Field of the Invention
The present invention relates to monosaccharide derivatives as anti-inflammatory agents. The compounds disclosed herein can be useful for inhibition and prevention of inflammation and associated pathologies including inflammatory, cancer, cardiovascular and autoimmune diseases such as bronchial asthma, rheumatoid arthritis, type-I diabetes, multiple sclerosis, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, pruritis or allergic rhinitis. Pharmacological compositions containing compounds disclosed herein and the methods of treating diseases such as bronchial asthma, rheumatoid arthritis, type-I diabetes, multiple sclerosis, cancer, cardiovascular diseases, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, pruritis or allergic rhinitis and other inflammatory and/or autoimmune disorders, using the compounds are also provided.
Background of the Invention
Inflammation is a key defence mechanism of the body that is activated as a result of tissue injury. The inflammatory process is self-containing, however, under certain pathophysiological conditions
i • •.
the inflammatory process tends to perpetuate itself, giving rise to chronic inflammatory diseases like bronchial asthma, rheumatoid arthritis etc.
Although the exact cellular and molecular basis of most chronic inflammatory disease remain unclear, it has become apparent that several inflammatory cells act in concert towards initiation and perpetuation of an inflammatory response by releasing a wide range of chemokine, cytokine, proteolytic enzymes and other bioactive molecules. Mast cells primed by lymphocytes interact with environmental allergens and release mediators like histamine, prostaglandin, leukotrienes etc (din. Exp. Allergy 32, 1682, 2002) to initiate an early inflammatory response. This is followed by a delayed inflammatory response due to release of cytokines (IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF and TNF-alpha), chemokines and proteolytic enzymes (chymase, tryptase) (Chest 112, 523, 1997: Lancet 350, 59, 1997) that not only bring about tissue damage, but attract other inflammatory cells and initiate tissue fibrosis, and the cycle continues. Eosinophils infiltrate inflamed tissue following allergen - mast cell interaction in bronchial asthma and allergic rhinitis. Evidence is emerging that mast cells also interact with bacterial endotoxins leading to generation of cytokines like TNF-alpha. that encourage neutrophil influx into the site of inflammation (Br. J. Pharmacol. 123, 31, 1998; Br. J, Pharmacol. 128. 700, 1999; Br. J. Pharmacol. 136. Ill, 2002; J. din. Invest. 109, 1351, 2002-). Involvement of mast cells in the inflammatory response of chronic obstructive pulmonary disease (New Eng. J. Med. 347. 1040, 2002; Thorax 57, 649, 2002), inflammatory bowel disease (Gut. 4_f: Suppl. 116, 1999) as well as in rheumatoid arthritis (Science 297, 1626, 2002), pathologies prominent neutrophilic inflammation, has been proposed.

U.S. Patent 6,329,344 Bl discloses several monosaccharide derivatives said to be useful as cell adhesion inhibitors. It generally relates to substituted pentose and hexose monosaccharide derivatives, which are said to exhibit cell adhesion inhibitory and anti-inflammatory activities. U.S. Patent 6,590,085 Bl discloses several monosaccharide derivatives described as inhibitors of .eel! adhesion and cell adhesion mediated pathologies, including inflammatory and autoimmune diseases. U.S. Patent Application US 2002/0173632 Al discloses furanose and amino furanose compounds reportedly useful for rheumatoid arthritis, immunomodulatory diseases, inflammatory and proliferative diseases. U.S. Patent 5,298,494 discloses derivatives of monosaccharides, which are said to exhibit anti-proliferative and/or anti-inflammatory activity and are useful for treating mammals having inflammatory disorders and/or autoimmune disorders. U.S Patent 4,996,1,95 discloses derivatives of a-D-glucofuranose and a-D-allofuranose described as useful for treating animals and mammals with inflammatory and/or autoimmune disorders.
WO 93/13117 and U.S. Patent 5,360,792 discloses 5- or 6-deoxy hexose monosaccharides having a saturated nitrogen containing heterocycle described as useful as anti-proliferative and anti-inflammatory compounds. WO 94/28910 discloses 5,6-dideoxy-5-amino derivatives of iodose and 6-deoxy-6-amino derivatives of glucose, which reportedly exhibit immunomodulatory, anti-ihflammatory and anti-proliferative activity. WO 94/11381 discloses derivatives of pentose monosaccharides described as useful as anti-proliferative and anti-inflammatory compounds. U.S. Patent 5,010,058 discloses 1, 2-O-isopropylidene-a-O-glucofuranoside derivatives useful for treating inflammatory and autoimmune disorders. U.S. Patent 4,849,512 discloses 3-acylamino-3-deoxyallose derivatives. U.S. Patent 5,367,062 discloses disubstituted and deoxy disubstituted derivatives of a-D-lyxofuranosides reportedly having anti-inflammatory and anti-proliferative activity. U.S. Patent 5,360,794 discloses disubstituted derivatives of a-D-mannofuranoside reportedly having anti-inflammatory and anti proliferative activity. WO 03/029263 discloses 3-deoxy-3-amide derivatives of carbohydrates described as useful as inducers of erythroid cell differentiation. FR 2735130 discloses regiospecific synthesis of new carbamic polyesters.
Summary of the Invention ',•
Monosaccharide derivatives which can be used for the inhibition and prevention of inflammation and associated pathologies, including inflammatory, cancer, cardiovascular and autoimmune diseases such as bronchial asthma, rheumatoid arthritis, type-I diabetes, multiple sclerosis, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, pruritis or allergic rhinitis are described herein. Pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers or N-oxides of these compounds having the same type of activity are also provided. Pharmaceutical compositions containing the compounds, and which may

also contain pharmaceutically acceptable carriers or diluents, which may be used for the treatment of inflammatory, cancer, cardiovascular and autoimmune diseases such as bronchial asthma, rheumatoid arthritis, type-I diabetes, multiple sclerosis, allograft rejection, psoriasis, inflammatory bowel disease, ulcerative colitis, acne, atherosclerosis, pruritis or allergic rhinitis are provided herein.
Other aspects will be set forth in accompanying description which follows and in part will he apparent from the description or may be learnt by the practice of the invention.
In accordance with one aspect, there are provided compounds having the structure of Formula I
and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esterg; enantiomers, diastereomers, N-oxides, polymorphs, metabolites, wherein
RI and Ra can together form a five-membered acetal, wherein the carbon atom joining the oxygen^ can be substituted with RL and Rm [wherein RL and Rm are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; or RL and Rm can together join to form a'3-8 membered ring, wherein the ring may optionally contain one or more heteroatoms selected from O, N or S, and the ring may be optionally substituted with one or more of alkyl, alkenyl, alkynyl, amino, substituted amino, cycloalkyl, oxo, hydroxy, carboxy, -COQRe (wherein Q is O or NH and Rg is selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, and cycloalkyl), alkoxy, aryloxy, halogen (F, Cl, Br, I), aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, or heterocyclylalkyl; or RL and Rm can together join to form an oxo group].
R3 can be
A) -(CH2)nG wherein n is an integer from 0-5 and G is selected from
1) ORe (wherein Re is selected from
a) acyl (with the proviso that n cannot be 0), an'd
b) -C(=O)NRfRq [wherein Rf and Rq can be independently selected from hydrogen, hydroxy (with the restriction that both Rf and Rq cannot both be hydroxy), alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, and S(O)2R? (wherein Ry is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl, and optionally substituted amino)]; and Rf and Rq may also together join to form a

heterocyclyl ring; also, when n is zero, then Rf and Rq cannot be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl and Rf and Rq together cannot join to form a heterocyclyl ring};
2) -NRjC(=O)ORs (wherein Rj is selected from hydrogen, lower (Ci-Ce) alkyl, lower (O
C6) alkenyl, lower (C2-C6) alkynyl, lower (C3-C6) cycloalkyl, aryl, heteroaryl (with the proviso that
the heteroaryl ring is not linked through a heteroatom), aralkyl (Ci-C4), heteroarylalkyl (Ci-C4), and
heterocyclylalkyl (Ci-C4), and Rs is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyi.
heterocyclylalkyl, or heteroarylalkyl); •
3) NRjYRu (wherein R, is the same as defined above and Y is -C(=O), -C(=S) or SO2 and
RI, is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl
heteroarylalkyl, and heterocyclylalkyl; and when n is 0 then Y cannot be -C(=O));
4) -NRjC(=T)NRtRx (wherein Rt is OH or Rx and T is O, S, -N(CN), -N(NO2), -CH(NO?),
RJ is the same as defined above and Rx is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl.
aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, heterocyclylalkyl, and -S(O)2R7 wherein R7 is
the same as defined above);
5) heterocyclyl;
6) heteroaryl; and
7) -(C=O)NRaRb (wherein R a and Rb are independently selected from hydrogen, and Ru
wherein Ru is same as defined earlier, also, Ra and Rb together with the nitrogen atom carrying them
can be the N-terminus of an amino acid or di-tetrapeptide or Ra and Rb may together join to form a
heterocyclyl ring).
RJ can also be
B) -NRjRm (wherein Rj is the same as defined above and Rm is selected from alkyl, cycloalkyl, aryl,
aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, and heterocyclylalkyl);
C) -O(CH2)WG] [wherein w is an integer from 1-5 (and G] is selected from ORe (wherein Re is the
same as defined above), -NRjC(=O)ORs (wherein Rj and Rs are the same as defined above), -
NRjC(=T)NR,Rx (wherein Rj, T, Rt and Rx are the same as defined above), -NRjYRu (wherein Y, Ru
and Rj are the same as defined above), heterocyclyl, and heteroaryl)];
D) -NRj(CH2)wGi (wherein w, Rj and GI are the same as defined above);
E) -O(CH2)VVG2 [wherein w is the same as defined above (and G2 is selected from
*C(=0)NRaRb (wherein Ra and Rb are the same as defined above), and -C(=O)ORk (wherein R|< is H
or R6 and Re is the same as defined above); or
F) -NRj(CH2)wG2 (wherein w is as defined above, Rj and G2 are the same as defined above))].

Also, when Rj is ORe then RI and Re may together join to form a five membered acetal wherein the carbon linking the two oxygens is substituted with RL and Rm (wherein RL and Rm are the same as defined earlier) (and R\ is independently selected from
a) -(CH2)tG| (wherein t is an integer from 2-4 and GI are the same as defined above and also when GI is heterocyclylalkyl group then the said group cannot be 4-(l-pyrrolidinyl) butyl),
B) -(CH2)wG2 (wherein w and GI are the same as defined above),
c) aryl,
d) aralkyl (with the proviso that aralkyl cannot be phenylpropyl),
e) heteroaryl, and
f) heterocyclyl (wherein the heteroaryl and heterocyclyl rings are not linked through a heteroatom),
and cycloalkyl (with the proviso that cycloalkyl cannot be cyclooctyl).
R4 and RS can independently be selected from hydrogen, lower (Ci-Ce) alkyl, lower (Ca-Ce) alkenyl, lower (C2-C6) alkynyl, lower (Cs-Cg) cycloalkyl, aryl, acyl, heterocyclyl, heteroaryl, lower (C|-C/i) heterocyclylalkyl, and lower (Ci-C/O heteroarylalkyl; or R4 and RS may together form a five-membered acetal wherein the carbon linking the two oxygens is substituted with RL and Rm (wherein RL and Rm are the same as defined earlier) with the proviso that when RS is ORe then the acetal must be isopropylidene acetal.
i'j
The following definitions apply to terms as used herein.
The term "alkyl" unless otherwise specified, refers to a monoradical branched or unbranched
saturated hydrocarbon chain having from 1 to 20 carbon atoms. This term is exemplified by groups
such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-hexyl, n-decyl, tetradecyl,
and the like.
Alkyl may further be substituted with one or more substituents selected from alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyand, halogen, hydroxy, oxo, thiocarbonyl, carboxy, -COORe (wherein Rg is the same as defined earlier), arylthio, thiol, alkylthio, aryloxy, aminosulfonyl, -NRjC(=O)Ru, -NR,RX, -C(=O)NRaRb, -NHC(=O)NRXR,, -N(OH)C(=O)NRxRt, -C(=0)heteroaryl, C(=O)heterocyclyl, -OC(=O)NRXR, (wherein Rj, Ra, Rb, RU, Rx and Rt are the same as defined earlier), nitro, -S(O)mR7 (wherein m is an integer from 0-2 and Ry is the same as defined earlier). Unless otherwise constrained by the definition, all substituents may be further substituted by 1-3 substituents chosen from alkyl, carboxy. -COOR6 (wherein R6 is the same as defined earlier), -NRtRx, -C(=O)NRaRb, -OC(=O)NRXR,, -N(OH)C(=O)NRXR,, -NHC(=O)NRxRt (wherein Ra, Rb Rx and R, are the same as defined earlier)! hydroxy, alkoxy, halogen, CFa, cyano, and -S(O)mR7 (where Ry and m are the same as defined

earlier); or an alkyl group as defined above may also be interrupted by 1-5 atoms of group.; independently chosen from oxygen, sulfur and -NRf, where Rt- is chosen from hydrogen, alkyi, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, acyl, aralkyl, -C(=O)OR6 (wherein R6 is the same as defined earlier), -S(O)2R? (where R7 is same as defined earlier), -C(=O)NRaRb (wherein Ra, Rb, R; and Rt are as defined earlier).
The term "alkenyl," unless otherwise specified, refers to a monoradical of a branched or unbranched unsaturated hydrocarbon group preferably having from 2 to 20 carbon atoms with cis or traj s geometry. In the event that alkenyl is attached to the heteroatom, the double bond cannot be alpha to the heteroatom. Alkenyl groups may further be substituted with one or more substituents selected from alkyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, -NRjC(=O)Ru, -NRXR,, -C(=O)NRaRb, -N(OH)C(=O)NRxRt, -NHC(=O)NRXR,, -OC(=O)NRxRt (wherein Rj, Rh, RllvRb, Rx and Rt are the same as defined earlier), alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo, thiocarbonyl, carboxy, -COORg (wherein R6 is the same as defined earlier), arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalky', aminosulfonyl, alkoxyamino, nitro, and S(O)mR7 (wherein Ry and m are the same as defined earlier) Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1 -3 substituents chosen from alkyl, carboxy, -COORe (wherein Re is the same as defined earlier), hydroxy, alkoxy, halogen, -CF3, cyano, -NRxRt, -C(=O)NRaRb, -OC(=O)NRxRt (wherein Rx, Ra, K;, and Ry are the same as defined earlier) and -S(O)mR7 (where Ry and m are the same as defined earlier).
The term "alkynyl" unless otherwise specified, refers to a monoradical of an unsaturated hydrocarbon, preferably having from 2 to 20 carbon atoms. In the event that alkynyl is attached to the heteroatom, the triple bond cannot be alpha to the heteroatom. Alkynyl groups may further be substituted with one or more substituents selected from alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxo. thiocarbonyl, carboxy, -COORg (wherein R(, is the same as defined earlier), arylthio, thiol, alkylthio, aryl, aralkyl, aryloxy, aminosulfonyl, nitro, heterocyclyl, heteroaryl, heterocyclylalkyf, heteroarylalkyl, -NRjC(=O)Ru, -NRtRx, -C(=O)NRaRh, -N(OH)C(=O)NRxRt, -NHC(=O)NRxRt, -OC(=O)NRxRt (wherein Rj, Ra, Rb, Ru, Rx and Rt are the same as defined earlier). Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents chosen from alkyl, carboxy, -COORe (wherein R& is the same as defined earlier), hydroxy, alkoxy, halogen, -CF3, -NR,RX, -C(=O)NRaRb, -N(OH)C(=O)NRXR,, -NHC(=O)NRXR, (wherein Ra, Rb, Rx and Rt are the same as defined earlier), cyano, and -S(O)mR7 (where Ry and m are the same as defined earlier).

