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., 1, 264, 2001), allergic rhinitis (Clin. Exp. Allergy Rev. 1, 235, 2001), urticaria, atopic dermatitis (Clin. Exp. Allergy Rev. 1, 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. 1, 196, 2001; Curr. Drug Targets—Inflammation &Allergy, 1, 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 CysLT1 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., 1, 196, 2001; Clin. Exp. Allergy Rev. 1, 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 FEV1 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. 91, 917, 1992; J Pharmacol. Exp. Ther. 297, 458, 2000) as well as in human subjects (Thorax 51, 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, 1, 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. Pat. No. 6,329,344 discloses several derivatives of monosaccharides as cell adhesion inhibitors. U.S. Pat. No. 6,329,344 discloses classes of monosaccharides compounds useful for inhibitition and prevention of cell adhesion and cell adhesion mediated pathologies. U.S. Pat. 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,

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

wherein,

R is C₁to C₁₅alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl;

R′ is SO₂C₆H₅, SO₂C₆H₄CH₃-p or SO₂C₆H₄—Cl, phenyl or substituted phenyl, represented as C₆H₄—R′″-p R′″ being Cl, NO₂, OCH₃, CH₃, CH₂COOH, CH₂COOCH₃, CH₂COLDVP, CH₂CODVP, CH₂COVP, wherein LDVP DVP and VP represent tetrapeptide (Leucyl-aspartyl-alyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl) respectively;

R″ is H or CH₃and

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

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

R is C₁to C₁₅alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkyl aryl;

R′ is SO₂C₆H₅, SO₂C₆H₅CH₃-p, SO₂C₆H₄Cl-p, phenyl or substituted phenyl, represented as C₆H₄—R′″-p, wherein R′″ being Cl, NO₂, OCH₃, CH₃, CH₂COOH, CH₂COOCH₃, CH₂COLDVP, CH₂CODVP, CH₂COVP, 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 CH₃.

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,

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

wherein

R′ is COLDVP, CODVP, COVP or CH₂NHCONHR″ wherein LDVP, DVP and VP represent tetrapeptide (Leucyl-aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl), respectively; R″ is C₆H₄R′″-p (R′″ is Cl, NO₂, OCH₃, CH₃, CH₂COOH, CH₂CO-LDVP, CH₂CO-DVP or CH₂CO—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.

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

R is C₁to C₁₅alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl;

R₁is phenyl, o-m- or p-chlorophenyl, tolyl, methoxyphenyl or nitrophenyl; and

R₂is H, pyrrolidinyl, piperidinyl, morphilinyl or hexamethyleneimino or a radical of the Formula—NHR₃wherein R₃is C₁to C₁₅alkyl, 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,

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:

1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-β-L-idofuranose (Compound No. 1),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 2),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 3),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 4),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 5),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 6),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 7),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 8),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-β-L-idofuranose (Compound No. 9),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-β-L-idofuranose (Compound No. 10),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-β-L-idofuranose (Compound No. 11),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 12),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 13),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 14),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 15),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-idofuranose (Compound No. 16),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]amino carbonyl amino}-β-L-talofuranose (Compound No. 17),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl aminocarbonylamino}-β-L-talofuranose (Compound No. 18),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 19),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-β-L-talofuranose (Compound No. 20),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino carbonylamino}-β-L-talofuranose (Compound No. 21),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-5-epiallofuranose (Compound No. 22),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 23),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 24),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-β-L-talofuranose (Compound No. 25),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 26),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}-β-L-talofuranose (Compound No. 27),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-β-L-talofuranose (Compound No. 28),
1,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 29),
1,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 30),
1,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 31),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β-L-talofuranose (Compound No. 32),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-(α,D-xylofuranose (Compound No. 33),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-(α,D-xylofuranose (Compound No. 34),
1,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-(α,D-xylofuranose (Compound No. 35),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-(α,D-xylofuranose (Compound No. 36),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-(α,D-xylofuranose (Compound No. 37),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]amino carbonylamino}α,D-xylofuranose (Compound No. 38),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]amino carbonylamino}α,D-xylofuranose (Compound No. 39),
1,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-chlorophenyl]amino carbonylamino}α,D-xylofuranose (Compound No. 40),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]amino carbonylamino}α,D-xylofuranose (Compound No. 41),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]amino carbonylamino}α,D-xylofuranose (Compound No. 42),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}α,D-xylofuranose (Compound No. 43),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 44),
1,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 45),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 46),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 47),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}β, D-xylofuranose (Compound No. 48),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 49),
1,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 50),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 51),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α,D-xylofuranose (Compound No. 52),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenyl acetyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-xylofuranose (Compound No. 53),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenylacetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-xylofuranose (Compound No. 54),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenylacetyl-alyl-L-Proline}-α,D-xylofuranose (Compound No. 55)
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-ribofuranose (Compound No. 56),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-ribofuranose (Compound No. 57),
1,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-ribofuranose (Compound No. 58),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-ribofuranose (Compound No. 59),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-ribofuranose (Compound No. 60),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 61),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 62),
1,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}1α,D-ribofuranose (Compound No. 63),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 64),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 65),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 66),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 67),
1,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}1α,D-ribofuranose (Compound No. 68),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 69),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-ribofuranose (Compound No. 70),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α, D-ribofuranose (Compound No. 71),
1,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α, D-ribofuranose (Compound No. 72),
1,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α, D-ribofuranose (Compound No. 73),
1,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α, D-ribofuranose (Compound No. 74),
1,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}β, D-ribofuranose (Compound No. 75),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyl]acetyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-ribofuranose (Compound No. 76),
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyl]acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-ribofuranose (Compound No. 77), and
1,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyl]acetyl-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-1-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-β,L-gulofuranoside (Compound No. 79),
2,3-O-isopropylidene-1-O-hexyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-β,L-gulofuranoside (Compound No. 80),
2,3-O-isopropylidene-1-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-β,L-gulofuranoside (Compound No. 81),
2,3-O-isopropylidene-1-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-β,L-gulofuranoside (Compound No. 82),
2,3-O-isopropylidene-1-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 83),
Tris salt of 2,3-O-isopropylidene-1-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 84)
Sodium salt of 2,3-O-isopropylidene-1-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 85)
2,3-O-isopropylidene-1-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 86),
2,3-O-isopropylidene-1-O-hexyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 87),
2,3-O-isopropylidene-1-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 88),
2,3-O-isopropylidene-1-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 89),
2,3-O-isopropylidene-1-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 90),
2,3-O-isopropylidene-1-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 91),
2,3-O-isopropylidene-1-O-hexyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 92),
2,3-O-isopropylidene-1-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 93),
2,3-O-isopropylidene-1-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}-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}-α,L-gulofuranoside (Compound No. 96),
2,3-O-isopropylidene-1-O-hexyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 97),
2,3-O-isopropylidene-1-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 98),
2,3-O-isopropylidene-1-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 99),
2,3-O-isopropylidene-1-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-β,L-gulofuranoside (Compound No. 100),
2,3-O-isopropylidene-1-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-lyxofuranoside (Compound No. 101),
2,3-O-isopropylidene-1-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-lyxofuranoside (Compound No. 102),
2,3-O-isopropylidene-1-O-heptyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-lyxofuranoside (Compound No. 103),
2,3-O-isopropylidene-1-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-α,D-lyxofuranose (Compound No. 104),
2,3-O-isopropylidene-1-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-α,D-lyxofuranoside (Compound No. 105),
2,3-O-isopropylidene-1-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 106),
2,3-O-isopropylidene-1-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 107),
2,3-O-isopropylidene-1-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 108),
2,3-O-isopropylidene-1-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 109),
2,3-O-isopropylidene-1-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 110),
2,3-O-isopropylidene-1-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 111),
2,3-O-isopropylidene-1-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 112),
2,3-O-isopropylidene-1-O-heptyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No. 113),
2,3-O-isopropylidene-1-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonylamino}α,D-lyxofuranoside (Compound No. 114),
2,3-O-isopropylidene-1-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]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-lyxofuranoside (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-1-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α, D-lyxofuranoside (Compound No. 120),
2,3-O-isopropylidene-1-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenylacetyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside (Compound No. 121),
