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 world over (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 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 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 has 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), cancer (Current Drug Targets - Inflammation & Allergy, 3, 19, 2004), inflammatory bowel disease (Lab Invest. 85, 808, 2005; Indian J Exp Biol. 42, 667, 2004), acne (Dermatology 210, 36, 2005; Arch. Dermatol. 139, 668, 2003), pruritis(J Invest Dermatol. 117, 1621, 2001), as well as atherosclerosis (N Engl J Med. 350,4, 2004; Med Res Rev. 24, 399, 2004).
Several leukotriene receptor antagonists, Montelukast, Zafirlukast, and Pranlukast, and one 5-lipoxygenase inhibitor, Zileuton, has 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 property and adverse events like elevation of hepatic transaminases. 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
In one of our US Patent 6,329,344 we disclose several derivatives of monosaccharides are
disclosed as cell adhesion inhibitors. The US Patent 6,329,344 discloses compounds of Formulae I,
II and III (Formula Removed)

wherein R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or
alkyl aryl;
R' is SO2C6H5, SO2C6H4CH3-p or SO2C6H4-C1, 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 tetra peptide (Leucyl-aspartyl-alyl-prolyl),
tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl) respectively;
R" is H or CH3;
(~~ ) represents idofuranose, talofuranose, xylofuranose or ribofuranose configurations and
methods of manufacturing such compounds.
A compound of Formula II,
(Formula Removed)
wherein
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkyl aryl; R' is SO2C6H5, SO2C6H5CH3-p, SO2 C6H4Cl-p, phenyl or substitutd 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;
R" isHorCH3
and methods of manufacturing such compounds.
A compound of Formula III
(Formula Removed)
wherein
R' is CO-LDVP, CO-DVP, CO-VP or CH2NHCONHR" wherein LDVP, DVP and VP represent
tetra peptide (Leucyl-aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl), respectively; R" is C6H4R"'-p ( R'" is Cl, NO2, OCH3, CH3, CH2COOH, CH2COLDVP,
CH2CODVP or CH2COVP wherein LDVP, DVP and VP are the same as defined earlier) and methods of manufacturing such compounds.
In another of our US Patent 6,590,085 derivatives of monosaccharides having the general Formula I (represented as Formula IV) have been disclosed.
(Formula Removed)
wherein
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl
and R1 is phenyl, o-m- or p-chlorophenyl, tolyl, methoxyphenyl or nitrophenyl and R2 is H,
pyrrolidinyl, piperidinyl, morphilinyl or hexamethyleneimino or a radical of the Formula - NHRs
wherein R3 is C1 to C15 alkyl, alkene or alkyne (straight chain or branched) or a radical of the
Formula
(Formula Removed)
in which n is a whole number upto 5 and
(Formula Removed)
is a five membered, six-membered or a seven membered heterocyclic ring containing
one of more hetero atoms,
(Formula Removed)
preferably
are pyrrolidinyl, piperidinyl, morpholinyl or hexamethyleneimino moieties.
In continuation of our work, in the present application we disclose the use of monosaccharide derivatives of Formulae I, II, III and IV as 5-lipoxygenase inhibitors.
SUMMARY OF THE INVENTION
According to the first object of the invention there is provided a method for inhibiting 5 Lipoxygenase enzyme, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formulae I,
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides,
prodrugs or metabolites
wherein,
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl;
R' is SO2C6H5, SO2C6H4CH3-p or SO2C6H4-C1, phenyl or substituted phenyl, represented as C6H4-
R'"-p R'" being CI, 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 CH3;
(~~) represents idofuranose, talofuranose, xylofuranose or ribofuranose configurations.
According to the second object of the invention there is provided a method for inhibiting 5 Lipoxygenase enzyme, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formulae II
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides,
prodrugs or metabolites
wherein
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkyl aryl;
R' is SO2C6H5, SO2C6H5CH3-p, SO2 C6H4Cl-p, phenyl or substitutd 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;
R" isHorCH3
According to the third object of the invention there is provided a method for inhibiting 5
Lipoxygenase enzyme, comprising the administration to a patient in need of such treatment a
therapeutically effective amount of a compound, having the structure of Formulae III,
(Formula Removed)
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-
prolyi), 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 the fourth object of the invention there is provided a method for inhibiting 5 Lipoxygenase enzyme, comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, having the structure of Formulae I, II, III and IV.
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides,
prodrugs or metabolites
wherein
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or alkylaryl;
R1 is phenyl, o-m- or p-chlorophenyl, tolyl, methoxyphenyl or nitrophenyl; and
R2 is H, pyrrolidinyl, piperidinyl, morphilinyl or hexamethyleneimino or a radical of the Formula -
NHR3 wherein R3 is C1 to C15 alkyl, alkene or alkyne (straight chain or branched) or a radical of the
Formula
(Formula Removed)
in which n is a whole number upto 5 and
(Formula Removed)
is a five membered, six-membered or a seven membered heterocyclic ring containing one
of more hetero atoms, preferably
(Formula Removed)
are pyrrolidinyl, piperidinyl, morpholinyl or hexamethyleneimino moieties.