•:.
The term "cycloalkyl," refers to cyclic alkyl groups of from 3 to 20 carbon atoms having a single cyclic ring or multiple condensed rings, which may optionally contain one or more olefmic bonds, unless otherwise constrained by the definition. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclooctyl, cyclopentenyl, and the like, or multiple ring structures such as adamantanyl, and bicyclo [2.2.1] heptane, or cyclic alkyl groups to which is fused an aryl group, for example indane, and the like. Cycloalkyl groups may further be substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, alkoxycarbonylamino, azido, cyano, halogen, hydroxy, oxq, .thiocarbonyl, carboxy, -COORe (wherein Re is the same as defined earlier), arylthio, thiol, alkylthk . aryl, aralkyl, aryloxy, aminosulfonyl, -NRjC(=O)Ru, -NRtRx, -C(=O)NRaRb, -N(OH)C(O)NRXR,. -NHC(-O)NRxRt, -OC(=O)NRxRt (wherein R,, Ra, Rb, Ru, Rx and Rt are the same as defined earlier), nitro, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, and -S(O)mR7 (wherein R? and m are the same as defined earlier). Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents chosen from alkyl, carboxy, -COORe (wherein Re is the same as defined earlier), hydroxy, alkoxy, halogen, -CF3, -NRtRx, -C(=O)NRaRt,, -N(OH)C(=O)NRxRt, -NHC(=O)NRXR,, -C(=O)NRxRy, -NHC(=0)NRxRt, -OC(=O)NRxRy (wherein Ra, RI,, R,x, Rt and Ry are the same as defined earlier), cyano, and -S(O)mR7 (where R? and m are the same as defined earlier).
The term "alkoxy" denotes the group O-alkyl wherein alkyl is the same as defined above.
The term "aralkyl" refers to alkyl-aryl linked through alkyl (wherein alkyl is the same as defined above) portion and the said alkyl portion contains carbon atoms from 1-6 and aryl is as defined below. Examples of aralkyl groups include benzyl, phnylethyl, phenylpropyl and the like.
The term "aryl" herein refers to a carbocyclic aromatic group, for example phenyl, biphenyl or naphthyl ring and the like optionally substituted with 1 to 3 substituents selected from -(CH2)wC(=O)Rg (wherein w is an integer from 1-4 and Rg is hydroxy), -ORZ (wherein Rz is hydrogen, alkyl, aralkyl, heteroarylalkyl), nitro, -NRXR,, -NHORZ or -NHOH, halogen (F, Cl, Br, I), hydroxy. alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, acyl, aryloxy, cyano, nitro, -NRjC(=O)Ru, -NRxRh -C(=O)NRaRb, -N(OH)C(=O)NRxRt, -NHC(=O)NRxRt, -S(O)mR7 (wherein R7, Rx, Rt, Ru, Rz and R, and m are the same as defined earlier), carboxy, -COORe (wherein R& is the same as defined earlier), heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl. The aryl group may optionally be fused with cycloalkyl group wherein the cycloalkyl group may optionally contain heteroatoms selected from the group consisting of O, N, S.
The term "aryloxy" denotes the group O-aryl wherein aryl is the same as defined above. The term "carboxy" as defined herein refers to -C(=O)OH.

The term "heteroaryl," unless otherwise specified, refers to an aromatic ring structure containing 5 or 6 atoms, or a bicyclic aromatic group having 8 to 10 atoms, with one or more heteroatom(s ;> independently selected from N, O and S optionally substituted with 1 to 3 substituent(s) selected from halogen (F, Cl, Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, carboxy, -COOR.6 (wherein Rg is the same as defined earlier), aryl, alkoxy, aralkyl, cyano, nitro, -NRxRt, -(CH2)wC(=O)Rg (wherein w is an integer from 1-4 and Rg is hydroxy, -ORZ, NRxRt, -NHORZ or -NHOH), -C(=O)NRaRb, -N(OH)C(=O)NRxRt and -NHC(=O)NRxRt, -SO2R7, and -OC(=O)NRxli (wherein R?, Rz, Rt, Rx, Ra and Rb are the same as defined earlier). Unless otherwise constrained by the definition, the substituents are attached to the ring atom, be it carbon or heteroatom. Examples of heteroaryl groups can include pyridinyl, pyridazinyl, pyrimidinyl, pyrrolyl, oxazolyl, thiazolyl, thienyl, pyrazinyl, isoxazolyl, triazinyl, furanyl, benzofuranyl, indolyl, benzothiazolyl, benzoxazolyl, and the like.
The term 'heterocyclyl," unless otherwise specified, refers to a non-aromatic monocyclic or bicyclic cycloalkyl group having 5 to 10 atoms in which 1 to 3 carbon atoms in the ring are replaced by heteroatoms selected from O, S or N, and are optionally benzofused or fused heteroaryl of 5-6 riri<;, members and/or are optionally substituted wherein the substituents are selected from halogen (F,'t-]j Br, I), hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, acyl, aryl, alkoxy, alkaryl, cyano, nitro, oxo, carboxy, -COORe (wherein R6 is the same as defined earlier), -C(=O)NRaRb, -SOaR?, -OC(=0)NRXR,, -N(OH)C(=O)NRxRt, -NHC(=O)NRxRt, and -NRXR, (wherein Ra, Rb, R7, Rx and R, are the same as defined earlier). Unless otherwise constrained by the definition, the substituents are attached to the ring atom, be it carbon or heteroatom. Also unless otherwise constrained by the definition, the heterocyclyl ring may optionally contain one or more olefinic bond(s). Examples of Heterocyclyl groups can include tetrahydro furanyl, dihydrofuranyl, dihydropyridinyl, dihydrobenzofuryl, azabicyclohexyl, dihydroindolyl, piperidinyl or piperazinyl.
"Heteroarylalkyl" refers to alkyl-heteroaryl group linked through alkyl portion, wherein the alkyl and heteroaryl are the same as defined earlier.
t '•
"Heterocyclylalkyl" refers to alkyl-heterocyclyl group linked through alkyl portion, wherein
the alkyl and heterocyclyl are the same as defined earlier. ,
"Acyl" refers to -C(=O)R" wherein R" is selected from the group alkyl, cycloalkyl, aryl, araLkyl. heteroaryl, heterocyclyl, heteroarylalkyl or heterocyclylalkyl.
"Substituted amino" unless otherwise specified, refers to -N(Rk)2 wherein each Rk is independently selected from hydrogen (provided that both Rk groups are not hydrogen, defined as
-" i : " i . •
"amino"), alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl, acyl, -S(O)mR7 (wherein m and R7 is the same as defined above).

-C(=RV)NRXR, or -NHC(=Rv)NRtRx (wherein Rv is O or S and Rt and Rx are the same as defined earlier). Unless otherwise constrained by the definition, all substituents may optionally be further substituted by 1-3 substituents chosen from alkyl, aralkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, carboxy, -COORe (wherein Re is the same as defined earlier), hydroxy, alkoxy, halogen, -CFj, cyano, -C(=Rv)NRxRt, -O(OO)NRxRt (wherein Rx, Rt and Rv are the same as defined earlier). -OC(=Rv)NRxRt, and -S(O)mR7, (where Ry is the same as defined above and m is 0, 1 or 2).
The term "leaving group" generally refers to groups that exhibit the properties of being labile under
the defined synthetic conditions and also, of being easily separated from synthetic products under
defined conditions. Examples of such leaving groups include, but are not limited to, halogen (F, Ql,
Br, I), triflates, tosylate, mesylates, alkoxy, thioalkoxy, hydroxy radicals and the like. ":
The term "activated derivative of a carboxylic acid," can include, for example, protected ami no acids, aliphatic acids or aromatic acids converted to their corresponding acyl halides (e.g., acid fluoride, acid chloride and acid bromide), corresponding activated esters (e.g., nitro phenyl ester, the ester of 1 -hydroxybenzotriazole or the ester of hydroxysuccinimide, HOSu) or mixed anhydrides, for example, anhydride with ethyl chloroformate and other derivatives within the skill of the art.
The term "protecting groups" is used herein to refer to moieties which have the property of preventing specific chemical reaction at a site on the molecule undergoing chemical modification intended to be left unaffected by the particular chemical modification. Also the term protecting group, unless otherwise specified, may be used with groups such as hydroxy, amino and carboxy. Examples of such groups are found in T.W. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis", 2nd Ed., John Wiley and Sons, New York, N.Y. The species of the carboxylic protecting groups, amino protecting groups or hydroxy protecting group employed are not critical, so long as the derivatised moieties/moiety is/are stable to conditions of subsequent reactions and can be removed without disrupting the remainder of the molecule.
"Amino acid" refers to both natural and unnatural amino acids. The term "natural amino acid," as used hereind, is intended to represent the twenty two naturally-occurring amino acids glycine, alanine, valine, leucine, isoleucine, serine, methionine, threonine, phenylalanine, tyrosine, tryptophan, cysteine, proline, histidine, aspartic acid, asparagine, glutamic acid, glutamine, y-carboxyglutamic acid, arginine, ornithine and lysine in their L form. The term "unnatural amino acid," as used herein, is intended to represent the 'D' form of the twenty two naturally-occurring amino acids described above. It is further understood that the term unnatural amino acid includes homologues of natural amino acids, and synthetically modified form of the natural amino acids commonly utilized by those in the peptide chemistry art when preparing synthetic analogues of naturally occurring peptides, including D and L forms. The synthetically modified forms include

. . araino acids having alkylene chains shortened or lengthened by up to two carbon atoms, amino acids
comprising optionally substituted aryl groups, and amino acids comprised halogenated groups preferably halogenated alkyl and aryl groups. The term "unnatural amino acids" as used herein is also intended to represent beta amino acids.
The term "peptide" refers to a molecule comprising amino acids linked through amide linkages. Dipeptide comprises of two amino acids, tripeptide refers to a peptide having three amino acids and tetrapeptide refers to one having four amino acids, wherein the term amino acid is as defined earh'et. "LDVP" refers to a tetrapeptide leucyl-aspartyl-valyl-prolyl. "DVP" refers to a tripeptide aspartyl-valyl-prolyl. "VP" refers to a dipeptide valyl-prolyl.
Compounds disclosed herein contain one or more asymmetric carbon atoms and thus can exist as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. All such isomeric forms of these compounds are expressly included herein. Each stereogenic carbon may be of the R or S configuration. Although the specific compounds exemplified in this application may be depicted in a particular stereochemical configuration, compounds having either the opposite stereochemistry at any given chiral center or mixtures thereof are envisioned. Although amino acids and amino acid side chains may be depicted in a particular configuration, both natural and unnatural forms are envisioned.
Detailed Description of the Invention
Compounds disclosed herein may be prepared by techniques well known in the art and familiar to, a-,
practitioner of ordinary skill in art. In addition, compounds disclosed herein may be prepared by the
processes described herein, these processes are not the only means by which the compounds '.•'•
described may be synthesised. Further, synthetic steps described herein may be performed in an • alternate sequence or order to give the desired compounds.

Compounds of Formula X can be prepared by Scheme I. Thus, a compound of Formula II (wherein RI , R2, R4 and RS are the same as defined earlier) can be reacted with a compound of Formula Ila [wherein L is a leaving group such as tosyl, triflyl or mesyl and hal is a halogen (Cl, Br, I)] to give a compound of Formula III, which can be reacted with sodium azide to form a compound of Formula IV, which can undergo reduction to form a compound of Formula V, which can be reacted with a compound of Formula VI (wherein Ru is the same as defined earlier) or with a compound of Formula XVIII (wherein X is oxygen or sulphur and Rx is the same as defined earlier) to furnish a compound of Formula VII (wherein W is -(CH2)n or -NH and where fl is an integer from 1-3), which can be hydrolyzed to give a compound of Formula VIII, which can be reacted with a compound of Formula IX (wherein f is an integer from 0-2) to give a compound of Formula X.
The reaction of a compound of Formula II with a compound of Formula Ila to form a compound of Formula III can be carried out in the presence of an organic base, such as pyridine, trimethylamine. triethylamine, diisopropylethylamine or 2,6-lutidine.
Alternatively, the hydroxyl group in a compound of Formula II can also be converted to a triflyl
group with triflic anhydride.

