DERIVATIVES OF MONOSACCHARIDES AS 5-LIPOXYGENASE INHIBITORS

Field of Invention

The present invention relates to the use of derivatives of monosaccharides as 5- lipoxygenase inhibitor. Background of Invention

5- Lipoxygenase is a key enzyme that oxidizes arachidonic acid into biologically active leukotrienes, namely cysteinyl leukotrienes and leukotriene B4 (Clin. Exp. Allergy Rev., 1 196, 2001). Leukotrienes play important role in the pathophysiology of inflammatory / allergic diseases including bronchial asthma (Clin. Exp. Allergy Rev., I, 264, 2001), allergic rhinitis (Clin. Exp. Allergy Rev. I, 235, 2001), urticaria, atopic dermatitis (Clin. Exp. Allergy Rev. I, 305, 2001), chronic obstructive pulmonary disease (Eur. Respir. J., 22, 926, 2003) etc. Incidence of allergic / inflammatory diseases are on the rise globally (Emerging Therapeutic Targets, 3, 229, 1999; Expert Opin. Investigational Drugs, 10, 1361, 2000).

A variety of stimuli namely antigen-antibody reaction, cold or hyperosmotic shock etc, that elevates intracellular calcium level, can evoke arachidonic acid release from cell membrane under the influence of cytosolic phospholipase A2. Arachidonic acid is transferred to nuclear membrane by 5 -lipoxygenase binding protein (FLAP) and acted upon by 5- lipoxygenase enzyme to generate 5-hydroperoxyeicosatetraenoic acid (HPETE). HPETE is converted to LTA4 by 5 -lipoxygenase. Depending upon cell type, LTA4 is converted to either cysteinyl leukotrienes and/or leukotriene B4 (Clin. Exp. Allergy Rev. J_, 196, 2001; Curr. Drug Targets - Inflammation & Allergy, \, 23, 2002; Drug Safety, 26, 484, 2003).

Leukotrienes are generated by a variety of inflammatory cell types. Neutrophils and monocytes generate LTB4 whereas mast cells, basophils, eosinophils and bronchial epithelial cells produce cysteinyl leukotrienes. LTB4 acts as a chemoattractant for neutrophils through specific cell surface receptors. Cysteinyl leukotrienes, which include LTC4, LTD4 and LTE4, act on CysLTl and CysLT2 receptors and increase bronchial smooth muscle contractility, promote mucosal secretion, increase vascular permeability and encourage eosinophils recruitment. (Am. J. Respir. Critic Care Med. 157, S210, 1998; Thorax 55, S32, 2000; Clin.

Exp. Allergy Rev., \, 196, 2001; Clin. Exp. Allergy Rev. \, 220, 2001; Drug Safety, 26, 484, 2003).

There is evidence suggesting that cysteinyl leukotrienes can increase airway smooth muscle contractility in preclinical (Am. J. Respir Crit. Care Med,. 157 S214, 1998) and clinical studies (Clin. Exp. Allergy Rev. 1, 220, 2001). Inhalation of leukotrienes also increase influx of inflammatory cells in the airway of animals (Clin. Exp. Allergy Rev. 1, 220, 2001) and humans (Am. J. Respir Crit. Care Med., 157, S210, 1998). In patients with asthma, urinary excretion of LTE4 correlates with exercise or cold air induced bronchoconstriction (Lancet, 1, 584, 1989) allergen induced early and late phase response (Clin. Exp Aller. 28, 1332, 1998; Am. J. Respir. Crit. Care Med 157, S210, 1998), as well as with reduction of FEVl in patients with nocturnal asthma (Am. J. Respir. Crit. Care Med. 157, S233, 1998). Efficacy of leukotriene biosynthesis inhibitors and leukotriene receptor antagonists have been tested in numerous trials involving asthma patients (Clin. Exp. Aller. Review 1, 254, 2001; Drug Safety, 26, 483, 2003; NEJM, 340, 197, 1999; Am. J. Respir. Crit. Care Med. 157, S233, 1998).

Evidence is emerging that leukotrienes also contribute towards pathophysiology of COPD. Two major cell types, neutrophils and macrophages, that generate LTB4 and are modulated by the same in turn are believed to participate in the pathogenesis of COPD (Am. J. Respir. Crit. Care Med. 157, S210, 1998). Patients with COPD exhibit elevated sputum neutrophilia and LTB4 levels (Chest, 121, 197S, 2002). Elevated levels of LTB4 were shown to be present in the exhaled breath condensate of COPD patients (Thorax., 58, 585 2003) as well as in patients experiencing exacerbation of COPD (Thorax., 58, 294, 2003). Inhibitors of leukotriene biosynthesis as well as LTB4 receptor antagonists have shown to reduce airway reactivity, airway inflammation and airway neutrophilia in animals (J. Clin. Exp. Aller. 9J_, 917, 1992; J Pharmacol. Exp. Ther. 297, 458, 2000) as well as in human subjects (Thorax 5J_, 1178, 1996; Chest,. 122, 289, 2002). Cysteinyl leukotriene antagonists like Montelukast have shown protective effect in hypertonic saline induced bronchoconstriction in COPD patients (Eur. Respir. J. 22:926, 2003).

