Human beta-like globih genes are encoded in a cluster located on chromosome 11. This cluster includes two genes encoding gamma, or fetal, globin and one gene encoding beta, or adult globin. Expression of globin genes is tightly regulated during ontogeny. A developmental switch from production of predominantly fetal hemoglobin (HbF; a272) to production of adult hemoglobin (HbA ; 272) occurs beginning at about 28 to 34 weeks of gestation and continuing shortly after birth until HbA becomes predominant.

This switch in the production of homoglobin results primarily from decreased transcription of the gamma globin genes and increased transcription of the beta globin gene.

The basis for many congenital hematological diseases is a defect in the structure or production of beta globin.

For example, sickle cell anemia results from a point mutation in the beta globin structural gene, leading to production of abnormal HbS. Beta-thalassemias result from a partial or complete defect in the expression of the beta globin gene, leading to deficient or absent HbA.

Certain populations of adult patients with beta chain abnormalities have higher than normal levels of HbF and these patients have been observed to have a milder clinical course of disease than patients with normal adult levels of HbF.

Therefore, the pharmacological regulation of the expression of human y-globin genes is one of the most interesting approaches in the search for potential therapeutic agents for hematological disorders.

Increased production of fetal haemoglobin (HbF) can be indeed clinically beneficial either in (3-thalassemia by reducing the imbalance between y and (3 chains and in sickle cell disease though inhibition of polymerization of S haemoglobin and reduction of free a chains.

Accordingly, a number of studies have been carried out in order to identify compounds able to stimulate expression of y-globin genes.

Chemioterapic (antiproliferative) agents, such as 5- azacitidine and cytosine arabinoside, have been for instance proposed for this purpose. These cytotoxic agents influence the growth kinetics of erythroid cells for example by accelerating erythropoiesis so that more early erythroid cells are produced which synthetise higher levels of HbF.

Hydroxyurea-the only drug approved for the treatment of sickle cell anemia, as well another ribonucleotide reductase inhibitor (Didox)-has a cytotoxic effect on the bone marrow, causing a selection of a subpopulation of red cell precursors capable of sinthesising increased amounts of HbF (Mitchell T. E. et al. , Exp. Opin. , Invest. , Drugs. , 1999,8, 1823).

Among other possible less toxic biological response modifiers, one of the most interesting classes of compounds comprises butyrates and structural analogues and salts threof.

Butyrate treatment has been reported to increase levels of HbF in experimental models and in humans (Perrine S. P. et al.

(N. Engl. J. Med. , 1993,328, 81).

Besides regulating y-globin expression, butyrate and other Short Chain Fatty Acids (SCFA) induce phenotypic maturation in many eukaryotic cell types, and have been demonstrated to cause growth arrest and reversal of neoplastic characteristics in cultured cells (Kruh, J and al., In: Cumming J. H. et al. ,"Physiology and clinical aspects of short chain fatty acids", Cambridge University Press, London, 1995).

Butyrate is very interesting for therapeutic applications, given the lack of acute cytotoxicity in normal tissues even at high concentrations. In fact, butyrate promotes the survival of normal colonic epithelia in culture and in vivo, whereas several cell lines, especially several cell lines derived from lymphoma, ovarian cancer, and adenocarcinoma of prostate, colon and breast, have been found to undergo terminal differentiation and/or apoptosis when treated with millimolar concentrations of sodium n-butyrate.

Yet, butyrates and related compounds such as isobutyrates and phenylbutyrates have some disadvantages. They are active at quite large dosages and they also exhibit extremely short half-life.

The low activity and the rapid clearance of these agents results in an inability to deliver and maintain high plasma levels necessary in intravenous infusion administration, so reducing patient compliance.

Another potential obstacle to the use of butyrate salts is represented by salt over-load and its physiological effects.

In view of these observations, various prodrugs of butyric acid and related analogues have been studied, which allow to achieve higher and more persistent plasma levels.

Such produgs include tributyrin and n-butyric acid mono-and polyesters derived from mono-saccharides (Chen et al. Cancer Res. 54,3494-99, 1994; Newmark et al Cancer Letts. , 78,1-5, 1994; Pouillart et al. J. Pharm. Sci. , 81,241-44, 1992; Calabresse et al. Biochem. Biophys. Res. Comm. 201,266-82, 1994).