The reaction of a compound of Formula III with sodium azide to give a compound of Formula IV can be carried out in an organic solvent such as dimethylformamide, dimethylsulphoxide, N-methylmorpholine, tetrahydrofuran, acetonitrile, dioxane or diethyl ether.
Alternatively, one may also use trimethylsilyl azide or lithium azide in place of sodium azide in the presence of catalytic amount of ammonium chloride.
The reduction of a compound of Formula IV to yield a compound of Formula V can be carried out in an organic solvent such as tetrahydrofuran, dimethylformamide, diethylether or dioxane, with, ?• reducing agent such as lithium aluminium hydride or sodium borohydride.
A compound of Formula V can be reacted with a compound of Formula VI to give a compound of
Formula VII in the presence of coupling agents such as l-(3-dimethylaminopropyl)-3-ethyl-
carbodimide, N, N'- dicyclohexylcarbodiimide, 2-(l-H-benzotriazol-l-yl)-l,l,3,3
tetramethyluronium hexafluorophosphate (HBTU), O-(7-azabenzotriazol-l-yl)-N,N,N',N'-
tetramethyluronium hexafluorophosphate(HATU), (benzotriazol-1 -yloxy)tris-
(dimethylamino)phosphonium hexafluorophosphate (BOP), propane phosphonic acid anhydrid0 (T3P), O-(benzotriazol-l-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), S-(l-oxido-2-pyridinyl)-l,l,3,3-tetramethylthiouronium tetrafluoroborate (TOTT), N,N,N',N'-tetramethyl-0-(3,4-dihydro-4-oxo-l,2,3-benzotriazin-3-yl)uronium tetrafluoroborate (TDBTU), O-(l,2-dihydro-2-oxo-pyridyl]-N,N,N',N'-tetramethyluronium tetrafluoroborate (TPTU), O-((ethoxycarbonyl) cyanomethylenamino)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU), chlortripyrrolidino phosphoniumhexafluorophosphate (PyClop), benzotriazol-1 -yl-oxy-tris-pyrrolidino-phosphoniurii hexafluorophosphate (PyBOP), chlorodipyrrolidinocarbenium hexafluorophosphate (PyClU), benzotriazol-1-yloxy)dipiperidinocarbenium hexafluorophosphate (HBPipU) or mixtures thereof in the presence of one or more of additives or activating agents such as 1-hydroxybenzotriazole, acetone oxime, 2-hydroxypyridine, N-hydroxysuccinimide, pentafluorophenol or mixtures thereof and in the presence of one or more of organic bases, for example, N-methylmorpholine, • N-methylmorpholine oxide, N-ethylmorpholine, 1-methylpiperidine, triethylamine, tribenzylamirie, piperidine, N-ethyldiisopropylamine, 2,6-lutidine or mixtures thereof, polar aprotic solvents such ^s dimethylformamide or dimethylsulphoxide, ethers, for example, tetrahydrofuran, dioxane or diethyl ether, halogenated solvents, for example, dichloromethane, dichloroethane, carbon tetrachloride or chloroform or mixtures thereof.
The reaction of a compound of Formula V with XVIII to give a compound of Formula VII can be carried out in an organic solvent such as acetonitrile, dichloromethane, dichloroethane, chloroform or carbon tetrachloride.

Alternatively, a compound of Formula VII can also be prepared by reacting a compound of Formuia V with an appropriate amine in the presence of reagents such as carbonyldiimidazole (GDI) or wvn earbamates such as phenyl carbamate or p-nitrophenyl carbamate of an amine. Also, optionally thiocarbonyldiimidazole or an isothiocyanate can be used in place of carbonyldiimidazole' or isocyanate, respectively in the reaction.
The hydrolysis of a compound of Formula VII to give a compound of Formula VIII can be carried out with the reagents, for example aqueous perchloric acid, aqueous acetic acid, aqueous sulphuric-acid or Dowex 50W-8X (commercially available) in an organic solvent such as methanol, ethanol, tetrahydrofuran, dimethylformamide, dioxane or diethyl ether.
The reaction of a compound of Formula VIII with a compound of Formula IX to give a compound of Formula X can be carried out in an organic solvent , for example toluene, dioxane, xylene or acetonitrile and molecular sieves in the presence of catalytic amount of the acid , for example para-toluenesulphonic acid or camphorsulphonic acid.
Particular compounds are described below: ; ' *,
1, 2-O-isopropylidene-3-deoxy-3-[(3-bromobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D- , ' glucofuranoside (Compound No. 1)
1, 2-O-isopropylidene-3-deoxy-3-[(3-chlorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 2)
1, 2-O-isopropylidene-3-deoxy-3-[(2,4-difluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 3)
1, 2-O-isopropylidene-3-deoxy-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 4)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 5)
1, 2-O-isopropylidene-3-deoxy-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 6)
1, 2-O-isopropylidene-3-deoxy-3-[(2,5-dimethylbenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 7)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-propionamido)-a-D-glucofuranoside (Compound No. 31)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-propionamido]-a-D-glucofuranoside
(Compound No. 32) >
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-propionamido]-a-D-glucofuranoside (Compound No. 33)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-glucofuranoside (Compound No 37)
1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-a-D-glucofuranoside (Compound No. 38)
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-a-D-glucofuranoside (Compound No. 39)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-a-D-glucofuranoside (Compound No. 40)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-a-D-glucofuranoside
(Compound No. 41)
;'

1 ,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-a-D-glucofuranoside
(Compound No. 42)
1 ,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-glucofuranoside
(Compound No. 43)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-a-D-glucofuranoside
(Compound No. 44)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-a-D-glucofuranoside (Compound No.
45)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-glucofuranoside (Compound No.
46)
1 , 2-0-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-a-D-glucofuranoside
(Compound No. 47)
1 . 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 48)
1 , 2-0-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 49)
1, 2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-dioxaspiro[4,5]decane-a-D-
glucofuranoside (Compound No. 50)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 51)
1 , 2-0-isopropylidene-3-deoxy-3-(octyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-glucofuranoside
(Compound No. 52)
1 , 2-0-isopropylidene-3-deoxy-3-(phenyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-glucofuranoside
(Compound No. 53)
1, 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 54)
1, 2-0-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-5,6-dioxaspiro[4,5]decane-a-D-
glucofuranoside (Compound No. 55)
1, 2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 56)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 57)
1, 2-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-5,6-dioxaspiro[4,5]decane-'
a-D-glucofuranoside (Compound No. 58)
1, 2-0-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 59)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-phenyl)propionamido]-a-D-glucofuranoside (Compound
No. 103)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[3-(l,3-benzodioxol-5-yl)propionamido]-a-D-
glucofuranoside (Compound No. 104)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-glucofuranoside (Compound No. 107)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-bromophenyl)-acetamido]- a-D-glucofuranoside
(Compound No. 108)
1.2-O-isopropylidene-3-deoxy-3-[(3-bromophenyl)-amido]-a-D-glucofuranoside (Compound No.
and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, metabolites.


Compounds of Formula X can also be prepared by Scheme II. Thus, a compound of Formula II (wherein RI, RI, R4 and RS are the same as defined earlier) can be oxidized to form a compound of Formula XI, which can be reacted with hydroxylamine hydrochloride to form a compound of Formula XII, which can undergo reduction to form a compound of Formula V, which can be reacted with a compound of Formula VI (Ru is the same as defined earlier) or with a compound of Formula XVIII (wherein X and Rx are the same as defined earlier) to furnish a compound of Formula VII (wherein W is the same as defined earlier), which can be hydrolyzed to give a compound of Formula VIII, which can be reacted with a compound of Formula IX (wherein f is an integer from 0-2) to give a compound of Formula X.
The oxidation of a compound of Formula II to form a compound of Formula XI can be carried out under various conditions. For example, one may use Swern's oxidation utilizing dimethyl sulphoxide and acetic anhydride or oxalyl chloride, optionally in either dimethyl sulphoxide or dichloromethane as solvents. One may also utilize oxidizing agents such as pyridinium chlorochromate, pyridinium

dichromate, pyridine-sulfurtrioxide or periodinane in an organic solvent such as dichloromethane o1 chloroform.
Thus, the oxidation of a compound of Formula II can be carried out utilizing dimethyl sulphoxide
and acetic anhydride to furnish a compound of Formula XI. ,
The reaction of a compound of Formula XI with hydroxylamine hydrochloride to form a compound pf Formula XII can be carried out in an organic solvent such as ethanol, methanol, propanol or isopropyl alcohol, in the presence of an organic base such as pyridine, triethylamine or diisopropylethylamine.
The reduction of a compound of Formula XII to yield a compound of Formula V can be carried out' in an organic solvent such as tetrahydrofuran, dimethylformamide, diethylether or dioxane, with a reducing agent such as lithium aluminium hydride or sodium borohydride.
A compound of Formula V can be reacted with a compound of Formula VI to give a compound of Formula VII in the presence of coupling agents such as l-(3-dimethylaminopropyl)-3-ethyl-carbodimide, N,N'-dicyclohexylcarbodiimide, 2-( 1 -H-benzotriazol-1 -yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), 0-(7-azabenzotriazol-1 -yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), (benzotriazol-l-yloxy)tris-(dimethylamino)phosphoniuni hexafluorophosphate (BOP), propane phosphonic acid anhydride (T3P), O-(benzotriazol-l-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), S-(l-oxido-2-pyridinyl)-l, 1,3,3-tetramethylthiouronium tetrafluoroborate (TOTT), N,N,N',N'-tetramethyl-O-(3,4-dihydro-4-oxo-l,2,3-benzotriazin-3-yl)uronium tetrafluoroborate (TDBTU), O-(l,2-dihydro-2-oxo-pyridyl]-N,N,N',N'-tetramethyluronium tetrafluoroborate (TPTU), O-((ethoxycarbonyl) cyanomethylenamino)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU), chlortripyrrolidino phosphoniumhexafluorophosphate (PyClop), benzotriazol-1 -yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), chlorodipyrrolidinocarbenium hexafluorophosphate (PyClU), benzotriazol-1-yloxy)dipiperidinocarbenium hexafluorophosphate (HBPipU) or mixtures thereof in the presence of one or more of additives or activating agents such as 1 -hydroxybenzotriazole, acetone oxime, 2-hydroxypyridine, N-hydroxysuccinimide, pentafluorophenol or mixtures thereof • and in the presence of one or more of organic bases, for example, N-methylmorpholine, N-methylmorpholine oxide, N-ethylmorpholine, 1-methylpiperidine, triethylamine, tribenzylamine, piperidine, N-ethyldiisopropylamine, 2,6-lutidine or mixtures thereof, polar aprotic solvents such as dimethylformamide or dimethylsulphoxide, ethers, for example, tetrahydrofuran, dioxane or diethyl ether, halogenated solvents, for example, dichloromethane, dichloroethane, carbon tetrachloride or chloroform or mixtures thereof.

The reaction of a compound of Formula V with XVIII to give a compound of Formula VII can be carried out in an organic solvent such as acetonitrile, dichloromemane, dichloroethane, chloroform or carbon tetrachloride.
Alternatively, a compound of Formula VII can also be prepared by reacting a compound of Formula V with an appropriate amine in the presence of reagents such as carbonyldiimidazole (GDI) or with carbamates such as phenyl carbamate or p-nitrophenyl carbamate of an amine. Also, optionally thiocarbonyldiimidazole or an isothiocyanate can be used in place of carbonyldiimidazole or isocyanate, respectively in the reaction.
The hydrolysis of a compound of Formula VII to give a compound of Formula VIII can be carried out with the reagents, for example aqueous perchloric acid, aqueous acetic acid, aqueous sulphuric acid or Dowex 50W-8X (commercially available) in an organic solvent such as methanol, ethanol. tetrahydrofuran, dimethylformamide, dioxane or diethyl ether.
The reaction of a compound of Formula VIII with a compound of Formula IX to give a compound oi Formula X can be carried out in an organic solvent, for example toluene, dioxane, xylene or acetonitrile and molecular sieves in the presence of catalytic amount of the acid , for example para-toluenesulphonic acid or camphorsulphonic acid.
Particular illustrative compounds prepared following Scheme II include:
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-ot-D-a'llofuranoside (Compound No. 8)
1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 9)
1, 2-O-isopropylidene-3-deoxy-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 10)
1, 2-O-isopropylidene-3-deoxy-3-[(3-bromobenzyl)-amido]-5,6-dioxaspiro[4,4]nonane-a-D-allofuranoside (Compound No. 11)
1, 2-O-isopropylidene-3-deoxy-3-[(3-chlorobenzyl)-amido]-5,6-dioxaspiro[4,4]nonane-a-D-allofuranoside (Compound No. 12)
1, 2-O-isopropylidene-3-deoxy-3-[(2,5-dimethylbenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 13)
1, 2-O-isopropylidene-3-deoxy-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 14)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-propionamido)-a-D-allofuranoside (Compound No.
34)
t"
i,2;5,6-Di-0-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-propionamido]-a-D-allofuranoside
(Compound No. 35)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-propionamido]-a-D-allofuranoside (Compound No. 36)

1 , 2-O-isopropylidene-3-deoxy-3-[4-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. 60)
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. 61)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-a-D-allofuranoside
(Compound No. 62)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-allofuranoside (Compound No. 63)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-a-D-allofuranoside (Compound
No. 64)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[4-cyanophenyl)-urido]-a-D-allofuranoside (Compound No.
65)
1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-a-D-allofuranoside (Compound
No. 66)
1; 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-allofuranoside (Compound No. 67)
1, 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-a-D-allofuranoside (Compound No.
68)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-a-D-allofuranoside (Compound No. 69)
1, 2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-a-D-allofuranoside (Compound
No. 70)
1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound No.
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound No.
72)
1, 2-0-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 73)
1 , 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-thiourido]-a-D-allofuranoside (Compound
No. 74)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-thiourido)-a-D-allofuranoside (Compound No. 75)
1 , 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 76)
1 , 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-a-D-allofuranoside (Compound Nc> •
77)
1 , 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
dllofuranoside (Compound No. 78)
1, 2-0-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 79)
1 , 2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-
a-D-allofuranoside (Compound No. 80)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-thiourido)-5,6-dioxaspiro[4,5]decane-a-D-allofuranoside
(Compound No. 81)
1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-
a-D-allofuranoside (Compound No. 82)
1 , 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 83)
1, 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 84)
1.2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside (Compound
No. 85)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. 86)
1, 2-O-isopropylidene-3-deoxy-3-[(3-cyanophenyl)-urido]-a-D-allofuranoside (Compound No. 87)
l.,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-allofuranoside
(Compound No. 88)

l,2;5,6-Di-0-isopropylidene-3-deoxy-3-[3-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 89)
1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-5,6-dioxaspiro[4,5]decane-a-D-
allofuranoside (Compound No. 90)
1, 2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-dioxa spiro[4,5]decane- -D-
allofuranoside (Compound No. 91)
1, 2-0-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 92)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound No.
93)
1, 2-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 94)
1, 2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-thiourido]-a-D-allofuranoside (Compound
No. 95)
1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 96)
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 97)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 98)
1, 2-O-isopropylidene-3-deoxy-3-[(3-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 99) ; ''
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside
(Compound No. 100) •
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-urido]-a-D-allofuranoside (Compound
No. 101)
1, 2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-urido]-a-D-allofuranoside (Compound No.
102)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-phenyl)propionamido]-a-D-allofuranoside (Compound
No. 105)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[3-(l,3-benzodioxol-5-yl)propionamido]-a-D-allofuranosidc
(Compound No. 106)
l,2;5.6-Di-0-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-a-D-allofuranoside (Compound
No. 110)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside (Compound
No. Ill)
l,2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-amido]-a-D-allofuranoside (CompoundNo. 112)
and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, metabolites.