It is further an object of the invention to provide novel method for 5-lipoxygenase enzyme comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound or pharmaceutically acceptable salt of Formulae I, II, III and IV.
DETAILED DESCRIPTION OF THE INVENTION
In order to achieve the above mentioned objectives there is provided a method of use of certain monosaccharide derivatives of Formulae I, II, III and Formula IV as inhibitor of 5-lipoxygenase. List of compounds according to Formula I include: l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonyl amino}-ß -L-idofuranose (Compound No.l), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-ß -L-idofuranose (Compound No.2), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-ß -L-idofuranose (Compound No.3), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-ß -L-idofuranose (Compound No.4), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No.5), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No.6), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No.7), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No.8), l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino} -ß -L-idofuranose (Compound No.9), l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}-ß -L-idofuranose (Compound No. 10), l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}-ß -L-idofuranose (Compound No.l 1), l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No. 12),
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß -L-idofuranose (Compound No. 13),
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß -L-idofuranose (Compound No. 14),
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No. 15),
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
amino}-ß -L-idofuranose (Compound No.16),
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]amino carbonyl am ino}-ß-L-talofuranose (Compound No. 17),
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl
aminocarbonylamino}-ß-L-talofuranose (Compound No. 18),
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-ß-L-talofuranose (Compound No. 19),
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonyl amino}-ß-L-talofuranose (Compound No.20),
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino
carbonylamino} -ß-L-talofuranose (Compound No.21),
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino} α,D-5-epiallofuranose (Compound No.22),
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}-ß-L-talofuranose (Compound No.23),
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}-ß-L-talofuranose (Compound No.24),
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino} -ß-L-talofuranose (Compound No.25),
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
amino}-ß-L-talofuranose (Compound No.26),
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
amino}-ß-L-talofuranose (Compound No.27),
1,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl] amino carbonyl
amino} -ß-L-talofuranose (Compound No.28),
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
amino}-ß-L-talofuranose (Compound No.29),
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
am ino}-ß-L-talofuranose (Compound No.30),
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß-L-talofuranose (Compound No.31),
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß-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)phenyI] 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-chlorophenyl]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-chlorophenyl]amino carbonylamino}α,D-xylofuranose (Compound No.42), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}α,D-xylofuranose (Compound No.43),
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-xylofuranose (Compound No.44),
l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-xylofuranose (Compound No.45),
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-xylofuranose (Compound No.46),
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-xylofuranose (Compound No.47),
l,2-O-isopropylidene-3-O-dodecyI-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α, D-xylofuranose (Compound No.48),
l,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]aminocarbonylamino} α,D-xylofuranose (Compound No.50),
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,D-xylofuranose (Compound No.51),
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino}α,D-xylofuranose (Compound No.52),
l,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), l,2-O-isopropy!idene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenylacetyl-α,L-Aspartyl-L-Valyl-L-Proline}- α,D-xylofuranose (Compound No.54), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenylacetyl-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-ribofuranose (Compound No.56), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-ribofuranose (Compound No.57), l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-ribofuranose (Compound No.58), l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-ribofuranose (Compound No.59), l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-ribofuranose (Compound No.60), l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-ribofuranose(CompoundNo.61), l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}α,D-ribofuranose (Compound No.62),
l,2-O-isopropyIidene-3-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.63),
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.64),
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.65),
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.66),
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.67),
l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.68),
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-ribofuranose (Compound No.69),
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl aniino}α,D-ribofuranose (Compound No.70),
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-ribofuranose (Compound No.71),
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-ribofuranose (Compound No.72),
l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-ribofuranose (Compound No.73),
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-ribofuranose (Compound No.74),
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-ribofuranose (Compound No.75),
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyl] acetyI-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-{[aminocarbonylaminophenyl] acetyI-α,L-AspartyI-L-Valyl-L-Proline}-α,D-ribofuranose (Compound No.77),
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyl]acetyl-L-Valyl-L-Proline }-α,D-ribofuranose (Compound No.78).