Similarly, evidence is emerging based on animal and human data that leukotriene pathway modulators can play role in arthritis (J. Pharmacol. Exp. Ther. 285, 946, 1998) allergic rhinitis and urticaria (Clin. Exp. Aller. Review, J_, 235, 2001)

Several leukotriene receptor antagonists, Montelukast, Zafirlukast, and Pranlukast, and one 5 -lipoxygenase inhibitor, Zileuton, have been launched in the market. Both categories of molecules have shown efficacy in clinical trials of bronchial asthma. Inhibitors of 5- lipoxygenase exhibit greater potential to exhibit efficacy in COPD as well because of their inhibitory effect on LTB4 mediated processes. However, commercially available 5- lipoxygenase inhibitor is associated with poor pharmacokinetic properties and adverse events, like elevation of hepatic transaminase levels. This has prompted the search for novel inhibitors of 5 -lipoxygenase with improved pharmacokinetic profiles and reduced adverse effects.

WO2004/071515 discloses preparation of monosaccharides derivatives for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. U.S. Patent No. 6,329,344 discloses several derivatives of monosaccharides as cell adhesion inhibitors. U.S. Patent No. 6,329,344 discloses classes of monosaccharides compounds useful for inhibitition and prevention of cell adhesion and cell adhesion mediated pathologies. U.S. Patent No. 6,590,085 discloses further derivatives of monosaccharides similarly useful. Summary of the Invention

According to one aspect a method for inhibiting the 5 -Lipoxygenase enzyme is provided, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formula I,

Formula I

its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides, prodrugs or metabolites wherein, R is C ₁ to C ₁₅ alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl;

R' is SOiC ₆ H ₅ , Sθ2C ₆ H ₄ CH ₃ -p or SO2C ₆ H ₄ -C1, phenyl or substituted phenyl, represented as C ₆ H ₄ -R'"-p R'" being Cl, NO ₂ , OCH ₃ , CH ₃ , CH ₂ COOH, CH ₂ COOCH ₃ , CH ₂ COLDVP, CH ₂ CODVP, CH ₂ COVP, wherein LDVP DVP and VP represent tetrapeptide (Leucyl- aspartyl-alyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl) respectively;

R" is H or CH ₃ and

(^ ) represents idofuranose, talofuranose, xylofuranose or ribofuranose configurations.

According to another aspect a method for inhibiting the 5 -Lipoxygenase enzyme is provided, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formula II

Formula Il

its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides, prodrugs or metabolites, wherein R is C ₁ to C ₁₅ alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkyl aryl;

R' is SOiC ₆ H ₅ , Sθ ₂ C ₆ H ₅ CH ₃ -p, SO ₂ C ₆ H ₄ Cl-p, phenyl or substitutd phenyl, represented as C ₆ H ₄ -R'"-p, wherein R'" being Cl, NO ₂ , OCH ₃ , CH ₃ , CH ₂ COOH, CH ₂ COOCH ₃ , CH ₂ COLDVP, CH ₂ CODVP, CH ₂ COVP, wherein LDVP, DVP and VP represent tetrapeptide (Leucyl-aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl), respectively; and

R" is H or CH ₃ .

According to a further aspect a method for inhibiting the 5 Lipoxygenase enzymeis provided, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formula III,

FORMULA III its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides, prodrugs or metabolites wherein

R is COLDVP, CODVP, COVP or CH ₂ NHCONHR" wherein LDVP, DVP and VP represent tetrapeptide (Leucyl-aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl), respectively; R" is C ₆ H ₄ R ^m -p ( R"' is Cl, NO ₂ , OCH ₃ , CH ₃ , CH ₂ COOH,

CH ₂ CO-LDVP, CH ₂ CO-DVP or CH ₂ CO-VP wherein LDVP, DVP and VP are the same as defined earlier).

According to yet another aspect, a method for inhibiting the 5 -Lipoxygenase enzyme is provided, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formula IV.

Formula IV its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides, prodrugs or metabolites, wherein

R is C ₁ to C ₁₅ alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl; R ₁ is phenyl, o-m- or p-chlorophenyl, tolyl, methoxyphenyl or nitrophenyl; and

R ₂ is H, pyrrolidinyl, piperidinyl, morphilinyl or hexamethyleneimino or a radical of the Formula - NHR ₃ wherein R ₃ is C ₁ to C ₁₅ alkyl, alkene or alkyne (straight chain or branched) or a radical of the Formula

in which n is a whole number between 2 and 5 and

is a five, six or seven - membered, heterocyclic ring, For example,

N

can be pyrrolidinyl, piperidinyl, morpholinyl or hexamethyleneimino moieties.

It is another further aspect to provide novel methods for 5 -lipoxygenase enzyme inhibition comprising the administration to a patient in need of such treatment a therapeutically effective

amount of a compound or pharmaceutically acceptable salt of a compound of Formulae I, II, III and IV.