The compounds of Formula XVIIIa and XIX can be prepared by following the procedure as described in Scheme III. Thus the compound of Formula XIII (wherein RI and RI are the same as defined earlier) undergoes cyclization with a compound of Formula Xllla to give a compound of Formula XIV, which can be oxidized to give a compound of Fomrula XV, which can be reacted with hydroxyl amine hydrochloride to give a compound of Formula XVI, which can be reduced to give a compound of Formula XVII, which can be reacted with a compound of Formula XVI to give a compound of Formula XVIIIa. The compound of Formula XVII can be reacted with a compound of Formula XVIII (wherein X is oxygen or sulphur and Rx is the same as defined earlier) to give a compound of Formula XIX.
The cyclization of a compound of Formula XIII with a compound of Formula Xllla to give a compound of Formula XIV can be carried out in an organic solvent such as xylene, toluene or acetonitrile in the presenc of an acid such as, para-toluenesulphonic acid, camphor sulphonic acid or fomic acid.
Oxidation of a compound of Formula XIV to give a compound of Formula XV can be carried out under various conditions. For example, one may use Swern's oxidation utilizing dimethyl sulphoxide and acetic anhydride or oxalyl chloride, optionally in either dimethyl sulphoxide or dichloromethane as solvents. One may also utilize oxidizing agents such as pyridinium chlorochromate, pyridinium "

dichromate, pyridine-sulfurtrioxide or Des-Martin periodinane in an organic solvent such as dichloromethane, carbon tetrachloride, chloroform or dicloroethane.
Thus, the oxidation of a compound of Formula XIV can be carried out utilizing dimethyl sulphoxide and acetic anhydride to furnish a compound of Formula XV.
The reaction of a compound of Formula XV with hydroxylamine hydrochloride to form a compound of Formula XVI can be carried out in an organic solvent such as ethanol, methanol, propanol or isopropyl alcohol, in the presence of an organic base such as pyridine, trimethylamine, triethylamine, diisopropylethylamine or 2,6-lutidine.
Alternatively inorganic bases may be used in place of organic bases such as, potassium carbonate, sodium carbonate or sodium bicarbonate in an organic solvent such as methanol, ethanol, propanol or isopropylalcohol or mixture thereof.
The reduction of a compound of Formula XVI to yield a compound of Formula XVII can be carried out in an organic solvent such as tetrahydrofuran, dimethylformamide, diethylether or dioxane, with a reducing agent such as lithium aluminium hydride or sodium borohydride.
A compound of Formula XVII can be reacted with a compound of Formula VI to give a compound of Formula XVIIIa in the presence of coupling agents such as l-(3-dimethylaminopropyl)-3-ethyl-carbodimide,N,N'-dicyclohexylcarbodiimide, 2-(l-H-benzotriazol-l-yl)-l,l,3,3-tetramethyluroniujn hexafluorophosphate (HBTU), 0-(7-azabenzotriazol-1 -yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), (benzotriazol-l-yloxy)tris-(dimethylamino)phosphonium hexafluorophosphate (BOP), propane phosphonic acid anhydride (T3P), O-(benzotriazol-l-yl)-N,N,N^N'-tetramethyluronium tetrafluoroborate (TBTU), S-(l-oxido-2-pyridinyl)-l,1,3,3-tetramethylthiouronium tetrafluoroborate (TOTT), N,N,N',N'-tetramethyl-0-(3,4-dihydro-4-oxo-l,2,3-benzotriazin-3-yl)uronium tetrafluoroborate (TDBTU), O-(l,2-dihydro-2-oxo-pyridyl]-N,N,N',N'-tetramethyluroniurn tetrafluoroborate (TPTU), O-((ethoxycarbonyl) cyanomethylenamino)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU), chlortripyrrolidino phosphoniumhexafluorophosphate (PyClop), benzotriazol-1 -yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP), chlorodipyrrolidinocarbenium hexafluorophosphate (PyClU), benzotriazol- l-yloxy)dipiperidinocarbenium hexafluorophosphate (HBPipU) or mixtures thereof in the presence of one or more of additives or activating agents such as 1-hydroxybenzotriazole, acetone oxime, 2-hydroxypyridine, N-hydroxysuccinimide, pentafluorophenol or mixtures thereof •:• and in the presence of one or more of organic bases, for example, N-methylmorpholine, N-methylmorpholine oxide, N-ethylmorpholine, 1-methylpiperidine, triethylamine, tribenzylamine, piperidine, N-ethyldiisopropylamine, 2,6-lutidine or mixtures thereof, polar aprotic solvents such as dimethylformamide or dimethylsulphoxide, ethers, for example, tetrahydrofuran, dioxane or diethyl
ether, halogenated solvents, for example, dichloromethane, dichloroethane, carbon tetrachloride or chloroform or mixtures thereof.
The compound of Formula XVII can be rected with a compound of Formula XVIII to give a compound of Formula XIX in an organic solvent such as acetonitrile, dichloromethane, dichloroethane, chloroform or carbon tetrachloride.
Alternatively, a compound of Formula XIX can also be prepared by reacting a compound of Formula XVII with an appropriate amine in the presence of reagents such as carbonyldiimidazole (GDI) or with carbamates such as phenyl carbamate or p-nitrophenyl carbamate of an amine. Also, optionally thiocarbonyldiimidazole or an isothiocyanate can be used in place of carbonyldiimidazole or isocyanate, respectively in the reaction.
Particular compounds are disclosed below:
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorophenyl)-urido]-5,6-O-isopropylidene-a-D-
allofuranoside (Compound No. 15) ;
d$ 2-Dioxa spiro[2,5]octane-3-deoxy-3-(phenyl-urido)-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 16)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-O-isopropylidene a-D-allofuranoside (Compound No. 17)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 18)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 19)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorophenyl)-thiourido]-5,6-O-isopropylidene-a-D- . allofuranoside (Compound No. 20)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-(phenyl-thiourido)-5,6-O-isopropylidene-a-D-allofuranoside
(Compound No. 21) :
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-cyanophenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 22)
t, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 23)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-trifluoromethylphenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 24)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(3-chlorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 25)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(3-fluorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 26)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 27)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 28)

l,2-Dioxaspiro[2,5]octane-3-deoxy-3-[(2,5-dimethylbenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 29)
l,2-Dioxaspiro[2,5]octane-3-deoxy-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-O-isopropylidene-a-b-allofuranoside (Compound No. 30)
and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, esters, enantiomers, diastereomers, N-oxides, polymorphs, metabolites.
Also, in all the above representative examples wherever esters are specified, one skilled in the art could optionally hydrolyze them to their respective acids, for example hydrolysis of alkyl esters (such as ethyl, methyl or benzyl ester) to their corresponding acids can be carried out in the presence of a base, for example, lithium hydroxide, sodium hydroxide or potassium hydroxide. Alternative!}', hydrolysis of benzyl ester can be carried out hydrogenatically using catalysts, for example, palladium on carbon or platinum on carbon. Esters such as tert-butyl can be hydrolyzed to their corresponding acids in the presence of acid, for example, trifluoroacetic acid or hydrochloric acid.
In the above schemes, where specific bases, acids, solvents, condensing agents, hydrolyzing agents, etc., are mentioned, it is to be understood that other acids, bases, solvents, condensing agents, hydrolyzing agents, etc., may also be used. Similarly, the reaction temperature and duration of the reactions may be adjusted according to the requirements that arise during the process.
Examples set forth in general synthetic procedures for the preparation of representative compounds. The examples are provided to illustrate particular aspect of the disclosure and do not limit the scope of the present invention.
EXAMPLES -
General Synthesis:
Synthesis of l,2,5,6-Di-O-isopropylidene-3-deoxy-3-amino-q-D-gIucofuranoside
Step a: 1,2:5,6-Di-O-isopropvlidene-3-O-tolvl-a-D-allofuranoside
To a solution of the compound l,2;5,6-Di-O-isopropylidene-a-D-allofuranoside (20 g, 76.92 mmol) in dichloromethane (30 ml) was added pyridine (80 ml) and N, N-dimethylaminopyridine (0.200 g, 1.639 mmol) and stirred at 0 °C. To the resulting reaction mixture was added a solution ofpara-toluenesulphonyl chloride (29.33 g, 153.84 mmol) in dichloromethane (50 ml) dropwise at the same temperature under constant stirring. The reaction mixture was subsequently stirred at room temperature for 12 hours. The mixture was cooled to 0 °C followed by the addition of saturated solution of sodium bicarbonate till basic pH was attained. The solvent was evaporated under reduced pressure and the residue thus obtained was diluted with water under constant stirring. The solid thus

obtained was filtered, washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure to furnish the title compound. Yield: 23 g.
Step b: 1,2,5,6-Di-O-isopropvlidene-3-deoxy-3-azido-a-D-glucofuranoside
To a solution of the compound obtained from step a above (23 g, 55.55 mmol) in dry dimethylformamide (150 ml) was added sodium azide (18.058 g, 277.77 mmol) under an argon atmosphere. The reaction mixture was heated to 170 °C for 12-15 hours under an argon atmosphere. The solvent was evaporated under reduced pressure, diluted with water and extracted with ethyi acetate. The organic layer was separated, washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 5 % ethyl acetate in hexane as eluent to furnish the title compound.Yield: 18g.
Step c: l,2,5,6-Di-O-isopropvlidene-3-deoxy-3-amino-q-D-grucofuranoside
To a suspension of lithium aluminium hydride (6.91 g, 182.496 mmol) in dry distilled tetrahydrofuran (150 ml) and cooled to 0 °C was added the compound obtained from step b above (26 g, 91.228 mmol) dropwise under constant stirring at the same temperature. The reaction mixture •Was then stirred at room temperature for 3 hours. The reaction mixture was cooled to 0 °C followed by the addition of ethyl acetate and saturated solution of sodium sulphate dropwise. The reaction mixture was filtered through a celite pad, extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to furnish the title compound. Yield: 17.3 g.
Synthesis of l,2;5,6-Di-Q-isopropylidene-3-deoxy-3-amino-oc-D-alIofuranoside
Step a; l,2;5,6-Di-O-isopropylidene-3-oxo-a-D-glucofuranoside
To diacetoneglucose (25 g) (commercially available) was added dimethyl sulphoxide (100 ml) and
acetic anhydride (50 ml). The reaction mixture was stirred at 50-60 °C for 24 hours. Dimethyl
sulphoxide was evaporated under reduced pressure and water (2.5 ml) was added with vigorous
stirring followed by the addition of ether (10 ml) and hexane. The mixture was kept in refrigerator
for overnight. The solid thus separated was filtered to obtain the title compound (16 g). . ;
Step b: 1,2;5,6-Di-O-isopropvlidene-3-deoxy-3-hvdroxyimino-a-D-glucofuranoside
r
To a compound from step a above (12 g), was added hydroxylamine hydrochloride (2.5 g) pyridine (100 ml) and anhydrous ethanol (100 ml) at room temperature. The reaction mixture was stirred for half an hour. The temperature of the reaction was raised to 75 °C and the reaction mixture was stirred for 24 hours. The solvents were evaporated off under reduced pressure and the residue thus obtained was poured into ice cold water. The organic product was extracted with ethyl acetate followed by

