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New Dipeptidyl Peptidase Iv Inhibitors Process For Their Preparation And Compositions Containing Them

Abstract: The present invention relates to new dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (I), and their analogs, isomers, pharmaceutical compositions and therapeutic uses method of making the same.

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Patent Information

Application #
Filing Date
15 December 2003
Publication Number
03/2006
Publication Type
INA
Invention Field
BIOTECHNOLOGY
Status
Email
Parent Application

Applicants

GLENMARK PHARMACEUTICALS LIMITED
B/2, Mahalaxmi Chaambers, 22,Bhulabhai Desai Road, Post Box No. 26511 Mumbai 400 026

Inventors

1. HEMANT VASANT JOSHI
B/2, Mahalaxmi Chaambers, 22,Bhulabhai Desai Road, Post Box No. 26511 Mumbai 400 026
2. BALASUBRAMANIAN GOPALAN
B/2, Mahalaxmi Chaambers, 22,Bhulabhai Desai Road, Post Box No. 26511 Mumbai 400 026
3. DAISY MANISH SHAH
B/2, Mahalaxmi Chaambers, 22,Bhulabhai Desai Road, Post Box No. 26511 Mumbai 400 026

Specification

FORM 2 THE PATENTS ACT 1970 (Act 39 of 1970) COMPLETE SPECIFICATION (SECTION 10) NEW DIPEPTIDYL PEPTIDASE IV INHIBITORS; PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM Glenmark Pharmaceuticals Limited an Indian Company, registered under the Indian company's Act 1957 and having its registered office at B/2, Mahalaxmi Chambers 22, Bhulabhai Desai Road Post Box No. 26511 Mumbai- 400 026, India THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THE INVENTION; AND THE MANNER IN WHICH IT IS PERFORMED FIELD OF THE INVENTION The present invention relates to new dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (I), their analogs, tautomers, enantiomers, diastereomers, regioisomers, stereoisomers, polymorphs, pharmaceutically acceptable salts, N-oxides, pharmaceutically acceptable solvates and the pharmaceutical compositions containing them. BACKGROUND OF THE INVENTION Diabetes mellitus refers to a chronic metabolic disorder in which utilization of carbohydrates is impaired and that of lipid and proteins are enhanced. It is cause by an absolute or relative deficiency of insulin (the hormone which regulates the body's glucose utilization) and is characterized by elevated levels of plasma glucose or hyperglycemia in the fasting state or after administration of glucose during an oral glucose tolerance test. Persistent or uncontrolled hyperglycemia is associated with increased and premature morbidity and mortality. Often abnormal glucose homeostasis is associated both directly and indirectly with alterations of the lipid, lipoprotein and apolipoprotein metabolism and other metabolic and hemodynamic disease. Patients with diabetes mellitus are at increased risk of macrovasuclar and microvascular complications, including coronary heart disease, stroke, peripheral vascular disease, hypertension, nephropathy, neuropathy, and retinopathy. Therapeutic control of glucose homeostasis, lipid metabolism and hypertension are critically important in the clinical management and treatment of diabetes mellitus. Generally, there are two recognized forms of diabetes, known as type 1 and type 2. In type 1 diabetes, also known as insulin-dependent diabetes mellitus or "IDDM", patients produce little or no insulin. In type 2 diabetes, also known as non-insulin dependent diabetes mellitus or "NIDDM", patients often have plasma insulin levels that are the same or even elevated compared to nondiabetic subjects. NIDDM patients with elevated plasma insulin levels, however, often exhibit a developed resistance to the insulin stimulating effect on glucose and lipid metabolism in the main insulin-sensitive tissues, including: muscle, liver and adipose tissues. Thus, the plasma insulin levels, while elevated, are insufficient to overcome the pronounced insulin resistance. Insulin resistance is not primarily due to a diminished number of insulin receptors but to a post-insulin receptor-binding defect that is not yet understood. This resistance to insulin responsiveness results in insufficient insulin activation of glucose uptake, oxidation and storage in muscle and inadequate insulin repression of lipolysis in adipose tissue. In addition, insulin resistance results in insufficient glucose production and secretion in the liver. Diabetes mellitus often develops in certain "at risk" populations. One such population is individuals with impaired glucose tolerance (IGT). The ordinary meaning of impaired glucose tolerance is a condition intermediate between normal glucose tolerance and NIDDM. IGT may be diagnosed by a test procedure that assesses an affected person's postprandial glucose response. In this test, a measured amount of glucose is given to the patient and blood glucose levels are measured at regular intervals. These intervals occur every half hour for the first two hours and every hour thereafter. In a "normal" or non-IGT individual, glucose levels rise during the first two hours to a level less than 140 mg/dl and then drop rapidly. In an individual with IGT, the blood glucose levels are higher and the drop-off level occurs at a slower rate. A high percentage of the IGT population is known to progress to NIDDM. Insulin resistance is an abnormality of glucose disposal in tissues and organs, which can be measured by various tests, for example, the euglycemic glucose clamp test, the intravenous glucose tolerance test, or by measuring the fasting insulin level. It is well known that there is an excellent correlation between the height of the fasting insulin level and the degree of insulin resistance. Therefore, one could use elevated fasting insulin levels as a surrogate marker for insulin resistance for the purpose of identifying which NGT individuals have insulin resistance. U.S. Patent No. 5,702,012 discloses that a certain patient population that tests normal according to the fasting and two hour postprandial plasma glucose tests (i.e. normal glucose tolerance population) but exhibit insulin resistance using different tests, may progresses to NIDDM. This population is designated as having non-IGT (NIGT) or insulin resistant NIGT (IRNIGT). The reference further discloses that this population can be treated with thiazolidinedione class of compounds. It is important to distinguish between those individuals whose tests show normal glucose tolerance and who are not insulin resistant on the one hand, and those who exhibit normal glucose tolerance with a certain degree of insulin resistance on the other hand. The available treatments for type 2 diabetes, which have not changed substantially in many years, have recognized limitations. While physical exercise and reductions in dietary intake of calories may dramatically improve the diabetic condition, compliance with this treatment is very poor because of sedentary lifestyles and excess food consumption. Increasing the plasma level of insulin by administration of sulfonylureas (e.g. tolbutamide and glipizide) or meglitinide, which stimulate the pancreatic P-cells to secrete more insulin, and/or by injection of insulin when sulphonylureas or meglitinide becomes ineffective, can results in insulin concentrations high enough to stimulate the very insulin-resistance tissues. However, dangerously