Detailed Description of the Invention

An illustrative list of particular compounds according to Formula I includes: l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydr oxy-2-oxoethyl)phenyl] aminocarbonyl amino} -β -L-idofuranose (Compound No. 1), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl] aminocarbonylamino}-β -L-idofuranose (Compound No. 2), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydro xy-2-oxoethyl)phenyl] aminocarbonylamino}-β -L-idofuranose (Compound No. 3), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl] aminocarbonylamino}-β -L-idofuranose (Compound No. 4), l^-O-isopropylidene-S-O-dodecyl-S _j o-dideoxy-S-N-j^-chlorophenylJaminocarbonyl amino} -β -L-idofuranose (Compound No. 5), l^-O-isopropylidene-S-O-decyl-S _j o-dideoxy-S-N-j^-chlorophenylJaminocarbonyl amino} -β -L-idofuranose (Compound No. 6), l^-O-isopropylidene-S-O-heptyl-S _j o-dideoxy-S-N-j^-chlorophenylJaminocarbonyl amino} -β -L-idofuranose (Compound No. 7), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophe nyl]aminocarbonyl amino} -β -L-idofuranose (Compound No. 8), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxy phenyl]amino carbonylamino} -β -L-idofuranose (Compound No. 9), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyph enyl]amino carbonylamino} -β -L-idofuranose (Compound No. 10), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyp henyl]amino carbonylamino} -β -L-idofuranose (Compound No. 11), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyph enyl]aminocarbonyl amino} -β -L-idofuranose (Compound No. 12),

l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]a minocarbonyl amino} -β -L-idofuranose (Compound No. 13), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]ami nocarbonyl amino} -β -L-idofuranose (Compound No. 14), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]am inocarbonyl amino} -β -L-idofuranose (Compound No. 15), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]ami nocarbonyl amino} -β -L-idofuranose (Compound No. 16), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydr oxy-2-oxoethyl) phenyljamino carbonyl amino} -β-L-talofuranose (Compound No. 17), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl aminocarbonylamino}-β-L-talofuranose (Compound No. 18), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydro xy-2-oxoethyl)phenyl] aminocarbonylamino}-β-L-talofuranose (Compound No. 19), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl] aminocarbonyl amino} -β-L-talofuranose (Compound No. 20), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorop henyl]amino carbonylamino} -β-L-talofuranose (Compound No. 21), l^-O-isopropylidene-S-O-decyl-S _j o-dideoxy-S-N-j^-chlorophenylJaminocarbonyl amino} α,D-5-epiallofuranose (Compound No. 22), l^-O-isopropylidene-S-O-heptyl-S _j o-dideoxy-S-N-j^-chlorophenylJaminocarbonyl amino} -β-L-talofuranose (Compound No. 23), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophe nyl]aminocarbonyl amino} -β-L-talofuranose (Compound No.24), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxy phenyl]amino carbonylamino} -β-L-talofuranose (Compound No. 25), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyph enyl]aminocarbonyl amino} -β-L-talofuranose (Compound No. 26), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyp henyl]aminocarbonyl

amino} -β-L-talofuranose (Compound No. 27), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyph enyl] amino carbonyl amino} -β-L-talofuranose (Compound No. 28), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]a minocarbonyl amino} -β-L-talofuranose (Compound No. 29), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]ami nocarbonyl amino} -β-L-talofuranose (Compound No. 30), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]am inocarbonyl amino} -β-L-talofuranose (Compound No. 31), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]ami nocarbonyl amino} -β-L-talofuranose (Compound No. 32), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy- 2-oxoethyl)phenyl] aminocarbonylamino}-α,D-xylofuranose (Compound No. 33), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2- oxoethyl)phenyl] aminocarbonylamino} -α,D-xylofuranose (Compound No. 34), l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-(2-hydroxy-2- oxoethyl)phenyl] aminocarbonylamino} -α,D-xylofuranose (Compound No. 35), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2- oxoethyl)phenyl] aminocarbonylamino }-α,D-xylofuranose (Compound No. 36), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2 -oxoethyl) phenyl]aminocarbonylamino}-α,D-xylofuranose (Compound No. 37), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-chloropheny l]amino carbonylamino}α,D-xylofuranose (Compound No. 38), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl] amino carbonylamino}α,D-xylofuranose (Compound No. 39), l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-chlorophenyl] amino carbonylamino}α,D-xylofuranose (Compound No. 40), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl] amino carbonylamino}α,D-xylofuranose (Compound No. 41),

l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophe nyl]amino carbonylamino}α,D-xyloiuranose (Compound No. 42), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphen yl]amino carbonylamino}α,D-xyloiuranose (Compound No. 43), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl ]aminocarbonyl amino }α,D-xyloiuranose (Compound No. 44), l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-methoxyphenyl ]aminocarbonyl amino }α,D-xyloiuranose (Compound No. 45), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl ]aminocarbonyl amino} α,D-xyloiuranose (Compound No. 46), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxypheny l]aminocarbonyl amino }α,D-xyloiuranose (Compound No. 47), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]amino carbonylamino}α,