washing with water, brine and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure and the product was purified by column chromatography using 25% ethyl acetate in hexane as eluent to furnish the title compound (8.5 g).
Step c: 1,2;5,6-Di-O-isopropvlidene-3-deoxv-3-amino-oc-D-allofuranoside
To a suspension of lithium aluminum hydride (8.4 g) in tetrahydrofuran (50 ml) at 0 °C, was added the compound obtained from step b above (8.5 g in 50 ml tetrahydrofuran) with constant stirring. After complete addition, the reaction mixture was allowed to attain room temperature and stirred for 8 hours The excess of lithium aluminum hydride was decomposed by the addition of ethyl acetate (100 ml) followed by the addition of water and sodium hydroxide solution (2 ml, 15 %) dropwise at 0 °C .The reaction mixture was filtered off, washed with warm ethyl acetate and dried over anhydrous sodiuhi sulphate. The solvent was evaporated under reduced pressure and the crude product thus obtained was purified by column chromatography using 50% methanol in ethyl acetate as eluent to furnish the title compound (7.0 g).
Scheme I:
Example 1: Synthesis of l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-propionamido)-a-D-glucofuranoside (Compound No. 31)
To a solution of the compound l,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-a-D-glucofuranoside (0.300 g, 1.158 mmol) in dry dimethylformamide (5 ml) was added N-methylmorpholine (0.351 g, > 3.474 mmol) and 3-phenylpropionic acid (0.208 g, 1.389 mmol). The mixture was stirred at room • temperature for 10 minutes. To the resulting reaction mixture was added 1-hydroxybenzotriazole c (0.313 g, 2.316 mmol) and stirred the mixture at room temperature for 1 hour. To it was added l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.444 g, 2.316 mmol) at 0 °C and stirred at the same temperature for 1 hour and subsequently at room temperature for 12 hours. The reaction mixture was poured into water, extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by preparative thin layer chromatography using 50 % ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.45 g.
(H NMR (CDC13 + D2O exchange, 400 MHz): 5 7.32-7.19 (m, 5H, Ar-H), 6.06 (brs, 1H, -NH & D2O exchangeable), 5.60-5.59 (d, 1H, J = 4.00 Hz, -CH), 4.35-4.33 (m, 2H, 2x-CH), 4.23-4.22 (m, 1H, -CH), 4.13-4.11 (m, 1H, -CH), 4.08-4.04 (m, 1H, -CH), 3.83-3.78 (m, 1H, -CH), 2.99-2.95 (t, 2H, J-8.00 Hz, -CH2Ar), 2.54-2.43 (m, 2H, -CH2CO), 1.49 (s, 3H, -CH3), 1.41 (s, 3H, -CH3), 1.33 (s, 3H,-! CH3) and 1.27 (s,3H,-CH3) Mass (m/z, +ve ion mode): 392 [M++l].
Following compounds were prepared similarity,
l,2;5,6-O-isopropvlidene-3-deoxy-3-[(2-methoxvphenyl)-propionamido]-a-D-glucofuranoside (Compound No. 32)
l,2;5,6-Di-O-isopropvlidene-3-deoxv-3-[(4-fluorophenyl)-propionamido]-q-D-glucofuranoside
.- i ' •
(Compound No. 33)
,1.2:5,6-Di-O-isopropvlidene-3-deoxv-3-[(2-phenyl)propionamido]-a-D-glucofuranoside (Compound No. 103)
l,2;5,6-Di-O-isopropylidene-3-deoxv-3-r3-(1.3-benzodioxol-5-yl)propionamido'|-q-D-glucofuranoside (Compound No. 104)
U2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-bromophenyl)-acetamido1- a-D-glucofuranoside (Compound No. 108)
l,2;5,6-Di-O-isopropylidene-3-deoxv-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. Ill)
Example 2; Synthesis of l,2;5,6-Di-O-isopropylidene-3-deoxy-3-f(2-trifluoromethylphenyl)-uridol-a-D-glucofuranoside (Compound No. 41)
To a solution of the compound l,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-a-D-glucofuranoside (0.500 g, 1.1930 mmol) in dichloromethane (5 ml) was added triethyl amine (0.645 ml, 4.633 mmol) . and 2-trifluoromemylphenyl isocyanate (0.433 g, 2.316 mmol) and stirred the reaction mixture at room temperature for 6-7 hours. The solvent was evaporated under reduced pressure and the residue thus obtained was treated with dichloromethane and water. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 20% ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.838 g.
'H NMR (CDCb+MeOD, 400 MHz): 5 7.95-7.93 (d 1H, J= 8.00 Hz, Ar-H), 7.53-7.51 (m, 2H, Ar-H), 7.59-7.51 (m, 2H, Ar-H), 7.20-7.09 (m, 1H, Ar-H), 5.87-5.86 (d, 1H, J = 4.00 Hz, -CH), 4.60-4.59 (m, 1H, J = 4.00 Hz, -CH), 4.43-4.41 (m, 1H, -CH), 4.26-4.23 (m, 1H, -CH), 4.12-4.08 (m, 1H, -CH), 4.01-3.98 (m, 1H, -CH), 1.59 (s, 3H, -CH3), 1.50 (s, 3H, -CH3) and 1.34-1.33 (m, 6H, 2x-
CH3).
Mass (m/z, +ve ion mode): 446 [M++l].
Following compounds were prepared similarity by using appropriate cyanate or isocyanate, as applicable in each case,
1.2:5,6-Di-O-isopropvlidene-3-deoxv-3-[(2-methoxvphenvl)-urido]-a-D-glucofuranoside (Compound No. 42)
l,2:5,6-Di-O-isopropylidene-3-deoxv-3-[(3-fluorophenvl)-thiourido1-a-D-glucofuranoside (Compound No. 43)
l,2;5,6-Di-O-isopropvlidene-3-deoxv-3-[(3-trifluoromethvlphenyl)-thiourido]-q-D-glucofuranoside (Compound No. 44)

l,2;5,6-Di-0-isopropvlidene-3-deoxy-3-(phenyl-urido)-a-D-glucofuranoside (CompoundNo. 107) l,2:5,6-Di-O-isopropylidene-3-deoxv-3-r(3-fluorophenvl)-urido]-a-D-allofuranoside (Compound No. 85)
l,2;5,6-Di-0-isopropvlidene-3-deoxy-3-r(3-fluorophenvl)-thiourido]-a-D-allofuranoside (Compound No. 88)
L2;5.6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenvl)-urido]-a-D-allofuranoside (Compound No. 110)
Example 3: Synthesis of 1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-glucQfuranoside (Compound No. 37)
To a solution of 1,2;5,6-Di-0-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-glucofuranoside
(Compound No. 107) (0.712 g, 1.883 mmol) in tetrahydrofuran (5 ml) was added aqueous perchloric
acid (60%, 0.5 M, 3.76 ml, 1.883 mmol) dropwise at 0 °C and stirred the reaction mixture at this '
temperature for 2 hours. The reaction mixture was quenched with saturated solution of sodium
bicarbonate and extracted with ethyl acetate. The organic layer was separated, washed with water
and brine, dried over anhydrous sodium sulphate and filtered. The filtrate was evaporated under
reduced pressure and the crude product thus obtained was purified by preparative TLC using 70%
ethyl acetate in hexane as eluent to furnish the title compound. Yield: (0.461 g).
'H NMR (MeOD, 400 MHz): 8 7.76-7.75 (m, 2H, Ar-H), 7.36-7.34 (m, 2H, Ar-H), 6.99-6.97 (m,
1H, Ar-H), 5.87-5.86 (d, 1H, J = 4.00 Hz, -CH), 4.58-4.57 (d, 1H, J = 4.00 Hz, -CH), 4.31-4.30 (d,
1H, 1H, J = 4.00 Hz, -CH), 4.16-4.13 (m, 1H, -CH), 3.78-3.72 (m, 2H, 2x-CH), 3.61-3.57 (m, 1H. -
£H), 1.48 (s, 3H,- CH3) and 1.31 (s, 3H,- CH3) •''
Mass (m/z, +ve ion mode): 339 [M++l]. Following compounds were prepared similarily,
1, 2-Q-isopropvlidene-3-deoxv-3-[(4-fluorophenyl)-urido]-a-D-glucofuranoside (Compound No. 38) I, 2-O-isopropvlidene-3-deoxv-3-[(2-fluorophenyl)-urido1-a-D-glucofuranoside (Compound No. 39) 1, 2-O-isopropvlidene-3-deoxv-3-[(4-cvanophenvl)-urido1-q-D-glucofuranoside (Compound No. 40) 1, 2-O-isopropvlidene-3-deoxy-3-[(4-cvanophenyl)-thiourido1-a-D-glucofuranoside (Compound No.
45}
1, 2-O-isopropvlidene-3-deoxv-3-[3-fluorophenyl)-thiourido1-a-D-glucofuranoside (Compound No.
46}
1, 2-Q-isopropvlidene-3-deoxv-3-[(3-trifluoromethvlphenyl)-thiourido]-a-D-glucofuranoside
(Compound No. 47)
1, 2-O-isopropvlidene-3-deoxv-3-[(3-fluorophenvl)-thiourido1-a-D-allofuranoside (Compound No.
93}
1.2-O-isopropylidene-3-deoxv-3-[(3-bromophenyl)-amido]-a-D-glucofuranoside (Compound No.
J09)
!.2-O-isopropvlidene-3-deoxv-3-[(3-fluorophenyl)-amido1-a-D-allofuranoside (Compound No. 112)

Example 4: Synthesis of 1, 2-O-isopropylidene-3-deoxy-3-[(3-bromobenzyl)-amido1-5,6-dioxa spiro[4,41nonane-g-D-glucofuranoside (Compound No. 1)
To a solution of l,2-O-isopropylidene-3-deoxy-3-[(3-bromophenyl)-amido]-a-D-glucofuranoside (Compound No. 109) (0.100 g, 0.240 mmol) in a mixture of dry toluene (5 ml) and dry dimethylformamide (2 ml) was added dry and powdered molecular sieves (0.250 g) and fcyclopentanone dimethyl ketal ( 0.35 g, 2.403 mmol) and heated the contents at 120-130 °C for 8-10
hours. Filtered the reaction mixture through a celite pad prewashed with methanol and washed the
/'
celite with ethyl acetate several times. Evaporated the solvents under reduced pressure to afford a residue which was the purified through preparative TLC using 50% ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.050 g.
'H NMR (CDC13 + D2O exchange, 400 MHz): 5 7.72 -7.43 (m, 2H, Ar-H), 7.31-7.21 (m, 2H, Ar-H), 6.09-6.07 (brd, 1H, -NH & D2O exchangeable), 5.81-5.80 (d, 1H, J = 4.00 Hz, -CH), 4.60-4.59 (d, 1H, J = 4.00 Hz, -CH), 4.38-4.36 (m, 1H, 1H, -CH), 4.16-4.13 (m, 1H, -CH), 4.03-4.00 (m, 2H, 2x-CH), 3.81-3.80 (m, 1H, -CH), 3.52 (s, 2H, -CH2Ar), 1.84-1.81 (m, 2H, -CH2), 1.71-1.68 (m, 6H, 3x-CH2), 1.50 (s, 3H, -CH3) and 1.28 (s, 3H, -CH3)
Mass (m/z, +ve ion mode): 484 [M++l+2] and 482 [M++l]. Following compounds were prepared similarily,
1, 2-O-isopropvlidene-3-deoxv-3-[(3-chlorobenzvl)-amido]-5,6-dioxa spiro[4,51nonane-a-D-glucofuranoside (Compound No. 2)
1,2-O-isopropvlidene-3-deoxy-3-[(2,4-difluorobenzvl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 3)
1, 2-O-isopropvlidene-3-deoxv-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 4)
1, 2-O-isopropvlidene-3-deoxv-3-r(3-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 5)
1, 2-O-isopropylidene-3-deoxy-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 6)
1, 2-O-isopropylidene-3-deoxy-3-[(2,5-dimethvlbenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 7)
1,2-O-isopropylidene-3-deoxy-3-[(4-fluorophenvl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 48)
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenvl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 49)
1, 2-O-isopropvlidene-3-deoxv-3-[(2-trifluoromethylphenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 50)
1. 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 51)
1, 2-O-isopropylidene-3-deoxy-3-(octyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-glucofuranoside
(Compound No. 52)

1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-5,6-dioxa spiro[4,5]decane-g-D-g]ucofuranoside
(Compound No. 53)
1, 2-O-isopropvlidene-3-deoxy-3-[(2-methoxyphenvl)-urido]-5,6-dioxa spiro[4,51decane-q-D- ;
glucofuranoside (Compound No. 54)
1, 2-O-isopropvlidene-3-deoxy-3-[(4-trifluoromethvlphenyl)-urido1-5,6-dioxaspiro[4.5]decane-a-D-
glucofuranoside (Compound No. 55)
1, 2-0-isopropylidene-3-deoxv-3-|Y3-methoxyphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 56)
1, 2-O-isopropvlidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 57)
1, 2-0-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenvD-thiourido]-5,6-dioxa spiro[4.5]decane-
oc-D-glucofuranoside (Compound No. 58)
j, 2-O-isopropvlidene-3-deoxy-3-r(3-niethoxvphenyl)-urido]-516-dioxa spiro[4,51decane-a-D-
glucofuranoside (Compound No. 59)
Scheme II:
Example 5: Synthesis of l,2;5,6-Di-O-isopropylidene-3-deoxv-3-(phenyl-propionamido)-a-D-allofuranoside (Compound No. 34)
To a solution of the compound l,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-a-D-allofuranoside (0.300 g, 1.158 mmol) in dry dimethylformamide (5 ml) was added N-methylmorpholine (0.351 g, 3.474 mmol) and 3-phenylpropionic acid (0.208 g, 1.389 mmol). The mixture was stirred at room temperature for 10 minutes. To the resulting reaction mixture was added 1-hydroxybenzotriazole (0.313 g, 2.316 mmol) and stirred the mixture at room temperature for 1 hour. To it was added 1 -(3-dimethylaminopropyl)-3-ethylcarbodiirnide hydrochloride (0.444 g, 2.316 mmol) at 0 °C and stirred £t the same temperature for 1 hour and subsequently at room temperature for 12 hours. The reacti«ji mixture was poured into water, extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by preparative thin layer chromatography using 40 % ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.320 g.
*H NMR (CDC13 + D2O exchange, 400 MHz): 8 7.32-7.20 (m, 5H, Ar-H), 5.82-5.81 (d, 1H, J = 4.00 Hz, -CH), 5.75 (brs, 1H, -NH & D2O exchangeable), 4.56-4.54 (t, 1H, J = 4.00 Hz, -CH), 4.18-4.15 (m, 2H, 2x-CH), 4.09-4.05 (m, 1H, -CH), 3.92-3.90 (m, 1H, -CH), 3.83-3.80 (m, 1H, -CH), 2.97- -2.95 (t, 2H, J- 8.00 Hz, -CH2Ar), 2.56-2.53 (m, 2H, -CH2CO), 1.52 (s, 3H, -CH3), 1.43 (s, 3H, -CH3), 1.34 (s, 3H, -CH3) and 1.32 (s, 3H, -CH3) Mass (m/z, +ve ion mode): 414 [M++23].
Following compounds were prepared similarily,
r,2;5,6-Di-O-isopropvlidene-3-deoxv-3-[(2-methoxvphenyl)-propionamido]-a-D-allofuranoside . Compound No. 35)

w
1.2;5.6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenvl)-propionamido]-a-D-allofuranoside (Compound No. 36)
l,2;5.6-Di-O-isopropylidene-3-deoxy-3-[(2-phenvl)propionamido]-a-D-allofuranoside (Compound ' No. 105)
l,2;5,6-Di-0-isopropylidene-3-deoxv-3-[3-(l,3-benzodioxol-5-vl)propionamido]-a-D-allofuranoside • (Compound No. 106)
Example 6: Synthesis of l,2;5,6-Di-Q-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-uridol-a-D-allofuranoside (Compound No. 62)
The title compound was prepared following the procedure as described in Example 2, by using the compound l,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-a-D-allofuranoside in place of l,2;5,6-Di-0-isopropylidene-3-deoxy-3-amino-a-D-glucofuranoside.
'H NMR (CDC13 + D2O exchange, 400 MHz): 8 7.61-7.49 (m, 4H, Ar-H), 6.28-6.26 (m, 1H, -NH & D2O exchangeable), 5.87-5.86 (d, 1H, J = 4.00 Hz, -CH), 4.68-4.66 (m, 1H, -CH), 4.33-4.32 (m, IK, *CH), 4.15-4.11 (m, 2H, 2x-CH), 4.02-3.93 (m, 2H, 2x-CH), 1.58 (s, 3H, -CH3), 1.44 (s', 3H, -CH3). 1.36 (s, 3H,- CH3) and 1.35 (s, 3H,- CH3) Mass (m/z, +ve ion mode): 447 [M++l].
1 , i •
Following compounds were prepared similarity by coupling an amine with appropriate cyanate or isocyanate, as applicable in each case.
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenvl-urido)-a-D-aUofuranoside (Compound No. 63)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxvphenvl)-urido]-a-D-allofuranoside (Compound
No. 64)
L2;5,6-Di-O-isopropylidene-3-deoxv-3-[4-cyanophenyl)-urido1-a-D-allofuranoside (Compound No.
65}
1.2:5.6-Di-O-isopropylidene-3-deoxv-3-[3-trifluoromethvlphenvl)-thiourido1-a-D-allofuranoside
(Compound No. 89)
Example 7: Synthesis of 1, 2-O-isopropylidene-3-deoxy-3-[4-fluorophenyl)-urido1-a-P-allofuranoside (Compound No. 60)
To a solution of l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. 110) (0.617 g, 1.558 mmol) in tetrahydrofuran (7 ml) was added aqueous perchloric acid (60%, 0.5 M, 0.260 ml, 1.558 mmol) dropwise at 0 °C and stirred the reaction mixture at this temperature for 2 hours. The reaction mixture was quenched with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with water, brine and filtered. The filtrate was evaporated under reduced pressure and the crude product thus obtained was purified by preparative TLC using 100% ethyl acetate as eluent to furnish the title compound. Yield: (0.325 g).

