as a sulfoxide or a sulfone respectively (W = SO or S02). The composition C-6 can also be converted to an amine or amide bond by first converting the tosylate 11 to an azide (Reaction Scheme 5); this reaction can be carried out using sodium azide in a polar solvent such as N, N-dimethylformamide at 50 ° C. The intermediate can be reduced to a primary amine with triphenylphosphine and 5% water in tetrahydrofuran. The amine can be coupled to an appropriate acid chloride in the presence of a base such as pyridine in an aprotic solvent such as tetrahydrofuran or dichloromethane followed by standard hydrolysis conditions to provide compound 14. The amine or amide intermediate 14 can be an alkenyl halide in the presence of a base such as sodium hydride (for sterically-hindered systems) in a polar solvent such as N, N-dimethylformamide at temperatures ranging from 0 ° C to reflux. If desired during the development of the synthesis sequence, the free hydroxyl groups of the compounds 10, 13 and 14 can be derivatized (form derivatives). For example, the free hydroxyl groups of compounds 10, 13 and 14 can be acylated with an acid chloride or an acid anhydride in the presence of an amine base such as triethylamine or diisopropylethylamine in an aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures which vary from 0 ° C to room temperature. Alternatively, the free hydroxyl groups of compounds 10, 13 and 14 can be alkylated with an appropriate alkyl halide in the presence of a base such as sodium hydride or potassium hydroxide in a polar solvent such as N, -dimethylformamide or DMSO at temperatures that vary from 0 ° C to reflux. Reaction Scheme 1 acylation twenty Diagram of Reaction 2 C-4 ', 6' -formation of the acetal Reaction Scheme 3 Tosilation 10 peracetylation 20 Reaction Scheme 4 1) thioester formation W S, SO or S02 25 Reaction Scheme 5 1. Azide formation amide The compounds of this invention are useful as 25. antiproliferative agents. The following procedures show the evaluation of the representative compounds of this invention in a standard pharmacological test procedure which measures the ability of the evaluated compound to inhibit the proliferation of smooth muscle cells.

Effects of the Compounds on Cell Proliferation Using 3H Thymidine Incorporation Human and porcine smooth muscle cells are tested in an early passage (generally passage 3-7) under subconfluence conditions. The cultures are grown in 24 16 mm wells in multiple well culture plates in medium 199 supplemented with 10% fetal bovine serum and 2% antibiotic / antifungal. In the subconfluence, the cells are placed in a defined serum-free medium (AIM-V, Gibco) for 24-48 h before initiating the experimental protocol. It has been found that the compounds are more effective with longer preincubations, in general, the procedures are initiated with the addition of the compound, 3H-thymidine and serum / growth factor for synchronized cells lacking serum and the results are presented accordingly . The compounds are added to each well in a 50-fold dilution (20 μl / well) and the plates are incubated for 23-36 h at 37 ° C. in C02 5%. The compounds initially dissolve in 50% ethanol and are diluted serially in medium. The compounds are evaluated systematically at concentrations of 1 to 100 μM. As a control, heparin of porcine intestinal mucosa grade II (sodium salt) is systematically evaluated in all cell preparations at concentrations of 0.1 to 100 μg / ml. Upon completion of the test procedure, plates are placed on ice, washed three times with ice-cold phosphate buffered saline (PBS) and incubated in ice-cold 10% trichloroacetic acid (TCA) for 30 minutes to remove proteins. soluble in acid. The solution is transferred to scintillation flasks containing 0.4 N HCl (500 μl / bottle to neutralize NaOH) and each well is rinsed twice with 500 μl of water for a total volume of 2 ml / vial. The data is obtained in triplicate for both control and experimental samples. Control data (100%) are obtained from maximally stimulated cells, as a result of growth factor or serum stimulation. Experimental data are obtained from cells maximally stimulated with growth factor or serum and treated with compound. The data are expressed as IC50 in Table I below.

Table 1 The compounds of this invention are useful for treating or inhibiting diseases which are characterized by excessive proliferation of smooth muscle cells. (hyperproliferation of smooth muscle cells). The compounds are particularly useful for treating hyperproliferative vascular diseases which are characterized by hyperproliferation of smooth muscle cells, such as restenosis, which arise more frequently from vascular reconstructive surgery and transplantation, eg balloon angioplasty, vascular graft surgery , coronary artery bypass surgery and cardiac transplant. Other disease states in which there is "unwanted" vascular proliferation include hypertension, asthma, and congestive heart failure. The compounds of this invention are also useful as inhibitors of angiogenesis. Angiogenesis (neovascularization), the process by which new capillaries are formed, is of fundamental importance for numerous pathological processes that include chronic inflammation and malignant cancer processes. Thus, the compounds of this invention are useful as antineoplastic agents. The compounds of this invention can be formulated pure or with a pharmaceutical carrier for administration, the proportion of which is determined by the solubility and guialic nature of the compound, chosen route of administration and standard or conventional pharmacological practice. The pharmaceutical carrier can be a solid or a liquid. A solid carrier can include one or more substances which also act as flavoring agents, lubricants, solubilizers, suspension improving agents, fillers, fluidizers, compression aids, binders or tablet disintegrating agents.; It can also be an encapsulating material. In powders, the carrier is a finely divided solid which is in admixture with a finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and contacted in the size and shape desired. The powders and tablets preferably contain up to 99% active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidine, waxes with a low melting point and exchange resins. ionic. Liquid carriers are used for the preparation of solutions, suspensions, emulsions, syrups, elixirs and pressurized compositions. The active ingredient can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water or an organic solvent, or a mixture of both, or pharmaceutically acceptable oils or fats. The liquid carrier may contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspension improving agents, thickening agents, colors, viscosity regulators, stabilizers and osmo-regulators. Suitable examples of liquefied carriers for oral and parenteral administration include water (which partially contains additives as in the above, for example cellulose derivatives, preferably a solution of sodium carboxymethylcellulose), alcohols (including monohydric alcohols and polyhydric alcohols, for example glycols) and their derivatives, lecithins and oils (for example fractionated coconut oil and peanut oil). For parenteral administration, the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile, liguid carriers are useful in sterile, liguid form compositions for parenteral administration. The liquid carrier for pressurized compositions may be a halogenated hydrocarbon or other pharmaceutically acceptable propellant. Liquid pharmaceutical compositions which are sterile solutions or suspensions may be used, for example, by intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be given intravenously. The compounds of this invention can also be administered orally in either a liquid or a solid composition form. The compounds of this invention can be administered rectally or vaginally in the form of a conventional suppository. For administration by intranasal or intrabronchial inhalation or insufflation, the compounds of this invention can be formulated in an aqueous or partially aqueous solution, which can then be used in the form of an aerosol. The compounds of this invention can also be administered transdermally by means of the. use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is not toxic to the skin and allows the delivery of the agent for systemic absorption into the bloodstream via the skin. The carrier can take many of the forms such as creams and ointments, pastes, gels and occlusive devices. The creams and ointments can be a viscous liquid or semi-solid emulsions either oil-in-water or water-in-oil type. Pastes composed of absorptive powders dispersed in petroleum or hydrophilic oil containing the active ingredient may also be suitable. Various occlusive devices can be used to release the active ingredient into the bloodstream such as a semipermeable membrane that covers a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient. Other occlusive devices are known in the literature. The dosage requirements vary with the particular compositions used, the route of administration, the severity of the symptoms presented and the particular subject in question. Based on the results obtained in standard pharmacological test procedures, the daily dosages presented of the active compound would be 0.1 to 10 mg / kg administered parenterally (preferred intravenously) with a projected daily oral dosage of approximately 10 times greater. Early intravenous administration can last for approximately 5-30 days after acute vascular damage (ie, balloon angioplasty or transplarite) and for a longer duration for the treatment of chronic disorders. Treatment will generally begin with lower dosages than the optimal dose of the compound. Subsequently the dosage is increased until the optimum effect is reached under the circumstances; The precise dosages for oral, parenteral, nasal or intrabronchial administration will be determined by the doctor performing the administration based on the experience with the individual subject treated. Preferably, the pharmaceutical composition is in a unit dosage form, for example as tablets or capsules. In such form, the composition is subdivided into unit doses containing appropriate quantities of the active ingredient; the unit dosage forms may be packaged compositions, for example packaged powders, flasks, ampoules, pre-filled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. The following provides the preparation of representative compounds of this invention.EXAMPLE 1 H-. { 5 - [(2,3,2 ', 3'-tetra-O-acetyl-6-deoxy-6-benzylsulfane-4-d 6' -O-benzylidene-β-D-maltosyl) -oxy-methyl] -2 -chloro-phenyl. { -acetamide Stage 1 4-chloro-3-nitro-benzyl-β-D-maltoside heptaacetate To a stirred solution of 4-chloro-3-nitrobenzyl alcohol (6.70 g, 35.7 mmol) and HgBr2 (14.2 g, 39.3 mmol) in 239 ml of freshly distilled CH3CN are added, in one portion, Hg (CN) 2 (9.02). g, 35.7 mmoles). After 0.5 h, acetobromomaltose (25.0 g, 35.7 mmol) is added and the mixture is stirred for 18 h at room temperature (rt). Subsequently the reaction is suspended with a mixture of H20: brine (1: 1, 100 ml) and extracted with CH2C12 10% CH2C12: EtOAc. The combined organic extracts are dried with MgSO 4 and concentrated. Purification on silica gel (gradient from 10:90 to 80:20 of EtOAc: petroleum ether) gives 51.9 g (90%) of the title compound as a glassy oil which recrystallizes from Et20: petroleum ether for provide a vitreous white solid, mp 107-111 ° C; XH NMR (CDC13) d 2.00 (s, 3H), 2.02 (s, 3H), 2.03, (s, 3H), 2.04 (s, 6H), 2.11 (s, 3H), 2.15 (s, 3H), 3.70 (ddd, J = 2.9, 4.2, 9.7 Hz, 1H), 3.94-3.98 (m, 1H), 4.01-4.07 (m, 2H), 4.20-4.28 (m, 2H), 4.54 (dd, J = 2.9, 12.3 Hz, 1H), 4.63-4.68 (m, 2H), 4.84-4.94 (m, 3H), 5.06 (t, J = 10.1 Hz, 1H), 5.26 (t, J = 9.2 Hz, 1H), 5.36 ( dd, J = 9.7, 10.3 Hz, 1H), 5.42 (d, J = 4.2 Hz, 1H), 7.43 (d, J = 2.2, 8.3 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H); IR (KBr) 3450, 2950, 1755, 1550, 1375, 1230 and 1050 cm "1; mass spectrum [(+) ESI], m / z 823/825 (M + NH4 +), 828/830 (M + Na ) +; Calculated Analysis for C35H40ClNO20: C, 49.17; H, 5.00; N, 1.74, Found: C, 49.16; H, 4.88; N, 1.71.