However, such butyrate prodrugs have not been proved to be useful as therapeutics, due to factors such as short half- life, low bioavailability, or lack of effective oral deliverability.

Other prodrugs, such as AN-9 and AN-10 (Nudelman et al., J.

Med. Chem. , 35,687-94, 1992), elicit metabolites that may produce formaldehyde in vivo, leading to toxic effects in patients.

Accordingly, the need exists for derivatives of butyrate and related analogues having desirable pharamacokinetic properties for use in providing effective therapy for the diseases discussed above.

Recently, as a part of a research program aimed at studying derivates of n-butyric or isobutyric acid able of slowly releasing the acidic moiety, some monosaccharides esters were tested in the K562 cell line in an vitro model system.

These esters unexpectedly turned out to be more effective than parent compounds in inducing erythroid differentiation of K562 celles, thus suggesting that these compounds may be considered not only as butyrate prodrugs, but also as active agents not needing hydrolysis to work.

Further studies have also demonstrated that the glucide moiety plays an important role in favouring the cellular uptake of these products.

The tests showed the following: 1) The 3-0-isobutyryl derivative of 1, 2-0-isopropylidene-a- D-glucofuranose (indicated hereinafter by the test abbreviation GG6B) was more active in inducing differentiation of K562 cells than was isobutyric acid (54.2 vs. 14% at a concentration of 4 mM).

2) In erythroid cells from human blood, the in vitro activity of GG6B in inducing the expression of y-globins is significantly greater than that of isobutyric acid.

3) In a study suitable for evaluating the concentrations of the chemical species bringing about in vitro activity in erythroid cells, GG6B exhibits better penetration through the membranes than does isobutyric acid both after 1 hour and after 3 days.

However, the aforementioned ester compounds suffer the drawback of being rapidly metabolised in vivo due to the rapid hydrolysis of the ester bond by esterases.

In order to overcome this drawback, the present invention provides new glucide derivatives having biological activity as inducers of erythroid cell differentation, consituted by an acyl moiety linked to a 3-deoxyglucide unit through a stable bond, particularly an amide type bond.

The presence of a stable bond between the acyl moiety and the 3-deoxyglucide moiety of the molecule enables rapid enzymatic hydrolysis of these derivatives to be avoided.

These derivatives should also possess good bioavailability, which is a prerequisite for efficient oral administration and an adequate plasma half-life.

A subject of the present invention is therefore new glucide derivatives of formula I (furanoside form) or II (pyranoside form): in which R1 is the acyl of a carboxylic acid of the formula RCOOH, in which R is selected from the group consisting of linear or branched, saturated or unsaturated alkyl which has from 1 to 6 carbon atoms and which is optionally substituted by one or more aryl radicals or by one or more cycloalkyl radicals having from 3 to 6 carbon atoms, saturated or unsaturated cycloalkyl having from 3 to 6 carbon atoms, and aryl or heteroaryl optionally substituted by one or more substituents selected from alkoxy groups having from 1 to 3 carbon atoms, halogen atoms and aryl groups; X is-NR6 ; R2, R3, R4, R5 and R6 are selected, independently of one another, from the group consisting of hydrogen, cyclic or acyclic, saturated or unsaturated, branched or unbranched alkyl having from 1 to 8 carbon atoms, and cyclic or acyclic, saturated or unsaturated, branched or unbranched acyl having from 1 to 8 carbon atoms, or, alternatively, R2 and R3 together correspond to a group of the formula: <BR> <BR> <BR> <BR> <BR> <BR> <BR> CoR7<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> R8 in which R7-C-R8 is a protecting group selected from the group consisting of phenylmethylene, methylene, cyclohexylidene and isopropylidene, and R4, Rs and R6 are, independently of one another, as defined above.

When R is substituted aryl or heteroaryl, the one or more substituents are preferably selected from methoxy, phenyl, chlorine and fluorine.

The term aryl means aromatic rings having preferably 5 or 6 carbon atoms; the term heteroaryl means aromatic rings in which at least one hetero atom selected from nitrogen, sulphur and oxygen is present.