'HNMR(CDC13 + D2O exchange, 400 MHz): 5 7.31-7.20 (m,5H,Ar-H), 5.82-5.81 (d, 1H, J = 4.CO
Hz, -CH), 5.75-5.73 (brs, 1H, -NH & D2O exchangeable), 4.56-4.53 (m, 1H, -CH), 4.18-4.15 (m, 2rl
2x-CH), 4.09-4.05 (m, 1H, -CH), 3.92-3.90 (m, 1H, -CH), 3.82-3.80 (m, 1H, -CH), 2.99-2.95 (t, 2H,
J = 8.00 Hz, -CH2Ar), 2.56-2.52 (m, 2H, -CH2CO), 1.51 (s, 3H, -CH3), 1.43 (s, 3H, -CH3), 1.34 (s,
3H, -CH3) and 1.26 (s, 3H, -CH3)
Mass (m/z, +ve ion mode): 414 [M++Na],
Following compounds were prepared similarily,
1, 2-0-isopropvlidene-3-deoxv-3-[(2-fluorophenvl)-urido]-a-D-allofuranoside (Compound No. 61).
1. 2-O-isopropvlidene-3-deoxv-3-[(4-trifluoromethylphenyl)-urido]-a-D-allofuranoside (Compound
No. 66)
4. 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-allofuranoside (Compound No. 67)
1, 2-O-isopropvlidene-3-deoxv-3-[(2-methoxyphenvl)-urido]-q-D-allofuranoside (Compound No.
68]
1, 2-0-isopropylidene-3-deoxv-3-[(4-cvanophenvl)-urido]-q-D-allofuranoside (Compound No. 69)
1, 2-O-isopropvlidene-3-deoxv-3-[(2-trifluoromethvlphenvl)-urido]-a-D-allofuranoside (Compound
No. 70)
1, 2-O-isopropvlidene-3-deoxv-3-[(4-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound No.
71}
1, 2-O-isopropvlidene-3-deoxv-3-[(2-fluorophenvl)-thiourido]-a-D-allofuranoside (Compound No.
72} .
1, 2-0-isopropvlidene-3-deoxv-3-[(2-trifluoromethvlphenyl)-thiourido]-q-D-allofuranoside
(Compound No. 73)
1, 2-O-isopropvlidene-3-deoxv-3-[(2-methoxvphenyl)-thiourido]-a-D-allofuranoside (Compound
No. 74)
1, 2-O-isopropylidene-3-deoxv-3-(phenyl-thiourido)-a-D-allofuranoside (Compound No. 75)
1, 2-0-isopropvlidene-3-deoxv-3-[(4-trifluoromethvlphenvn-thiourido]-a-D-allofuranoside
(Compound No. 76) -
1, 2-O-isopropvlidene-3-deoxv-3-[(4-cvanophenvl)-thiourido1-q-D-allofuranoside (Compound No:':
77}
1, 2-O-isopropvlidene-3-deoxv-3-r(3-fluorophenyl)-urido1-a-D-allofuranoside (Compound No. 86)
1, 2-O-isopropvlidene-3-deoxy-3-[(3-cyanophenyl)-urido1-a-D-allofuranoside (Compound No. 87)
1, 2-0-isopropvlidene-3-deoxv-3-[(3-trifluoromethylphenvl)-thiourido]-a-D-allofuranoside
(Compound No. 94)
1. 2-O-isopropvlidene-3-deoxv-3-[(3-methoxyphenyl)-thiourido]-a-D-allofuranoside (Compound
No. 95)
1, 2-O-isopropvlidene-3-deoxv-3-[(3-methoxyphenyl)-urido]-a-D-allofuranoside (Compound No.
102)
Example 8: Synthesis of 1, 2-O-isopropvlidene-3-deoxv-3-[(3-fluorobenzvl)-amido1-5,6-dioxa spirof4,41nonane-a-D-allofuranoside (Compound No. 8)
To a solution of l,2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-amido]-a-D-allofuranoside (Compound No. 112) (0.100 g, 0.2801 mmol) in a mixture of dry toluene (3 ml) was added dry and powdered molecular sieves (0.250 g) and cyclopentanone dimethyl ketal ( 0.365 g, 2.814 mmol) and heated the contents at 110-120 °C for 8-10 hours. Filtered the reaction mixture through a celite pad prewashed with methanol and washed the celite with ethyl acetate several times. Evaporated the
;
'•*' solvents under reduced pressure to afford a residue which was the purified through preparative TLC
using 50% ethyl acetate in hexane as eluent to furnish the title compound. Yield : 0.050 g. , 'H NMR (CDC13, 400 MHz): 5 7.33 -7.26 (m, 2H, Ar-H), 7.07-6.98 (m, 2H, Ar-H), 5.86-5.80 (brs.
2H, -CH & -NH), 4.65-4.63 (brs, 1H, -CH), 4.16-4.09 (m, 2H, 2x-CH), 4.01-3.99 (m, 1H, -CH), ; 3.89-3.87 (m, 1H, -CH), 3.76-3.74 (m, 1H, -CH), 3.59 (s, 1H, -CH2Ar), 1.78-1.67 (m, 8H, 4x-CH2),
1.46 ( s, 3H, -CH3) and 1.31 ( s, 3H, -CH3)
Mass (m/z, +ve ion mode): 422 [M++l].
Following compounds were prepared similarily, .• <
1, 2-0-isopropvlidene-3-deoxy-3-[(4- fluorobenzyl)-amido]-5,6-dioxa spiror4,4]nonane-a-D-allofuranoside (Compound No. 9)
1, 2-O-isopropylidene-3-deoxv-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,41nonane-a-D-allofuranoside (Compound No. 10)
1, 2-O-isopropvlidene-3-deoxv-3-[(3-bromobenzyl)-arnido]-5,6-dioxa spiror4,41nonane-a-D-allofuranoside (Compound No. 11)
1, 2-O-isopropvlidene-3-deoxy-3-[(3-chlorobenzvl)-amido1-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 12)
1, 2-O-isopropvlidene-3-deoxv-3-[(2,5-dimethylbenzyl)-amido1-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 13)
I, 2-0-isopropylidene-3-deoxv-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-q-
D-allofuranoside (Compound No. 14)
1, 2-O-isopropvlidene-3-deoxv-3-[(4-fluorophenvl)-thiourido]-5,6-dioxa spiro[4,5]decane-q-D-
allofuranoside (Compound No. 78)
1, 2-O-isopropvlidene-3-deoxv-3-[(2-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-q-D-
allofuranoside (Compound No. 79)
1, 2-O-isopropylidene-3-deoxv-3-[(2-triiluoromethvlphenvl)-thiourido]-5.6-dioxaspiro[4,51decane-
q-D-allofuranoside (Compound No. 80)
1, 2-O-isopropylidene-3-deoxv-3-(phenvl-thiourido)-5.6-dioxaspiro[4,5]decane-a-D-allofuranoside
(.Compound No. 81)
1, 2-O-isopropvlidene-3-deoxv-3-[(4-trifluoromethylphenvl)-thiourido]-5,6-dioxaspiro[4,51decane-
oc-D-allofuranoside (Compound No. 82)
1, 2-0-isopropvlidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-5,6-dioxaspiro[4,51decane-a-D-
allofuranoside (Compound No. 83)
1. 2-O-isopropvlidene-3-deoxv-3-[(2-methoxyphenvl)-urido]-5,6-dioxa spiror4,51decane-a-D-
allofuranoside (Compound No. 84)
1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethvlphenyl)-urido1 -5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 90)
1, 2-O-isopropvlidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-dioxaspiro['4,5]decane-a-D
allofuranoside (Compound No. 91)
1. 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 92)
1,2-O-isopropvlidene-3-deoxv-3-[f4-fluorophenyl)-urido]-5.6-dioxa spiro[4,51decane-a-D-
allofuranoside (Compound No. 96)
1, 2-O-isopropvlidene-3-deoxy-3-[(2-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 97)
";
1, 2-0-isopropylidene-3-deoxy-3-IT3-cyanophenyl)-urido]-5,6-dioxa spiroK5]decane-a-D-allofuranoside (Compound No. 99)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-5,6-dioxa spiro[4,5]decane-g-D-allofuranoside (Compound No. 100)
l,2;5,6-Di-O-isopropvlidene-3-deoxv-3-[(3-methoxvphenvl)-urido]-a-D-allofuranoside (Compound No. 101)
Scheme III:
Example 9: Synthesis of 1, 2-Dioxa spiro[2,51octane-3-deoxy-3-f(4-fluorophenyl)-thiourido1-5,6-O-isoproDvlidene-g-D-allofuranoside (Compound No. 20)
Step a: 1, 2-Dioxa spiro[2,51octane-5,6-O-isopropylidene-a-D-glucofuranoside To a solution of 1, 2-Dioxa spiro[2,5]octane-a-D-glucofuranoside (Commercially available) (2.5 g, 9.605 mmol) in dry toluene (20 ml) was added powdered molecular sieves (5 g), excess 2,2-dimethoxy propane (25 ml) and catalytic amount of para toluenesulphonic acid. Refluxed the contents of the reaction for 1 hour. Filtered the reaction mixture through a celite pad and washed with ethyl acetate. Evaporated the solvent under reduced pressure and the residue so obtained was triturated with hexane to obtain the above product as white fluffy solid. Yield : 2.65 g. Step b: 1, 2-Dioxa spiro[2,5]octane-3-oxo-5,6-O-isopropylidene-a-D-glucofuranoside Toa solution of the compound obtained from step a above (2.60 g, 8.666 mmol) in dry distilled dimethyl sulphoxide (20 ml), added acetic anhydride (10 ml, 104.0 mmol) and heated the contents of the reaction at 70-80 °C for 5 hours. Added water to it and stirred at room temperature. Extracted the reaction mixture with ethyl acetate, washed with water, dried over anhydrous sodium sulphate, filtered and evaporated the solvent under reduced pressure to obtain the above product as thick brown oil. Yield: 4.0 g.
Step c: 1, 2-Dioxa spiro[2,51octane-3-deoxv-3-hvdroxvimino-5.6-O-isopropvlidene-a-D-glucofuranoside
To a solution of the compound obtained from step b above (4.00 g) in dry ethanol (20 ml) and dry
pyridine (20 ml) added hydroxylamine hydrochloride (2.779 g) and heated the contents of the
reaction at 70-80 °C for 7-8 hours. Evaporated the solvents under reduced pressure and added toluene
to remove pyridine azeotropically. Extracted the reaction mixture with dichloromethane, washed
with water, dried over anhydrous sodium sulphate, filtered and evaporated the solvent under reduced
pressure to obtain the above product as thick brown oil. Yield: 4.00 g. This product was used as such
for the next step without purification. '.<,..
Step d: 1, 2-Dioxa spiro[2,51octane-3-deoxy-3-amino-5.6-O-isopropylidene-a-D-allofuranoside :•••'•.