D-xyloiuranose (Compound No. 48), 1 ,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N- { [4-tolyl]aminocarbonylamino} α,D- xylofuranose (Compound No. 49), l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-tolyl]aminoca rbonylamino} α,D- xylofuranose (Compound No. 50), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminoca rbonylamino} α,D- xylofuranose (Compound No. 51), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-tolyl]aminoc arbonylamino}a,D- xylofuranose (Compound No. 52), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonyl amino]phenyl acetyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline}- α,D-xyloiuranose (Compound No. 53), l^-O-isopropylidene-S-O-dodecyl-S-deoxy-S-N-jfaminocarbonyla minolphenylacetyl-a _j L-

Aspartyl-L-Valyl-L-Proline}- α,D-xyloiuranose (Compound No. 54), l^-O-isopropylidene-S-O-dodecyl-S-deoxy-S-N-jfaminocarbonyla minolphenylacetyl- alyl-L-Proline}- α,D-xylofuranose (Compound No. 55) l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy- 2-oxoethyl)phenyl]

aminocarbonylamino}-α,D-riboiuranose (Compound No. 56), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2- oxoethyl)phenyl] aminocarbonylamino}-α,D-riboiuranose (Compound No. 57), l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-(2-hydroxy-2 -oxoethyl)phenyl] aminocarbonylamino}-α,D-riboiuranose (Compound No. 58), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2- oxoethyl)phenyl] aminocarbonylamino}-α,D-riboiuranose (Compound No. 59), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2 -oxoethyl)phenyl] aminocarbonylamino}-α,D-riboiuranose (Compound No. 60), l^-O-isopropylidene-S-O-dodecyl-S-deoxy-S-N-j^-chlorophenylJ aminocarbonyl amino} α,D-riboiuranose(Compound No. 61), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl] aminocarbonyl amino} α,D-riboiuranose (Compound No. 62), l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl ]aminocarbonyl amino} α,D-riboiuranose (Compound No.63), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl] aminocarbonyl amino} α,D-riboiuranose (Compound No. 64), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophenyl ]aminocarbonyl amino} α,D-riboiuranose (Compound No. 65), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphen yl]aminocarbonyl amino} α,D-riboiuranose (Compound No. 66), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl ]aminocarbonyl amino} α,D-riboiuranose (Compound No. 67), l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-methoxypheny l]aminocarbonyl amino} α,D-riboiuranose (Compound No. 68), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl ]aminocarbonyl amino} α,D-riboiuranose (Compound No. 69), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxypheny l]aminocarbonyl amino} α,D-riboiuranose (Compound No. 70),

l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]am inocarbonylamino}α,

D-ribofuranose (Compound No. 71), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-tolyl]aminoca rbonylamino} α,

D-ribofuranose (Compound No. 72), l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-tolyl]aminoc arbonylamino} α,

D-ribofuranose (Compound No. 73), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminoca rbonylamino} α,

D-ribofuranose (Compound No. 74), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-tolyl]aminoc arbonylamino}α, D-ribofuranose (Compound No. 75), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonyl aminophenyl] acetyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline }-α,D-ribofuranose (Compound No. 76), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonyl aminophenyl] acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-ribofuranose (Compound No. 77), and l^-O-isopropylidene-S-O-dodecyl-S-deoxy-S-N-jfaminocarbonyla minophenylJacetyl-

L-Valyl-L-Proline }-α,D-ribofuranose (Compound No.78).

An illustrative list of particular compounds according to Formula II includes:

2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-(2-hyd roxy-2-oxoethyl)phenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 79), 2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 80), 2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydro xy-2-oxoethyl) phenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 81), 2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 82),

2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-h ydroxy-2-oxoethyl) phenyl]aminocarbonylamino}-β, L-gulofuranoside (Compound No. 83),

Tris salt of 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydr oxy-2-

oxoethyl)phenyl]aminocarbonylamino}-β, L-gulofuranoside (Compound No. 84)

Sodium salt of 2,3-O-isopropylidene- 1 -O-dodecyl-Sjό-dideoxy-S-N- { [4-(2-hydroxy-2- oxoethyl)phenyl]aminocarbonylamino}-β, L-guloiuranoside (Compound No. 85)

2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-chloro phenyl]aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 86),

2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-chloro phenyl]aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 87),

2,3 -O-isopropylidene- 1 -O-heptyl-5 , 6-dideoxy-5 -N- { [4-chlorophenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 88), 2,3-O-isopropylidene- 1 -O-decyl-5,6-dideoxy-5-N- { [4-chlorophenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 89),

2,3 -O-isopropylidene- 1 -O-dodecyl-5 , 6-dideoxy-5 -N- { [4-chlorophenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 90),

2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-methox yphenyl]aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 91),

2,3 -O-isopropylidene- 1 -O-hexyl-5 , 6-dideoxy-5 -N- { [4-methoxyphenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 92),

2,3 -O-isopropylidene- 1 -O-heptyl-5 , 6-dideoxy-5 -N- { [4-methoxyphenyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 93), 2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-methoxyph enyl]aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 94),

2,3 -O-isopropylidene- 1 -O-dodecyl-5 , 6-dideoxy-5 -N- { [4-methoxyphenyl] amino carbonylamino}-β, L-gulofuranoside (Compound No. 95),