In a preferred embodiment of the invention, RCOOH is selected from the group consisting of n-butyric acid (HCO2CH2CH2CH3), 2-methylpropionic acid (HC02CH (CH3) 2), 2,2-dimethylpropionic acid (HC02C (CH3) 3), 3,3-diphenylpropionic acid (HC°2 CH2CH (C6H5) 2)/3-methylbutyric acid (HC02CH2CH (CH3) 2), 3- phenylbutyric acid (HCO2CH2CH (CH3) C6H5), 3, 3-dimethylbutyric acid (HC02CH2C (CH3) 3), 3-methylpentanoic acid (HC02CH2CH (CH3) CH2CH3), 4-phenylbenzoic acid, isonicotinic acid, nicotinic acid, picolinic acid, benzoic acid, 4- methoxybenzoic acid.

In another preferred embodiment, the protecting group R7-C-R8 is isopropylidene.

The general formulae I and II illustrated above are to be interpreted as comprising all the possible configurational stereoisomers of the 3-deoxyglucide groups represented therein, which differ therefrom by the manner in which the atoms are arranged in space.

In another preferred embodiment of the invention, the 3- deoxyglucide group is the 3-deoxy derivative of D- glucofuranose or of D-allofuranose.

Within the scope of the present invention, greater preference is given to the derivatives of formulae VII and VIII: in which R is selected from the group consisting of - CH (CH3) 2,-C (CH3) 3, and-CH2CH2CH3.

The advantages afforded by using the derivatives of the invention as inducers of erythroid cell differentiation were evaluated by means of a comparative study, the results of which are represented in Tables 3 and 4 of Example 3, which follows. The aim of this study was to compare the level of differentiation in the erythroid manner obtained by treating ) the human cell line K562 with, each independently, a compound covered by the present application (that is to say, 3-deoxy- 3-amino-N-butyryl-1 : 2-0-isopropylidene-a-D-glucofuranose, referred to as compound 73) and two reference compounds (that is to say, n-butyric acid and 1-0-butyryl-2 : 3-0- isopropylidene-D-mannofuranose, referred to hereinafter as a-MAM).

Another subject of the present invention are therefore the previously described derivatives for use as inducers of erythroid cell differentiation, optionally in combination with at least one other modifier of the biological response preferably selected from the group consisting of cytosine arabinoside, retinoic acid, plicamycin, mithramycin, hydroxyurea, guanine, guanosine triphosphate (GTP), guanosine diphosphate (GDP) and guanosine monophosphate (GMP). Cytosine arabinoside and retinoic acid are more preferred for this purpose.

A further the subject of the present invention is the use of the previously described derivatives, optionally in combination with at least one other modifier of the biological response as previously defined, for the preparation of a medicament for the therapeutic treatment of (3-thalassemia or tumors.

Still another subject of the present invention is a pharmaceutical composition comprising at least one of the previously described derivatives and a pharmaceutically acceptable carrier, optionally in combination with at least one other modifier of the biological response as previously defined.

< The derivatives according to the invention in which X is wNR6 can be prepared according to a general scheme which involves the following three general phases: 1. Preparation of the selected 3-deoxy-3-amino glucide derivative having the free alcohol functions protected by protecting groups.

2. Amide formation by treatment with the acyl chloride of the corresponding carboxylic acid.

3. Selective removal of the non desired protecting groups according to the commonly utilised deprotection techniques for alcohol groups.

An example of this process is reported in the following scheme 1.

Scheme 1 The following examples are given for illustration purposes only, and should not be interpreted to limit in any way the scope of the present invention.

Example 1: Synthesis of 3-amino-3-deoxy-glucofuranose derivatives The synthesis of 3-amino-3-deoxy-glucofuranose derivatives can be carried out in accordance with the following reaction scheme (scheme 2).

Scheme 2 OH PPh3, IZ OHo PPh3, 2 0 Imidazole, Toluene, O o O 120 C, 16 h 0 Olt | NaN3 DMB 130°C, 20h LiAIH4, Et2O __30 O III t H RCOC1, Et3N, CH2Cl2 0 HO HO R CH3COOH 80% R 0 0 0 0 Out ou 69a R = CH (CH3) 2 69 R = CH (CH3) 2 70a R = C (CH3) 3 70 R = C (CH3) 3 73a R = CH2CH2CH3 73 R = CH2CH2CH3 VII The various stages of the synthesis reaction illustrated in scheme 2 will now be described in more detail.