Stage 2 2-chloro-5- (hepta-O-acetyl-β-D-ptaltosyl-oxymethyl) -phenylamine A solution containing 4-chloro-4-nitro-benzyl-β-D-maltoside heptaacetate (19.3 g, 23.9 mmol) and tin (II) chloride dihydrate (37.7 g, 167 mmol) in 479 ml of EtOAc is subjected to reflux for 2 h. The reaction is cooled to rt, carefully suspended with saturated aqueous NaHCO3 (until it becomes basic), diluted with 250 mL of EtOAc, stirred for 0.5 h and filtered. The biphasic filtrate is separated and the aqueous phase is extracted with EtOAc. The organic extracts are dried with Na 2 SO 4 and concentrated. Purification on silica gel (gradient from 0 to 12% acetone / CHCl 3) gives 17.8 g (96%) of 2-chloro-5- (hepta-O-acetyl-β-D-maltosyl-oxymethyl) -phenylamine as a glassy solid, mp 78-79 ° C; 1 H NMR (CDC13) d 2.00 (s, 9H), 2.026 (s, 3H), 2.032 (s, 3H), 2.11, 3H), 2.16 (s 3H), 3.00-5.00 (s broad, 2H), 3.64- 3.68 (m, 1H), 3.97 (ddd, J = 2.4, 4.2, 10.1 Hz, 1H), 4.02-4.07 (m, 2H), 4.24 (dd, J = 2.2, 3.7. 1H), 4.27 (dd, J = 2.6, 4.0 Hz, 1H), 4.50-4.57 (m, 3H), 4.74 (d, J = 12.1 Hz, 1H), 4.83-4.90 (m, 2H), 5.05 (t, J = 10.1 Hz, 1H) , 5.22 (t, J = 9.2 Hz, 1H), 5.35 (dd, J = 9.7, 10.5 Hz, 1H), 5.42 (d, J = 4.0 Hz, 1H), 6.62 (dd, J = 2.0, 8.1 Hz, 1H), 6.76 (d, J = 2.0 Hz, 1H), 7.21 (d, J = 8.1, 1H); IR (KBr) 3450, 3350, 2950, 1755, 1650, 1425, 1375, 1230 and 1050 cm "1; mass spectrum [(+) ESI], m / z 776/778 (M + H) \ 798/800 (M + Na) +; Analysis calculated for C35H42C1N018; C, 51.07; H, 5.45; N, 1.80, Found: C, 50.94; H, 5.52; N, 1.60.

Stage 3 N- [2-chloro-5- (hepta-O-acetyl-β-D-maltosyl-oxymethyl) -phenyl] -acetamide To a stirred solution of 2-chloro-5- (hepta-O-acetyl-β-D-maltosyl-oxymethyl) -phenylamine (20.6 g, 26.5 mmol) and triethylamine (8.13 ml, 58.3 mmol) in 265 ml of THF a 0 ° C acetyl chloride (2.26 ml, 31.8 mmol) is added dropwise. After 0.5 h at this temperature, heat to rt and stir for an additional 6 h. At this point, the reaction is concentrated and taken up in 700 ml of EtOAc. This organic solution is washed with 70 ml of IN HCl, 70 ml of saturated aqueous NaHCO 3 and 70 ml of brine and then dried with MgSO 4. After concentration, the residue is purified on silica gel (gradient from 20.80 to 100: 0 EtOAc: petroleum ether) to give the product (16.2 g, 75%) as a glassy solid, m.p. 84-86 ° C XH NMR (CDCl3) d 2.00 (s, 6H), 2.020 (s, 3H), 2.027 (s, 3H), 2.03 (s, 3H), 2.11 (s, 3H), 2.16 (s, 3H), 2.24 (s, 3H). 3.66-3.69 (m, 1H), 3.94-3.98 (m, 1H), 4.00-4.06 (m, 2H), 4.22-4.28 (m, 2H), 4.50-4.61 (m, 3H), 4.80-4.91 (m , 3H), 5.05 (t, J = 10.1 Hz, 1H), 5.22 (t, J = 9.2 Hz, 1H), 5.35 (dd, J = 9.4, 10.5 Hz, 1H), 5.41 (d, J = 4.0 Hz, 1H), 6.99 (dd, J = 2.0, 8.1 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.62 (s, 1H), 8.32 (s, 1H); IR (KBr) 3400, 2950, 1750, 1690, 1600, 1540, 1425, 1375, 1230 and 1050 cm "1; mass spectrum [(+) ESI], m / z 818/820 (M + H) +, 840 (M + Na) +; Analysis calculated for C35H44C1N019: C, 51.38; H, 5.42; N, 1.71, Found: C, 51.03; H, 5.36; N, 1.59.

Stage 4 N- [2-chloro-5- (β-D-maltosyl-oxymethyl) -phenyl) -acetamide A solution containing N- [2-chloro-5-hepta-0-acetyl-β-D-maltosyloxymethyl) -phenyl] -acetamide (0.945 g, 1.12 mmol) and 25% by weight of NaOMe in MeOH (19.2 μl, 0.036 mmole) in 27.6 ml of MeOH, refluxed for 2.5 h. The reaction is cooled to room temperature and concentrated, and the resulting residue is triturated with Et20 to provide the product (0.583 g, 99%) as a foam; 2 H NMR (DMSO-d 6) d 2.07 (s, 3 H), 3.03-3.16 (m 2 H), 3.19-3.49 (m, 7 H), 3.55-3.62 (m, 2H), 3.67-3.73 (m, 1H), 4.28 (d, J = 7.7 Hz, 1H), 4.33-5.76 (s broad, 7H), 4.67 (ABc, J = 12.5 Hz,? d = 0.22, 2H), 5.01 (d, J = 3.7 Hz, 1H), 7.21 (dd, J = 1.8, 8.1 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.64 (d, J = 1.5 Hz. 1H), 9.33-9.69 (broad s, 1H); IR (KBr) 3400, 2900, 1680, 1600, 1540, 1430, 1375, 1310, 1150 and 1035 cm "1, mass spectrum [(+) ESI], m / z 524/526 (M + H) +, 546 (M + Na) +; Analysis calculated for C21H30ClNO12 1.0 MeOH: C, 47.53: H, 6.16. N, 2.52. Found: C. 47.94; H, 6. 3. 4; N, 2.42.

Stage 5 N-. { 5 - [(4 ', 6'-O-benzylidene-β-D-maltosiloxy) -methyl] -2-chloro-phenyl} acetamide To a stirred solution of N- [2-chloro-5- (β-D-maltosyl-oxymethyl) -phenyl] -acetamide (14.15 g, 27.0 mmol) in 325 ml of DMF at rt was added benzaldehyde dimethyl acetal (8.11 ml, 54.0 mmol) dropwise followed by TsOH.H20 (2.57 g, 13.5 mmol). The reaction mixture is heated at 60 ° C for 6 h and then suspended with K2CO3 (1.87 g, 13.5 mmol) with an additional heating of 0.5 h at this temperature. At this point, the solution is filtered hot and the solvent is distilled off using high vacuum. The residue is purified on silica gel (gradient from 80: 2: 1 to 20: 2: 1 EtOAc: EtOH: H20) to give the product (10.8 g, 65%) as a white solid, 143-147 ° C.; E NMR (DMSO-d6) d 2.08 (s, 3H), 3.07-3.12 (m, 1H), 3.28-3.50 (m, 5H), 3.51-3.60 (m, 2H), 3.64-3.75 (m, 3H) , 4.10-4.12 (m, 1H), 4.30 (d, J = 7.9 Hz, 1H), 4.67 (t, 5.9 Hz, 1H), 4.68 (ABc, J = 12.5 Hz,? D = 0.22, 2H), 5.14 (d, J = 4.0 Hz, 1H), 5.25 (d, J = 5.1 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 5.51 (d, J = 3.3 Hz, 1H), 5.57 (s) , 1H), 5.63 d, J = 6.8 Hz, 1H), 7.22 (dd, J = 1.5, 8.3 Hz, 1H), 7.35-7.38 (m, 3H), 7.42-7.46 (m, 3H), 7.66 (s) , 1H), 9.53 (s, 1H); IR (KBr) 3500, 3410, 2910, 2850, 1700, 1600, 1550, 1440, 1425. 1375, 1310, 1230, 1150, 1070, and 1030 cm "1; mass spectrum [(+) FAB] m / z 634 (M + Na) +; Analysis calculated for C28H34C1N012, 1.0 H20: C, 53.38, H, 5.76, 2.22, Found: C, 53.58, H, 5.62, N, 2.25.

Stage 6 N- (5- { [4 ', 6'-O-benzylidene-6-O- (4-toluensulfonyl) -β-D-maltosyl] oxy-methyl.} -2-chloro-phenyl) - acetamide At 0 ° C, to a stirred solution of N-. { 5- [(4 ', 6' -07 benzylidene-β-D-maltosiloxy) -methyl] -2-chloro-phenyl] -acetamide (1.81 g, 2.96 mmol) in 6.0 ml of pyridine is added a chloride solution of p-toluenesulfonyl (0.86 g, 3.60 mmol) in 3.75 ml of CH2C12. After 2 h, additional p-toluenesulfonyl chloride (0.686 g, 3.60 mmol) in 3.75 mL of CH2C12 is added and the solution is stirred at 0 ° C for 2 h. The reaction is suspended with 50 ml of ice-cooled H20 and extracted with EtOAc. The combined organic extracts are washed successively with saturated aqueous NaHCO3 (2x), saturated aqueous CuSO4 (2x), brine (2x), dried with Na2SO4 and concentrated. The purification on silica gel (gradient of 5-10% of MeOH: CH2Cl2) gives 0.930 g (41%) of a white solid, m.p. 105-120 ° C; H NMR (DMSO-d6) d 2.08 (s, 3H), 2.33 (s, 3H), 3.04- 3.09 (m, 1H) 3.27-3.45 (m, 4H), 3.49-3.53 (m, 1H), 3.60- 3.65 (m, 3H), 3.95 (d, 1H), 4.13 (dd, 1H), 4.29-4.33 (m, 2H), 4.46 (d, 1H), 4.62 (d, 1H), 5.05 (d, 1H), 5.33-5.35 (m, 2H) 5.55 (d, 1H), 5.57 (s, 1H), 5.75 (d, 1H), 7.18 (d, 1H), 7.35-7.47 (m, 8H), 7.78 (2H), 9.53 (s, 1H); mass spectrum [(+) ESI], m / z 766/768 (M + H) \ 783/785 (M + NH4) \ - Analysis calculated for C35H40NC1014S H20 C, 53.60; H, 5.40; N, 1.79, Found: 53.46; H, 5.18; N, 1.80. stage 7 N- (5- { [2,3,2 ', 3' -tetra-O-asethyl-4 ', 6 • -O-benzylidene-6-O- (4-toluenesulfonyl) -β-D-maltosyl ] -oxi-methyl.} -2-chloro-phenyl) -acetamide At 0 ° C, to a stirred solution containing N- (5 { [4 ', 6' -0-benzylidene-6-0- (4-toluenesulfonyl) -β-D-maltosyl] -oxi-methyl -2-chloro-phenyl) -acetamide (0.782 g, 1.02 mmole), pyridine (0.991 ml, 12.3 mmole) and 4-dimethylaminopyridine (0.457 g, 4. 08 mmol) in 20 ml of CH2C12 is added acetic anhydride (0.764 ml, 8.17 mmol). After 2 h, the reaction is diluted with 100 ml of diethyl ether, washed successively with H20 (2x), with saturated aqueous NaHCO3 (2x) and saturated aqueous CuS04 (2x), with brine (2x), dried with Na2SO4 and concentrated. Purification on silica gel (gradient of 1.2 and 3% MeOH / Cl 3) gives 0.942 g (99%) of the title compound as a white solid, m.p. 116-122 ° C; XH NMR (DMS0-d6) d 1.91 (s, 3H), 1.92 (s, 3H), 1.96 (s, 3H), 2.00 (s, 3H), 2.08 (s, 3H), 2.29 (s, 3H), 3.68 (dd, 1H), 3.77 (t, 1H), 3.85 (t, 1H), 3.90 (t, 1H), 3.97-4.00 (m, 1H), 4.21 (dd, 1H), 4.32 (s, 2H) , 4.39 (d, 1H), 4.56 (d, 1H), 4.60 (d, 1H), 4.78 (d, 1H), 4.86 (dd, 1H), 5.17-5.30 (m, 3H), 5.65 (s, 1H) ), 7.03 (d, 1H), 7.34-7.41 (m, 7H), 7.46 (d, 1H), 7.59 (s, 1H), 7.80 (d, 2H), 9.52 (s, 1H); mass spectrum [(+) ESI], m / z 934/936 (M + H) +; Analysis . calculated for C43H48NCI018S: C, 55. 27; H, 5 17; N, 1.50, Found: C, 55. 07; H, 5 05; N, 1 .47. stage 8 N-. { 5 - [(2,3,2 ', 3'-tetra-O-acetyl-6-deoxy-6-benzylsulphane-4', 6'-O-benzylidene-β-D-maltosyl) -oxy-methyl] - 2-chloro-phenyl} -acetamide At room temperature, to a solution of benzylmercaptan (43.3 μl, 0.370 mmol) 1 ml of DMF is added 60% sodium hydride / mineral oil (13.4 mg, 0.336 mmol) and the mixture is stirred for 0.5 h. To the reaction is added a solution of N- (5- { [2,3,2 ', 3'-tetra-O-acetyl-4', 6'-O-benzylidene-6-0- (4- toluenesulfonyl) -β-D-maltosyl] -oxi-methyl) -2-chloro-phenyl) -acetamide (0.314 g, 0.336 mmol) in 2 ml of DMF. After 1 h, the reaction is suspended with 50 ml of ice-cooled H2 and extracted with EtOAc. The organic extracts are dried with Na 2 SO 4 and concentrated. Purification on silica gel eluting with 40% acetone / hexane followed by crystallization from EtOAc: hexane afforded 0.236 g (79%) of the title compound as a white solid, m.p. 185 ° C; 1 H NMR (DMSO-d 6) d 1.91 (s, 3 H), 1.94 (s, 3 H), 1.96 (s, 3 H), 2.00 (s, 3 H). 2.07 (s, 3H), 1.76, (dd, 1H), 2.87 (d, 1H), 3.68-3.71 (m, 1H), 3.74-3.92 (m, 6H), 4.18 (dd, 1H), 4.58 (d , 1H), 4.68-4.83 (m, 3H), 4.87 (dd, 1H), 5.20-5.29 (m, 3H), 5.63 (s, 1H), 7.08 (dd, 1H), 7.14-7.19 (m. ), 7.26-7.32 (m, 4H), 7.34-7.40 (m, 5H), 7.45 (d, 1H), 7.65 (s, 1H), 9.50 (s, 1H), IR (KBr) 3400, 2900, 1750 , 1380, 1240 and 1075 cm "1; mass spectrum [(+) FAB] .m / z 886/888 (M + H) +, 908/910 (M + Na) +; Analysis calculated for C43H48NCI015S: C, 58.27, H. 5.46; N, 1.58, Found: C, 58.12: H, 5.39; N, 1.60.