2,3-O-isopropylidene- 1 -O-butyl-5,6-dideoxy-5-N- { [4-tolyl]aminocarbonylamino} -β, L- gulofuranoside (Compound No. 96),

2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-tolyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 97),

2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl ]aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 98),

2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-tolyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 99),

2,3 -O-isopropylidene- 1 -O-dodecyl-5 , 6-dideoxy-5 -N- { [4-tolyl] aminocarbonyl amino} -β, L-gulofuranoside (Compound No. 100), 2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2 -oxoethyl)phenyl] aminocarbonylamino}-α,D-lyxofuranoside (Compound No. 101),

2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy -2-oxoethyl)phenyl] aminocarbonylamino}-α,D-lyxofuranoside (Compound No. 102),

2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-(2-hydrox y-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-lyxofuranoside (Compound No. 103),

2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy -2-oxoethyl)phenyl] aminocarbonylamino}-α,D-lyxofuranose (Compound No. 104),

2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-(2-hydro xy-2-oxoethyl)phenyl] aminocarbonyl amino} -α,D-lyxofuranoside (Compound No. 105), 2,3-O-isopropylidene- 1 -O-methyl-S-deoxy-S-N- { [4-chlorophenyl] aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 106),

2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-chlorophen yl]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 107),

2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-chlorophe nyl]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 108),

2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-chlorophen yl]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 109),

2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-chloroph enyl]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 110), 2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-methoxypheny l]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. I l l),

2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-methoxyphe nyl]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 112),

2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-methoxyph enyl]aminocarbonyl

amino} α,D-lyxofuranoside (Compound No. 113),

2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-methoxyphe nyl]aminocarbonyl amino} α,D-lyxofuranoside (Compound No. 114),

2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-methoxyp henyl]amino carbonylamino} αD-lyxofuranoside (Compound No. 115),

2,3-O-isopropylidene- 1 -O-methyl-5-deoxy-5-N- { [4-tolyl]aminocarbonylamino} α,

D-lyxofuranoside (Compound No. 116),

2,3-O-isopropylidene- 1 -O-butyl-5-deoxy-5-N- { [4-tolyl]aminocarbonylamino} α,

D-lyxoiuranoside (Compound No. 117), 2,3-O-isopropylidene- 1 -O-heptyl-5-deoxy-5-N- { [4-tolyl]aminocarbonylamino} α,

D-lyxofuranoside (Compound No. 118),

2,3-O-isopropylidene- 1 -O-decyl-5-deoxy-5-N- { [4-tolyl]aminocarbonylamino} α,

D-lyxofuranoside (Compound No. 119),

2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-tolyl]am inocarbonylamino}α, D-lyxofuranoside (Compound No. 120),

2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[aminocarbo nylamino]phenylacetyl-

L-Leucyl- α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside (Compound No. 121),

2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[aminocarbo nylamino]phenyl acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside (Compound No. 122), and 2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[aminocarbonyl amino]phenyl acetyl-L-Valyl-L-Proline}-α,D-lyxofuranoside (Compound No. 123).

An illustrative list of particular compounds according to Formula III includes:

2,3 ;4,6-Di-O-isopropylidene- 1 -carbonyl-L-Leucyl-α^-Aspartyl-L-Valyl-L-Proline-α, L-xylo-2-hexulofuranosonic acid (Compound No. 124), 2,3 ;4,6-Di-O-isopropylidene- 1 -carbonyl-α,L-Aspartyl-L-Valyl-L-Proline-α,L-xylo-2- hexulofuranosonic acid (Compound No. 125),

2,3-O-isopropylidene-l-carbonyl-L-Leucyl-α,L-Aspartyl-L- Valyl-L-Proline-α,L- xylo-2-hexulofuranosonic acid (Compound No. 126),

2,3-O-isopropylidene-l-carbonyl-α,L-Aspartyl-L-Valyl-L-P roline-α,L-xylo-2- hexulofuranosonic acid (Compound No. 127),

2,3-O-isopropylidene-l-carbonyl-L-Valyl-L-Proline-α,L-xy lo-2-hexulofuranosonic acid

(Compound No. 128), 2,3 ;4,6-Di-O-isopropylidene- 1 -deoxy-1 -N- { [4-chlorophenyl]aminocarbonyl amino} -α,L-xylo-2-hexulofuranose (Compound No. 129),

2,3 ;4,6-Di-O-isopropylidene- 1 -deoxy- 1 -N- { [4-methoxyphenyl]aminocarbonyl amino} -α,L-xylo-2-hexulofuranose (Compound No. 130),

2,3 ;4,6-Di-O-isopropylidene- 1 -deoxy- 1 -N- { [4-tolyl]aminocarbonylamino} -α,L-xylo- 2-hexulofuranose (Compound No. 131),

2,3 -O-isopropylidene- 1 -deoxy- 1 -N- { [4-(2-hydroxy-2oxoethyl))phenylaminocarbonyl amino} -α,L-xylo- 2-hexuloiuranose (Compound No. 132),