List of compounds according to Formula II include:
2,3-O-isopropylidene-l-O-butyI-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.79), 2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.80), 2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyljaminocarbonyl amino}-ß, L-gulofuranoside (Compound No.81), 2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.82), 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonylamino}-ß, L-gulofuranoside (Compound No.83), Tris salt of 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-ß, L-gulofuranoside (Compound No.84) Sodium salt of 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-ß, L-gulofuranoside (Compound No.85) 2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.86),
2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.87),
2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.88),
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.89),
2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.90),
2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.91),
2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyI amino}-ß, L-gulofuranoside (Compound No.92),
2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.93),
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.94),
2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß, L-gulofuranoside (Compound No.95),
2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonylamino}-ß, L-gulofuranoside (Compound No.96),
2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.97),
2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.98),
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß, L-gulofuranoside (Compound No.99),
2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß, 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-hydroxy-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-hydroxy-2-oxoethyl)phenyl] aminocarbonyl amino}-α,D-lyxofuranoside (Compound No. 105), 2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No. 106),
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No.107),
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No. 108),
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No. 109),
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No.l 10),
2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No.l 11),
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No.l 12),
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No.l 13),
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl amino}α,D-lyxofuranoside (Compound No.l 14),
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}αD-lyxofuranoside (Compound No.l 15),
2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-lyxofuranoside (Compound No.l 16),
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-lyxofuranoside (Compound No.l 17),
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-lyxofuranoside (Compound No.l 18),
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-lyxofuranoside (Compound No.l 19),
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α, D-lyxofuranoside (Compound No. 120),
2,3-O-isopropylidene-l-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-l-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenyl acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside (Compound No. 122), 2,3-O-isopropylidene-l-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 include:
2,3;4,6-Di-O-isopropylidene-l-carbonyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline-a,
L-xylo-2-hexulofuranosonic acid (Compound No. 124),
2,3;4,6-Di-O-isopropylidene-l-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-Proline-α,L-xylo-2-
hexulofuranosonic acid (Compound No. 127),
2,3-O-isopropylidene-l-carbonyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid
(Compound No. 128),
2,3;4,6-Di-O-isopropylidene-l-deoxy-l-N-{[4-chlorophenyl]aminocarbonyl
amino}-α,L-xylo-2-hexulofuranose (Compound No. 129),
2,3;4,6-Di-O-isopropylidene-l-deoxy-l-N-{[4-methoxyphenyl]aminocarbonyl
amino}-α,L-xylo-2-hexulofuranose (Compound No. 130),
2,3;4,6-Di-O-isopropylidene-l-deoxy-l-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-hexulofuranose (Compound No. 132),
2,3-O-isopropylidene-l-deoxy-l-N-{[4-chlorophenyl]aminocarbonylamino}-α,L-xylo-
2-hexulofuranose (Compound No. 133),
2,3-O-isopropylidene-1-deoxy-l-N-{ [4-methoxyphenyl]aminocarbonylamino}-α,L-xylo-
2-hexulofuranose (Compound No. 134),
2,3-O-isopropylidene-1 -deoxy-1 -N- {[4-toly l]aminocarbony lamino} -α,L-xylo-2-
hexu!ofuranose(Compound No. 135),
2,3-O-isopropylidene-1 deoxy-l-N-{ [aminocarbonylaminophenylacetyl-L-
Leucyl-α,L-Aspartyl-L-Valyl-L-Proline)}-α,L-xylo-2-hexulofuranose(Compound No. 136),
2,3-O-isopropyl idene-1 -deoxy-1 -N- {[aminocarbonylaminophenylacetyl-α,L-
Aspartyl-L-Valyl-L-Proline)}-α,L-xylo-2-hexulofuranose (Compound No. 137),
2,3-O-isopropylidene-l deoxy-l-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) -6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 139),
2,3-O-isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl) -6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 140),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 141),
2,3-O-lsopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 142),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 143),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 144)
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-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-chlorophenyIaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 147),
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 148),
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 149),
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-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-hexulofuranose (Compound No. 151),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 152),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-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-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-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-hexulofuranose (Compound No. 156),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 157),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 158),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 159),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 160),
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 161),
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-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-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 163),
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 164),
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-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-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 166),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 167),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 168),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose (Compound No. 169),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-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-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-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-L-
xylo-2-hexulofuranose (Compound No. 173),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-l-
yl-α-L-xylo-2-hexulofuranose (Compound No. 174),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-l-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-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-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-
α-L-xylo-2-hexulofuranose (Compound No. 179),
2,3-O-Isopropyl idene-1 -O-decyl-4-O-(4-nitrophenylam inocarbonyl)-6-deoxy-6-piperidin-1 -y 1-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-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-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-L-xylo-