2,3-O-isopropylidene-1-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenyl acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside (Compound No. 122), and
2,3-O-isopropylidene-1-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]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,L-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-1-carbonyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid (Compound No. 126),
2,3-O-isopropylidene-1-carbonyl-α,L-Aspartyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid (Compound No. 127),
2,3-O-isopropylidene-1-carbonyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid (Compound No. 128),
2,3;4,6-Di-O-isopropylidene-1-deoxy-1-N-{[4-chlorophenyl]aminocarbonylamino}-α,L-xylo-2-hexulofuranose (Compound No. 129),
2,3;4,6-Di-O-isopropylidene-1-deoxy-1-N-{[4-methoxyphenyl]aminocarbonylamino}-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))phenylaminocarbonylamino}-α,L-xylo-2-hexulofuranose (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-1-deoxy-1-N-{[4-tolyl]aminocarbonylamino}-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-1-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 139),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 140),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 141),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 142),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 143),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 144)
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 145),
2,3-O-Isopropylidene-1-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 146),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-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-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 149),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 150),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 151),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-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-hexulofuranose (Compound No. 153),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 154),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 155),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 156),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 157),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 158),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 159),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 160),
2,3-O-Isopropylidene-1-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 161),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 162),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 163),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 164),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 165),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 166),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-morpholin-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-yl-α-L-xylo-2-hexulofuranose (Compound No. 168),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 169),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 170),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 171),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 172),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 173),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 174),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 175),
2,3-O-Isopropylidene-1-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 176),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 177),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 178),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 179),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 180),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 181),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 182),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 183),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 184),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 185),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 186),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-azepan-1-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-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 189),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-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-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-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-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-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-1-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-1-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-1-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-1-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 200),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 201),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-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-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 203),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-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-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 206),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 207),
2,3-O-Isopropylidene-1-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 208),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 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-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 211),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 212),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 213),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-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-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 216),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 217),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 218),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-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-hexulofuranose (Compound No. 220),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 221),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-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-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-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-hexulofuranose (Compound No. 225),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 226),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (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-hexulofuranose (Compound No. 228),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 229),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 230),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 231),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 232),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 233),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-(2-ethylmorphilin-4-yl)-α-L-xylo-2-hexulofuranose (Compound No. 234),
2,3-O-Isopropylidene-1-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-1-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 236),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 237),
2,3-O-Isopropylidene-1-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-1-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 239),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 240),
Hydrochloride salt of 2,3-O-Isopropylidene-1-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 241),
2,3-O-Isopropylidene-1-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 242),
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 243),
2,3-O-Isopropylidene-1-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-1-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 245),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 246),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 247),
2,3-O-Isopropylidene-1-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 248),
2,3,O-Isopropylidene-1-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 249),
2,3,O-Isopropylidene-1-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 250),
2,3,O-Isopropylidene-1-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 251),
2,3,O-Isopropylidene-1-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 252),
2,3,O-Isopropylidene-1-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-1-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 254),
2,3,O-Isopropylidene-1-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 255),
2,3,O-Isopropylidene-1-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 256),
2,3,O-Isopropylidene-1-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 257),
2,3,O-Isopropylidene-1-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No. 258),
2,3,O-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-1-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 260),
2,3,O-Isopropylidene-1-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 261),
2,3,O-Isopropylidene-1-O-heptyl-4-O— (methylaminocarbonyl)-6-deoxy-6-piperidin-1-yl-α-L-xylo-2-hexulofuranose (Compound No. 262),
2,3,O-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-1-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 (0.2×10⁶cells/ml) were taken, and added 19 μl of Hank's Buffer salt solution along with 1 μl 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⁺⁺/Mg⁺⁺ 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 LTB₄assay (J. Pharmacol. Exp. Ther. 297:267, 2001) using LTB₄ELISA kits (Assay Design Inc., USA). The amount of LTB₄was quantified and percent inhibition in LTB₄release was calculated with respect to negative and positive controls to compute IC₅₀values.

Compound Nos. 1, 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 IC₅₀val—of between about 2.5 μm and abμm out 30 μm, or between about 2.5 μm and about 10 μm, or between about 2.5 μm and about 5 μm.

DERIVATIVES OF MONOSACCHARIDES AS 5-LIPOXYGENASE INHIBITORS

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