2,3 -O-isopropylidene- 1 -deoxy- 1 -N- { [4-chlorophenyl] aminocarbonylamino } -α,L-xylo-

2 -hexulofuranose (Compound No. 133), 2, 3 -O-isopropylidene- 1 -deoxy-1 -N- { [4-methoxyphenyl] aminocarbonylamino} -α,L-xylo-

2 -hexulofuranose (Compound No. 134),

2,3-O-isopropylidene-l-deoxy-l-N-{[4-tolyl]aminocarbonyla mino}-α,L-xylo-2- hexulofuranose(Compound No. 135),

2,3 -O-isopropylidene- 1 deoxy- 1 -N- { [aminocarbonylaminophenylacetyl-L- Leucyl-α,L- Aspartyl-L- Valyl-L-Proline) } -α,L-xylo-2-hexulofuranose(Compound No. 136),

2,3 -O-isopropylidene- 1 -deoxy- 1 -N- { [aminocarbonylaminophenylacetyl-α,L-

Aspartyl-L-Valyl-L-Proline)}-α,L-xylo-2-hexulofuranose (Compound No. 137),

2,3 -O-isopropylidene- 1 deoxy- 1 -N- { [aminocarbonylaminophenylacetyl-L- Valyl-L-

Proline)}-α,L-xylo-2-hexulofuranose (Compound No. 138). An illustrative list of particular compounds according to Formula IV include:

2,3-O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl) -ό-deoxy-ό-pyrrolidin-l-yl-α- L-xylo-2-hexulofuranose (Compound No. 139),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl ) -ό-deoxy-ό-pyrrolidin-l-yl- α-L-xylo-2-hexuloiuranose (Compound No. 140),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl )-6-deoxy-6-pyrrolidin-l-yl-α-

L-xylo-2-hexuloiuranose (Compound No. 141), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocar bonyl)-6-deoxy-6- pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 142),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbony l)-6-deoxy-6-pyrrolidin-l-yl-α-

L-xylo-2-hexulofuranose (Compound No. 143),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylamin ocarbonyl)-6-deoxy-6- pyrrolidin-l-yl-α-L-xylo-2-hexuloiuranose (Compound No. 144)

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminoc arbonyl)-6-deoxy-6-pyrrolidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 145),

2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)- 6-deoxy-6-pyrrolidin-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 146), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbo nyl)-6-deoxy-6-pyrrolidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 147),

2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin- 1 -yl-α-L- xylo-2-hexulofuranose (Compound No. 148),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminoc arbonyl)-6-deoxy-6- pyrrolidin-l-yl-α-L-xylo-2-hexuloiuranose (Compound No. 149),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocar bonyl)-6-deoxy-6-pyrrolidin-l- yl-α-L-xylo-2-hexulofuranose (Compound No. 150),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl) -6-deoxy-6-pyrrolidin-l-yl-α-

L-xylo-2-hexuloiuranose (Compound No. 151), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarb onyl)-6-deoxy-6-pyrrolidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 152),

2,3 -O-Isopropylidene- 1 -O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin- 1 -yl-α-

L-xylo-2-hexuloiuranose (Compound No. 153),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylamino carbonyl)-6-deoxy-6- pyrrolidin-l-yl-α-L-xylo-2-hexuloiuranose (Compound No. 154),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminoca rbonyl)-6-deoxy-6-pyrrolidin-l- yl-α-L-xylo-2-hexulofuranose (Compound No. 155), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6 -deoxy-6-morpholin-4-yl- α-L-xylo-2-hexuloiuranose (Compound No. 156),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylamino carbonyl)-6-deoxy-6- morpholin-4-yl-α-L-xylo-2-hexuloiuranose (Compound No. 157),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbony l)-6-deoxy-6-morpholin-4-yl-α- L-xylo-2-hexuloiuranose (Compound No. 158),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylamin ocarbonyl)-6-deoxy-6- morpholin-4-yl-α-L-xylo-2-hexuloiuranose (Compound No. 159),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminoc arbonyl)-6-deoxy-6-moφholin-

4-yl-α-L-xylo-2-hexulofuranose (Compound No. 160), 2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-d eoxy-6-morpholin-4-yl-α-L- xylo-2-hexulofuranose (Compound No. 161),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminoca rbonyl)-6-deoxy-6-morpholin-

4-yl-α-L-xylo-2-hexulofuranose (Compound No. 162),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl) -6-deoxy-6-moφholin-4-yl-α-L- xylo-2-hexulofuranose (Compound No. 163),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminoc arbonyl)-6-deoxy-6- morpholin-4-yl-α-L-xylo-2-hexuloiuranose (Compound No. 164),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocar bonyl)-6-deoxy-6-morpholin-4- yl-α-L-xylo-2-hexulofuranose (Compound No. 165), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6- deoxy-6-moφholin-4-yl-α-

L-xylo-2-hexuloiuranose (Compound No. 166),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminoc arbonyl)-6-deoxy-6-moφholin-

4-yl-α-L-xylo-2-hexulofuranose (Compound No. 167),

2,3 -O-Isopropylidene- 1 -O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-y l-α-