2-hexuIofuranose (Compound No. 183),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-
α-L-xylo-2-hexulofuranose (Compound No. 184),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-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-chlorophenylaminocarbonyl)-6-deoxy-6-azepan-l-yl-α-L-xylo-2-hexulofuranose (Compound No. 187),
2,3-O-Isopropylidene-l-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-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-IsopropyIidene-l-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-l-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-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-azepan-1-yl -α-L-xylo-2-hexulofuranose (Compound No. 197),
2,3-O-Isopropylidene-l -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-methoxyphenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose (Compound No.201),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose (Compound No.202),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl]amino-α-L-xylo-2-hexulofuranose (Compound No.203),
2,3-O-Isopropylidene-l-O-dodecyl-4-0-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyljamino -α-L-xylo-2-hexulofuranose (Compound No.204),
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.205),
2,3-O-Isopropylidene-l-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-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyljamino -α-L-xylo-2-hexulofuranose (Compound No.207),
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-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-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-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-l-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-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-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-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.214),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.215),
2,3-O-Isopropylidene-l-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-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-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-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-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-l-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-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-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-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-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-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.227),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.228),
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-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-hexulofuranose (Compound No.230),
2,3-O-Isopropylidene- l-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-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-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-(morphilin-4-yl) ethyl] amino-α-L-xylo-2-hexulofuranose (Compound No.233), 2,3-O-Isopropylidene-l-O-dodecyl-4-0-(4-chlorophenylaminocarbonyl)-6-deoxy-6-(2-ethylmorphilin-4-yl)-α-L-xylo-2-hexu!ofuranose (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-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.236), 2,3-O-Isopropylidene-l-O-dodecyl-4-0-(4-nitrophenylaminocarbonyl)-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-chlorophenylaminocarbonyl)-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-(morphilin-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(CompoundNo.241), 2,3-O-Isopropylidene-l-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-l-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-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-chlorophenylaminocarbonyl)-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-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose (Compound No.246),
2,3-O-Isopropylidene-l-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-l-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-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-morpholin-4-yl-α-L-
xyIo-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-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-( pyrrolidin-1-yl)
ethyl] amino-cc-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-deoxy-6-morpholin-4-yl-α-L-xylo-
2-hexulofuranose (Compound No.254),
2,3,0-Isopropylidene-1 -O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-1 -yl-α-L-xylo-2-
hexulofuranose (Compound No.255),
2,3,0-Isopropylidene-1 -O-decyl-4-O-(methylaminocarbony l)-6-deoxy-6-piperidin-1 -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-l-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-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-hexulofuranose (Compound No.260),
2,3,0-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-l-O-heptyl-4-O- (methylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-L-xylo-
2-hexulofuranose (Compound No.262),
2,3,0-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyI)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl]
amino -α-L-xylo-2-hexulofuranose (Compound No.263),
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 assay were performed on the compounds of Formula 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 of neutrophil suspension (0.2xl06 cells/ml) was 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 1hr. 3 min before the end of test compound incubation, 0.25 mM Ca++/Mg++ were added. Then, 0.3 µg/ml A23187 was added and incubated for further 10 min. 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 LTB4 assay (J Pharmacol Exp Ther. 297:267, 2001) using LTB4 ELISA kits (Assay Design Inc., USA). The amount of LTB4 was quantified and percent inhibition in LTB4 release was calculated w.r.t. negative and positive control to compute ICso values.
INVITRO SCREENING DATA
(Table Removed)
5-Lipoxygenase Assay
Assay was carried out in 96 well UV plate containing 100 µL reaction mixture (DTT, 200 µ.M; ATP, 100 uM; and calcium chloride, 100 µM; in phosphate buffered saline) in the absence and presence of different concentrations of test compound (100 nM - 30 µM) and 12 U (3U/µl) of human recombinant 5-lipoxygenase (Cayman Chemicals Co., USA). Reaction mixture was incubated at 37°C for 5 min, reaction was initiated by adding 1 µl of 1 mM freshly prepared arachidonic acid. Increase in absorbance was monitored at 234 nm for 10 min. (J. Biol, Chem., 261, 11512-11519). A plot of absorbance vs. time curve was prepared and area under curve (AUC) was computed for each well. Percent inhibition of AUC for different treatments was calculated with respect to the difference between the Arachidonic acid stimulated and negative control values, to compute IC50 values. 15-Lipoxygenase Assays:
100 µL reaction mixture (DTT, ImM; ATP, 1 mM; calcium chloride, 2mM; in phosphate buffered saline) containing 30U of soybean 15 lipoxygenase (Cayman Chemicals Co., USA) was incubated in the absence and presence of test compound (100 nM - 600 uM) for 5 min at 37°C. 5 min later freshly prepared 14C-arachidonic acid (final concentration-27 uM) was added to the reaction mixture and incubated in a shaking water bath for a further 20 min. The reaction was terminated with 16 µl of 0.5N hydrochloric acid, to this 75 µ1 of ice-cold methanol was added and stored at -20°C till assayed by HPLC. For HPLC analysis, a solvent containing acetonitrile: methanol: water: acetic acid in the ratio of 70:15:14:1, with pH 5.56. HPLC was run at a flow rate of Iml/min and 30 min per sample. 5-LO product (15-HETE) and the substrate (arachidonic acid) were monitored by a radioactive flow scintillation analyzer connected to the HPLC. The retention time for arachidonic acid varied between 9.5 - 11 minutes and that of 15-HETE varied between 3.5 - 4.3 minutes. Results are expressed as percent control and the IC50 values of test compounds are reported.