low levels of plasma glucose can result from administration of insulin or insulin secretagogues (sulfonylureas or meglitinide). In addition, the even higher plasma insulin levels may result in increased insulin resistance. The biguanide class of compounds can increase insulin sensitivity resulting in some correction of hyperglycemia. However, two biguanides, phenformin and metformin, can also induce lactic acidosis and nausea/diarrhea. Metformin, which has fewer side effects than phenformin, is often prescribed for the treatment of type 2 diabetes. More recently, the glitazone class of compounds (i.e. 5-benzylthiazolidine-2,4-diones) have been used to ameliorate many symptoms of type 2 diabetes. These agents substantially increase insulin sensitivity in muscle, liver and adipose tissue resulting in partial or complete correction of the elevated plasma glucose levels without occurrence of hypoglycemia. The glitazones that are currently marketed are agonists of the peroxisome proliferator activated receptor (PPAR), primarily the PPAR-gamma subtype. This PPAR-gamma agonism is generally believed to be responsible for the improved insulin sensitization that is observed with the glitazones. Newer PPAR agonists that are being tested for treatment of Type II diabetes are agonists of the alpha, gamma or delta subtype, or a combination of these, and in many cases are chemically different from the glitazones (i.e., they are not thiazolidinediones). Serious side effects (e.g. liver toxicity) have occurred with some of the PPAR agonists, such as troglitazone. Dipeptidyl peptidase-IV ("DPP-IV") has been implicated in the control of glucose metabolism because its substrates include the insulinotropic hormones glucagons-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP). GLP-1 and GIP are active only in their intact forms and removal of their two N-terminal amino acids will inactivate them. DPP-IV, a serine protease belonging to the group of post-proline/alanine cleaving amino-dipeptidases, specifically removes the two N-terminal amino acids from proteins such as GIP and GLP-1 which have proline or alanine in position 2. Although the physiological role of DPP-IV has not been completely established, it is believed to play an important role in at least impaired fasting glucose (IFG) and diabetes. In vivo administration of synthetic inhibitors of DPP-IV prevents N-terminal degradation of GLP-1 and GIP, which results in (1) higher plasma concentrations of these hormones; (2) increased insulin secretion; and (3) improved glucose tolerance. Thus, such DPP-IV inhibitors have been proposed for the treatment of patients with type II diabetes, a disease characterized by decreased glucose tolerance. In addition, since the body produces these hormones only when food is consumed, DPP-IV inhibition is not expected to increase the level of insulin at inappropriate times, such as between meals, which can lead to excessively low blood sugar (hypoglycemia). Inhibition of DPP-IV is therefore expected to increase insulin without increasing the risk of hypoglycemia, which is dangerous side effect associated with the use of insulin secretagoguese. Currently there are a few compounds under review in advanced stages of human clinical trials that have been shown to inhibit DPP-IV. For example, such compounds have been disclosed in U.S. Patent No. 6,124,305, WO 98/19998, WO 03002530, WO 02083109, WO 00/34241, and WO 99138501, and, for example, Novartis "NVP-DPP-728", Probiodrug "P32/98", and Novartis "NVP-LAF-237". Although the above DPP-IV inhibitors have been described in the literature, all have limitations relating to their potency, stability, selectivity and/or toxicity. Therefore, there still exists a need for novel DPP-IV inhibitors, which are therapeutically useful in the treatment of medical conditions mediated by DPP-IV inhibition. SUMMARY OF THE INVENTION The present invention relates to new Dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (I), their analogs, their tautomers, their enantiomers, their diastereomers, their regioisomers, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their N-oxides, their pharmaceutically acceptable solvates and the pharmaceutical compositions containing them. The new compounds are of general formula (I) wherein: X is selected from -S(O)m, -CH2-, CHF, and -CF2; m is 0, 1 or 2; n is 0, 1 , 2, 3 or 4; R1 is selected from the group consisting of hydrogen, nitrile (-CN), COOH, or isosteres of carboxylic acids, wherein said of isosteres of carboxylic acids are selected from the group consisting of SO3H, CONOH, B(OH)2, PO3R3R4, SO2NR3R4, tetrazole, amides, esters and acid anhydrides; wherein R2 is selected from groups consisting of hydrogen, cyano, oxo (=O), formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, -COOR , CH2OR3, COR3, CONR3R4, NR3R4 and NR3CONR3R4, -NR3COR4,NR3COOR4, NR3S(O)mR4, -S(O)mNR3R4, -OCONR3R4,- OR3 ,-R3 ,-SR3. R3 and R4 may be same or different and are independently selected from the group consisting of hydrogen, nitro, hydroxy, cyano, formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylakyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl and substituted or unsubstituted carboxylic acid derivatives or the analogs, tautomeric forms, regioisomers, stereoisomers, enantiomers, diastereomers, polymorphs, solvates, N-oxides, or pharmaceutically acceptable salts thereof. The present invention also includes compounds of the general formula (II) wherein: X is selected from -S(O)m, -CH2-, CHF, and -CF2; m is 0, 1 or 2; R1 is selected from hydrogen, nitrile (-CN), COOH, or isosteres of carboxylic acids, wherein said isosteres of carboxylic acids are selected from the group consisting of SO3H, CONOH, B(OH)2, PO3R3R4, SO2NR3R4, tetrazole, amides, esters and acid anhydrides; wherein R is selected from groups consisting of hydrogen, cyano, oxo (=0), formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, -COOR , - CH2OR3, COR3, CONR3R4, NR3R4 and NR3CONR3R4, -NR3COR4,NR3COOR4, NR3S(O)mR4, -S(O)mNR3R4, -OCONR3R4,- OR3 ,-R3 ,-SR3. R3 and R4 may be same or different and are independently selected from the group consisting of hydrogen, nitro, hydroxy, cyano, formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl and substituted or unsubstituted carboxylic acid derivatives or the analogs, tautomeric forms, regioisomers, stereoisomers, enantiomers, diastereomers, polymorphs, solvates, N-oxides, or pharmaceutically acceptable salts thereof. Further preferred is the compound of general formula (II) Further preferred is a compound of general formula (II), wherein R1 is Hydrogen. Further preferred is a compound of general formula (II), wherein R1 is -CN. Further preferred is a compound of general formula (II), wherein R1 is -CONH2. Further preferred is a compound of general formula (II), wherein X is selected from -CH2- ,-CHF- and -S(O)m- ;wherein m is 0. Further preferred is a compound of general formula (II), wherein R is chosen from the group consisting of CN, COR3' COOR3, -CH2OR3 and CONR3R4. Further preferred is a compound of general formula (II), wherein R is hydrogen. Further preferred is a compound of general formula (II), wherein R is Methyl Further preferred is a compound of general formula (II), wherein R is Pyrrolidin-lyl