•
To a suspension of lithium aluminium hydride (0.728 g, 19.169 mmol) in dry distilled tetrahydrofuran (30 ml) cooled to 0 °C was added a solution of compound obtained from step c • above (3.00 g) in dry distilled tetrahydrofuran (5 ml). Stirred the reaction mixture at 0 °C for 2 hours and then at room temperature for 1 hour. Cooled the reaction mixture to 0 °C and added ethyl acetate dropwise. A saturated solution of sodium sulphate was then added slowly under stirring at 0 °C till a white gelatinous precipitate was formed. Filtered the reaction mixture through a celite pad and washed with ethyl acetate. Added water to it and extracted with ethyl acetate. Washed the organic layer with water, dried over anhydrous sodium sulphate, filtered and evaporated the solvent under , reduced pressure to obtain the above product as yellow oil. Yield: 2.20 g.
Step e: 1, 2-Dioxa spiro[2,51octane-3-deoxy-3-[(4-fluorophenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside
To a solution of compound obtained from step d above (0.100 g, 3.344 mmol) in dichloromethane (3.0 ml) was added triethyl amine (1.398 ml, 10.033 mmol) and 4-fluoromethylphenyl isocyanate (0.1024 g, 6.688 mmol) and stirred the reaction mixture at room temperature for 6-7 hours. The solvent was evaporated under reduced pressure and the residue thus obtained was treated with dichloromethane and water. The organic layer was separated, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 50 % ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.050 g.
'H NMR (CDC13, 400 MHz): 8 7.96 (brs, 1H, -NH & D2O exchangeable), 7.28-7.24 (m, 2H, Ar-H); 7.15-7.11 (m, 2H, Ar-H), 6.33-6.32 (brs, 1H, -NH & D2O exchangeable) 5.86-5.85 (d, 1H, J = 4.00 Hz, -CH), 4.75-4.73 (m, 2H, 2x -CH), 4.40-4.39 (m, 1H, -CH), 4.17-4.16 (m, 1H, -CH), 4.00-3.96 (m, 1H, -CH), 3.87-3.84 (m, 1H, -CH), 1.62-1.43 (brm, 10H, 5x -CH2), 1.36 (s, 3H, -CH3) and 1.34 (s, 3H, -CH3). Mass (m/z, +ve ion mode): 453 [M++l].
Following compounds were prepared similarity,
I, 2 -Dioxa spiro[2,5]octane-3-deoxv-3-[(4-trifluorornethvlphenyl)-urido]-5,6-O-isopropvlidene-a-D-allofuranoside (Compound No. 18)
1, 2-Dioxa spiro[2,5]octane-3-deoxv-3-(phenvl-thiourido)-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 21)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-cyanophenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 22)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-5.6-O-isopropylidene-q-D-allofuranoside (Compound No. 23)
1, 2-Dioxa spiro[2,5]octane-3-deoxv-3-[(2-trifluoromethvlphenyl)-thiourido]-5.6-O-isopropvlidene-q-D-allofuranoside (Compound No. 24)

Following compounds can also be prepared similarity,
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-(phenyl-urido)-5,6-O-isopropylidene-q-D-allofuranoside (Compound No. 16)
1, 2-Dioxa spiro[2,51octane-3-deoxy-3-[(4-cyanophenylVurido]-5,6-O-isopropylidene-q-D-allofuranoside (Compound No. 17)
1, 2-Dioxa spiro[2,51octane-3-deoxv-3-[(2-trifluoromethvlphenyl)-urido]-5,6-O-isopropvlidene-a-D-allofuranoside (Compound No. 19)
Example 10: Synthesis of 2-Dioxa spiro[2,51octane-3-deoxy-3-[(3-chlorobenzyl)-amido1-5,6-Q-isopropylidene-q-D-allofuranoside (Compound No. 25)
To a solution of the compound obtained from step d of Example 9 above (0.090 g, 0.301 mmol) in dry dimethylformamide (3 ml) was added N-methylmorpholine (0.0913 g, 0.903 mmol) and 3-chlorophenylacetic acid (0.103 g, 0.602 mmol). The mixture was stirred at room temperature for 10 minutes. To the resulting reaction mixture was added 1-hydroxybenzotriazole (0.0813 g, 0.602 mmol) and stirred the mixture at room temperature for 1 hour. To it was added l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.115 g, 0.602 mmol) at 0 °C and stirred at the same temperature for 1 hour and subsequently at room temperature for 12 hours. The reaction mixture was poured into water, extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue thus obtained was purified by preparative thin layer chromatography using 50 % ethyl acetate in hexane as eluent to furnish the title compound. Yield: 0.065 g.
'H NMR (CDC13 + D20 exchange, 400 MHz): 5 7.31-7.27 (m, 3H, Ar-H), 7.20-7.17 (m, 1H, Ar-H), 5.85 (brs, 1H, -NH & D2O exchangeable), 5.83-5.82 (d, 1H, J = 4.00 Hz, -CH), 4.60-4.59 (m, 1H, -CH), 4.20-4.17 (m, 1H, -CH), 4.10-4.06 (m, 1H, -CH), 4.08-4.04 (m, 1H, -CH), 3.92-3.90 (m, 1H, -CH), 3.59 (s, 2H, -CH2Ar), 1.66-1.61 (m, 6H, 3x-CH2), 1.55-1.52 (m, 4H, 2x-CH2),1.39 (s, 3H, -CH3), and 1.33 (s, 3H,-CH3). Mass (m/z, +ve ion mode): 454 [M++l+2] and 452 [M++l].
Following compounds were prepared similarily,
I, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(3-fluorobenzyl)-amido1-5,6-0-isopropylidene-a-D-
allofuranoside (Compound No. 26) ;;
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorobenzvl)-amido1-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 27)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-chloro-4-fluorobenzvl)-amido1-5.6-O-isopropvlidene-a-D-allofuranoside (Compound No. 28)
j. 2-Dioxa spiror2,51octane-3-deoxv-3-r(2.5-dimethvlbenzvlVamido1-5.6-O-isopropvlidene-a-D-allofuranoside (Compound No. 29)

K 2-dioxa spirop^joctane-S-deoxv-S-tfS^.S-trimethoxyobenzyD-amidoj-S^-O-isopropylidene-a-D-allofuranoside (Compound No. 30)
Pharmacological activity
'. '
The compounds of the present invention are tested in one or both of the assays described herein. Standard assays are used to evaluate activity of compounds in present invention on inflammatory cells as well as recombinant human 5-lipoxygenase enzyme. Inhibiton of 5-lipoxygenase enzyme or attenuation of A23187-induced release of lipid mediator of neutrophil chemotaxis, leukotriene B4 (LTB4), is used to evaluate inhibitory effect on neutrophils.
A23187 induced LTBj release
Venous blood was collected from healthy human donors using heparin as an anti-coagulant. Neutrophils were isolated from freshly drawn blood after dextran sedimentation and ficoll separation (Enr. J. Biochem. 169, 175, 1987). 180 ul of the neutrophil suspension (0.2xl06 cells/ml) was taken and added 19 ul of Hank's Buffer salt solution along with lul of the test drug (200 times concentrated) in a 24 well plate and incubated at 37 °C for 1 hour. Three minutes before the end of test compound incubation, 0.25 mM Ca+7Mg++ were added. Then, 0.3 ug/ml A23187 (Sigma Chem, USA) was added and incubated for further 10 min at 37 °C. The reaction was stopped by adding 80 ul of cold methanol and centrifuged to remove cell debris (J. Pharmacol. Exp. Ther. 297:267, 2001). The samples were analysed for LTB4 release using LTB4 ELISA kits (Assay Design Inc., USA). The amount of LTB4 released was quantified and percent inhibition of LTB4 release was calculated with respect to the difference between the A23 1 87 stimulated and negative control cells, to compute IC^ values. In vitro data obtained on the disclosed compounds shows ICso values of active compounds of < 10 uM and moderately active compounds with >10uM, IC^o values
Assay for 5-Lipoxygenase Activity
In a 96 well UV-plate, 100 ul of phosphate buffer saline (PBS) containing DTT (200 uM), ATP (100 uM) and calcium chloride (TOO uM) was added. To each well 0.5 jj.1 of test drug (200 tim^ concentrated) or vehicle was added, followed by 4 ul of recombinant 5-Lox (3 units/ul) and was incubated at 37 °C for 5 min. The reaction was initiated by adding 1 ul of 1 mM freshly prepared arachidonic acid and increase in absorbance was monitored at 236 nm for 10 min. (J. Biol. Chem. 26_1:1 1512, 1986). A plot of absorbance verses 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 ICso values.

WE CLAIM:
1. The compound of Formula I
wherein
RI and RI together form a five-membered acetal, wherein the carbon atom joining the oxygens can be substituted with RL and Rm [wherein RL and Rm are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; or RL and Rm can together join to form a 3-8 membered ring, wherein the ring may optionally contain one or more heteroatoms selected from O, N or S, and the ring may be optionally substituted with one or more of alkyl, alkenyl, alkynyl, amino, substituted amino, cycloalkyl, oxo, hydroxy, carboxy, -COQRe (wherein Q is O or NH and Re is selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, and cycloalkyl), alkoxy, aryloxy, halogen (F,C1, Br, I), aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, or heterocyclylalkyl; or RL and Rm can together join to form an oxo group];
RB is selected from
A) -(CH2)nG wherein n is an integer from 0-5 and G is selected from
1) ORe {wherein Re is selected from
a) acyl (with the proviso that n cannot be 0), and
b) -C(=O)NRtRq [wherein Rf and Rq can be independently selected from hydrogen, hydroxy (with the restriction that both Rf and Rq cannot both be hydroxy), alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, and S(O)iR7 (wherein R-j is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl, and optionally substituted amino)}; and Rf and Rq may also together join to form a heterocyclyl ring; also, when n is zero, then Rf and Rq cannot be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl and Rf and Rq together cannot join to form a heterocyclyl ring};
2) -NRiC(=O)ORs (wherein Rj is selected from hydrogen, lower (d-C6) alkyl, lower (C2-C6)
alkenyl, lower (Ca-Ce) alkynyl, lower (Cs-Cg) cycloalkyl, aryl, heteroaryl (with the proviso that

the heteroaryl ring is not linked through a heteroatom), aralkyl (Ci-C4), heteroarylalkyl (Ci-C4), and heterocyclylalkyl (Ci-C4), and Rs is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, or heteroarylalkyl);
3) NRjYRLI (wherein Rj is the same as defined above and Y is -C(=O), -C(=S) or SO2 and Ru is
selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl,
heteroarylalkyl, and heterocyclylalkyl; and when n is 0 then Y cannot be -C(=O));
4) -NRjC(=T)NRtRx (wherein R, is OH or Rx and T is O, S, -N(CN), -N(NO2), -CH(N02), Rj is
the same as defined above and Rx is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,
aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, heterocyclylalkyl, and S(O)iR7 wherein
R? is the same as defined above);
5) heterocyclyl;
6) heteroaryl; and
7) -(C=O)NRaRb (wherein R a and Rb are independently selected from hydrogen, and Ru wherein
Ru is same as defined earlier, also, Ra and Rh together with the nitrogen atom carrying them can
be the N-terminus of an amino acid or di-tetrapeptide or Ra and Rbinay together join to form a
heterocyclyl ring);
Rj is alternately selected from
B) -NRjRm (wherein Rj is the same as defined above and Rm is selected from alkyl, cycloalkyl,
aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, and heterocyclylalkyl);
C) -O(CH2)wGi [wherein w is an integer from 1-5 (and GI is selected from ORe (wherein Re is
the same as defined above), -NRjC(=0)ORs (wherein Rj and Rs are the same as defined above), -
NRjC(=T)NRtRx (wherein Rj, T, Rt and Rx are the same as defined above), -NRjYRu (wherein
Y, Ru and R, are the same as defined above), heterocyclyl, and heteroaryl)];
D) -NRj(CH2)wGi (wherein w, Rj and GI are the same as defined above);
E) -O(CH2)WG2 [wherein w is the same as defined above (and G2 is selected from
-C(=O)NRaRb (wherein Ra and Rb are the same as defined above), and -C(=O)ORk (wherein Rk
is H or R6 and R6 is the same as defined above); or
F) -NRj(CH2)wG2 (wherein w is as defined above, Rj and G2 are the same as defined above))];
further, when R} is ORe then R2 and Re may together join to form a five membered acetal wherein the carbon linking the two oxygens is substituted with RL and Rm (wherein RL and Rm are the same as defined earlier, and RI is independently selected from

a) -(CH2)tGi (wherein t is an integer from 2-4 and GI are the same as defined above and also
when GI is heterocyclylalkyl group then the said group cannot be 4-(l-pyrrolidinyl) butyl),
b) -(CH2)vVG2 (wherein w and G2 are the same as defined above),
c) aryl,
d) aralkyl (with the proviso that aralkyl cannot be phenylpropyl),
e) heteroaryl, and
f) heterocyclyl (wherein the heteroaryl and heterocyclyl rings are not linked through a
heteroatom), and cycloalkyl (with the proviso that cycloalkyl cannot be cyclooctyl); and
R4 and R5 are independently selected from hydrogen, lower (Ci-Cg) alkyl, lower (Cz-Cg) alkenyl, lower (Ca-Ce) alkynyl, lower (Cs-Cg) cycloalkyl, aryl, acyl, heterocyclyl, heteroaryl, lower (Ci-Ct) heterocyclylalkyl, and lower (Ci-C4) heteroarylalkyl; or R4 and RS may together form a five-membered acetal wherein the carbon linking the two oxygens is substituted with RL and Rm (wherein RL and Rm are the same as defined earlier) with the proviso that when Rj is ORe then the acetal must be isopropylidene acetal.
2. A compound selected from the group consisting of:
1, 2-O-isopropylidene-3-deoxy-3-[(3-bromobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 1)
1,2-O-isopropylidene-3-deoxy-3-[(3-chlorobenzyl)-amido]-5,6-dioxa spiro[4,5]nonane-a-D-glucofuranoside (Compound No. 2)
1,2-O-isopropylidene-3-deoxy-3-[(2,4-difluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 3)
1, 2-O-isopropylidene-3-deoxy-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 4)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 5)
1, 2-O-isopropylidene-3-deoxy-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-glucofuranoside (Compound No. 6)
1,2-O-isopropylidene-3-deoxy-3-[(2,5-dimethylbenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-ot-D-glucofuranoside (Compound No. 7)

1,2-O-isopropylidene-3-deoxy-3-[(3-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 8)
1,2-O-isopropylidene-3-deoxy-3-[(4-fluorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 9)
1,2-O-isopropylidene-3-deoxy-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-dioxa ;
spiro[4,4]nonane-a-D-allofuranoside (Compound No. 10)
l,2-O-isopropylidene-3-deoxy-3-[(3-bromobenzyl)-amido]-5,6-dioxaspiro[4,4]nonane-a-D-allofuranoside (Compound No. 11)
1, 2-O-isopropylidene-3-deoxy-3-[(3-chlorobenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 12)
1, 2-O-isopropylidene-3-deoxy-3-[(2,5-dimethylbenzyl)-amido]-5,6-dioxaspiro[4,4]nonane-a-D-allofuranoside (Compound No. 13)
1, 2-O-isopropylidene-3-deoxy-3-[(3,4,5-trimethoxybenzyl)-amido]-5,6-dioxa spiro[4,4]nonane-a-D-allofuranoside (Compound No. 14)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorophenyl)-urido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 15)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-(phenyl-urido)-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 16)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 17)
1, 2 -Dioxa spiro[2,5] octane-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 18)
1,2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 19)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorophenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 20)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-(phenyl-thiourido)-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 21)
1,2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-cyanophenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 22)