L-xylo-2-hexuloiuranose (Compound No. 168),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylamino carbonyl)-6-deoxy-6- morpholin-4-yl-α-L-xylo-2-hexuloiuranose (Compound No. 169), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbo nyl)-6-deoxy-6-morpholin-4- yl-α-L-xylo-2-hexulofuranose (Compound No. 170),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl )-6-deoxy-6-piperidin-l-yl-α-

L-xylo-2-hexuloiuranose (Compound No. 171),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylamino carbonyl)-6-deoxy-6-piperidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 172),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbony l)-6-deoxy-6-piperidin-l-yl-α-

L-xylo-2-hexuloiuranose (Compound No. 173),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylamin ocarbonyl)-6-deoxy-6- piperidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 174), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarb onyl)-6-deoxy-6-piperidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 175),

2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)- 6-deoxy-6-piperidin-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 176),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminoca rbonyl)-6-deoxy-6-piperidin-l- yl-α-L-xylo-2-hexulofuranose (Compound No. 177),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl) -6-deoxy-6-piperidin-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 178),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminoc arbonyl)-6-deoxy-6-piperidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 179), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbon yl)-6-deoxy-6-piperidin-l- yl-α-L-xylo-2-hexulofuranose (Compound No. 180),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl) -6-deoxy-6-piperidin-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 181),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminoc arbonyl)-6-deoxy-6-piperidin- l-yl-α-L-xylo-2-hexulofuranose (Compound No. 182),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl )-6-deoxy-6-piperidin-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 183), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocar bonyl)-6-deoxy-6- piperidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 184),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminoca rbonyl)-6-deoxy-6-piperidin-l- yl-α-L-xylo-2-hexulofuranose (Compound No. 185),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl )-6-deoxy-6-azepan-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 186),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylamino carbonyl)-6-deoxy-6-azepan-l- yl-α-L-xylo-2-hexulofuranose (Compound No. 187),

2,3 -O-Isopropylidene- 1 -O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- azepan- 1 -yl -α-

L-xylo-2-hexulofuranose (Compound No. 188), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminoca rbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexuloiuranose (Compound No. 189),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminoc arbonyl)-6-deoxy-6- azepan-1- yl -α-L-xylo-2-hexulofuranose (Compound No. 190),

2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6- azepan- 1 -yl -α-L- xylo-2-hexulofuranose (Compound No. 191),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminoca rbonyl)-6-deoxy-6- azepan-1-yl

-α-L-xylo-2-hexulofuranose(Compound No. 192),

2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- azepan- 1 -yl -α-L- xylo-2-hexulofuranose (Compound No. 193), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarb onyl)-6-deoxy-6- azepan- 1-yl -α-L-xylo-2-hexulofuranose (Compound No. 194),

2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6- azepan- 1 -yl - α-L-xylo-2-hexulofuranose (Compound No. 195),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl) -6-deoxy-6- azepan-1-yl -α-L- xylo-2-hexulofuranose (Compound No. 196),

Hydrochloride salt of 2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6- deoxy- 6- azepan-1-yl -α-L-xylo-2-hexulofuranose (Compound No. 197), 2,3 -O-Isopropylidene- 1 -O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6- azepan- 1 - yl -α-L-xylo-2-hexulofuranose (Compound No. 198),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl )-6-deoxy-6- azepan-1-yl -α-L- xylo-2-hexulofuranose (Compound No. 199), Hydrochloride salt of 2,3 -O-Isopropylidene- l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy- 6- azepan-1-yl -α-L-xylo-2-hexulofuranose (Compound No. 200),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylamino carbonyl)-6-deoxy-6- azepan- 1-yl -α-L-xylo-2-hexulofuranose (Compound No. 201),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminoca rbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose (Compound No. 202), 2,3-O-Isopropylidene- 1 -O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidi n- 1 - yl) ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 203), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocar bonyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyljamino -α-L-xylo-2-hexulofuranose (Compound No 204), 2,3 -O-Isopropylidene- 1 -O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- [2-(pyrrolidin- 1 - yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 205),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylamin ocarbonyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyljamino -α-L-xylo-2-hexulofuranose (Compound No. 206), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarb onyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyljamino -α-L-xylo-2-hexulofuranose (Compound No. 207), 2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-d eoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 208), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbo nyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose(CompoundNo. 209),

2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- [2-(pyrrolidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 210), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarb onyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 211), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbon yl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 212), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6- deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 213), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarb onyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 214),

2,3 -O-Isopropylidene- 1 -O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- [2-(pyrrolidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 215), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocar bonyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 216), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbo nyl)-6-deoxy-6-[2- (pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 217), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6 -deoxy-6-[2-(piperidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 218), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocar bonyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 219),

2,3 -O-Isopropylidene- 1 -O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- [2-(piperidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexuloiuranose (Compound No. 220),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylamin ocarbonyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 221), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarb onyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 222), 2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6- [2-(piperidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 223),