Example 2 N-. { 5 - [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfañyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide A solution containing N- [5- [(2, 3, 2 ', 3' -tetra-O-acetyl-6-deoxy-6-benzylsulfa il-4 ', 6' -O-benzylidene-β-D -maltosyl) -oxi-methyl] -2-chloro-phenyl} -acetamide (0.148 g, 0. 167 mmol) and 25% by weight of Na OMe in MeOH (18 mg, 0.0835 mmol) in 4 mL of MeOH is refluxed for 3 h. The reaction is cooled to room temperature and concentrated. Purification on silica gel eluting with 10% MeOH: CH2C12 followed by crystallization from CH2Cl2: petroleum ether provides 0.100 g (83%) of the title compound as a white solid, m.p. 96-110 ° C; ? NMR (DMS0-d6) d 2.06 (s, 3H), 2. 62 (dd, 1H), 2.86 (dd.1H), 3.11 (dd, 1H), 3.35-3.55 (m, 6H), 3.64 (d, 2H), 3.79 (dd, 2H), 3.99 (d, 1H) , 4.30 (d, 1H), 4.59 (d, 1H), 4.76 (d, 1H), 5.16 (d, 1H), 5.31 (d, 2H), 5.50 (d, 1H), 5.56 (s, 1H), 5.65 (d, 1H), 7.18-7.23 (m, 2H), 7.26-7.31 (m, 4H), 7.35-7.38 (m, 3H), 7.43-7.46 (m, 3H), 7.68 (s, 1H), 9.51 (s, 1H); mass spectrum [(+) FAB], m / z 718/720 (M + H) +; Analysis calculated for C35H40NClO?: LS. 0.5 H20: C, 57.81; H, 5.68; N, 1.93, Found: C, 57.78; H, 5.62; N, 1.94. Found: C, 57.65; H, 5.56; N, 1.94.

Example 3 N- (5-- [[2, 3, 2 ', 3' -tetra-O-acetyl-6-deoxy-6- (2,4-dichloro-benzisulfane) -4 ', 6'-O-benzylidene- ß-D-maltosyl] -oxi-methyl.} -2-chloro-phenyl) -acetamide The title compound is prepared as a white solid (0.222 g, 70%) from 2,4-dicyclobenzyl mercaptan using a procedure similar to step 8 of Example 1, mp 190 ° C; "-H NMR (DMSO-d6) d 1.91 (s, 3H), 1.94 (s, 3H), 1.96 (s, 3H), 2.00 (s, 3H), 2.06 (s, 3H), 2.84 (dd, 1H) ), 2.96 (d.1H), 3.69-3.80 (m, 2H), 3.84-3.96 (m, 5H), 4.19 (dd, 1H), 4.57 (d, 1H), 4.68-4.76 (m, 2H), 4.83 (d.1H), 4.87 (dd, 1H), 5.22 (d, 1H), 5.26-5.31 (m, 2H), 5.63 (s, 1H), 7.07 (dd, 1H), 7.31 (dd, 1H) , 7.34-7.38 (m, 5H), 7.41-7.45 (m, 2H), 7.58 (d, 1H), 7.64 (s, 1H), 9.49 (s, 1H), IR (KBr) 3400, 2900, 1760, 1370, 1240 and 1050 cm "1; mass spectrum [(+) FAB], m / z - 41 -954 / 956/958/960 (M + H) +; Analysis calculated for C43H46NC13015S: C 54. 07; H, 4 85, N, 1. 47, Found: C, 53. 96; H, 4 73; N, 1 52 Example 4 N- (5 - { [4 ', 6' -0-benzylidene-6-deoxy-6- (2,4-dichloro-benzylsulfane) -β-D-maltosyl] -oxy-methyl I -2 -chloro - phenyl) -acetamide A solution containing N- (5- { [2, 3, 2 ', 3' -tetra-O-acetyl-6-deoxy -6- (2,4-dichloro-benzylsulfanyl) -4 ', 6' -O-benzylidene-β-D-maltosyl] -oxi-methyl.} -2-chlorophenyl) -acetamide and 25% by weight of NaOMe in MeOH (16.1 mg, 0.0743 mmol) in 4 ml of MeOH is refluxed for 3 h. The reaction is cooled slowly to 0 ° C. The resulting crystals are collected and dried to provide 63 mg (99%) of the title compound as a white solid, m.p. 125-128 ° C; NMR (DMSO-d6) d 2.06 (s, 3H), 2.71 (dd, 1H), 2.93 (dd, 1H), 3.12 (t, 1H), 3.37-3.40 (m, 2H), 3.43-3.46 (m, 2H), 3.54 (t, 2H), 3.65 (d, 2H), 3.87 (s, 2H), 4.00 (d, 1H), 4.32 (d, 1H), 4.58 (d, 1H), 4.75 (d, 1H) ), 5.16 (d, 1H), 5.35 (broad s, 2H), 5.55 (broad s, 2H), 5.56 (s, 1H), 7.20 (dd, 1H), 7.33-7.38 (m, 4H), 7.42- 7.45 (m, 4H), 7.58 (d, 1H), 7.66 (s, 1H), 9.50 (s, 1H); mass spectrum [(+) FAB], m / z 786/788/790/792 (M + H) + Analysis calculated for C35H38NC1201; LS. 0.5 H20: C, 52.80; H, 4.94; N, 1.76, Found: C, 52.82; H, 4.77; N, 1.76. Found: C, 52.70; H, 4.77; N, 1.70.

Example 5 N-. { 2- [(2,3,2 ', 3' -tetra-0-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxi-metill -2 - chloro-phenyl} -acetamide At room temperature, to a stirred two-phase solution of N-. { 5- [(2, 3, 2 ', 3' -tetra-0-acetyl-6-deoxy-6-benzylsulfanyl-4 ', 6' -O-benzylidene-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide (14.48 g, 16.34 mmol) in 163 ml of CH2C12 and 163 ml of saturated aqueous NaHCO3 is added in one portion 85% of 3-chloroperoxybenzoic acid (3.32 g, 16.34 mmol). After 1 h, the reaction is suspended with 150 ml of brine and extracted with EtOAc. The combined organic extracts are dried with Na 2 SO 4 and concentrated. Purification on silica gel eluting with a gradient of 1, 2 and 3% MeOH: CHCl3 gives 12.89 g (87%) of the title compound as a 1: 1 mixture of diastereomers, as a white solid, m.p. 212-213 ° C; H NMR (DMSO-d6) d 1.91, 1.92 (2s, 3H), 1.93, 1.95 (2s, 3H), 1.96, 1.97 (2s, 3H), 2.00, 2.01 (2s, 3H), 3.01-3.11 (m, 2H), 3.74-4.08 (m, 6H), 4.21-4.32 (m, 2H), 4.57 (t, J = 13.0 Hz, 1H), 4.70-4.93 (m, 4H), 5.19-5.33 (m, 3H) , 5.64, 5.68 (2s, 1H), 7.07 (d, 1H), 7.27-7.39 (m, 9H), 7.44 (dd, 2H), 7.62, 7.63 (2s, 1H), 9.51 (s, 1H); IR (KBr) 3400, 2920, 1750, 1375, 1240 and 1050 cm- "1; mass spectrum [(+) FAB], m / z 902/904 (M + H) +; Analysis calculated for C43H48NC1016S: C, 57.24; H, 5.36; N, 1.55, Found: C, 56.85; H, 5.19; N, 1.51.