1.1 Synthesis of 3-deoxy-3-iodo-1 : 2,5 : 6-di-0-isopropylidene- a-D-allofuranose (scheme 2, compound I) Diacetone glucofuranose (scheme 2, compound 1) (5g, 19. 21 mmol), triphenylphosphine (15. 1g, 57.63 mmol), imidazole (3.9g, 57.63), iodine (9.76g, 38.43 mmol) and toluene (370 ml) are introduced into a 1 litre three-necked flask with a bubble coolant. The reaction mixture is heated at the reflux temperature of the solvent for 16 hours. The reaction is ; monitored by TLC (AcOEt/toluene = 2/8). When the reaction is complete, the reaction mixture is brought to ambient temperature and 400 ml of saturated NaHCO3 solution are added, agitation being maintained for 5 minutes until the solution becomes clear. Is is then added in portions until the organic phase remains slightly coloured. Agitation is then maintained for 10 minutes. In order to remove the excess I2, a saturated Na2S203 solution is added until decoloration occurs. The mixture is transferred to a separating funnel, washing the reaction flask with small quantities of acetone.

The organic phase is diluted with toluene and, after separation, the organic phase is washed with water, dried over MgS04, filtered and concentrated under vacuum. A solid white crude substance is obtained. Finally, Et20 is added to cause the triphenylphosphine oxide (Ph3P=O, white solid) to precipitate. Filtration is carried out and the filtrate is concentrated to give a yellow solid weighing 7.68g. The compound is used without further purification for the subsequent reaction.

1H-NMR (CDCl3) : 1.37-1. 57 (3s, 12H, (CH3) 2C) ; 3.7-4. 3 (m, 5H, H3, H4,H5,H6, H6'); 4.6 (d, 1H, H2) ; 5. 83 (d, 1H, H1).

3C-NMR (CDC13) : 19.16-26. 52 ((CH3)2C) ; 65.72 (C6) ; 75.44 (C3); 81.46 (C4) ; 81.7 (C2) ; 103.1 (Cl) ; 109.98 (C5, 6 quat.) ; 111.65 (CI, 2 quat. ) ; 1.2 Synthesis of 3-deoxy-3-azido-1 ; 2,5 : 6-di-O-isopropylidene- α-D-glucofuranose (scheme 2, compound II) The crude compound I (7.68g, 26.92 mmol), NaN3 (7.88g, 121.19 mmol) and DMF (270 ml) are introduced into a 500 ml three- necked flask with a bubble coolant. The whole is heated at 130°C for 20 hours. Monitoring is effected by TLC (hexane/AcOEt = 5/1). When the reaction is complete, the brown solution is cooled to ambient temperature and the solvent is removed under reduced pressure. The remainder is taken up in water and CHC12 and the organic phase is extracted with CH2C12. The organic phases are dried over MgS04, and then filtration and concentration are carried out.

A yellow solid weighing 6.08g is obtained. The solid is purified by flash chromatography on a column of silica gel to give a yellow oil weighing 3g (yield of 55% starting from compound I), almost pure compound II.

1H-NMR (CDC13) : 1. 31-1. 55 (4s, 12H, (CH3) ; 3.96 (dd, 1H, H3) ; 4.05-4. 24 (m, 4H, H4, H5, H6, H6'); 4.61 (d, 1H, H2) ; 5. 85 (d, 1H, Hui).