2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminoca rbonyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 224), 2,3 -O-Isopropylidene- 1 -O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- [2-(piperidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexuloiuranose (Compound No. 225), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarb onyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 226), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbon yl)-6-deoxy-6-[2-(piperidin- 1-yl) ethyl] amino -α-L-xylo-2-hexuloiuranose (Compound No. 227), 2,3 -O-Isopropylidene- 1 -O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6- [2-(piperidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexuloiuranose (Compound No. 228),

2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminoc arbonyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 229), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6 -deoxy-6-[2-(piperidin-l-yl) ethyl] amino -α-L-xylo-2-hexuloiuranose (Compound No. 230), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocar bonyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 231), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbo nyl)-6-deoxy-6-[2- (piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 232), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6 -deoxy-6-[2-(moφhilin-4- yl) ethyl] amino-α-L-xylo-2-hexulofuranose (Compound No. 233),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylamino carbonyl)-6-deoxy-6-(2- ethylmoφhilin-4-yl)-α-L-xylo-2-hexuloiuranose (Compound No. 234), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)- 6-deoxy-6-[2-(morphilin-4- yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.235), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminoca rbonyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 236), 2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarb onyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 237),

2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)- 6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 238), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbo nyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino-α-L-xylo-2-hexulofuranose (Compound No. 239), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6- deoxy-6-[2-(moφhilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 240),

Hydrochloride salt of 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6- deoxy- 6- [2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose(Co mpoundNo. 241 ), 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarb onyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 242),

2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminoc arbonyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 243), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6- deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 244), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarb onyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.245), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6 -deoxy-6-[2-(moφhilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 246), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocar bonyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 247), 2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbo nyl)-6-deoxy-6-[2- (morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 248), 2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6 -deoxy-6-azepan-l-yl-α-L- xylo-2-hexulofuranose (Compound No.249), 2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6 -deoxy-6-moφholin-4-yl-α- L-xylo-2-hexulofuranose (Compound No. 250),

2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl )-6-deoxy-6-piperidin-l-yl-α- L-xylo-2-hexulofuranose (Compound No. 251),

2,3 ,0-Isopropylidene- 1 -O-dodecyM-O-tmethylaminocarbonyty-ό-deoxy-ό- [2-( pyrrolidin- 1 - yl) ethyl] amino-α-L-xylo-2-hexulofuranose (Compound No. 252),

2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl )-6-deoxy-6-[2-(morphilin-4- yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 253), 2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-d eoxy-6-morpholin-4-yl-α-L- xylo-2-hexulofuranose (Compound No. 254),

2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)- 6-deoxy-6-azepan-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 255),

2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)- 6-deoxy-6-piperidin-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 256),

2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)- 6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 257),

2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)- 6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 258), 2,3 ,0-Isopropylidene- 1 -O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin- 1 -yl-α-

L-xylo-2-hexulofuranose (Compound No. 259),

2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl) -6-deoxy-6-morpholin-4-yl-α-

L-xylo-2-hexuloiuranose (Compound No. 260),

2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl) -6-deoxy-6-azepan-l-yl-α-L- xylo-2-hexulofuranose (Compound No. 261),

2,3,O-Isopropylidene-1 -O-heptyl-4-O- (methylaminocarbonyl)-6-deoxy-6-piperidin-l -yl-α-L- xylo-2-hexulofuranose (Compound No. 262),

2,3 ,0-Isopropylidene- 1 -O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6- [2-(pyrrolidin- 1 -yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No. 263), and 2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl)-6- deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.264).

Pharmacological activity

The compounds of Formulae I, II, III and IV showed inhibitory activity on A23187- induced LTB4 release from human neutrophils. Standard assays were performed on particular illustrative compounds of Formulae I, II, III and Formula IV, and are mentioned below. A23187 Induced LTB4 Release from Human Neutrophils

Neutrophils were isolated from freshly drawn human blood after dextran sedimentation and ficoll separation (Eur J Biochem., 169, 175, 1987). 180 μl of the neutrophil suspension (0.2 x 10 ⁶ cells/ml) were taken, and added 19μl of Hank's Buffer salt solution along with lμl of the test drug (200 times concentrated) in a 24-well plate and incubated at 37°C for 1 hr. 3 min before the end of test compound incubation, 0.25 mM Ca ^4- TMg ⁺ * was added. Then, 0.3 μg/ml A23187 was added and incubated for 10 min further. The reaction was stopped by adding 80 μl of cold methanol and spun at 3500 rpm for 10 min. to remove cell debris. The samples were analysed for LTB ₄ assay (J. Pharmacol. Exp. Ther. 297:267, 2001) using LTB ₄ ELISA kits (Assay Design Inc., USA). The amount of LTB ₄ was quantified and percent inhibition in LTB ₄ release was calculated with respect to negative and positive controls to compute IC ₅₀ values.

Compound Nos.l, 2, 6, 10, 14, 33, 36, 79, 80, 83 - 85, 87, 92, 99, 101, 102, 105, 110, 115, 120, 168, 177, 193, 194, 197, 200, 210, and 241 were tested, giving IC ₅₀ val— of between about 2.5 μm and abμm out 30μm, or between about 2.5 μm and about 10 μm, or between about 2.5 μm and about 5 μm.