Example 6-8 N-Í5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxy-metip-2-chloro-phenyl} -acetamide Example 6 (racemate); Example 7 (diastereomer # 1); Example 8 (diastereomer # 2) The title compound is prepared as a 1: 1 mixture of diastereomers, as a white solid (0.068 g, 99%) from N-. { 5- [(2, 3, 2 ', 3' -tetra-O-acetyl-4 ', 6' -O-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide using a procedure similar to that of Example 2, p.f. 128-133 ° C; XH NMR (DMS0-d6) 3 2.06 (s, 3H), 2.96-3.05 (m, 1H), 3.11-3.18 (m, 1H), 3.25-3.72 (m, 8H), 3.88-3.98 (m, 2H) , 4.06-4.10 (m, 1H), 4.18, 4.22 (2d, 1H), 4.35, 4.44 (2d, 1H), 4.56, 4.60 (2d, 1H), 4.72, 4.76 (2d, 1H), 5.18, 5.20 ( 2d, 1H), 5.34-5.39 (m, 2H), 5.56-5.59 (ra, 2H), 5.67, 5.75 (2d, 1H), 7.19 (d, 1H), 7.29-7.37 (m, 9H), 7.41- 7.47 (m, 2H), 7.65 (s, 1H), 9.51 (s, 1H); mass spectrum [(+) FAB], m / z 734/736 (M + H) +; Analysis calculated for C35H40NClO12S. 0.5 H20: C, 56.56; H, 5.56; N, 1.88, Found: C, 56.44; H, 5.38; N, 1.85. The racemic mixture is separated by CLAP (Primesphere SIL; 5% MeOH: CH 2 Cl 2) to give the two diastereomers of opposite sulfoxide: Diastereomer # 1, a white solid, 214 -215 ° C; XH NMR (DMSO-d6) d 2.06 (s, 3 H), 2.99 (dd, J = 13.9, 7.6 Hz, 1H), 3.13-3.18 (m, 1H), 3.25-3.59 (m, 6H), 3.61- 3.72 (m, 2H), 3.88-3.93 (m, 1H), 4.07 (dd.1H), 4.08 (ABc, J = 12.7 Hz,? D = 0.10, 2H), 4.44 (d, J = 7.7 Hz, 1H ), 4.68 (ABc, J = 12.5 Hz,? D = 0.06, 2H), 5.18 (d, J = 3.7 Hz, 1H), 5.34 (d, J = 5.3 Hz, 1H), 5.38 (d, J = 5.3 Hz, 1H), 5.56 (s, 1H), 5.58 (d, J = 2.9Hz, 1H), 5.75 (d, J = 6.6 Hz, 1H), 7.19 (dd, J = 8.2, 1.9 Hz, 1H), 7.28-7.37 (m, 8H), 7.41-7.45 (m, 3H), 7.65 (s, 1H), 9.51 (s, 1H); IR (KBr) 3400. 2900, 1675, 1070 and 700 cm * 1; mass spectrum [(-) FAB], m / z 732 (M-H) +; Analysis calculated for C ^ H ^ NdO ^ S. 0.5 H20: C, 56.56: H, 5.56; N, 1.88, Found: C, 56.59; H, 5.51; N, 1.98. Diastereomer # 2, a white solid 202-208 ° C; XH NMR (DMSO-d6) d 2.06 (s, 3H), 2.99-3.05 (m, 2H), 3.11-3.16 (m, 1H), 3.36-3.42 (m, 3H), 3.46-3.56 (m, 2H) , 3.65-3.72 (m, 3H), 4.05 (ABc, J = 13.0 Hz? D = 0.15, 2H), 4.09 (d, J = 4.8 Hz, 1H), 4.35 (d, J = 7.9 Hz, 1H), 4.65 (ABc, J = 12.4 Hz,? D = 0.07, 2H), 5.20 (d, J = 4.0 Hz, 1H), 5.34 (d, 2H), 5.56 (d, J = 3.1 Hz, 1H), 5.58 ( s, 1H), 5.67 (d, J = 6.6 Hz, 1H), 7.18 (dd, J = 8.2, 1.9 Hz, 1H), 7.28-7.38 (m, 8H), 7.42-7.48 (m, 3H), 7.65 (s, 1H), 9.51 (s, 1H); IR (KBr) 3400, 2900, 1675, 1070 and 700 cm "1; mass spectrum [(-) FAB], m / z 732 (M-H)"; Analysis calculated for C ^ H ^ NClO ^ S: C, 57.26; H, 5.49; N, 1.91, Found: C, 56.90; H, 5.64; N, 1.95.

Example 9 N- (5-T (4 ', 6'-O-benzyl iden-6-deoxy-6-benzyl sulfonyl-1-ß-D-maltosyl) -oxi-methyl-2-chloro-phenyl) acetamide stage 1 N-. { 5- t (2,2 ', 3,3' -tetra-O-acetyl-41,6 '-0-benzylidene-6-deoxy-6-benzylsulfonyl-β-D-maltosyl) -oxi-methyl] -2 -chloro-phenyl} -acetamide At room temperature, to a two-phase solution of N-. { 5 - [(2,3,2 ', 3' -tetra-0-acetyl-6-benzylsulfanyl-4 ', 6'-O-benzylidene-β-D-maltosyl) -oxi-methyl] -2-chloro- phenyl } -acetamide (0.287 g, 0.324 mmoles) in 5 ml of CH2Cl2 and 5 ml of saturated aqueous NaHCO3 is added in one portion 80% 3-chloroperoxybenzoic acid (0.147 g, 0.681 mmol). After 1 h, the reaction is suspended with 150 ml of brine and extracted with EtQAc. The combined organic extracts are dried with (Na2SO4) and concentrated. Purification on silica gel (gradient of 1, 2 and 3% MeOH: CHCl 3) provides 0.244 g (82%) of N-. { 5- [(6-benzylsulfonyl-2, 2 ', 3,3'-tetra-O-acetyl-4', 6'-O-benzylidene-β-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide 1H NMR (DMSO-d6) d 1.94 (s, 3H), 1.96 (s, 3H), 1.98 (s, 3H), 2.00 (s, 3H), 2.07 (s, 3H), 3.47-3.61 (m , 2H), 3.75-3.81 (m, 2H), 3.91 (t, J = 9.2 Hz, 1H), 4.01 (t, J = 9.2 Hz, 1H), 4.19 (d.J = 5.6 Hz, 1H), 4.30 -4.34 (m, 1H), 4.53 (s, 2H), 4.64 (d, J = 12.6 Hz. 1H), 4.74-4.80 (m.2H), 4.83-4.98 (m, 1H), 5.23-5.30 (m. , 2H), 5.37 (t, J = 9.2 Hz, 1H), 5.64 (s, 1H), 7.08 (dd, J = 6.4, 1. 8 Hz, 1H), 7.33-7.46 (m, 11 H), 7.66 (s, 1 H), 9.51 (s, 1 H). stage 2 N-. { 5- [(41, 6'-O-benzylidene-6-deoxy-6-benzylsulfonyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl) -acetamide The title compound is prepared as a white solid (0.118 g, 67%) from N-. { 5- [(2, 2 ', 3, 3' -tetra-0-acetyl-4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulphyl-β-D-maltosyl) -oxi-methyl ] -2-chloro-phenyl} -acetamide using a procedure similar to that of Example 2, p.f. > 225 ° C; * "H NMR (DMSO-d6) d 2.05 (s, 3H), 3.15-3.20 (m, 1H), 3.36-3.46 (m, 4H), 3.49-3.59 (m, 3H), 3.60-3.69 (m, 2H), 3.94 (t, J = 9.2 Hz, 1H), 4.00 (c, 1H), 4.40 (d, J = 13.6 Hz, 1H), 4.50 (d, J = 13.4, 1H), 4.52 (d, J = 7.7 Hz, 1H), 4.66 (d, J = - 12.5 Hz, 1H), 4.81 (d, J = 12.5 Hz, 1H), 5.12 (d, J = 4.0 Hz, 1H), 5.37 (d, J = 5.3 Hz, 1H), 5.41 (d, J = 5.5 Hz, 1H), 5.55 (s) , 2H), 5.78 (d, J = 6.6, 1H), 7.19 (dd, J = 8.3, 2.0 Hz, 1H), 7.33-7.44, (m, 1 1H), 7.67 (s, 1H), 9.48 (s, 1H); mass spectrum [(+) ESI], m / z 750/752 (m + H) +; Analysis calculated for C35H40NClO13S:: C, 56.03; H, 5.37; N, 1.87, Found: C, 55.84; H, 5.23; N, 1.78.

Example 10 N-. { 5- [(2, 2 ', 3, 3' -tetra-O-acetyl-4 ', 6' -Q-benzylidene-6-deoxy-6-phenylsulfanyl-β-D-maltosyl) -oxi-metill -2 -chloro-phenyl} -acetamide At room temperature, to a thiophenol solution (0.027 ml, 0.250 mmol) in 2.27 ml of DMF is added 95% potassium t-butoxide (26.8 mg, 0.227 mmol) and the mixture is stirred for 0.5 h. To the reaction is added in one portion N- (5- { [2,3,2 ', 3'-tetra-0-acetyl-4', 6'-O-benzylidene-6-O- (4- toluenesulfonyl) -β-D-maltosyl] -oxi-methyl.} -2-chloro-phenyl) -acetamide (0.212 g, 0.227 mmol). After 16 h, the reaction is suspended with 50 ml of ice-cooled H20 and extracted with EtOAc. The organic extracts are dried with Na 2 SO 4 and concentrated. Purification on silica gel (40% acetone: hexane) followed by crystallization from EtOAc: hexane afforded 98 mg (49%) of the title compound as a white solid, m.p. 173-177 ° C; X H NMR (DMSO-d 6) d 1.92 (s, 3 H), 1.94 (s, 3 H), 1.97 (s, 3 H), 1.99 (s, 3 H), 2.07 (s, 3 H), 3.34-3.47 (m, 2 H) ), 3.73-3.85 (m, 2H), 3.90 (d, J = 9.4 Hz, 1H), 3.95 (d, J = 9.0 Hz, 1H), 4.02-4.05 (m, 1 H), 4.17 (dd, J) = 9.0, 5.3 Hz, 1H), 4.52 (ABc, J = 12.5 Hz,? D = 0.06, 2H), 4.70 (dd, J = 9.6, 8.0 Hz, 1H), 4.84 (d, 1H), 4.89 (dd) , J = 10.2, 4.1 Hz, 1H), 5.24-5.32 (m, 3H), 5.61 (s, 1H), 7.03 (d, J = 8.2, 1.9 Hz. 1H), 7.14 (t, J = 7.4 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.30-7.41 (m, 8H), 7.44 (d.J 8.1 Hz, 1H), 7.61 (s, 1H), 9.50 (s, 1H); IR (KBr) 3400, 2925, 1750, 1375, 1240 and 1050 crn "1; mass spectrum [(+) ESI], m / z 872/874 (M + H) +; Analysis calculated for C42H46NC1015: C, 57.83; H, 5.32; N, 1.61, Found: C. 57.95; H. 5.40; N, 1.62.

Example 11 N- (5 - [(4 ', 6'-O-benzyl iden-6-deoxy-6-f eni l sulf ani l -β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl l- acetamide The title compound is prepared as a white solid (0.185 g, 78%) from N-. {5- [(2,2-, 3, 3'-tetra-O-acetyl-4 ', 6 '-O-benzylidene-6-deoxy-6-phenylsulfanyl-β-D-maltosyl) -oxi-methyl] -2-chloro-phenyl] -acetamide using a procedure similar to that of Example 2, mp 105 -120 ° C; * -H NMR (DMSO-d6) d 2.07 (s, 3H), 3.09-3.14 (m, 1H), 3.20 (dd, J = 8.24, 5.49 Hz, 1H), 3.35-3.47 (m, 5H), 3.53-3.73 (m , 4H), 3.91 (dd, 1H), 4.31 (d, J = 7.7 Hz, 1H), 4.54 (ABc, J = 12.3 Hz,? d = 0.06, 2H), 5.19 (d, J = 4.0 Hz. 1H), 5.30-5.34 (m, 2H), 5.55-5.57 (m, 2H), 5.73 (di J = 6.4 Hz, 1H), 7.14-7.18 (m, 2H), 7.26-7.30 (m, 2H), 7.35-7.44 (m, 8H), 7.63 (s, 1H), 9.52 (s, 1H); IR (KBr) 3400, 2900, 1675, 1050 cm "1; mass spectrum [(-) FAB], m / z 7021704 (M - H) +; Analysis calculated for C34H38NC1011S: 0.5 H20: C, 57.26; H, 5.51 N, 1.96, Found: C, 57.33; H, 5.40; N, 1.99.