Further preferred is a compound of general formula (II), wherein R3 is 4-Nitro phenyl Further preferred is a compound of general formula (II), wherein R is 4-Cyano phenyl Further preferred is a compound of general formula (II), wherein R4 is methyl Further preferred is a compound of general formula (II), wherein R4 is ethyl Further preferred is a compound of general formula (II), wherein R4 is isopropyl Further preferred is a compound of general formula (II), wherein R4 is n-hexyl. Further preferred is a compound of general formula (II), wherein R n-butyl. Further preferred is a compound of general formula (II), wherein R4 is 4-fluro phenyl Some of the representative compounds according to the present invention are specified below but should not construed to be limited thereto: 1. Methyl( 1 RS,2RS)-2-{(1RS)-1 -amino-2-[(2S)-2-cyanopyrrolidin-1 -yl]-2-oxoethyl} cyclopropane-1 -carboxylate 2. Methyl (1S, 2S)-2-{(15)-l-amino-2-[(2S)-2-cyanopyrrolidin-l-yl]-2-oxoethyl} cyclopropane-1 -carboxylate trifluoroacetate 3. Methyl (1R, 2R)-2-{(lR)-l-amino-2-[(2,S)-2-cyanopyrrolidin-l-yl]-2-oxoethyl} cyclopropane-1 -carboxylate trifluoroacetate 4. 1 - {(2S)-2- Amino-2- [(1S',2S)-2-cyanocyclopropyl] ethanoyl} pyrrolidine-2-(2S)-carbonitrile trifluoroacetate 5. 1 -{(2S)-amino-2-[(1S, 2S)-2-methylcarbarnoylcyclopropyl]ethanoyl}pyrrolidine-2-(2,S)-carboxamide trifluoroacetate 6. l-{2(S)-2-Amino-2-[(lS,2S)-2-methylcarbamoylcyclopropyl]acetyl}-pyrrolidine-2(S)-carbonitrile trifluoroacetate 7. 1 - {2(S)-2-Amino-2- [(1 .S',2S)-2-methylcarbamoylcyclopropyl] acetyl} -pyrrolidine-2(S)-carbonitrile hydrochloride. 8. l-{2(R)-2-Amino-2-[(lR,2R)-2-methylcarbamoylcyclopropyl]acetyl} pyrrolidine-2(S)-carbonitrile hydrochloride 9. l-{(2S)-2-Amino-2-[(lS,2S)-2-ethylcarbamoylcyclopropyl]acetyl}-pyrrolidine-2-(2S)-carbonitrile trifluoroacetate 10. 1 - {(2S)-2-Amino-2-[( 1S',2S)-2-isopropylcarbamoylcyclopropyl] acetyl} -pyrrolidine-2-(2S)-carbonitrile trifluoroacetate 11. 1 -{2(R)-2-Amino-2-[(lR,2R)-2-isopropylcarbamoylcyclopropyl]acetyl}-pyrrolidine-2(S)-carbonitrile trifluoroacetate 12. 1 - {2(S)-2-Amino-2-[( 1S',2S)-2-butylcarbamoylcyclopropyl] acetyl} pyrrolidine-2(S)-carbonitrile trifluoroacetate 13.1- {2(S)-2-Amino-2- [(1S',2S)-2-hexylcarbamoylcyclopropyl] acetyl} -pyrrolidine-2(S)-carbonitrile trifluoroacetate 14.1- { 2(S)-2-Amino-2-[( 1S',2S)-2-azolanylcarbamoylcyclopropyl] acetyl} pyrrolidine-2(S)-carbonitrile trifluoroacetate 15. 1 -{2-(2S)-Amino-2-[(1S',2S)-2-(4-fluorophenylcarbamoyl)cyclopropyl]ethanoyl}-pyrrolidine-2-(2S)-carbonitriletrifluoroacetate 16.1- {(2S)-2-Amino-2-[(1S,2S)-2-(4-nitrophenoxymethyl)cyclopropyl]ethanoyl} pyrrolidin-2-yl-(2S)-carbonitrile trifluoroacetate 17. l-{(2R)-2-Amino-2-[(lR,2R)-2-(4-nitrophenoxymethyl)cyclopropyl]ethanoyl}-pyrrolidine-2-(2S)-carbonitrile trifluoroacetate 18. l-{(2S)-2-Amino-2-[(1S,2S)-2-(4-cyanophenoxymethyl)cyclopropyl]ethanoyl}-pyrrolidine-2-(2S)carbonitrile trifluoroacetate 19. l-{(2R)-2-Amino-2-[(lR,2R)-2-(4-cyanophenoxymethyl)cyclopropyl]ethanoyl}-pyrrolidine-2-(2S)-carbonitrile trifluoroacetate 20. 1 - {(2S)-2-(fert-Butoxycarbonyl)amino-2-[( 1S, 2S)-2-(4-cyanophenoxymethyl)-cyclopropyl] ethanoyl} pyrrolidine trifluoroacetate 21. N1 -Methyl-( 1 S,2S)-2- [(1S) 1 -amino-2-(pyrrolidin-1 -yl)-2-oxoethyl] cyclopropane-1 -carboxamide hydrochloride 22.N1-Methyl-(lJS,25)-2-{(1S)-l-amino-2-[(3S)-3-fluoropyrrolidin-l-yl]-2-oxoethyl} -cyclopropane-1 -carboxamide hydrochloride 23. Methyl( 1 RS,2RS)-2-(( 1RS)-1 -amino-2-oxo-2-( 1,3-thiazolan-3-yl)ethyl)cyclo-propane-1 -carboxylate hydrochloride 24.M-Methyl-(lRS,2RS)-2-[(lRS)-l-amino-2-oxo-2-(l,3-thiazolan-3-yl)ethyl] cyclopropane-1 -carboxamide hydrochloride 25. N1 -Methyl-( 1 S,2S)-2-[(1S)-amino-2-oxo-2-( 1,3-thiazolan-3-yl)ethyl]cyclo-propane-1 -carboxamide hydrochloride 26.N1-Methyl-(15,21S)-2-[(15)-amino-2-oxo-2-(4-(45)-cyano-l,3-thiazolan-3-yl)ethyl] -cyclopropane-1-carboxamide trifluoroacetate 27. M -methyl-( 1 S,2S)-2-{(1S)-1 -ethoxycarbonylamino-2-[(2S)-2-cyanopyrrolidin-1 -yl] -2 -oxoethyl} cyclopropane-1 -carboxaamide 28. N1 -methyl-( 1 S,2S)-2- {(1S)-1 -acetoxyethoxycarbonylamino-2- [(2S)-2-cyanopyrrolin-1 -yl]-2-oxoethyl}cyclopropane-1 -carboxaamide 29. N1-methyl-(lS,2S)-2-{(lS)-l-[(2S)pyrrolidin-2-ylcarboxamido]-2-[(2S)-2-cyano pyrrolidin-1 -yl] -2-oxoethyl} cyclopropane-1 -carboxamide trifluoroacetate A further aspect of the present invention is also the corresponding pharmaceutically acceptable salts such as trifluoroacetate salt, hydrochloride salt etc. but not to be limited thereto for the above five compounds. A further aspect of the present invention is a pharmaceutical composition useful in the treatment and/or prophylaxis of diseases, which are associated with DPP-IV, the composition comprising, as an active ingredient, a compound according to Formula I thereof together with a pharmaceutically acceptable carrier or diluent. A further aspect of the present invention is a method for the treatment and/or prophylaxis of diseases which are associated with DPP-IV, selected from the group consisting of diabetes, non-insulin dependent diabetes mellitus, impaired glucose tolerance, inflammatory bowel disease, ulcerative colitis, Crohn's disease, obesity, and metabolic syndrome, which method comprises administering to a host suffering therefrom a therapeutically effective amount of a compound according to Formula I. A further aspect of the present invention is a method of treating insulin resistant non-impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus comprising administering to a host suffering therefrom a therapeutically effective amount of a compound according to Formula I. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of a condition that may be regulated or normalized via inhibition of DPP-IV. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of metabolic disorders. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for blood glucose lowering. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of Type II diabetes. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of impaired glucose tolerance (IGT). A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of impaired fasting glucose (IFG). A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the prevention of hyperglycemia. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for delaying the progression of impaired glucose tolerance (IGT) to Type II diabetes. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for delaying the progression of non-insulin requiring Type II diabetes to insulin requiring Type II diabetes. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for increasing the number and/or the size of beta cells in a subject. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of beta cell degeneration, in particular apoptosis of beta cells. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of disorders of food intake. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of obesity. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for appetite regulation or induction of satiety. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of dyslipidemia. A further aspect of the present invention is the use of a compound of formula (I) as a pharmaceutical composition in a therapeutically effective amount for the treatment of functional dyspepsia, in particular irritable bowel syndrome. DETAILED DESCRIPTION The term 'alkyl' refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing solely of carbon and hydrogen atoms, containing no unsaturation, having from one to eight carbon atoms, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, 1,1-dimethylethyl (t-butyl), and the like. The term "alkenyl " refers to aliphatic hydrocarbon group containing a carbon-carbon double bond and which may be a straight or branched or branched chain having about 2 to about 10 carbon atoms, e.g., ethenyl, 1-propenyl, 2-propenyl (allyl), iso-propenyl, 2-methyl- 1-propenyl, 1-butenyl, 2-butenyl and the like. The term " alkynyl" refers to straight or branched chain hydrocarbyl radicals having at least one carbon-carbon triple bond, and having in the range of about 2 up to 12 carbon atoms (with radicals having in the range of about 2 up to 10 carbon atoms presently being preferred) e.g., ethynyl, propynyl, butnyl and the like. The term "alkoxy" denotes alkyl group as defined above attached via oxygen linkage to the rest of the molecule. Representative examples of those groups are -OCH3, -OC2H5 and the like. The term "cycloalkyl" denotes a non-aromatic mono or multicyclic ring system of about 3 to 12 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and examples of multicyclic cycloalkyl groups include perhydronapththyl, adamantyl and norbornyl groups bridged cyclic group or sprirobicyclic groups e.g. sprio (4,4) non-2-yl. The term "cycloalkylalkyl" refers to cyclic ring-containing radicals containing in the range of about 3 up to 8 carbon atoms directly attached to alkyl group which are then attached to the main structure at any carbon from alkyl group that results in the creation of a stable structure such as cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl, and the like. The term "cycloalkenyl" refers to cyclic ring-containing radicals containing in the range of about 3 up to 8 carbon atoms with at least one carbon- carbon double bond such as cyclopropenyl, cyclobutenyl, cyclopentenyl and the like. The term "aryl" refers to aromatic radicals having in the range of 6 up to 14 carbon atoms such as phenyl, naphthyl, tetrahydronapthyl, indanyl, biphenyl and the like. The term "arylalkyl" refers to an aryl group as defined above directly bonded to an alkyl group as defined above, for example, -CH2C6H5, -C2H5C6H5 and the like. The term "heterocyclic ring" refers to a stable 3 to 15 membered ring radical which consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, phosphorus, oxygen and sulfur. For purposes of this invention, the heterocyclic ring radical may be a monocyclic, bicyclic or tricyclic ring system, which may include fused, bridged or spiro ring systems, and the nitrogen, phosphorus, carbon, oxygen or sulfur atoms in the heterocyclic ring radical may be optionally oxidized to various oxidation states. In addition, the nitrogen atom may be optionally quaternized; and the ring radical may be partially or fully saturated (i.e., heteroaromatic or heteroaryl aromatic). Examples of such heterocyclic ring radicals include, but are not limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl, benzofurnyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl, naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrazoyl, imidazolyl, tetrahydroisouinolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl, oxasolidinyl, triazolyl, indanyl, isoxazolyl, isoxasolidinyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolyl, isoquinolyl, decahydroisoquinolyl, benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzooxazolyl, furyl, tetrahydrofurtyl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide thiamorpholinyl sulfone, dioxaphospholanyl, oxadiazolyl, chromanyl, isochromanyl and the like. The heterocyclic ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. The term "heteroaryl" refers to heterocyclic ring radical as defined above. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. The term "heteroarylalkyl" refers to heteroaryl ring radical as defined above directly bonded to alkyl group. The heteroarylalkyl radical may be attached to the main structure at any carbon atom from alkyl group that results in the creation of a stable structure. The term "heterocyclyl" refers to a heterocyclic ring radical as defined above. The heterocyclyl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. The term "heterocyclylalkyl" refers to a heterocyclic ring radical as defined above directly bonded to alkyl group. The heterocyclylalkyl radical may be attached to the main structure at carbon atom in the alkyl group that results in the creation of a stable structure. The term "halogen" refers to radicals of fluorine, chlorine, bromine and iodine. The term isosteres of carboxylic acids include but are not limited to SO3H, CONOH, B(OH)2, PO3R3R4, SO2NR3R4, tetrazole, amides, esters and acid anhydrides. The term amide includes but is not limited to CONR3R4 where R3 and R4 are independently selected for each occurrence and are as previously defined. The term ester includes but is not limited to COOR3 where R3 is independently selected for each occurrence and is as previously described except R3 cannot be hydrogen. The substituents in the 'substituted alkyl', 'substituted alkoxy', 'substituted alkenyl', 'substituted alkynyl', 'substituted cycloalkyl', 'substituted cycloalkylalkyl', 'substituted cyclocalkenyl', 'substituted arylalkyl, 'substituted aryl', 'substituted heterocyclic ring', 'substituted heteroaryl ring', 'substituted heteroarylalkyl', 'substituted heterocyclylalkyl ring', 'substituted amino', and 'substituted carboxylic acid derivative' may be the same or different which one or more selected from the groups such as hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (=O), thio(=S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, 'substituted heterocyclylalkyl ring' substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted guanidine, -COORx, -C(O)Rx, -C(S)Rx, -C(O)NRxRy, -C(O)ONRxRy, -NRxCONRyRz, -N(Rx)SORy, -N(Rx)SO2Ry, -(=N-N(Rx)Ry), -NRxC(O)ORy, -NRxRy, -NRxC(O)Ry-, -NRxC(S)Ry -NRxC(S)NRyRz, -SONRxRy-, -S02NRxRy-, -ORx, -ORxC(0)NRyRz, -ORxC(O)ORy-, -OC(O)Rx, -OC(O)NRxRy, -RxNRyC(O)Rz, -RxORy, -RxC(O)ORy, -RxC(O)NRyRz, -RXC(O)RX, -RxOC(O)Ry, -SRX, -SORx, -SO2RX, -ONO2, wherein RX, Ry and Rz in each of the above groups can be hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, 'substituted heterocyclylalkyl ring' substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic ring, The term "treating" or "treatment" of a state, disorder or condition as used herein means: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a mammal that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (II) inhibiting the state, disorder or condition, i.e., arresting or reducing the development of the disease or at least one clinical or subclinical symptom thereof, or (III) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms. The benefit to a subject to be treated is either statistically significant or at least perceptible to the patient or to the physician. The term "therapeutically effective amount" as used herein means the amount of a compound that, when administered to a mammal for