12-Lipoxygenase Assay
100 µL reaction mixture (DTT, ImM; ATP, 1 mM; calcium chloride, 2mM; and indomethacin 10 µM; in phosphate buffered saline) was incubated in the absence and presence of test compound (100 nM - 600 µM) and 5.3 U of porcine 12 lipoxygenase (Cayman Chemicals Co., USA) at 37°C for 5 min. Reaction was initiated by adding freshly prepared 14C arachidonic acid (final concentration 27 µM). Reaction mixture was incubated in a shaking water bath for a further 20 min. The reaction was terminated with by adding 16 µl of 0.5N hydrochloric acid, to this 75 µl of ice-cold methanol was added and store at -20°C till assayed by HPLC. For HPLC analysis, samples were subjected to separation by HPLC using solvent containing acetonitrile: methanol: water: acetic acid in the ratio of 70:15:14:1, with pH 5.56. HPLC was run at a flow rate of Iml/min and 30 min per sample. 12-LO product (12-HETE) and the substrate (arachidonic acid) were monitored by a radioactive flow scintillation analyzer connected to the HPLC. The retention time for arachidonic acid varied between 9.5 -l 1 minutes and that of 12-HETE varied between 3.5 - 4.5 minutes. Results were expressed as percent control and the IC50 values of test compounds are reported. In vitro potency and selectivity of data of Compound 85
(Table Removed)
Ex-vivo LTB4 Release in rat
Overnight fasted male wistar rats (180 - 220 gm) were treated with test compound at a dose of 0.1, 1, and 10 mg/kg, p.o., (dissolved in 3% tween 80) or vehicle. Blood was collected, under light ether anaesthesia from retro-orbital plexus, 1 hr post dosing. Whole blood (180)0,1) was mixed with PBG (20 u.1) and incubated at 37°C for 15 min. LTB4 synthesis was initiated with A23187 (10 µg/ml; 30 min). LTB4 released, was assayed using ELISA kit as described above. The amount of LTB4 released was quantitated and fold-shift in LTB4 release w.r.t. negative controls was calculated. All the results were expressed as Mean ± S.E.M.
(Table Removed)
* indicates significantly different from vehicle treated group using one way ANOVA followed by dunnett's multiple comparison test, p ≤ 0.5 was considered significant.

WE CLAIM:
1. The use of a compound having the structure of Formula I, in the manufacture of a medicament for the inhibition of 5-lipoxygenase enzyme or related processes in a mammal comprising administering to the said animal a therapeutically effective amount of
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides,
prodrugs or metabolites
wherein
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or
alkyl aryl;
R' is SO2C6H5, SO2C6H4CH3-p or SO2C6H4-Cl-p, 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 tetra peptide (Leucyl-
aspartyl-alyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl)
respectively;
R" is H or CH3;
(~~ ) represents idofuranose, talofuranose, xylofuranose or ribofuranose configurations.
2. The use of a compound having the structure of Formula II, in the manufacture of a medicament for the inhibition of 5-lipoxygenase enzyme or related processes in a mammal comprising administering to the said animal a therapeutically effective amount of
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides,
prodrugs or metabolites
wherein;
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or
alkyl aryl;
R' is SO2C6H5, SO2C6HsCH3-p, SO2 C6H4Cl-p, phenyl or substitutd phenyl, represented as
C6H4-R'"-p, wherein R'" being Cl, NO2, OCH3, CH3, CH2COOH, CH2COOCH3,
CH2COLDVP, CH2CODVP, CH2COVP, wherein LDVP, DVP and VP represent tetra
peptide (Leucyl-aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide
(valyl-prolyl), respectively;
R" isHorCH3
3. The use of a compound having the structure of Formula III, in the manufacture of a
medicament for the inhibition of 5-lipoxygenase enzyme or related processes in a mammal
comprising administering to the said animal a therapeutically effective amount of
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides,
amides, prodrugs or metabolites wherein
R' is CO-LDVP, CO-DVP, CO-VP or CH2NHCONHR" wherein LDVP, DVP and VP
represent tetra peptide (Leucyl-aspartyl-valyl-prolyl), tripeptide (aspartyl-valyl-prolyl) and dipeptide (valyl-prolyl), respectively; R" is C6H4R'"-p ( R1" is Cl, NO2, OCH3, CH3,
CH2COOH, GH2COLDVP, CH2CODVP or CH2COVP wherein LDVP, DVP and VP are the same as defined earlier).