Example 12 N-. { 5- i (2, 2 ', 3,3' -tetra-0-acetyl-4 ', 6' -O-benzylidene-6-deoxy-6-phenylsulfinyl-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl-acetamide The title compound is prepared as a mixture 1: 1 diastereomers, white solid (0.335 g, 69%) from N-. { 5- [(2,2 ', 3, 3' -tetra-O-acetyl- ', 6' -O-benzylidene-6-deoxy-6-phenylsulphane-β-D-maltosyl) -oxy-methyl] -2 -chloro-phenyl} -acetamide using a procedure similar to that of Example 5, p.f. 160-187 ° C; XH NMR (DMSO-d6) d 1.91, 1.92, 1.93, 1.95, 1.96, 1.97. 1.98, 1.99, 2.00, 2.08 (lOs, 15H), 3.09 (d, 1H), 3.25-3.28 (m, 1H), 3.60-4.09 (m.4H), 4.14-4.45 (m, 2H), 4.61-4.99 (m, 5H), 5.12-5.40 (M, 3H), 5.54, 5.63 (2s, 1 H) 7.04, 7.12 (2dd, 1 H), 7.30-7.33 (m, 1 H), 7.46-7.56 (m, 4H), 7.62, 7.68 (2s, 1H), 7.72-7.74 (m, 2H), 9.51, 9.53 (2s, 1H); IR (KBr) 3400, 2900, 1750. 1375, 1240 and 1050 cm "1; mass spectrum [(+) FAB], m / z 888/890 (M + H) +; Analysis calculated for C42H46NC1016S 0.5 H20: C , 56.22; H, 5.28; N, 1.56, Found: C, 56.04; H, 5.21; N, 1.53.

Example 13 N-. { 5- T (2, 2 ', 3, 3' -tetra-O-acetyl- ', 6' -0-benzylidene-6-deoxy-6-phenethylsulfanyl-β-D-maltosyl) -oxi-methyl] -2 -cloro-f enil} acetamide The title compound is prepared as a white solid (0.712 g, 61%) from N- (5 { [2, 3, 2 •, 3 '-tetra-O-acetyl-, 6' - O-benzylidene-6-O- (4-toluensulfonyl) -β-D-maltosyl] -oxi-methyl.} -2-chloro-f-enyl) -acetamide using f-methylmercaptan and a procedure similar to that of step 8 of Example 1, pf 132-147 °; 2 H NMR (DMSO-d 6) d 1.92 (s, 1.94 (s, 3 H), 1.97 (s, 3 H), 2.00 (s, 3 H), 2.07 (s, 3 H), 2.80-2.91 (m, 5 H), 3.05 (d, 1H), 3.76-3.82 (m, 2H), 3.90-4.00 (m, 3H), 4.24 (d, J = 5.5 Hz, 1H), 4.54 (d, J = 12.7 Hz. 1H), 4.67-4.72 (m, 2H), 4.83-4.90 (m, 2H), 5.24-5.32 (m, 3H), 5.63 (s, 1H), 7.02 (dd, J = 8.2, 1.9 Hz, 1H), 7.14- 7.21 (m, 5H), 7.30-7.37 (m, 5H), 7.42 (d, J = 8.3 Hz, 1H), 7.62 (s, 1H), 9.51 (s, 1 H), IR (KBr) 3400, 2900 , 1750, 1240 and 1050 cm * 1, mass spectrum [(+) FAB], m / z 900 (M + H) +, Analysis calculated for C44H50NC1015S: 2 H20: C, 56.44; H, 5.81 N, 1.50, Found: C, 56.40; H, 5.42; N, 1.48.

Example 14 N-. { 5 - [(4 ', 6'-O-benzylidene-6-deoxy-6-phenethylsulphane-β-D-maltosyl) -oxi-methyl-2-chloro-phenyl} acetamide The title compound is prepared as a white solid (0.130 g, 90%) from N- (5- { [2, 2 ', 3, 3' -tetra-O-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6-phenethylsulfane) -β-D-maltosyl] -oxy-methyl} -2-chloro-phenyl) -acetamide using a procedure similar to that of Example 2, p.f. 193-195 ° C, XK NMR (DMS0-d6) d 2.06 (s, 3H), 2.74 (dd, J = 14.3, 7.25 Hz, 1H), 2. 79-2.87 (m, 4H), 3.00 (dd, J = 14.3, 2.2 Hz, 1H), 3.11 (t, J = 8.35 Hz, 1H), 3.37-3.59 (m.6H), 3.69-3.72 (m, 2H), 4.08 (d, 1H), 4.32 (d, J = 7.9 Hz, 1H), 4.63 4.54 (ABc, J = 12.4 Hz,? D = 0.08, 2H), 5.17 (d, J = 4.0 Hz, 1H), 5.31 (s broad, 2H), 5.00 (broad s, 1H), 5.57 (s, 1H), 5.66 ( s broad, 1 H), 7.13-7.21 (m, 6H), 733-7.36 (m, 3H), 7.39-7.43 (m, 3H), 7.63 (s.1H), 9.51 (s, 1H); IR (KBr) 3325, 2900. 1700. 1525, 1300 and 1070 cm "1; mass spectrum [(+) FAB], m / z 754 (M + Na) '; Analysis calculated for C ^ H ^ NdO ^ S : C, 59.05; H, 5.78; N, 1.91, Found: C, 58.99; H, 5.86; N, 1.86.

Example 15 N- (5- (T4 ', 6' -0-benzylidene-6-deoxy-6- (phenyl-ethyl-sulfinyl) -β-D-maltosyl] -oxy-methyl.} -2-chloro-phenyl) -acetamide stage 1 n- (5- { [2,3,2 ', 3' -tetra-O-acetyl-4 ', 6'-O-benzylidene-6-deoxy-6- (phenyl-ethyl-sulfinyl) -β -D-maltosyl] -oxi-methyl.} -2-chloro-phenyl) • acetamide The title compound is prepared as a 1: 1 mixture of diastereomers, white solid (0.189 g, 47%) from N-. { 5- [(2, 2 ', 3, 3' - tetra-O-acetyl-4 ', 6'-O-benzylidene-6-phenethylsulphane-ß-D-maltosyl) -oxy-methyl] -2-chloro- phenyl) -acetamide using a procedure similar to that of Example 5; ? NMR (DMSO-d6) d 1.94 (s, 3H), 1.95 (s, 3H), 1.96 (s, 3H), - 5 $ -2.00 (s, 3H), 2.09 (s, 3H), 2.96-3.29 ( m, 6H), 3.76-4.46 (m, 6H), 4.50-4.79 (m, 3H), 4.88-4.94 (m, 2H), 5.23-5.40 (m, 3H), 5.63, 5.64 (2s, 1H), 7.00-7.07 (m, 1H), 7.17-7.37 (m, lOH), 7.42-7.47 (m, 1H), 7.60-7.63 (m, 1H), 9.52 (s, 1H). stage 2 N- (5- { [4 ', 6' -O-benzylidene-6- (phenyl-ethyl-sulfinyl) -β-D-maltosyl] -oxy-methyl.} -2-chloro-phenyl) - acetamide The title compound is prepared as a 1: 1 mixture of diastereomers, white solid (0.123 g, 92%) from N- (5- { [2,3,2 *, 3'-tetra-O- acetyl-4 ', 6'-O-benzylidene-6- (phenylethylsulfinyl) -β-D-maltosyl] -oxy-methyl} -2-chloro-phenyl) -acetamide using a procedure similar to Example 2, pf 202-205 ° C; 'H NMR (DMS0-d6) d 2.07 (s, 3H), 2.97-3.16 (m, 6H), 3.28-3.76 (m, 9H), 4.14 (m, 1H), 4.38 (t, J = 7.7 Hz, 1H), 4.47-4.56 (m, 3H), 4.67 (d, J = 12.5 Hz, 1H), 5.16 (s, 1H), 5.36 (s broad, 2H), 5.56 (s, 2H), 5.75 (s broad) , 1 H), 7.14-7.19 (m, 2H), 7.24-7.26 (m, 4H), 7.33-7.39 (m, 3H), 7.41-7.43 (m, 3H), 7.57.7.63 (2s, 1H). 9.52 (s, 1H.) *: IR (KBr) 3400, 2900, 1670, 1425 and 1070 cm "1: mass spectrum [(+) FAB], m / z 748 (M + H) +; Analysis calculated for C36H42NC1012S 0.5 H20: C, 57.10; H, 5.72 N, 1.85, Found: C, 57.16; H, 5.72; N, 1.79.

Example 16 N- (5- { [4 ', 6' -0-benzylidene-6-deoxy-6- (3-phenyl-propylsulfane) -β-D-maltosyl-oxy-methyl.} -2-chloro-phenyl ) -acetamide stage 1 N- (5- { [2,2 ', 3,3' -tetra-O-acetyl-4 ', 6 * -0-benzylidene-6-deoxy-6- (3-f-enyl-propylsulf-indigo) -β-D-maltosyl] -oxi-methyl.} -2-chlorophenyl) -acetamide The title compound is prepared as a white solid (0.172 g, 57%) from N- (5- { [2,3,2 ', 3' -tetra-0-acetyl-4", 6 ' -O-benzylidene-6-0- (4-toluenesulfonyl) -β-D-maltosyl] -oxy-methyl.} -2-chloro-phenyl) -acetamide using 3-methylpropylmercaptan and a procedure similar to that of the step 8 of Example 1, pf XH NMR (DMS0-d6) d 1.82-1.90 (m, 2H), 1.93 (s, 3H), 1.95 (s, 3H), 1.98 (s, 3H), 2.00 (s, 3H) , 2.07 (s, 3H), 2.57 - 2.65 (m, 4H), 2.88 (d, 1H), 3.00 (d, 1H), 3.75-3.81 (m, 2H), 3.90-3.95 (m, 3H), 4.24 (d, J = 5.4 Hz, 1H), 4.52 (d, J = 12.6 Hz, 1H), 4.66-4.72 (m, 2H), 4.81-4.91 (m, 2H), 5.23-5.33 (m, 3H), 5.65 (s, 1H), 7.05 (dd, J = 8.3, 1.8 Hz, 1H), 7.14-7.17 (m, 3H), 7.21-7.26 (m, 2H), 7.36 (s, 5H), 7.46 (d, J = 8.3 Hz, 1H), 7.64 (s, 1H), 9.52 (s, 1H). stage 2 N- (5- { [4 *, 6 '-0-benzylidene-6-deoxy-6- (3-phenyl-propylsulfane) -β-D-maltosyl] -oxy-methyl.} -2-chloro phenyl) -acetamide The title compound is prepared as a white solid (0.161 g, 93%) from N- (5- { [2, 3, 2 ', 3' -tetra-O-acetyl-4 ', 6' -O-benzylidene-6-0- (4-toluenesulfonyl) -β-D-maltosyl] -oxy-methyl.} -2-chloro-phenyl) -acetamide using a procedure similar to Example 2, mp. 78-88 ° C; XR NMR (DMSO-d5) d 1.78-1.85 (m, 2H), 2.06 (s, 3H), 2.56 (t, J = 7.2 Hz, 2H), 2.62 (t, J = 7.6 Hz, 2H), 2.70 ( dd, J = 14.1, 7.2 Hz, 1H), 2.94 (dd, J = 13.9, 2.1 Hz, 1H), 3.07-3.13 (m, 1H), 3.28-3.48 (m, 5H), 3.53-3.59 (m, 1H), 3.69 (d, J = 7.2 Hz, 2H), 4.05 (d, J = 5.3 Hz, 1H), 4.29 (d, 1H), 4.61 (ABc, J = 12.3 Hz,? D = 0.07, 2H) , 5.15 (d, J = 4.0 Hz, 1H), 5.30 (d, J = 5.3 Hz, 1H), 5.33 (d, J = 5.1 Hz, 1H), 5.52 (d, J = 2.9 Hz, 1H). 5.57 (s, 1H), 5.70 (d, J = 6. 6 Hz. 1H), 7.11-7.24 (m, 6H), 7.35-7.37 (m, 3H), 7.41-7.45 (M, 3H), 7.65 (s, 1H), 9.52 (s, 1H); mass spectrum [(+) FAB], m / z 768 (M + Na) +; Analysis calculated for C37H44NC1011S 0.5 H20: C, 58.80; H, 6.01, N, 1.85, Found: C. 58.79; H, 5.95; ?, 1.82.