treating a state, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, physical condition and responsiveness of the mammal to be treated. The term "delivering" as used herein means providing a therapeutically effective amount of an active ingredient to a particular location within a host means causing a therapeutically effective blood concentration of the active ingredient at the particular location. This can be accomplished, e.g., by local or by systemic administration of the active ingredient to the host. The term "prophylaxis" involves the administration of a compound of the invention prior to the clinical appearances of the disease or prior to the induction of the disease. The term "subject" or "a patient" or "a host" as used herein refers to mammalian animals, preferably human. Pharmaceutically acceptable salts forming part of this invention include salts derived from inorganic bases such as Li, Na, K, Ca, Mg, Fe, Cu, Zn, Mn; salts of organic bases such as N,N'-diacetylethylenediamine, glucamine, triethylamine, choline, hydroxide, dicyclohexylamine, metformin, benzylamine, trialkylamine, thiamine, and the like; chiral bases like alkylphenylamine, glycinol, phenyl glycinol and the like, salts of natural amino acids such as glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, proline, hydroxy proline, histidine, ornithine, lysine, arginine, serine, and the like; quaternary ammonium salts of the compounds of invention with alkyl halides, alkyl sulphates like Mel, (Me)2SO4 and the like, non-natural amino acids such as D-isomers or substituted amino acids; guanidine, substituted guanidine wherein the substituents are selected from nitro, amino, alkyl, alkenyl, alkynyl, ammonium or substituted ammonium salts and aluminum salts. Salts may include acid addition salts where appropriate, which are sulphates, nitrates, phosphates, perchlorates, borates, hydrohalides, acetates such as trifluroacetate, tartrates, maleates, citrates, fumarates, succinates, palmoates, methanesulphonates, benzoates, salicylates, benzenesulfonates, ascorbates, glycerophosphates, ketoglutarates and the like. Pharmaceutically acceptable solvates may be hydrates or comprise other solvents of crystallization such as alcohols. The compounds of the present invention may form solvates with standard low molecular weight solvents using methods known to the skilled artisan. In another aspect, the present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one compound of the invention which inhibits the enzymatic activity of DPP-IV or a pharmaceutically acceptable salt or prodrug or hydrate thereof together with a pharmaceutically acceptable carrier or diluent. Pharmaceutical compositions containing a compound of the invention of the present invention may be prepared by conventional techniques, e.g. as described in Remington: The Science and Practice of Pharmacy, 19th Supp. Ed., 1995. The compositions may appear in conventional forms, for example capsules, tablets, aerosols, solutions, suspensions or topical applications. Typical compositions include a compound of the invention which inhibits the enzymatic activity of DPP-IV or a pharmaceutically acceptable basic addition salt or prodrug or hydrate thereof, associated with a pharmaceutically acceptable excipient which may be a carrier or a diluent or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, paper or other container. In making the compositions, conventional techniques for the preparation of pharmaceutical compositions may be used. For example, the active compound will usually be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of an ampoule, capsule, sachet, paper, or other container. When the carrier serves as a diluent, it may be solid, semi-solid, or liquid material that acts as a vehicle, excipient, or medium for the active compound. The active compound can be adsorbed on a granular solid container for example in a sachet. Some examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavoring agents. The formulations of the invention may be formulated so as to provide quick, sustained, or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art. The pharmaceutical compositions can be sterilized and mixed, if desired, with auxiliary agents, emulsifiers, salt for influencing osmotic pressure, buffers and/or coloring substances and the like, which do not deleteriously react with the active compounds. The route of administration may be any route, which effectively transports the active compound of the invention which inhibits the enzymatic activity of DPP-IV to the appropriate or desired site of action, such as oral, nasal, pulmonary, buccal, subdermal, intradermal, transdermal or parenteral, e.g., rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic solution or an ointment, the oral route being preferred. If a solid carrier is used for oral administration, the preparation may be tabletted, placed in a hard gelatin capsule in powder or pellet form or it can be in the form of a troche or lozenge. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatin capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution. For nasal administration, the preparation may contain a compound of the invention, which inhibits the enzymatic activity of DPP-IV, dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application. The carrier may contain additives such as solubilizing agents, e.g., propylene glycol, surfactants, absorption enhancers, such as lecithin (phosphatidylcholine) or cyclodextrin, or preservatives such as parabenes. For parenteral application, particularly suitable are injectable solutions or suspensions, preferably aqueous solutions with the active compound dissolved in polyhydroxylated castor oil. Tablets, dragees, or capsules having talc and/or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Preferable carriers for tablets, dragees, or capsules include lactose, cornstarch, and/or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed. A typical tablet that may be prepared by conventional tabletting techniques may contain: 1 Core: Active compound (as free compound or salt thereof) 250 mg Colloidal silicon dioxide (Aerosil®) 1.5 mg Cellulose, microcryst. (Avicel®) 70 mg Modified cellulose gum (Ac-Di-Sol®) 7.5 mg Magnesium stearate Ad. Coating: HPMC approx. 9 mg *Mywacett 9-40 T approx. 