4. The use of a compound having the structure of Formula IV, in the manufacture of a
medicament for the inhibition of 5-lipoxygenase enzyme or related processes in a mammal
comprising administering to the said animal a therapeutically effective amount of
(Formula Removed)
its pharmaceutically acceptable salts, esters, enantiomers, diastereomers, N-oxides, amides,
prodrugs or metabolites
wherein
R is C1 to C15 alkyl, alkene, alkyne (straight chain or branched), aryl, substituted aryl or
alkyl aryl ;
R1 is phenyl, o-m- or p-chlorophenyl, tolyl, methoxyphenyl or nitrophenyl; and
R2 is H, pyrrolidinyl, piperidinyl, morphilinyl or hexamethyleneimino or a radical of the
Formula - NHR3 wherein R3 is C1 to C15 alkyl, alkene or alkyne (straight chain or branched)
or a radical of the Formula
(Formula Removed)
in which n is a whole number in the range of 2-5 and
(Formula Removed)
is a five membered, six-membered or a seven membered heterocyclic ring
containing one of more hetero atoms.
5. The use of a compound selected from the group consisting of:
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-ß -L-idofuranose, l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-ß -L-idofuranose, l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-ß -L-idofuranose, l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonylamino} -[3 -L-idofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonyi
amino}-ß -L-idofuranose ,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino} -ß -L-idofuranose,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl] aminocarbonylamino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß -L-idofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]amino carbonyl amino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonylamino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethy!) phenyl]aminocarbonylamino}-ß-L-talofuranose,
1,2-O-isopropyl idene-3-O-buty 1-5,6-dideoxy-5-N-{ [4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonyl amino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino
carbonylamino} -ß-L-talofuranose,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}α,D-5-epiallofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}-(3-L-talofuranose,
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}-p-L-talofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino} -ß-L-talofuranose,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl] aminocarbonylamino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl] aminocarbonylamino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino} -ß-L-talofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl am ino} -ß-L-talofuranose,
l,2-O-isopropylidene-3-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl am ino}-ß-L-talofuranose,
l,2-O-isopropylidene-3-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl am ino} -ß-L-talofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonylamino}-α,D-xylofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-xylofuranose,
l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonylamino}-α,D-xylofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl] aminocarbonylamino}-α,D-xylofuranose, l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]aminocarbonylamino}-α,D-xylofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]amino
carbonylamino}α,D-xylofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]amino
carbonylamino}α,D-xylofuranose,
l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-chlorophenyl]amino
carbony lamino} α,D-xy lofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]amino
carbonylamino}α,D-xylofuranose,
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]amino
carbony lamino} α,D-xylofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}α,D-xylofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
amino}α,D-xylofuranose,
l,2-O-isopropy!idene-3-O-hexyl-5-deoxy-5-N-{[4-methoxyphenyl]
aminocarbonylamino}α,D-xylofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
am ino} α,D-xylofuranose,
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]
aminocarbonylamino}α,D-xylofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,D-
xylofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,D-
xylofuranose,
l,2-O-isopropylidene-3-O-hexyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,D-
xylofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,D-
xylofuranose,
l,2-O-isopropy!idene-3-O-methyl-5-deoxy-5-N-{[4-tolyl] aminocarbonylamino} α,D-
xylofuranose,
l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbony lam ino} α,D-ribofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
am ino} α,D-ribofuranose,
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}α,D-ribofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,D-
ribofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,
D-ribofuranose,
l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-tolyI]aminocarbonylamino} α,D-
ribofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,
D-ribofuranose,
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-olyl]aminocarbonylamino} α,
D-ribofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyI]
acetyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline }-α,D-ribofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylaminophenyl]
acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-ribofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-[aminocarbonylamino phenyl]acetyl-L-
Valyl-L-Proline }-α,D-ribofuranose.
in the manufacture of a medicament for the inhibition of 5-lipoxygenase enzyme_and related
processes in a mammal.