13C-NMR (CDCl3) : 24.93-26. 62 ((CH3) 2C) ; 66. 19 (C6) ; 67.42 (Cs) ; 72.84 (C3) ; 80.32 (C4) ; 83.23 (C2) ; 104. 85 (C1) ; 109. 30 ; (C5,6 quat. ) ; 112. 02 (Cl, 2 quat.) ; 1.3 Synthesis of 3-deoxy-3-amino-1 : 2,5 : 6-di-O-isopropylidene- a-D-glucofuranose (scheme 2, compound III) LiAlH4 (1.27g, 34.32 mmol) and anhydrous diethyl ether (100 ml) are introduced into a one-necked 250 ml flask. Compound II (3g, 10.52 mmol) is added dropwise at 0°C. When the addition is complete, the whole is heated at the reflux temperature of the solvent for 6 hours. Monitoring is effected by TLC (hexane/AcOEt = 1/1). When the reaction is complete, 6 ml of water, 6 ml of 10% NaOH and 18 ml of water are added at 0°C. The whole is filtered over celite and washing is carried out with AcOEt. The filtrate is dried, filtered and concentrated. A colourless syrup is obtained which weighs 2. lg (yield 800) and which is identified as compound III.

1H-NMR (CDC13) : 1.20-1. 50 (4s, 12H, (CH3) 2C); 3.55 (dd, 1H, H3) ; 3.97-4. 18 (m, 4H, H4, H5, H6, H6,) ; 4.4 (m, 1H, H2) ; 5. 89 (d, 1H, H1).

3C-NMR (CDC13) : 25.14-29. 55 ((CH3)2C); 57.27 (C5) ; 68.03 (C6) ; 72.84 (C3); 81. 30 (C4) ; 86. 34 (C2) ; 104. 95 (Ci) ; 109. 26 (C5, 6 quat. ) ; 111.47 (C1, 2 quat.) 1.4 Synthesis of 3-deoxy-3-amino-N-acyl-1 : 2,5 : 6-di-O- isopropylidene-a-D-glucofuranose derivatives (scheme 2, compounds 69a, 70a, 73a) The preparation of the three amides follows the same procedure for each derivative.

Compound III (820 mg, 3.16 mmol), triethylamine (13.7 ml) and CH2Cl2 (50 ml) are introduced into a one-necked 250 ml flask. t The corresponding acyl chloride (6.32 mmol) is added dropwise at 0°C. When the addition is complete, the whole is brought to ambient temperature. Monitoring is effected by TLC (AcOEt/hexane = 1/1). When the reaction is complete, 30 ml of saturated NaHCO3 solution are added and agitation is maintained for 15 minutes. The organic phase is extracted with CH2C12. The organic phases are dried, filtered and concentrated. The three crude substances are all solid residues in quantitative yield which do not undergo further purification.

The characteristic signals of the three derivatives are identified by NMR analysis (Table 1).

1.5 Synthesis of 3-deoxy-3-amino-N-acyl-1 : 2-O-isopropylidene- a-D-glucofuranose derivatives (scheme 2, compounds of the general formula VII: 69,70, 73) The final preparation of the three mono-protected amides follows the same procedure for'each derivative.

The completely protected amide (1. 04 g, 3.16 mmol) and CH3 COOH 80% v/v (47 ml) are introduced into a 250 ml flask.

Agitation is maintained for 15 minutes at 70°C. Monitoring is effected by TLC (AcOEt/hexane = 1/1). When the reaction is complete, the acetic acid is coevaporated with toluene under reduced pressure. Coloured oils are thus obtained.

The three amides are then purified by flash chromatography over a column of silica gel, eluting with CH2Cl2/MeOH = 95/5.

The following compounds are thus obtained (see Table 2): 69 white solid 530 mg (yield 60 %) t 70 white solid 610 mg (yield 63 %) 73 white solid 500 mg (yield 60 %) Example 2: Synthesis of 3-amino-3-deoxy-allofuranose derivatives The synthesis of the 3-amino-3-deoxy-allofuranose derivatives can be carried out in accordance with the following reaction scheme. (scheme 3).

Scheme 3 O O Tf20, Pyridine p O OH J/ OTf CHOC12 out 0 CH2CI2 v | NaN3, DMF 0 0 LiAIH4, Et20 0 0 NH2 O\ . Ns O\ ' VI I V vi v RCOCI, Et3N, CH2CI2 1 0 f, --0- HO'rTO- CH3COOH 80° ! a HH O p Ry NH Olt R y NH O O'' 71a R = CH (CH3) 2 71 R = CH (CH3) 2 72a R = C (CH3) 3 72 R = C (CH3) 3 74a R = CH2CH2CH3 74 R = CH2CH2CH3 VIII The various stages of the synthesis reaction illustrated in scheme 3 will now be described in more detail.