0.9 mg *Acylated monoglyceride used as plasticizer for film coating. Where the term compound of Formula I is used, it is understood that this also encompasses subgeneric formula II. The compounds of the invention may be administered to a mammal, especially a human in need of such treatment, prevention, elimination, alleviation or amelioration of the various diseases as mentioned above, e.g., Type II diabetes, IGT, IFG, obesity, appetite regulation or as a blood glucose lowering agent, and especially Type II diabetes. Such mammals include also animals, both domestic animals, e.g. household pets, and non-domestic animals such as wildlife. The compounds of the invention are effective over a wide dosage range. For example, in the treatment of adult humans, dosages from about 0.05 to about 1000 mg, preferably from about 0.1 to about 500 mg, per day may be used. More preferably, the dosage is about 0.5 mg to about 250 mg per day. In choosing a regimen for patients it may frequently be necessary to begin with a higher dosage and when the condition is under control to reduce the dosage. The exact dosage will depend upon the mode of administration, on the therapy desired, form in which administered, the subject to be treated and the body weight of the subject to be treated, and the preference and experience of the physician or veterinarian in charge. Generally, the compounds of the present invention are dispensed in unit dosage form comprising from about 0.05 to about 1000 mg of active ingredient together with a pharmaceutically acceptable carrier per unit dosage. Usually, dosage forms suitable for oral, nasal, pulmonal or transdermal administration comprise from about 0.05 mg to about 1000 mg, preferably from about 0.5 mg to about 250 mg of the compounds admixed with a pharmaceutically acceptable carrier or diluent. The invention also encompasses prodrugs of a compound of the invention, which on administration undergo chemical conversion by metabolic processes before becoming active pharmacological substances. In general, such prodrugs will be functional derivatives of a compound of the invention, which are readily convertible in vivo into a compound of the invention. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985. The invention also encompasses active metabolites of a compound of the invention. The present invention discloses a process for the preparation of compounds of general formula (I). wherein: X is selected from -S(O)m, -CH2, CHF, and -CF2; m is 0, 1 or 2; n is 0, 1 , 2, 3 or 4; R1 is selected from the group consisting of hydrogen, nitrile (-CN), COOH, or isosteres of carboxylic acids, wherein said of isosteres of carboxylic acids are selected from the group consisting of SO3H, CONOH, B(OH)2, PO3R3R4, SO2NR3R4, tetrazole, amides, esters and acid anhydrides; wherein R2 is selected from groups consisting of hydrogen, cyano, oxo (=0), formyl, acetyl, halogen, substituted or Unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, -COOR , CH2OR3, COR3, CONR3R4, NR3R4 and NR3CONR3R4, -NR3COR4,NR3COOR4, NR3S(O)mR4, -S(O)mNR3R4, -OCONR3R4,- OR3 ,-R3 ,-SR3. R3 and R4 may be same or different and are independently selected from the group consisting of hydrogen, nitro, hydroxy, cyano, formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylakyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl and substituted or unsubstituted carboxylic acid derivatives or the analogs, tautomeric forms, regioisomers, stereoisomers, enantiomers, diastereomers, polymorphs, solvates, N-oxides, or pharmaceutically acceptable salts thereof. The present invention also includes compounds of the general formula (II) disclosed wherein Formula (II) has the structure; wherein: X is selected from -S(O)m, -CH2-, CHF, and -CF2; m is 0, 1 or 2; R1 is selected from hydrogen, nitrile (-CN), COOH, or isosteres of carboxylic acids, wherein said isosteres of carboxylic acids are selected from the group consisting of SO3H, CONOH, B(OH)2, PO3R3R4, S02NR3R4, tetrazole, amides, esters and acid anhydrides; wherein R is selected from groups consisting of hydrogen, cyano, oxo (=0), formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, -COOR3, CH2OR3, COR3, CONR3R4, NR3R4 and NR3CONR3R4, -NR3COR4,NR3COOR4, NR3S(O)mR4, -S(O)mNR3R4, -OCONR3R4,- OR3 ,-R3 ,-SR3. wherein R3 and R4 may be same or different and are independently selected from the group consisting of hydrogen, nitro, hydroxy, cyano, formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl and substituted or unsubstituted carboxylic acid derivatives or the analogs, tautomeric forms, regioisomers, stereoisomers, enantiomers, diastereomers, polymorphs, solvates, N-oxides, or pharmaceutically acceptable salts thereof. The compounds according to the invention may be prepared by the following processes. The symbols X, R1and R2 when used in the formulae below are to be understood to present those groups described above in relation to formula (I) unless otherwise indicated The present invention discloses a process for the preparation of compounds of general formula (I). In one embodiment the desired compounds of the formula (I) as described in the general description can be synthesized as described in the general synthetic scheme I. which comprises coupling a compound of general formula (III) with a compound of the general formula (IVA) under standard peptide coupling conditions, for example, using EDC, HOBt, and a base, generally diisopropylethylamine, in a solvent such as DMF or methylene chloride for about 3 to about 48 hours at ambient temperature followed by de-protection using common methods known in the art to give the compounds of general formula (I). It is also understood that the compounds of general formula (III) used for the coupling reaction may be further modified before formation of the compounds of general formula (I), for example, by manipulation of substituents on R2. These manipulations may include, but are not limited to, substitution, reduction, oxidation, alkylation, acylation, and hydrolysis reaction which are commonly known to those skilled in the art. Further, the preferred compounds of the general formula (II) wherein all groups are as previously described; may be prepared by a process as described in the scheme 2 Scheme 2 which comprises coupling a compound of general formula (IIIa) with a compound of the general formula (IVA) under standard peptide coupling conditions, for example, using EDC, HOBt, and a base, generally diisopropylethylamine, in a solvent such as DMF or methylene chloride for about 3 to about 48 hours at ambient temperature to provide intermediate (Va) .This is then treated with dehydrating agent such as POCI3 /Pyridine followed by deprotection using common methods known in the art to give the preferred compounds of the formula (II) wherein R1 is nitrile. It is also understood that the compounds of general formula (Ilia) and/or (Va) as described in Scheme 2 may be further modified before formation of the preferred compound of the formula (I) wherein R1 is nitrile, for example, by manipulation of substituents on R . These manipulations may include, but are not limited to, substitution, reduction, oxidation, alkylation, acylation, and hydrolysis reaction which are commonly known to those skilled in the art. The compounds of general formula (III) and formula (IV) can be prepared using a variety of methods known in the literature and known to those skilled in the art. The compounds of the formula (III.a) can be prepared in accordance to the Scheme 3: wherein, Z is alkyl such as methyl, ethyl, t-butyl; arylalkyl such as benzyl group. Synthesis of compound VI can be found in the following reference: O'Donnell et al., J. Org. Chem., 1982, 47, 2663-2666. R is selected from groups consisting of cyano, formyl, acetyl, substituted or unsubstituted amide, -COOR3, COR3, CONR3R4, and nitro. Similarly compound VII with different stereochemistry can be synthesized as given above or in the following references: Chavan et al., J. Org. Chem., 2003, 68, 6817-6819, Chavan et al., Tetrahedron Letters, 1996, 37, 2857-2858, Kurokowa et al., Tetrahedron Letters, 1985, 26, 83-84, Shimamoto et al., Tetrahedron Letters, 1989, 29, 3803-3804, Yamanoi et al., Tetrahedron Letters, 