6. The use of compounds selected from the group consisting of:
2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-ß, L-gulofuranoside, 2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-ß, L-gulofuranoside, 2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyljaminocarbonyl amino}-ß, L-gulofuranoside,
l,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,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino] phenylacetyl-α,L-
Aspartyl-L-Valyl-L-Proline}-α,D-xylofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino] phenylacetyl-alyl-
L-Proline}- α,D-xylofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl
]aminocarbonylamino}-α,D-ribofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
am inocarbony lamino} -α,D-ribofuranose,
l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]aminocarbonylamino}-α,D-ribofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-α,D-ribofuranose,
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]aminocarbonylamino}-α,D-ribofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]amino carbonylamino}
a,D-ribofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
am ino} α,D-ribofuranose,
l,2-O-isopropylidene-3-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}α,D-ribofuranose,
l,2-O-isopropylidene-3-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino} α,D-ribofuranose,
l,2-O-isopropylidene-3-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
am ino} α,D-ribofuranose,
l,2-O-isopropylidene-3-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}α,D-ribofuranose,
l,2-O-isopropylidene-3-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
am ino} α,D-ribofuranose,
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonyl amino}-ß, L-gulofuranoside, 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl) phenyl]aminocarbonylamino}-ß, L-gulofuranoside,
Ditris salt of 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-ß, L-gulofuranoside,
Sodium salt of 2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]aminocarbonylamino}-(3, L-gulofuranoside,
2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-chlorophenyl] aminocarbonylamino}-p, L-gulofuranoside,
2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino carbonylamino}-P, L-gulofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino carbonylamino}-P, L-gulofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-chlorophenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-methoxyphenyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-butyl-5,6-dideoxy-5-N-{[4-tolyl]amino carbonylamino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-hexyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl amino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
amino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-decyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
amino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5,6-dideoxy-5-N-{[4-tolyl]aminocarbonyl
amino}-ß, L-gulofuranoside,
2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]aminocarbonylamino}-α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]aminocarbonylamino}-α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)phenyl]
aminocarbonylamino}-α,D-lyxofuranose,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-(2-hydroxy-2-oxoethyl)
phenyl]aminocarbonyl amino}-α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
amino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl
am ino} α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-chlorophenyl]aminocarbonyl.
amino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-chlorophenyl]amino
carbonylamino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
amino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-methoxyphenyl]aminocarbonyl
amino}α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-methoxyphenyl]amino
carbonylamino}αD-lyxofuranoside,
2,3-O-isopropylidene-l-O-methyl-5-deoxy-5-N-{[4-tolyl]amino carbonylamino}α,D-
lyxofuranoside,
2,3-O-isopropylidene-l-O-butyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,
D-lyxofuranoside,
2,3-O-isopropylidene-l-O-heptyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,
D-lyxofuranoside,
2,3-O-isopropylidene-l-O-decyl-5-deoxy-5-N-{[4-tolyl]aminocarbonylamino} α,
D-lyxofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[4-tolyl]amino carbonylamino}α,D-
lyxofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino] phenylacetyl-L-
Leucyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenyl
acetyl-α,L-Aspartyl-L-Valyl-L-Proline}-α,D-lyxofuranoside,
2,3-O-isopropylidene-l-O-dodecyl-5-deoxy-5-N-{[aminocarbonylamino]phenyl
acetyl-L-Valyl-L-Proline}-α,D-lyxofuranoside.
in the manufacture of a medicament for the inhibition of 5-lipoxygenase enzyme_and related
processes in a mammal.
7. The use of a compound selected from the group consisting of:
2,3;4,6-Di-O-isopropylidene-l-carbonyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid,
2,3;4,6-Di-O-isopropylidene-l-carbonyl-α,L-Aspartyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid,
2,3-O-isopropylidene-l-carbonyl-L-Leucyl-α,L-Aspartyl-L-Valyl-L-ProIine-α,L-xylo-2-hexulofuranosonic acid,
2,3-O-isopropylidene-l-carbonyl-α,L-Aspartyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid,
2,3-O-isopropylidene-l-carbonyl-L-Valyl-L-Proline-α,L-xylo-2-hexulofuranosonic acid,
2,3;4,6-Di-O-isopropylidene-l-deoxy-l-N-{[4-chlorophenyl]aminocarbonyl
amino}-α,L-xylo-2-hexulofuranose,
2,3;4,6-Di-O-isopropylidene-l-deoxy-l-N-{[4-methoxyphenyl]aminocarbonyl
amino}-α,L-xylo-2-hexulofuranose,,
2,3 ;4,6-Di-O-isopropylidene-1 -deoxy-1 -N- {[4-tolyl]aminocarbony lamino} -α,L-xylo-2-
hexulofuranose,
2,3-O-isopropylidene-1 -deoxy-1 -N-{ [4-(2-hydroxy-
2oxoethyl)phenyl]aminocarbonylamino}-α,L-xylo- 2-hexuIofuranose,
2,3-O-isopropylidene-1-deoxy-l-N-{[4-chlorophenyl]aminocarbonylamino}-α,L-xylo-2-
hexulofuranose,
2,3-O-isopropylidene-1-deoxy-l-N-{[4-methoxyphenyl]aminocarbonylamino}-α,L-xylo-2-
hexulofuranose,
2,3-O-isopropylidene-1-deoxy-l-N-{[4-tolyl]aminocarbonylamino}-α,L-xylo-2-
hexulofuranose,
2,3-O-isopropylidene-1 deoxy-1 -N-{ [aminocarbonylaminophenylacetyl-L-
Leucyl-α,L-Aspartyl-L-Valyl-L-Proline)}-α,L-xylo-2-hexulofuranose,
2,3-O-isopropylidene-l-deoxy-l-N-{[aminocarbonylaminophenylacetyl-α,L-
Aspartyl-L-Valyl-L-Proline)}-α,L-xylo-2-hexulofuranose,
2,3-O-isopropylidene-ldeoxy-l-N-{[aminocarbonylaminophenylacetyl-L-Valyl-L-
Proline)}-α,L-xylo-2-hexulofuranose.
in the manufacture of a medicament for the inhibition of 5-lipoxygenase enzyme_and related
processes in a mammal.