2.1 Synthesis of 3-O-triflyl-1 : 2,5 : 6-di-O-isopropylidene-α-D- glucofuranose (scheme 3, compound IV) Diacetone glucofuranose (scheme 3, compound 1) (5g, 19.21 mmol), anhydrous pyridine (4.6 ml, 4. 52g, 57. 24 mmol) and CH2Cl2 (300 ml) are introduced into a one-necked 500 ml flask. Triflic anhydride Tf2O (4 ml, 6.84g, 24.26 mmol) is added dropwise at-15°C. When the addition is complete, agitation is maintained for 1 hour. Monitoring is effected by TLC (toluene/Et20 =1/2). When the reaction is complete, a saturated NaHC03 solution and ice are added. The organic phase is extracted with CH2C12. The extracts are concentrated several times, co-evaporating with toluene. Finally, the extracts are dried, filtered and concentrated. The brown residue is taken up in hexane to extract the triflic ester IV. Filtration is carried out and the filtrate is concentrated. The crude substance (7.4g) is then crystallized from hexane.

White needle-shaped crystals weighing 7.21g are thus obtained (yield 96 %).

1H-NMR (CDCl3) : 1.33-1. 52 (4s, 12H, (CH3) 2C); 3.96-4. 23 (m, 4H, H4, H5, H6, H6'); 4.77 (m, 1H, H2) ; 5. 25 (m, 1H, H3) ; 5. 99 (d, 1H, H1).

3C-NMR (CDCl3) : 24.81-26. 75 ( (CH3) 2C) ; 67.56 (C6) ; 71.67 (C5) ; 79.86 (C3) ; 83. 21 (C4) ; 88. 14 (C2) ; 104.98 (Ci) ; 109.83 (Cs, 6 quat. ) ; 113.09 (cl 2 quat.); 2.2 Synthesis of 3-deoxy-3-azido-1 : 2,5 : 6-di-O-isopropylidene- a-D-allofuranose (scheme 3, compound V) Compound IV (7.21g, 18. 38 mmol), NaN3 (2.4g, 36.92 mmol) and DMF (240 ml) are introduced into a one-necked 500 ml flask.

The whole is heated at 100°C for two hours. Monitoring is effected by TLC (toluene/Et2O = 9/1). When the reaction is complete, the reaction mixture is brought to ambient temperature and the solvent is removed under reduced ., pressure. The remainder is taken up in CH2Cl2 and water. The organic phases are extracted with CH2C12. The organic phases are dried, filtered and concentrated under vacuum. A crude substance is obtained in the form of a yellow oil weighing 5. 1g. The substance is purified by flash chromatography over a column of silica gel, eluting with hexane/AcOEt = 8/2, to yield a colourless syrup identified as V weighing 2.46 g (yield 50%) and a white solid identified as A, weighing 1.76g (yield 34%).

1H-NMR (CDC13) : 1.36-1. 58 (4s, 12H, (CH3) 2C) ; 3.54 (dd, 1H, H3) ; 3.96-4. 22 (m, 4H, H4, H5, H6, H6') ; 4.74 (dd, 1H, H2) ; 5.79 (d, 1H, Hui).

"C-NMR (CDC13) : 25., 01-26.38 ( (CH3)2C); 62.65 (CS) ; 66.7 (C6) ; 75.73 (C3) ; 78.00 (C4) ; 80.52 (C2) ; 103.88 (C1) ; 110. 03 (C5, Ei quat. ) ; 113.19 (CI, 2 quat.) ; 2.3 Synthesis of 3-deoxy-3-amino-1 : 2,5 : 6-di-O-isopropylidene- a-D-allofuranose (scheme 3, compound VI) LiAlH4 (790 mg, 21.35 mmol) and anhydrous diethyl ether (80 ml) are introduced into a one-necked 250 ml flask. Compound V (2.46g, 8.62 mmol) is added dropwise at 0°C. When the addition is complete, heating is carried out at the reflux temperature of the solvent for 1 hour. Monitoring is effected by TLC (hexane/AcOEt = 8/2). When the reaction is complete, 3 ml of water, 3 ml of 10% NaOH and 9 ml of water are added at 0°C. The whole is filtered over celite and washing is carried out with AcOEt. The filtrate is dried, filtered and concentrated. A white solid weighing 2. lg (yield 94%) is obtained and is identified as VI. The solid is crystallized from diethyl ether to give white needles weighing 2g (yield 90%).