1988, 29, 1181 -1184 . R3 and R4 may be same or different and are independently selected from the groups consisting of hydrogen, nitro, hydroxy, cyano, formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstitued alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylakyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroarylalkyl and substituted or unsubstituted carboxylic acid derivatives or the analogs, tautomeric forms, regioisomers, stereoisomers, enantiomers, diastereomers, polymorphs, solvates, N-oxides, or pharmaceutically acceptable salts thereof. Further R2 group in the compound (VII) may be modified to give before converting it to Compound (Ilia). These modifications may include, but are not limited to, substitution, reduction, oxidation, alkylation, acylation and hydrolysis reaction which are commonly known to those skilled in the art. In specific, the compounds of formula (IVA) can be prepared in accord to the Scheme 4 wherein, Pg represents a suitable nitrogen protecting group such as BOC, CBZ, and FMOC. X is selected from -S (O) m, -CH2-, CHF, and -CF2; wherein, m is 0, 1 or 2. One of the possible routes for synthesis of compound of formula (IVA) shown in scheme 4 involves treatment of a carbamate derivative (VIII) with N-hydroxy succinimide (NHS) and DCC or other suitable coupling agent in a solvent such as dichloromethane for about 1 to about 24 hours. The resulting product (IX) is then treated with a base, for example, aqueous ammonium hydroxide in a solvent such as dioxane. Deprotection of compound (X) using common methods known in the art gives the desired compound (IVA). Further the carbamate derivative (VIII) is commercially available or may be conveniently prepared by methods in the literature or known to those skilled in the art. The compounds in accordance to the invention are isolated and purified in a manner known per se, for example, by distilling off the solvent in vacuum and recrystallizing the residue obtained from a suitable solvent or subjecting it to one of the customary purification methods, such as column chromatography on a suitable support material. Salts are obtained by dissolving the free compound in a suitable solvent, for example, in a chlorinated hydrocarbon, such as methylene chloride or chloroform, or a low molecular weight aliphatic alcohol (for example, ethanol or isopropanol), which contains the desired acid or base, or to which the desired acid or base is then added. The salts are obtained by filtering, reprecepitating, precipitating with a non-solvent for the addition salt or by evaporating the solvent. Salts obtained can be converted by basification or by acidifying into the free compounds which, in turn, can be converted into salts. In general, the ethereal solvents used in the above described processes for the preparation of compounds of the formula (I) are selected from diethyl ether, 1,2-dimethoxyethane, tetrahydrofuran, diisopropyl ether, 1,4 dioxane and the like. The chlorinated solvent which may be employed may be selected from dichloromethane, 1,2-dichloroethane, chloroform, carbontetrachloride and the like. The aromatic solvents which may be employed may be selected from benzene and toluene. The alcoholic solvents which may be employed may be selected from methanol, ethanol, n-propanol, iso propanol, tert-butanol and the like. The aprotic solvents which may be employed may be selected from N, N-dimethylformamide, dimethyl sulfoxide and the like. In general, the compounds prepared in the above described processes are obtained in pure form by using well known techniques such as crystallization using solvents such as pentane, diethyl ether, isopropyl ether, chloroform, dichloromethane, ethyl acetate, acetone, methanol, ethanol, isopropanol, water or their combinations, or column chromatography using alumina or silica gel and eluting the column with solvents such as hexane, petroleum ether (pet.ether), chloroform, ethyl acetate, acetone, methanol or their combinations. Various polymorphs of a compound of general formula (I) forming part of this invention may be prepared by crystallization of compound of formula (I) under different conditions, for example, using different solvents commonly used or their mixtures for recrystallization, crystallizations at different temperatures, various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymorphs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of polymorphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calorimetry, powder X-ray diffraction or such other techniques. The present invention provides new organic compounds, their analogs, their tautomers, their regioisomers, their stereoisomers, their enantiomers, their diastereomers, their polymorphs, their pharmaceutically acceptable salts, their appropriate N-oxides and their pharmaceutically acceptable solvates. The present invention also provides pharmaceutical compositions, containing compounds of general formula (I) as defined above, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their enantiomers, their diastereomers, their pharmaceutically acceptable salts or their pharmaceutically acceptable solvates in combination with the usual pharmaceutically employed carriers, diluents and the like. The pharmaceutical compositions according to this invention can be used for the treatment of allergic disorders. It will be appreciated that some of the compounds of general formula (I) defined above according to the invention can contain one or more asymmetrically substituted carbon atoms. The presence of one or more of these asymmetric centers in the compounds of general formula (I) can give rise to stereoisomers and in each case the invention is to be understood to extend to all such stereoisomers, including enantiomers and diastereomers and their mixtures, including racemic mixtures. The invention may also contain E & Z geometrical isomers wherever possible in the compounds of general formula (I) which includes the single isomer or mixture of both the isomers The invention is explained in detail in the examples given below which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention. Intermediates Intermediate 1 Benzyl (2SR)-2-amino-2-[(lSR, 2SR)-2-methyloxycarbonylcyclopropyl] acetate Step 1: Benzyl iV-(diphenylmethylene) glycinate: This intermediate is commercially available. Alternatively it can be prepared from diphenylimine and benzyl glycinate by a literature procedure (O'Donnel, M. J.; Polt, R. L. J. Org. Chem. 1982, 47, 2663-2666). Step 2: Benzyl (2SR)-2-(diphenylmethyleneamino-2-[(1SR,2SR)-2-methyloxycarbonyl-cyclopropyl]acetate hydrochloride: To a solution of benzyl N-(diphenylmethylene)-glycinate (50.0 g, 151.79 mmol), methyl-4-bromocrotonate (34.0 g, 189.74 mmol) and lithium bromide (19.8 g, 189.74 mmol) in dry THF (900 ml) was added triethylamine (26.4 ml, 189.74 mmol) in dry THF (100 ml) over a period of 45 min. The reaction mixture was stirred for 20 h at room temperature. The mixture was diluted with cold water (500 ml) and then extracted with ethyl acetate (4 x 500 ml). The combined organic extracts were acidified with 10JV hydrochloric acid (40 ml) and the mixture was stirred for 30 min at room temperature. The amine hydrochloride precipitated out was collected by filtration to