EXAMPLE 17 N- (5- [(4 ', 6' -O-Benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl] -acetamide stage 1 N-. { 5 - [(2,2I, 3,3I-tetra-O-acetyl-4 ', 6'-O-benzylidene-6-deoxy-6-amino-β-D-maltosyl) -oxy-methyl] -2- chlorine-phenyl} -acetamide At room temperature, to a stirred solution of N-. { 5 - [(2,2 ', 3,3- -tetra-0-acetyl-6-deoxy-6-0-azidomethyl-4', 6'-0-benzylidene-β-D-maltosyl) -oxi-methyl ] -2-chloro-phenyl} -acetamide (0.371 g, 0.461 mmol) in 9.2 ml of H2? / 5% THF is added triphenylphosphine (0.121 g). After 3 days, the reaction is diluted with 50 ml of EtOAc, washed with brine, dried with Na 2 SO 4 and concentrated. Purification on silica gel (gradient of 1, 2 and 3% MeOH: CHCl 3) gives 0.346 g (96%) of the title compound; J H NMR (DMSO-d 6) d 1.92 (s, 3 H), 1.94 (s, 3 H), 1.95 (s, 3 H), 1.98 (s, 3 H), 2.01 (s, 3 H), 2.75 (dd, 1 H), 3.00 (d, 1H), 3.33-3.64 (m, 1H), 3.78-3.95 (m, 4H), 4.23 (d, J = 5.1 Hz, 1H), 4.59 (d, J = 12.7 Hz, 1H), 4.67 -4.82 (m, 3H), 4.88 (dd, J = 10.2, 4.0 Hz, 1H), 5.20-5.30 (m, 3H), 5.65 (s, 1H), 7.09 (d, 1H), 7.38 (s, 5H) ), 7.47 (d, J = 8.2 Hz, 1H), 7.65 (s, 1H), 9.52 (s, 1H).

Stage 2 N-. { 5- [(2,2 ', 3,3"-tetra-O-acetyl-41,6' -O-benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxi-methyl] -2 -chloro-phenyl.}. -acetamide At room temperature, to a stirred solution containing N-. { 5- [(2,2 ', 3,3' -tetra-0-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6-amino-β-D-maltosyl) -oxy-methyl] - 2-chloro-phenyl} -acetamide (0.201 g, 0.258 mmol) and pyridine (0.063 ml, 0.774 mmol) in 5.2 ml of THF was added benzoyl chloride (0.033 ml, 0.284 mmol). After 1.5 h, the reaction is suspended with 25 ml of H20, extracted with EtOAc, washed successively with saturated aqueous NaHCO3 (3x), saturated aqueous CuS04 (3x), brine (3x), dried with Na2SO4 and concentrate to provide 0.224 g (98%) of the title compound. This material is used without any additional purification; 1 H NMR (DMSO-d 6) d 1.94 (s, 3 H), 1.96 (s, 3 H), 1.99 (s, 3 H), 2.02 (s, 3 H), 2.07 (s, 3 H), 3.39 (m, 1 H), 3.76-3.79 (m, 1H), 3.89-4.00 (m, 5H), 4.20-4.24 (m, 1H), 4.55 (d, J = 12.7 Hz, 1H), 4.73-4.81 (m, 3H), 4.93 ( dd, J = 10.2, 4.0 Hz. 1H), 5.24-5.32 (m, 3H), 5.63 (s, 1H), 6.99 (dd, J 8.2, 1.8 Hz. 1H), 7.35-7.40 (m, 6H), 7.44-7.53 (m, 3H), 7.61 (s, 1H), 7.87-7.89 (M, 2H), 8.56-8.60 (m, 1H), 9.51 (s, 1H).

Stage 3 N-. { 5 - [(4 ', 6'-O-benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide The title compound is prepared as a white solid (0.138 g, 82%) from N-. { 5- [(2, 2 ', 3, 3' -tetra-O-acetyl-4 ', 6' -O-benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide using a procedure similar to that of Example 2, p.f. 133-144 ° C; XH NMR (DMS0-d6) d 2.06 (s, 3H), 3.12-3.18 (m, 3H), 3.28-3.48 (m, 4H), 3.58-3.69 (m, 2H), 3.86-3.88 (m, 1H), 4.07 -4.09 (m, 1H), 4.23-4.27 (m, 2H), 4.66 (ABc, J = 12.3 Hz, As = 0. 10, 2H), 5.16 (di J = 4.0 HZ, 1 H), 5.27 (d , J = 5.5 Hz. 1H), 5.36 (d, J = 5.1 Hz, 1H), 5.56-5.58 (m, 2H), 5.82 (d, J = 6.2 Hz, 1H), 7.12 (dd, J = 8.2, 1.9 Hz, 1H), 7.34-7.50 (m, 9H), 7.62 (s, 1H), 7.82-7.85 (m, 2H), 8.47 (m, 1 H), 9.51 (s, 1 H). IR (KBr) 3400, 2900, 1650, 1550 and 1070 cm "1; mass spectrum [(+) FAB], m / z 715/717 (M + H) +; Analysis calculated for C35H39NC102: C, 58.78; H , 5.50; N, 3.91, Found: C, 58.49; H, 5.60; N, 3.73.

Example 18 N- (5- { [4 ', 6'-O-benzylidene-6-deoxy -6- (2-phenyl-1-oxo-ethyl-amino) -β-D-maltosyl-oxy-methyl}. -2-chloro-phenyl) -acetamide Step 1 N- (5- { [2,2 ', 3,3' -tetra-O-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6- (2-phenyl-1- oxo-ethyl-amino) -β-D-maltosyl] -oxy-methyl) -2-chloro-phenyl) -asetanide The title compound is prepared as a solid (0.176 g, 94%) from N-. { 5- [(2, 2 ', 3, 3' -tetra-O-acetyl- ', 6' -0-benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxymethyl] -2-chloro -phenyl} -acetamide using phenylacetyl chloride and a procedure similar to that of step 2 of Example 17; X H NMR (DMSO-d 6) d 1.93 (s, 3 H), 1.95 (s, 3 H), 1.97 (s, 3 H), 2.00 (s, 3 H), 2.09 (s 3 H), 3.20 (m, 1 H), 3.50 (s, 2H). 3.70-3.92 6H), 4.18-4.20 (m, 1H), 4.48 (d, J 12.6 Hz, 1H), 4.71-4.77 (m, 3H), 4.90 (dd, J 10.2, 4.1 Hz, 1H), 5.19 - 5.28 (m. 3H), 5.61 (s, 1H), 7.04 (dd, J = 8.3, 1.6 Hz, 1H), 7.19-7.30 (m, 5H), 7.37 (s, 5H), 7.47 (d, J = 8.3 Hz, 1H), 7.64 (s, 1H), 8.16 (s, 1H), 9.54 (s, 1H). stage 2 N- (5- { [4 ', 6' -O-benzylidene-6-deoxy-6- (2-phenyl-1-oxo-ethylamino) -β-D-maltosyl-oxy-methyl) -2- chloro-phenyl) -acetamide The title compound is prepared as a white solid (0.109 g, 85%) from N-. { 5- [(2, 2 ', 3, 3' -tetra-O-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6- (2-phenyl-1-oxo-ethylamino) -β- D-maltosyl) -oxi-methyl] -2-chloro-phenyl} -acetamide using a procedure similar to that of Example 2, p.f. 115 ° C: - "? RMN (DMS0-d6) d 2.09 (s, 3H), 2.90-2.95 (m, 1H), 3.09-3.14 (, 1H), 3.25-3.50 (m, 7H), 3.53-3.63 (m, 2H), 3.73- 3.79 (m, 1H), 3.90 (dd, J = 13.0, 6.8 Hz, 1H), 4.20-4.23 (m, 2H), 4.63 (ABc, J = 12.5 Hz,? d = 0.13, 2H), 5.08 (d, J = 3.7 Hz, 1H), 5.26 (d, J = 5.3 Hz, 1 H), 5.34 (d, J = 5.1 Hz, 1 H), 5.52 (d, J = 2.9 Hz, 1H), 5.55 (s, 1H), 5.18 (d, J = 6.4 Hz, 1H), 7.15-7.27 (m, 6H), 7.34-7.37 (m, 3H), 7.41-7.46 (m , 3H), 7.66 (s, 1H), 8.01-8.03 (m, 1H), 9.54 (s, 1H), IR (KBr) 3375, 2900, 1650, 1540 and 1070 cm "1; mass spectrum [(+ ) FAB], m / z 729 (M + H) +, Analysis calculated for C36H41NC1012, H20: C, 57.87, H, 5.80, N, 3.75, Found: C. 57.87, H, 5.66, N, 3.66.

Example 19 Methyl ester of N- acid. { 5- f (4 ', 6' -0-benzylidene-6-deoxy-6-phenethylsulfanyl-β-D-maltosyl-oxy-methyl-2-chloro-phenyl} -carbamic acid stage 1 Methyl ester of N- acid. { 5- [(hepta-O-acetyl-β-D-maltosyl) oxymethyl] -2-chloro-phenyl} -carbamic solution A stirred solution of 2-chloro-5- (hepta-O-acetyl-β-D-maltosyl-oxymethyl) -phenylamine (1.40 g, 1.80 mmol) in 18 ml of THF at 0 ° C is added NaH (0.108) g, 2.70 mmoles). After 10 min at this temperature, methyl chloroformate (0.167 ml, 2.16 mmol) is added and then the reaction is heated to rt for 3 h. At this point, the reaction is concentrated and the residue is diluted with 300 ml of EtOAc. This solution is washed with 30 ml of IN HCl, 30 ml of saturated aqueous NaHCO 3, and 30 ml of brine, and then dried with MgSO 4. After concentration, the resulting oily residue is purified by flash chromatography (2:98 to 10:90 of a gradient of acetone: CHC13) to give the product (1.33 g, 88%) as a white foam, m.p. > 79 ° C (decomposed) 1 H NMR (DMSO-d 6) d 1.93 (s, 3 H), 1.94 (s, 6 H), 1,970 (s, 3 H), 1,973 (s, 3 H), 2.01 (s, 3 H), 2.08 (s, 3H), 3.64 (s 3H), 3.91-4.03 (m, 4H), 4. 12-4.23 (m, 2H), 4.38 (dd, J = 1.8, 11.9 Hz, 1H), 4.54 (d, J = 12.7 Hz, 1H), 4.69-4.75 (m, 2H), 4.83-4.88 (m, 2H), 4.97 (t, J = 9.7 Hz, 1H), 5.21 (dd, J = 9.7, 10.3 Hz, 1H), 5.27 (d, J = 3.7 Hz, 1H), 5.30 (dd, J = 8.6, 9.2 Hz, 1H) 7.07 (dd, J = 2.0, 8.3 Hz, 1 H), 7.44 (di J = 8. 1 Hz, 1 H), 7.48 (di J 1. 8 Hz, 1H), 9.08 (s, 1H); IR (KBr) 3420, 2950, 1755, 1590, 1530, 1450, 1420, 1375, 1230, 1130, and 1040 cm "; mass spectrum [(+) FAB], m / z 834 (M + H) ', 856 (M + Na) ', Analysis, calculated for C35H44C1N02D - 0.5 HzO: C, 49.86; H, 5.38; N, 1.66, Found: C, 49.68; H, 5.14;?, 1.58. stage 2 acid methyl ester. { 2-Chloro-5- [(ß-D-maltosyl) -oxy-methyl] -phenyl} -carbamic The title compound is prepared as a white foam (0.753 g, 99%) from the methyl ester of N- acid. { 5- [(hepta-O-acetyl-β-D-maltosyl) -oxymethyl] -2-chloro-phenyl} -carbamic using a procedure similar to that of Example 2, p.f. > 109 ° C (decomposition); - ** H NMR (DMSO-d6) d 3.01-3.11 (m, 2H), 3.19-3.27 (m, 2H), 3.28-3.38 (m, 2H), 3.38-3.50 (m, 3H), 3.52-3.64 (m, 2H), 3.64 (s, 3H), 3.72 (d, J = 11.2 Hz, 1H), 4.28 (di J = 7.9 Hz, 1H), 4.44-4.57 (m, 2H), 4.67 (ABc, J = 12.5 Hz,? D = 0.22, 2H), 4.83-4.96 (broad s, 2H), 5.01 (d, J = 4.0 Hz, 1H), 5.16-5.32 (s broad, 1H), 5.34-5.58 (s) broad, 2H), 7.21 (dd, J = 2.0, 8.1 Hz. 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.53 (d, J = 1.8 Hz, 1H), 9.07 (s, 1H); IR (KBr) 3420, 2920, 1725, 1590, 1530, 1450, 1425, 1370, 1310, 1255, 1230, 1140, 1070, and 1030 crn "1; mass spectrum [(+) FAB], m / z 562 / 564 (M + Na) +, Analysis calculated for C21H30ClNO13 0.5 H20: C, 45.95; H, 5.69; N, 2.55, Found: C, 45.8 1; H, 5.82; N, 2.39. stage 3 methyl ester of the N- acid. { 5- [(4 ', 6'-O-benzylidene-β-D-maltosyl) -oxi-methyl] -2-chloro-phenyl} sarbamic The title compound is prepared as a white solid (0.552 g, 71%) from the methyl ester of the acid. { 2-Chloro-5- [(ß-D-maltosyl) -oxy-methyl] -phenyl} -carbamic using a procedure similar to that of step 5 of Example 1, p.f. 142-145 ° C; XH NMR (DMS0-d6) d 3.06-3.13 (m, 1H), 3.28-3.41 (m, 4H), 3.46 (td, J = 2.4, 8.8 Hz, 1H), 3.50-3.61 (m, 2H), 3.65 (s, 3H), 3.65-3.75 (m. 3H), 4.11 (dd, J = 3.1, 8.1 Hz, 1H), 4.30 (d, J = 7.7 Hz, 1H), 4.64-4.69 (m, 1H), 4.68 (ABc, J = 12.5 Hz,? D = 0.22, 2H), 5.14 (d, J = 3.7 Hz, 1H), 5.26 (d, J = 5.1 Hz, 1H). 5.30 (d, J = 4.8 Hz, 1H), 5.51 (d, J = 2.9 Hz, 1H), 5.57 (s, 1H), 5.63 (d, J = 6.4 Hz, 1H), 7.22 (dd, J = 2.0 , 8.1 Hz, * lH), 7.34-7.38 (m, 3H), 7.41-7.46 (m, 3H), 7.54 (d.