1H-NMR (CDC13) : 1.34-1. 54 (4s, 12H, (CH3) 2C) ; 3.15 (dd, 1H, H3) ; 3.62 (m, 1H, H4) ; 3.98-4. 18 (m, 3H, H5, H6, H6.) ; 4.56 (m, 1H, H2) ; 5. 76 (d, 1H, Hui).

13C-NMR (CDCl3) : 25.16-26. 66 ((CH3) 2C) ; 58.21 (C5) ; 67.12 (C6); 76.37 (C3) ; 81.18 (C4) ; 81.55 (C2) ; 104. 11 (C1); 109.61 (C5,6 quat.) ; 112.17 (C1, 2 quat.) ; 2. 4 Synthesis of 3-deoxy-3-amino-N-acyl-1 : 2,5 : 6-di-O- isopropylidene-a-D-allofuranose derivatives (scheme 3, compounds 71a, 72a, 74a) The preparation of the three amides follows the same procedure for each derivative.

Compound VI (600 mg, 2.31 mmol), triethylamine (10 ml) and CH2Cl2 (50 ml) are introduced into a one-necked 250 ml flask.

The corresponding acyl chloride (4.63 mmol) is added dropwise at 0°C. When the addition is complete, the whole is brought to ambient temperature. Monitoring is effected by TLC (AcOEt/hexane = 1/1). When the reaction is complete, 30 ml of < saturated NaHCO3 solution are added and agitation is maintained for 15 minutes. The organic phase is extracted with CH2Cl2. The organic phases are dried, filtered and concentrated. The three crude substances are all solid white residues in quantitative yield which do not undergo further purification.

The characteristic signals of the three derivatives are identified by NMR analysis (Table 1).

2.5 Synthesis of 3-deoxy-3-amino-N-acyl-1 : 2-0-isopropylidene- a-D-allofuranose (scheme 3, compounds of the general formula VIII : 71,72, 74) The final preparation of the three amides follows the same procedure for each derivative.

The completely protected amide (800 mg, 2.43 mmol) and CH3COOH 80% v/v (36.5 ml) are introduced into a 250 ml flask.

Agitation is maintained for 15 minutes at 70°C. Monitoring is effected by TLC (AcOEt/hexane-1/1). When the reaction is complete, the acetic acid is coevaporated under reduced pressure with toluene. Coloured oils are thus obtained. The three amides are then purified by flash chromatography over a column of silica gel, eluting with CH2Cl2/MeOH = 95/5.