give 31 g (68 %) of the product as a white solid; Mp: 208 °C, IR (KBr) 3423, 2953, 2627, 2464, 1756, 1717, 1499, 1398, 1367, 1297, 1220, 1037, 753 cm-1; 1H NMR(300 MHz, DMSO-d6) 5 1.11-1.17 (m, 1H), 1.21-1.27 (m, 1H), 1.66-1.71 (m, 1H), 2.00-2.06 (m, 1H), 3.61 (s, 3H), 3.74-3.77 (br d, J= 9.3 Hz, 1H), 5.22-5.26 (d, J= 12.3 Hz, 1H), 5.27-5.31 (d, J= 12.3 Hz, 1H), 7.38-7.41 (m, 5H), 8.78 (br s, 3H). Step 3: Benzyl (2SR)-2-(diphenylmethyleneamino-2-[(1SR,2SR)-2-methyloxycarbonyl-cyclopropyl]acetate: The amine hydrochloride (30.0 g, 100.07 mmol) from Step 2 was basified to pH 8.0 using 2N NaOH solution. The aqueous solution was extracted with ethyl acetate (3 x 300 ml) and the combined organic extracts were dried (Na2SO4) and evaporated under reduced pressure to give to 24.0 g (91 %) of the product as a viscous liquid; IR (neat) 3362, 3032, 2953, 1731, 1455, 1278, 1210, 1175, 1024, 930, 751, 699 cm-1;1H NMR (300 MHz, CDC13) 5 1.09 (m, 1H), 1.19 (m, 1H), 1.70 (m, 2H), 2.04 (br s, 2H), 3.65 (s, 3H), 3.68 (m, 1H), 5.20 (m, 2H) 7.29-7.4 (m, 5H). Intermediate 2 (2SR)-2-(tert-Butyloxycarbonylamino)-2-[(1SR,2SR)-2-methyloxycarbonylcyclo-propyl] acetic acid Step 1: Benzyl (2SR)-2-(tert-Butoxycarbonylamino-2-[(1SR,2SR)-2-methyloxy-carbonylcyclopropyl]acetate: Di-tert-butyl dicarbonate (7.3 g, 33.84 mmol) was added to a solution of Intermediate 1 (8.1 g, 30.76 mmol) in dichloromethane (200 ml) and the mixture was stirred at room temperature for 20 h. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography using 10 % ethyl acetate in petroleum ether as eluent to afford 9.1 g (81%) of the product as a viscous oil; IR (neat) 3367, 3033, 2978, 1715, 1722, 1514, 1344, 1248, 1168, 1024, 752 cm-1;1H NMR (300 MHz, CDC13) 5 1.10-1.08 (m, 1H), 1.19-1.22 (m, 1H), 1.43 (s, 9H), 1.71-1.76 (m, 2H), 3.64 (s, 3H), 4.06-4.13 (m, 1H), 5.10-5.27 (m, 2H), 7.34-7.38 (m, 5H). Step 2: To a solution of Step 1 intermediate (9.1 g, 25.04 mmol) in methanol (200 ml) was added 5 % Pd-C (2.0 g) and the mixture was stirred under hydrogen atmosphere for 15 h. The reaction mixture was filtered to remove the catalyst and the solvent was evaporated under reduced pressure to give 6.25 g (92 %) of the product as a viscous oil; IR(neat): 3368,3071,2653, 1747, 1724, 1651, 1457, 1406, 1356, 1254, 1181, 1049 cm"1; 1H NMR (300 MHz, CDCI3) 8 1.08-1.14 (m, 1H), 1.26-1.33 (m, 1H), 1.45 (s, 9H), 1.77-1.79 (m, 2H), 3.68 (s, 3H), 3.97 (br s, 1H), 5.14 (br d, J= 6.9 Hz, 1H), 6.80 (br s, 1H). Intermediate 3 Benzyl (2S)-2-amino-2- [(lS,2S)-2-methyloxycarbonylcyclopropyl] acetate A mixture of Intermediate 1 (10 g, 37.98 mmol) and dibenzoyl-D-tartaric acid (13.61 g, 37.98 mmol) in acetonitrile (50 ml) was heated to reflux. A minimum amount of methanol was added to the refluxing mixture to result a clear solution. The hot solution was diluted with acetonitrile (250 ml) and further allowed to cool to room temperature over a period of 30 min. The mixture was further stirred at RT to result a white precipitate. The precipitated diastereomeric salt was collected by filtration. The free amine was regenerated by basification of the salt using aqueous sodium hydroxide. The aqueous solution was extracted with dichloromethane (3 x 100 ml) and the combined organic extracts were washed with brine (50 ml) and dried over anhydrous potassium carbonate. The solvent was evaporated under reduced pressure to yield 2.5 g of the product in >98 % ee as determined by chiral HPLC; [a]D20 = + 47.23 (c = 0.81, CHCI3); IR(neat) 3383, 2952, 1729, 1607,1498, 1454, 1277, 1208, 1171, 1027, 926, 740 cm-1; 1H NMR (300 MHz, CDCI3) 5 1.05-1.12 (m, 1H), 1.19-1.24 (m, 1H), 1.16-1.66 (m, 1H), 1.68-1.76 (m, 1H), 3.16 (d, J= 7.2 Hz, 1H), 3.65 (s, 3H), 5.14 (d, J= 12 Hz, 1H), 5.20 (d, J= 12.3 Hz, 1H), 7.25-7.28 (m, 5H). The absolute stereochemistry of the product was assigned by its conversion to methyl 2-tert-butoxycarbonylamino(methyloxycarbonyl)methyl-1 -cyclopropanecarboxylate having known its relative and absolute stereochemistry; [CC]D = + 109.5 (c = 0.89, CHCI3) Lit. [δx]D = + 108.6 (c = 0.88, CHCI3), J. Org. Chem. 2003, 68, 6817. Intermediate 4 Benzyl (2R)-2-amino-2-[(lR,2R)-2-methyloxycarbonylcyclopropyl] acetate This intermediate was prepared by the resolution of Intermediate 1 using dibenzoyl-L-tartaric acid as described for Intermediate 2.; [α]D20 = - 42.86 (c = 0.74, CHC13); IR (neat) 3383, 2952, 1729, 1607, 1498, 1454, 1277, 1208, 1171, 1027, 926, 740 cm-1; [H NMR (300 MHz, CDCI3) 5 1.05-1.12 (m, 1H), 1.18-1.24 (m, 1H), 1.64-1.66 (m, 1H), 1.68-1.74 (m, 1H), 3.16 (d, J= 7.2 Hz, 1H), 3.65 (s, 3H), 5.14 (d, J= 12.6 Hz, 1H), 5.20 (d, J = 12.6 Hz, 1H), 7.26-7.29 (m, 5H). Intermediate 5 Benzyl (2S)-2-(tert-butyloxycarbonylamino)-2-[(1S,2S)-2-methyloxycarbonyIcyclo-propyl] acetate A solution of di-tert-butyl dicarbonate (0.20 g, 0.919 mmol) in dichloromethane (5 ml) was added to a solution of Intermediate 3 (0.22 g, 0.836 mmol) in dichloromethane (10 ml) and the mixture was stirred at room temperature for 20 h. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography using 10 % ethyl acetate in petroleum ether as eluent to afford 0.32 g of the product as a viscous oil; [αx]D = + 45.14 (c = 0.65, CH3OH); IR (neat) 3362, 2928, 1713, 1509, 1367, 1208, 1164, 1047, 1021, 751 cm-1; 1H NMR (300 MHz, CDC13) δ 1.02-1.08 (m, 1H), 1.19-1.26 (m, 1H), 1.43 (s, 9H), 1.68-1.76 (m, 2H), 3.65 (s, 3H), 4.04 (brt, 1H), 5.10 (br s, 1H), 5.15 (d, J= 12.3 Hz, 1H), 5.26 (d, J = 12.3 Hz, 1H), 7.15-7.21 (m, 5H). Intermediate 6 Benzyl (2R)-2-(tert-butyloxycarbonylamino)-2-[(lR,2R)-2-methyloxycarbonylcyclo-propyl] acetate This intermediate was prepared from Intermediate 4 (0.20 g, 0.76 mmol) and di-tert-butyl dicarbonate (0.18 g, 0.83 mmol) in dichloromethane (10 ml) as described for Intermediate 5 to give 0.260 g ( 94 %) of the product as a viscous liquid; [α]D = - 44.33 (c = 0.623, CH3OH); IR (neat): 3361, 2929, 1710, 1512, 1365, 1212, 1162, 1044, 1025, 754 cm-1; 1H NMR (300 MHz, CDCI3) 5 1.01-1.08 (m, 1H), 1.19-1.25 (m, 1H), 1.43 (s, 9H), 1.71-1.76 (m, 2H), 3.64 (s, 3H), 4.04 (br t, 1H), 5.09 (br s, 1H), 5.13 (d, J= 12.6 Hz, 1H), 5.23 (d, J= 12.6 Hz, 1H), 7.26-7.28 (m, 5H). Intermediate 7 Benzyl (2S)-2-(tert-butyloxycarbonylamino)-2-[(lS,2S)-2-methyloxycarbonylcyclo-propyl] acetic acid To a solution of Intermediate 5 (0.30 g, 0.825 mmol) in methanol (20 ml) was added 5 % Pd-C (0.125 g) and the mixture was stirred under hydrogen atmosphere for 15 h. The reaction mixture was further filtered to remove the catalyst and the solvent was evaporated under reduced pressure to give 0.220 g (98 %) of the product as a viscous oil; [αx]D = + 107.36 (c = 0.61, CH3OH); IR (neat): 3355, 2979, 1713, 1516, 1452, 1395, 1368, 1171, 1050, 1023, 933 cm-1; 1H NMR (300 MHz, CDCI3) 5 0.83-0.88 (m, 1H), 1.01-1.20 (br m, 1H), 1.21-1.35 (brm, 1H) 1.43, 1.45 (s,9H), 1.68-1.88 (m, 1H), 3.68 (s, 3H), 3.88-4.08 (br s, 1H), 5.17 (br s, 1H), 6.75 (br s, 1H). Intermediate 8 Benzyl (2R)-2-(fert-butoxycarbonylamino)-2-[(lR,2R)-2-methyloxycarbonylcyclo-propyl] acetic acid This compound was prepared from Intermediate 6 (0.28 g, 0.77 mmol) using 5 % Pd/C (0.120 g) in methanol (20 ml) as described in Intermediate 7 to give 0.163 g (77 %) of the product as a viscous oil; [

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