8. The use of a compound selected from the group consisting of:
2,3-O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-
α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-
α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyI)-6-deoxy-6-pyrrolidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyI-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-lsopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-pyrrolidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-pyrrolidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyI)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-
α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-
morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-
morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-
morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-
morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyI)-6-deoxy-6-morpholin-
4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-morpholin-4-yI-a-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-
morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyI)-6-deoxy-6-
morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-morpholin-
4-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-1 -O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-piperidin-1 -yl-
α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-
piperidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-
α-L-xylo-2-hexuIofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-piperidin-
1-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyI)-6-deoxy-6-piperidin-l-yl-α-L-
xylo-2-hexulofuranose,
2,3-O-Isopropyl idene-1 -O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-
piperidin-1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-l-
yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-piperidin-
1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-
piperidin-1-yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-piperidin-
1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-azepan-l-yl-α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-azepan-
1 -yl-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-
L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-
azepan-1 -yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6- azepan-1 -yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-1 -O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose ,
Hydrochloride salt of 2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-1 -O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
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,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-azepan-1 -yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6- azepan-1-yl -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl]amino-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl]amino -α-L-xylo-2-hexulofuranose,
2,3-O-IsopropyIidene-l-O-dodecyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl]amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl]amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-IsopropyIidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-1 -O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1 -yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
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,
2,3-O-Isopropylidene-1-O-dodecyl-4-O-(4-methoxypheny lam inocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose ,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-1 -O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1 -y 1) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -oc-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-l-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
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,
2,3-O-Isopropylidene- l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(piperidin-1-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino-α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene- l-O-dodecyI-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-(2-ethylmorphilin-4-yl)-α-L-xylo-2-hexulofuranose,
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,
2,3-O-Isopropylidene- l-O-dodecyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-decyl-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino-α-L-xylo-2-hexulofuranose,
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,
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, 2,3-O-Isopropylidene-l-O-decyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-dodecyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(phenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyI-4-O-(4-chlorophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yI) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-tolylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-methoxyphenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3-O-Isopropylidene-l-O-heptyl-4-O-(4-nitrophenylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-l-yl-α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-( pyrrolidin-1-yl) ethyl] amino-α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-dodecyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-
L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-l-yl-α-L-
xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-L-
xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-yl)
ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-decyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-yl)
ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3,0-Isopropyl idene-1 -O-heptyl-4-O-(methylaminocarbony l)-6-deoxy-6-pyrrolidin-1 -yl-α-
L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-morpholin-4-yl-α-
L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-azepan-l-yl-α-L-
xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-piperidin-l-yl-α-
L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(pyrrolidin-l-
yl) ethyl] amino -α-L-xylo-2-hexulofuranose,
2,3,O-Isopropylidene-l-O-heptyl-4-O-(methylaminocarbonyl)-6-deoxy-6-[2-(morphilin-4-
yl) ethyl] amino -α-L-xylo-2-hexulofuranose
in the manufacture of a medicament for the inhibition of 5-lipoxygenase enzyme_and related
processes in a mammal.
9. The use of composition having a compound as claimed in any one of the claim 1-8 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, in the manufacture of a medicament for inhibiting, preventing or suppressing the generation of leukotrienes, and related substances.
10. The use of a composition as claimed in claim 9, wherein the related substances are selected
from the group comprising of cytokines, chemokine gene expressions and proteolytic
enzymes.
11. A therapeutic method comprising treatment of a pathology wherein 5-lipoxygenase
activation is implicated and inhibition of 5-lipoxygenase is desired by administering a
compound according to any one of the claims 1-8 to a mammal in need of such therapy.
12. The use of a compound as claimed in any one of the claims 1-8, in the manufacture of a
medicament for the prophylaxis or direct treatment of a mammal suffering from diseases
selected from allergic rhinitis, chronic obstructive pulmonary disease, inflammatory bowel
disease, ulcerative colitis, acne, cancer, atherosclerosis or pruritis.
13. The use of compound as claimed in any one of the claims 1-8, in the manufacture of a
medicament for the prophylaxis or direct treatment of an animal suffering from allergic
rhinitis.
14. The use of compound as claimed in any one of the claims 1-8, in the manufacture of a
medicament for the prophylaxis or direct treatment of an animal suffering from chronic
obstructive pulmonary disease (COPD).
`