J = 1.8 Hz, 1H), 9.07 (s, 1H); IR (KBr) 3530, 3410, 2920, 2850, 1730, 1590, 1535, 1450, 1420, 1375, 1310, 1250, 1230, 1145, 1075, 1030, and 1000 cm "1; mass spectrum [(+) FAB], m / z 650/652 (M + Na) +; Analysis calculated for C28H34C1N013. 0.5 H20: C, 52.79; H, 5.54; N, 2.20, Found: C, 52.85; H, 5.77; N, 2.11.

Step 4: N- (5- {[4 ', 6' -O-benzylidene-6-O- (4-toluenesulfonyl) -β-D-maltosyl] -oxi-methyl} -2- methyl ester. -chloro-phenyl) -carbamic The title compound is prepared as a white solid (0.686 g, 70%) from the N- methyl ester. { 5- [(4 ', 6'-O-benzylidene-β-D-maltosyl) -oxi-methyl] -2-chlorophenyl} -carbamic using a procedure similar to that of Example 1; XH NMR (DMS0-ds) d 2.34 (s, 3H), 3.11 (t, 1H), 3.36-3.67 (m, 1H), 3.96 (d, J = 5.1 Hz, 1H), 4.14 (dd, 1H), 4.30-4.35 (m, 2H), 4.56 (ABc, J = 12.4 Hz,? D = 0.06, 2H), 5.07 (d, J = 3.7 HZ, 1H), 5.36 (broad s, 2H), 5.58 ( s, 2H), 5.77 (broad s, 1H), 7.20 (dd, J = 8.3, 2.0 Hz, 1H), 7.37-7.53 (m, 9H), 7.80 (d, J = 8.4 Hz, 2H), 9. 1 0 (s, 1 H). stage 5 N- (5-. {[2,2'-3,3'-tetra-0-acetyl-4 ', 6' -0-benzylidene-6-0- (4-toluenesulfonyl) -β-methyl ester -D-maltosyl] -oxi-methyl.} -2-chloro-phenyl) -carbamic The title compound is prepared as a white solid (0.812 g, 99%) from the N- (5 { [4 ', 6'-O-benzylidene-6-0- (4- toluenesulfonyl) -β-D-maltosyl] -oxi-methyl.} -2-chloro-phenyl) -carbamic acid using a procedure similar to that of step 7 of Example 1; 1 H NMR (DMS0-d6) d 1.92 (s, 3H), 1.93 (s, 3H), 1.97 (s, 3H), 2.01 (s, 3H), 2.30 (s, 3H), 3.66 (s, 3H), 3.69-4.04 (m, 5H). 4.19-4.22 (m, 1H), 4.23-4.43 (m, 3H), 4.56-4.65 (m, 2H). 4.80 (d, J = 8.1 Hz, 1H), 4.88 (dd, J = 10.2, 4.1 Hz, 1H), 5.18-5.33 (m, 3H), 5.66 (s, 1H), 7.05 (dd, J = 8.3, 1.8 Hz, 1H), 7.30-7.48 (m, 9H ), 7.82 (d, J = 8.4 Hz, 2H), 9.11 (s, 1H). stage 6 Methyl ester of N- acid. { 5- [(2,2 ', 3,3'-tetra-O-acetyl-4', 6'-O-benzylidene-6-deoxy-6-phenethylsulphane-β-D-maltosyl) -oxymethyl] -2 - chloro-phenyl} -carbámiso . The title compound is prepared as a white solid (0.217 g, 82%) from the N- (5- {. [2,2 ', 3,3'-tetra-O-acetyl-4-methyl ester. ', 6'-O-benzylidene-6-O- (4-toluenesulfonyl) -β-D-maltosyl] -oxy-methyl} -2-chloro-phenyl) -carbamic acid using a procedure similar to step 8 of Example 1; X H NMR (DMSO-d 6) d 1.93 (s, 3 H), 1.95 (s, 3 H), 1.98 (s, 3 H), 2.01 (s, 3 H), 2.81-2.93 (m, 5 H), 3'.04- 3.09 (m, 1H), 3.65 (s, 3H), 3.78 ~ 3.85 (m, 2H), 3.90-3.97 (m, 3H), 4.24-4.26 (m, 1H), 4.56 (d, J = 12.7 Hz, 1H), 4.68-4.74 (m, 2H), 4.84-4.92 (m, 2H), 5.24-5.34 (m, 3H), 5.65 (s, 1H), 7.04 (dd, J = 8.3, 1.7 Hz, 1H) , 7.14-7.30 (m, 5H), 7.30-7.40 (m, 5H), 7.42 (d, J = 8.2 Hz, 1H), 7.48 (s, 1 H), 9. 1 0 (s, 1 H). stage 7 Methyl ester of N- acid. { 5- [(4 *, 6 '-0-benzylidene-6-deoxy-6-phenethylsulfanyl-β-D-maltosyl) -oxy-methyl] -2-chloro-f-enyl} carbámiso The title compound is prepared as a white solid (0.135 g, 79%) from the N- methyl ester. { 5 - [(2,2 ', 3,3'-tetra-O-acetyl-4', 6'-O-benzylidene-6-deoxy-6-phenethylsulfonyl-ß-D-maltosyl) -oxy-methyl] -2-chloro-f enyl} -carbamic using procedure similar to that of Example 2, 85-90 ° C; ? NMR (DMS0-d6) d 2.74 (dd, J 14.2, 7.1 Hz. 1H), 2. 81-2.86 (m, 4H). 3.00 (dd, J = 14.2, 2.1 Hz, 1H), 3.09-3.14 (m, 1H), 3.37-3.47 (m, 4H), 3.51-3.59 (m, 2H), 3.64 (s, 3H), 3.69- 3.72 (m, 2H), 4.08 4.09 (m, 1H). 4.32 (d, J = 7.9 Hz, 1H), 4.63 (ABc, J = 12.3 Hz,? D = 0.07, 2H), 5.17 (d, J = 3.7 Hz, 1H), 5.31 (t, J = 5.7 Hz, 2H), 5.50 (d, J = 3.1 Hz, 1H), 5.57 (s, 1H), 5.66 (d, J = 6.6 Hz, 1H), 7.13-7.21 (m, 6H), 7. 33-7.36 (m, 3H), 7.39-7.43 (m, 3H), 7.51 (d, J = 1.8 Hz, 1 H), 9.06 (s, 1H); IR (KBr) 3400, 2900, 1740, 1540 and 1070 cm "1 mass spectrum [(-) FAB], m / z 746 (M - H) +; Analysis calculated for C36H42NC10-L2S 0.5 H20: C, 57.10; H, 5.72; N, 1.85, Found: C, 57.14; H, 5.53; N, 1.86.

Example 20 Methyl ester of N- acid. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxy-1-ethyl-2-chloro-phenyl} carbamic stage 1 Methyl ester of N- acid. { 5- [2, 2 ', 3, 3"-tetra-O-acetyl-4', 6 '-O-benzylidene-6-deoxy-6-benzylsulphane-β-D-maltosyl) -oxymethyl] -2-chloro -phenyl.

The title compound is prepared as a white solid (0.343 g, 66%) from the N- (5- {. [2,2 ', 3,3'-tetra-0-acetyl-4-methyl ester. ', 6'-O-benzylidene-6-0- (4-toluenesulfonyl) -β-D-maltosyl] -oxy-methyl.} -2-chloro-phenyl) -carbamic acid using benzyl mercaptan and a procedure similar to the step 8 of Example 1; * H NMR (DMS0-d6) d 1.92 (s, 3H), 1.95 (s, 3H), .1.97 (s, 3H), 2.02 (s, 3H), 2.75-2.80 (m, 1H), 2.90 (d , J = 13.0 Hz, 1H), 3.65 (s, 3H), 3.69-3.94 (m, 7H), 4.18-4.22 (m, 1H), 4.60 (d, J = 12.7 Hz, 1H), 4.69-4.91 ( m, 4H), 5.21-5.32 (m, 3H), 5.65 (s, 1H), 7.10 (dd, J = 8.2, 1.8 Hz, 1H), 7.16-7.21 (m, 1H), 7.27-7.41 (m, 9H), 7.46 (d, J * "» = 8.2 Hz, 1H), 7.52 (s, 1H), 9.10 (s, 1H). stage 2 Methyl ester of N- acid. { 5- [(2,2-, 3, 3 '-tetra-O-acetyl-4', 6'-O-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxymethyl] -2 - chloro-phenyl] The title compound is prepared as a mixture 1: 1 diastereomers, white solid (0.289 g, 89%) from the methyl ester of N- acid. { 5- [(2, 2 ', 3, 3' -tetra-O-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfanyl-β-D-maltosyl) -oxymethyl] -2- chlorine-phenyl} -carbamic using a procedure similar to that of Example 5; XH NMR (DMSO-d6) d 1.92, 1.93, 1.94, 1.95, 1.96, 1.98, 2.01. 2.09 (8s, 12H), 3.08-3.15 (m, 2H), 3.65 (s, 3H), 3.76-3.81 (m, 2H), 3.8 2-3.97 (m, 2H), 4.01-4.10 (m, 2H) , 4.22-4.33 (m, 2H), 4584.62 (m, 1H), 4.71-4.96 (m, '4H). 5.23-5.33 (m, 3H), 5.65, 5.69 (2s, 1H), 7.08 (dd, 1H), 7.2 8-7.51 (m, 12H), 9. 1 0 (s.1H).