The following compounds are thus obtained (see Table 2): 71 white solid 420 mg (yield 50%) 72 white solid 410 mg (yield 74%) 74 white solid 510 mg (yield 73%) Table 1. Protonic chemical shift (8, ppm) of derivatives 69a, 70a, 71a, 72a, 73a, 74a in CDCl3. Comp. H1 H2 H3-H6' C(CH3)2 CH CH2CO CH3CH2 CH3 69a 5.89 4.61 3.8-4. 4 1. 30-1. 34 2. 35 1. 15 (d) (d) (d) (m) 1.43-1. 51 (m) (4s) 70a 5.89 4.61 3.8-4. 4 1.30-1.34 1. 2 (s) (d) (d) (m) 1.43-1. 51 (4s) 71a 5.83 4.60 3.89-4. 23 1. 34-1. 56 (3s) 2. 4 (m) 1.17 (d) (d) (m) (m) 72a 5.83 4.60 3.87-4. 18 1.34-1. 56 (3s) 1.21 (s) (d) (m) (m) 73a 5.86 4.59 3.83-4. 47 1.29-1.34 2. 19 (t) 1.65 (m) 0.97 (t) (d) (d) (m) 1.43-1. 51 (4s) 74a 5.83 4.61 3.84-4. 25 1. 34-1. 56 (3s) 2.21 1. 68 (m) 0.96 (t) (d) (m) (m) (m) Table 2. Protonic chemical shift (8, ppm) of derivatives 69,70, 73,71, 72,74 in CDCl3 (*) and in CD33. Comp. Hi H2 H3-H6'C (CH3) 2 CH CH2CO CH3LH2 CH3 69 (*) 5. 88 (d) 4.61 3. 85-4. 4 1.43-1. 51 (2s) 2. 35 1. 15 (d) (d) (m) (m) 70 (*) 5. 89 (d) 4. 61 3.8-4. 4 1. 30-1.51 (2s) 1.2 (s) (d) (m) 73 (*) 5. 89 (d) 4. 58 3. 614. 59 1.3-1. 5 (2s) 2.23 (t) 1.57 (m) 0. 95 (t) (d) (m) 71 (*) 5. 83 (d) 4.63 3.6-4. 18 1.34-1. 56 2. 44 1. 17 (dd) (m) (m) (2s) (m) 72 5. 77 (d) 4.60 3. 494. 24 1.27 and 1. 49 1. 13 (s) (dd) (m) (2s) 74 (*) 5.83 (d) 4.63 3. 62-4.25 1.34-1. 56 2. 21 (t) 1. 68 (m) 0.96 (t) (m) (m) (2s) 74 5. 75 (d) 4.58 3. 50428 1.26 e 1. 47 2. 14 (t) 1. 53 (m) 0.87 (t) (dd) (m) (2s) Example 3: Evaluation of biological activity The biological activity of the compounds described in the present invention was evaluated by examining their capacity to induce erythroid differentiation in the human cell line K562, which is able to undergo erythroid differentiation- that is to say to express the genes for the y-globins-if subjected to a treatment with modifiers of the biological response adapted for this purpose. The level of differentiation was evaluated by evaluating the positivity of the cells to benzidine. The production of hemoglobin was evaluated by electrophoresis on cellulose acetate and staining of the gel with a solution based on benzidine-H202. The expression of genes for y-globins was evaluated by Northern Blot analysis.

Table 3 shows the results of a comparative study in which the level of erythroid differentiation (expressed as a percentage of the K562 cells which were positive to benzidine with respect to the total cells) was evaluated, after the treatment of a human cell line K562 with, independently, 3- deoxy-3-amino-N-butyril-1 : 2-O-isopropylidene-α-D- glucofuranose (compound 73), an ester derivative termed a- MAM (1-O-butyril-2 : 3-O-isopropylidene-D-mannofuranose) and n- butyric acid.

The evaluation was performed after 6 days of induction.

Table 3 Compound Optimal concentration Erythroid differentiation (% of K562 cells positive to benzidine) n-butyric acid* 2-5 mM 15-25% a-MAM * 2 mM 20% Compound 73 2 mM 25W * reference compounds Table 4 shows the results obtained by subjecting the K562 cells to four different combined treatments with: a) compound 69 of the invention at optimal concentration and 0.1 p1M cytosine arabinoside; b) compound 70 of the invention at optimal concentration and 0.1 iM cytosine arabinoside; c) compound 71 of the invention at optimal concentration and 0. 1 I1M cytosine arabinoside; and d) compound 73 of the invention at optimal concentration and 0. 1 uM cytosine arabinoside. The evaluation of compounds 69 and 73 was performed after 6 days of induction while that of compounds 70 and 71 after 7 days.

Table 4 Compound Concentration Erythroid differentiation (% of K562 cells positive to benzidine) 69 2 mM 38% 73 4 mM 85% 70 6 mM 68% 71 6 mM 32% On the basis of the results illustrated in Tables 3 and 4 it is evident that the compounds forming the subject of the present invention have a significant biological activity as inducers of erythroid differentiation.

Moreover, since they are not rapidly attacked by esterases, said compounds are characterised by a higher metabolic stability and should posses better bioavailability and half- life compared to the esters and to unmodified butyric acid.

These characteristics make them particularly suitable for the preparation of a medicament for the treatment of patients affected by @-thalassemia, making it possible to reduce the need to have recourse to transfusional therapy. These compounds are likewise suitable for the preparation of a medicament for the therapeutic treatment of tumors.