1,2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 23)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-trifluoromethylphenyl)-thiourido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 24)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(3-chlorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 25)
1,2-Dioxa spiro[2,5]octane-3-deoxy-3-[(3-fluorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 26)
1,2-Dioxa spiro[2,5]octane-3-deoxy-3-[(4-fluorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 27)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2-chloro-4-fluorobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 28)
1,2-Dioxa spiro[2,5]octane-3-deoxy-3-[(2,5-dimethylbenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 29)
1, 2-Dioxa spiro[2,5]octane-3-deoxy-3-[(3,4,5-trimethoxyobenzyl)-amido]-5,6-O-isopropylidene-a-D-allofuranoside (Compound No. 30)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-propionamido)-a-D-glucofuranoside (Compound No. 31)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-propionamido]-a-D-glucofuranoside (Compound No. 32)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-propionamido]-a-D-glucofuranoside (Compound No. 33)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-propionamido)-a-D-allofuranoside (Compound
No. 34)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-propionamido]-a-D-allofuranoside (Compound No. 35)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-propionamido]-a-D-allofuranoside (Compound No. 36)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-glucofuranoside (Compound No 37)

1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-a-D-glucofuranoside (Compound
No. 38)
1,2-0-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-a-D-glucofuranoside (Compound
No. 39)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-a-D-glucofuranoside (Compound
No. 40)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-a-D-glucofuranoside
(Compound No. 41)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-a-D-glucofuranoside
(Compound No. 42)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-glucofuranoside
(Compound No. 43)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-a-D-
glucofuranoside (Compound No. 44)
1,2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-a-D-glucofuranoside (Compound
No. 45)
1,2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-glucofuranoside (Compound
No. 46)
1, 2-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-a-D-glucofuranoside
(Compound No. 47)
1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-ot-D-
glucofuranoside (Compound No. 48)
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 49)
1,2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-dioxa spiro[4,5]decane-
a-D-glucofuranoside (Compound No. 50)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 51)
1,2-O-isopropylidene-3-deoxy-3-(octyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-glucofuranoside
(Compound No. 52)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 53)
1, 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-5,6-dioxaspiro[4,5]decane-a-D-
glucofuranoside (Compound No. 54)

1, 2-0-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-5,6-dioxa spiro[4,5]decane-
a-D-glucofuranoside (Compound No. 55)
1,2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-ot-
D-glucofuranoside (Compound No. 56)
1,2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-
glucofuranoside (Compound No. 57)
l,2-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-5,6-dioxa
spiro[4,5]decane-a-D-glucofuranoside (Compound No. 58)
1, 2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-urido]-5,6-dioxa spiro[4,5]decane-ot-D-
glucofuranoside (Compound No. 59)
1, 2-O-isopropylidene-3-deoxy-3-[4-fluorophenyl)-urido]-a-D-allofuranoside (Compound No.
60)
1, 2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-a-D-allofuranoside (Compound No.
61)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-a-D-allofuranoside
(Compound No. 62)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-allofuranoside (CompoundNo. 63)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-a-D-allofuranoside
(Compound No. 64)
1.2;5,6-Di-O-isopropylidene-3-deoxy-3-[4-cyanophenyl)-urido]-a-D-allofuranoside (Compound
No. 65)
1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-a-D-allofuranoside
(Compound No. 66)
1, 2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-allofuranoside (Compound No. 67)
1, 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-a-D-allofuranoside (Compound
No. 68)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-a-D-allofuranoside (Compound No.
69)
1,2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-a-D-allofuranoside
(Compound No. 70)
1, 2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound
No. 71)
1,2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound
No. 72)

l,2-0-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 73)
l,2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-thiourido]-a-D-allofuranoside (Compound No. 74)
1, 2-0-isopropylidene-3-deoxy-3-(phenyl-thiourido)-a-D-allofuranoside (Compound No. 75) 1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside (Compound No. 76)
1,2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-a-D-allofuranoside (Compound No. 77)
1,2-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside (Compound No. 78)
1,2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-ot-D-allofuranoside (Compound No. 79)
1, 2-O-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside (Compound No. 80)
1.2-O-isopropylidene-3-deoxy-3-(phenyl-thiourido)-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside (Compound No. 81)
1, 2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside (Compound No. 82)
1,2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-thiourido]-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside (Compound No. 83)
1, 2-O-isopropylidene-3-deoxy-3-[(2-methoxyphenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside (Compound No. 84)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. 85)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside (Compound No. 86)
1, 2-O-isopropylidene-3-deoxy-3-[(3-cyanophenyl)-urido]-a-D-allofuranoside (Compound No. 87)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound No. 88)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[3-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside (Compound No. 89)

1,2-O-isopropylidene-3-deoxy-3-[(4-trifluoromethylphenyl)-urido]-5,6-dioxa spiro[4,5]decane-
a-D-allofuranoside (Compound No. 90)
1,2-0-isopropylidene-3-deoxy-3-[(2-trifluoromethylphenyl)-urido]-5,6-dioxa spiro[4,5]decane-
a-D-allofuranoside (Compound No. 91)
1, 2-O-isopropylidene-3-deoxy-3-[(4-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 92)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-thiourido]-a-D-allofuranoside (Compound
No. 93)
1, 2-O-isopropylidene-3-deoxy-3-[(3-trifluoromethylphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 94)
1, 2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-thiourido]-a-D-allofuranoside
(Compound No. 95)
1, 2-0-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 96)
1,2-O-isopropylidene-3-deoxy-3-[(2-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 97)
1, 2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 98)
1, 2-O-isopropylidene-3-deoxy-3-[(3-cyanophenyl)-urido]-5,6-dioxa spiro[4,5]decane-a-D-
allofuranoside (Compound No. 99)
1,2-O-isopropylidene-3-deoxy-3-(phenyl-urido)-5,6-dioxa spiro[4,5]decane-a-D-allofuranoside
(Compound No. 100)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-urido]-a-D-allofuranoside
(Compound No. 101)
1, 2-O-isopropylidene-3-deoxy-3-[(3-methoxyphenyl)-urido]-a-D-allofuranoside (Compound
No. 102)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-phenyl)propionamido]-a-D-glucofuranoside
(Compound No. 103)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[3-(l,3-benzodioxol-5-yl)propionamido]-a-D-
glucofuranoside (Compound No. 104)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(2-phenyl)propionamido]-a-D-allofuranoside
(Compound No. 105)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[3-(l,3-benzodioxol-5-yl)propionamido]-a-D-
allofuranoside (Compound No. 106)

1,2;5,6-Di-O-isopropylidene-3-deoxy-3-(phenyl-urido)-a-D-glucofuranoside (Compound No.
107)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-bromophenyl)-acetamido]- a-D-glucofuranoside
(Compound No. 108)
l,2-O-isopropylidene-3-deoxy-3-[(3-bromophenyl)-amido]-a-D-glucofuranoside (Compound
No. 109)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(4-fluorophenyl)-urido]-a-D-allofuranoside
(Compound No. 110)
l,2;5,6-Di-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-urido]-a-D-allofuranoside
(CompoundNo. Ill)
1,2-O-isopropylidene-3-deoxy-3-[(3-fluorophenyl)-amido]-a-D-allofuranoside (Compound No.
112)
3. A method of making compounds of Formula X
Scheme I

L is a leaving group such as tosyl or mesyl and hal is a halogen (Cl, Br, I), F is an integer from 0-2, W is -CH2 or -NH2; X is oxygen or sulphur,
Rx is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, heterocyclylalkyl, and -S(O)2R?;
Ru is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, and heterocyclylalkyl,
RI and RI together form a five-membered acetal, wherein the carbon atom joining the oxygens can be substituted with RL and Rm [wherein RL and Rm are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; or RL and Rm can together join to form a 3-8 membered ring, wherein the ring may optionally contain one or more heteroatoms selected from O, N or S, and the ring may be optionally substituted with one or more of alkyl, alkenyl, alkynyl, amino, substituted amino, cycloalkyl, oxo, hydroxy, carboxy, -COQRe (wherein Q is O or NH and Re is selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, and cycloalkyl), alkoxy, aryloxy, halogen (F,C1, Br, I), aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, or heterocyclylalkyl; or RL and Rm can together join to form an oxo group]; and
R4 and RS are independently selected from hydrogen, lower (C\-C(,) alkyl, lower (C2-Ce) alkenyl, lower (C2-Ce) alkynyl, lower (Cs-Cs) cycloalkyl, aryl, acyl, heterocyclyl, heteroaryl, lower (Ci-C4) heterocyclylalkyl, and lower (Ci-C4) heteroarylalkyl; or R4 and RS may together form a five-membered acetal wherein the carbon linking the two oxygens is substituted with RL and Rm (wherein RL and Rm are the same as defined earlier),
RV is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl, and optionally substituted amino;
the method comprising
a. reacting a compound of Formula II with a compound of Formula Ila to give a compound of
Formula III,
b. reacting a compound of Formula III with sodium azide to form a compound of Formula IV,
c. reducing a compound of Formula IV to form a compound of Formula V,
d. reacting a compound of Formula V with a compound of Formula VI to furnish a compound of
Formula VII,
48

e. hydrolyzing a compound of Formula VII to give a compound of Formula VIII,
f. reacting a compound of Formula VIII with a compound of Formula IX to give a compound of
Formula X.

Wherein
Ru is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, and heterocyclylalkyl,
f is an integer from 0-2, W is -CH2 or -NH2; X is oxygen or sulphur;

RV is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl, and optionally substituted amino;
Rx is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, heterocyclylalkyl, and -S(O)2Ry;
RI and RI together form a five-membered acetal, wherein the carbon atom joining the oxygens can be substituted with RL and Rm [wherein RL and Rm are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; or RL and Rm can together join to form a 3-8 membered ring, wherein the ring may optionally contain one or more heteroatoms selected from O, N or S, and the ring may be optionally substituted with one or more of alkyl, alkenyl, alkynyl, amino, substituted amino, cycloalkyl, oxo, hydroxy, carboxy, -COQRg (wherein Q is 0 or NH and Re is selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, and cycloalkyl), alkoxy, aryloxy, halogen (F,C1, Br, I), aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, or heterocyclylalkyl; or RL and Rm can together join to form an oxo group]; and
wherein the method comprises:
a. oxidizing a compound of of Formula II to form a compound of Formula XI,
b. reacting a compound of Formula XI with hydroxylamine hydrochloride to form a
compound of Formula XII,
c. reducing a compound of Formula XII to form a compound of Formula V,
d. reacting a compound of Formula V with a compound of Formula VI to furnish a
compound of Formula VII,
e. hydrolyzing a compound of Formula VII to give a compound of Formula VIII,
f. reacting a compound of Formula VIII wth a compound of Formula IX to give a
compound of Formula X.
5. A method of making a compound of Formula XVIIIa and XIX

Wherein
Ru is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, and heterocyclylalkyl,
X is oxygen or sulphur,
Rx is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, heterocyclylalkyl, and -S(O)2Ry;
f is an integer from 0-2,
RI and RI together form a five-membered acetal, wherein the carbon atom joining the oxygens can be substituted with RL and Rm [wherein RL and Rm are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; or RL and Rm can together join to form a 3-8 membered ring, wherein the ring may optionally contain one or more heteroatoms selected from O, N or S, and the ring may be optionally substituted with one or more of alkyl, alkenyl, alkynyl, amino, substituted amino, cycloalkyl, oxo, hydroxy, carboxy, -COQRe (wherein Q is O or NH and Rg is selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, and

cycloalkyl), alkoxy, aryloxy, halogen (F,C1, Br, I), aryl, aralkyl, heteroaryl, heterocyclyl, heteroarylalkyl, or heterocyclylalkyl; or RL and Rm can together join to form an oxo group];
RV is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heterocyclylalkyl, heteroarylalkyl, and optionally substituted amino
and
wherein the method comprises:
a. cyclizing a compound of Formula XIII undergoes with a compound of Formula Xllla to
give a compound of Formula XIV,
b. oxidizing a compound of Formula XIV to give a compound of Fomrula XV,
c. reacting a compound of Formula XV with hydroxyl amine hydrochloride to give a
compound of Formula XVI,
d. reducing a compound of Formula XVI to give a compound of Formula XVII,
e. reactiong a compound of Formula XVII with a compound of Formula XVI to give a
compound of Formula XVIIIa.
f. reactiong a compound of Formula XVII with a compound of Formula XVIII to give a
compound of Formula XIX.
6. A pharmaceutical composition comprising a compound of claim 1 or 2 and a
pharmaceutically acceptable carrier.
7. The use of compounds according to claim 1 or 2 for the manufacture of medicament for
treating or preventing inflammation, cardiovascular, cancer or autoimmune diseases in mammal.

8. The use of compounds according to claim 1 or 2 for the manufacture of medicament for
treating or preventing bronchial asthma, chronic obstructive pulmonary disorder, rheumatoid
arthritis, type I diabetes, multiple sclerosis, allograft rejection, cancer, inflammatory bowel
disease, ulcerative colitis, psoriasis, acne, atherosclerosis, pruritis, allergic rhinitis in mammal.
9. The use of compounds according to claim 1 or 2 for the manufacture of medicament for
treating or preventing disease or disorder which is mediated through 5-lipoxygenase in mammal.
10. The use of pharmaceutical composition according to claim 6 for the manufacture of
medicament for treating or preventing inflammation, cardiovascular, cancer or autoimmune
diseases in mammal.
11. The use of pharmaceutical composition according to claim 6 for the manufacture of
medicament for treating or preventing bronchial asthma, chronic obstructive pulmonary
disorder, rheumatoid arthritis, type I diabetes, multiple sclerosis, allograft rejection, cancer,

inflammatory bowel disease, ulcerative colitis, psoriasis, acne, atherosclerosis, pruritis, allergic rhinitis in mammal.
12. The use of pharmaceutical composition according to claim 6 for the manufacture of medicament for treating or preventing disease or disorder which is mediated through 5-lipoxygenase in mammal.