Stage 3 N- methyl ester. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxy-methyl] -2-chloro-f-enyl} -carbamic The title compound is prepared as a 1: 1 mixture of diastereomers, white solid (0.212 g, 95%) from the N- methyl ester. { 5- [(2, 2 ', 3, 3' -tetra-O-acetyl-4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxymethyl] -2- chlorine-phenyl} -carbamic using a procedure similar to that of Example 2, p.f. 119-128 ° C; -H NMR (DMSO-d6) d 2.97-3.02 (m, 1H), 3.11-3.19 (m, 1H), 3.25-3.72 (m, 11H), 3.87-3.98 (m, 2H), 4.05-4.10 (m , 1H), 4.21 (d, J = 12.7 Hz, 1H), 4.35, 4.44 (2d, 1H), 4.59 (dd, 1H), 4.74 (t, J = 12.3 Hz, 1H), 5.19 (t, J = 4.5 Hz, 1H), 5.33-5.39 (m, 2H), 5.56-5.59 (m, 2H), 5.67, 5.75 (2d, 1H), 7.18-7.21 (m, 1H), 7.28-7.48 (m, 11H) 7.53-7.54 (m, 1H), 9.06 (s, 1H); IR (KBr) 3400, 2925, 1735, 1590, 1540 and 1075 cm "1; mass spectrum [(+) FAB], m / z 772 (M + Na) *; Analysis calculated for C35H40NClO13S: C, 56.04; H 5.37; N, 1.87, Found: C, 55.94; H, 5.39; N, 1.82.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the content of the following claims is claimed as property:

1. A compound of formula I, characterized by having the structure: where W is S, SO, S02, NR; Y is 0, S, NR or CH2; R is hydrogen or alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 and R7 are each independently alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms carbon, alkoxyalkyl of 2 to 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- - or trisubstituted with R8, pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, benzyl , wherein the phenyl portion is mono-, di- or tri-substituted with R8, benzoyl wherein the phenyl portion is mono-, di- or trisubstituted with R8; R8 is hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN. -N02, halogen or -FC3; R9 is hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, - NHC02R13, -NHS02R13, -NR14R15, R 10, R 11 and R 12 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms 0 benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R 13 is alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with halogen; R14 and R15 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n = 0-3; or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, characterized by porue Y is O; R3, R4, R5 and R6 are each independently hydrogen or acyl of 2 to 7 carbon atoms; R9 is hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, -CF3, -NHR3, -NR3R3, -NR3R3, -NHC02R13, -NHS02R13, or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2, characterized in that R1 is phenyl mono-, di- or trisubstituted with R8; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1, characterized in that it is N-. { 5- [(2, 3, 2 ', 3' -tetra-0-acetyl-6-deoxy-6-benzylsulfanyl-4 ', 6'-0-benzylidene-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl) -acetamide or an acceptable pharmaceutically acceptable salt thereof.

5. The compound according to claim 1, characterized in that it is N-. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfañyl-ßD-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

6. The compound according to claim 1, characterized in that it is N- (5- { [2, 3, 2 ', 3' -tetra-0-acetyl-6-deoxy-6- (2,4-dichloro- benzylsulphane) -4 ', 6'-O-benzylidene-β-D-maltosyl] -oxi-methyl.} -2-chloro-phenyl) acetamide or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1, characterized in that it is N- (5- { [4 ', 6' -O-benzylidene-6-deoxy-6 - (2,4-dichloro-benzylsulfane) -β-D -maltosyl] -oxi-methyl.} -2-chloro-phenyl) -acetamide or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1, characterized in that it is N-. { 5 - [(2,3,2 ', 3'-tetra-0-acetyl-4', 6 '-0-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

9. The compound according to claim 1, characterized in that it is N-. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfinyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

10. The compound according to claim 1, characterized in that it is N-. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzylsulfonyl-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

11. The compound according to claim 1, characterized in that it is N-. { 5 - [(2,2 ', 3,3'-Tetra-O-acetyl-4', 6 '-0-benzylidene-6-deoxy-6-phenylsulfanyl-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

12. The compound according to claim 1, characterized in that it is N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-phenylsulphane-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

13. The compound according to claim 1, characterized in that it is N-. { 5 - [(2,2 ', 3,3'-tetra-0-acetyl-4', 6 '-0-benzylidene-6-deoxy-6-phenylsulfinyl-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} acetamide or an acceptable pharmaceutically acceptable salt thereof.

1 . The compound according to claim 1, characterized in that it is N-. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-phenethylsulphane-ß-D-maltosyl) -oxymethyl] -2-chloro-phenyl} acetamide or an acceptable pharmaceutically acceptable salt thereof.

15. The compound according to claim 1, characterized in that it is N-. { 5 - [(2,2 ', 3,3'-tetra-O-acetyl-4', 6 '-0-benzylidene-6-deoxy-6-phenethylsulfanyl-β-D-maltosyl) -oxi-methyl] - 2-chloro-phenyl} -acetamide or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1, characterized in that it is N- (5- [(4 ', 6' -0-benzylidene-6-deoxy-6- (phenyl-ethyl-sulfinyl) -β-D-maltosyl) - oxymethyl] -2-chloro-phenyl.} .acetamide or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1, characterized in that it is N- (5- { [4 ', 6' -O-benzylidene-6-deoxy-6- (3-phenyl-propylsulfane) -β-D-maltosyl) -oxi -met il} 2-chloro-phenyl) -acetamide or an acceptable pharmaceutically acceptable salt thereof.

18. The compound according to claim 1, characterized in that it is N-. { 5- [(4 ', 6'-O-benzylidene-6-deoxy-6-benzoylamino-β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -acetamide or an acceptable pharmaceutically acceptable salt thereof.

19. The compound according to claim 1, characterized in that it is N- (5- { [4 ', 6'-O-benzylidene-6-deoxy-6- (2-phenyl-1-oxo-ethyl-amino) -β-D-maltosyl] .- oxi-met il.} - 2-cl oro-f eni l) -acetamide an pharmaceutically acceptable salt thereof.

20. The compound according to claim 1, characterized in that it is methyl ester of N- acid. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-phenethyl-sulfañyl) -β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -carbamic or an acceptable pharmaceutically acceptable salt thereof.

21. The compound according to claim 1, characterized in that it is methyl ester of N- acid. { 5- [(4 ', 6' -0-benzylidene-6-deoxy-6-benzylsulfinyl) -β-D-maltosyl) -oxy-methyl] -2-chloro-phenyl} -carbamic or an acceptable pharmaceutically acceptable salt thereof.

22. A method for treating or inhibiting hyperproliferative vascular disorders in a mammal in need thereof, characterized in that it comprises administering to the mammal an effective amount of a compound of formula I having the structure where W is S, SO, S02, NR; And it is O, S, NR or CH2; R is hydrogen or alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 and R7 are each independently alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms carbon, alkoxyalkyl of 2 to 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- - or trisubstituted with R8, pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R ^ and R6 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, benzyl, wherein the phenyl portion is mono-, di- or tri-substituted with R8, benzoyl wherein the phenyl portion is mono-, di- or trisubstituted with R8; R8 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN. -N02, halogen or -FC3; R9 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, - NHC02R13, -NHS02R13, -NR14R15, R 10, R 11 and R 12 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, - CN, -N02, halogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms 0 benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R 13 is alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with halogen; R14 and R1S are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n 0-3; or a pharmaceutically acceptable salt thereof.

23. The method according to claim 22, characterized by restenosis results from a vascular angioplasty procedure, vascular reconstructive surgery or organ or tissue transplantation.

24. A method for inhibiting angiogenesis in a malignant tumor, sarcoma or neoplastic tissue in a mammal in need thereof, characterized in that it comprises administering to the mammal an effective amount of a compound of formula I having the structure where W is S, SO, S02, NR; And it is O, S, NR or CH2; R is hydrogen or alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 and R7 are each independently alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms carbon, alkoxyalkyl of 2 to 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- - or trisubstituted with R8, pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, benzyl , wherein the phenyl portion is mono-, di- or trisubstituted with R8, benzoyl wherein the phenyl portion is mono-, di- or trisubstituted with R8.; R8 is hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN. -N02, halogen or -FC3; is hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, - NHC02R13, -NHS02R13, -NR14R15, R 10, R 11 and R 12 are each independently hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, - CN, -N02, halogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms 0 benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R13 is alipyl of 1 to 6 carbon atoms, perfluoroalguyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with halogen; R14 and R15 are each independently hydrogen, alkoyl 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n = 0 -3, - or a pharmaceutically acceptable salt thereof.

25. A pharmaceutical composition, characterized in that it comprises a compound of formula I having the structure where W is S, SO, S02, NR; And it is O, S, NR or CH2; R is hydrogen or alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 and R7 are each independently alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms carbon, alkoxyalkyl of 2 to 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- - or trisubstituted with R8, pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms, algayl of 1 to 6 carbon atoms, perfluoroalguyl of 1 to 6 carbon atoms, benzyl , wherein the phenyl portion is mono-, di- or tri-substituted with R8, benzoyl wherein the phenyl portion is mono-, di- or trisubstituted with R8; R8 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN. -'N02, halogen or - CF3; R9 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalguile of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, NHC02R13, - NHS02R13, - NR1 R15, R 10, R 11 and R 12 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, - CN, -N02, halogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms 0 benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R 13 is alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with halogen; R14 and R15 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n = 0-3; or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier. SUMMARY OF THE INVENTION This invention provides inhibitors of smooth muscle cell proliferation of formula I, which has the structure where W is S, SO, S02, NR; And it is O, S, NR or CH2; R is hydrogen or alkenyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; R1 and R7 are each independently alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, haloalkyl of 1 to 6 carbon atoms, nitroalkyl of 1 to 6 carbon atoms, cyanoalkyl of 1 to 6 carbon atoms carbon, alkoxyalkyl of 2 to 12 carbon atoms, nitriloalkyl of 1 to 6 carbon atoms, phenyl mono-, di- or trisubstituted with R8, phenylalkyl of 7 to 10 carbon atoms, wherein the phenyl ring is mono-, di- - or trisubstituted with R8, pyridyl substituted with R8, furyl substituted with R8, thienyl substituted with R8, and thiazolyl substituted with R8; R2 is hydrogen, R3, R4, R5 and R6 are each independently hydrogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, benzyl , wherein the phenyl portion is mono-, di- or trisubstituted with R8, benzoyl wherein the phenyl portion is mono-, di- or trisubstituted with R8; R8 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalguile of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen or -CF3; R9 is hydrogen, alkoyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, -CN, -N02, halogen, -NHC02R13, -NHS02R13, -NR1R15, R 10, R 11 and R 12 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, phenyl, - CN, -N02, halogen, acyl of 2 to 7 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms 0 benzoyl, wherein the phenyl portion of the benzoyl group is optionally mono-, di- or trisubstituted with alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, -CN, -N02, halogen or -CF3; R13 is alipyl of 1 to 6 carbon atoms, perfluoroalguyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with halogen; R14 and R15 are each independently hydrogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, acyl of 1 carbon atoms, perfluoroacyl of 2 to 7 carbon atoms; n 0-3; or a pharmaceutically acceptable salt thereof.